Serotonin Syndrome Associated With Vilazodone Overdose in a 22-Month-Old Treated With Dexmedetomidine

Alexandros G.Sfakianakis shared this article with you from Inoreader Serotonin Syndrome Associated With Vilazodone Overdose in a 22-Month-Old Treated With Dexmedetomidine Μέσω ScienceDirect Publication: The Journal of Emergency Medicine Publication date: Available online 4 November 2020 Source: The Journal of Emergency Medicine Author(s): Erica Schlichting, Chris Welter, Tammi Schaeffer, Tania D. Strout View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Self-reported health without clinically measurable benefits among adult users of multivitamin and multimineral supplements: a cross-sectional study

Alexandros G.Sfakianakis shared this article with you from Inoreader Self-reported health without clinically measurable benefits among adult users of multivitamin and multimineral supplements: a cross-sectional study Μέσω BMJ Open Current Issue Objective Multiple clinical trials fail to identify clinically measurable health benefits of daily multivitamin and multimineral (MVM) consumption in the general adult population. Understanding the determinants of widespread use of MVMs may guide efforts to better educate the public about effective nutritional practices. The objective of this study was to compare self-reported and clinically measurable health outcomes among MVM users and non-users in a large, nationally representative adult civilian non-institutionalised population in the USA surveyed on the use of complementary health practices. Design Cross-sectional analysis of the effect of MVM consumption on self-reported overall health and clinically measurable health outcomes. Participants Adult MVM users and non-users from the 2012 National Health Interview Survey (n=21 603). Primary and secondary outcome measures Five psychological, physical, and functional health outcomes: (1) self-rated health status, (2) needing help with routine needs, (3) history of 10 chronic diseases, (4) presence of 19 health conditions in the past 12 months, and (5) Kessler 6-Item (K6) Psychological Distress Scale to measure non-specific psychological distress in the past month. Results Among 4933 adult MVM users and 16 670 adult non-users, MVM users self-reported 30% better overall health than non-users (adjusted OR 1.31; 95% CI 1.17 to 1.46; false discovery rate adjusted p<0.001). There were no differences between MVM users and non-users in history of 10 chronic diseases, number of present health conditions, severity of current psychological distress on the K6 Scale and rates of needing help with daily activities. No effect modification was observed after stratification by sex, education, and race. Conclusions MVM users self-reported better overall health despite no apparent differences in clinically measurable health outcomes. These results suggest that widespread use of multivitamins in adults may be a result of individuals' positive expectation that multivitamin use leads to better health outcomes or a self-selection bias in which MVM users intrinsically harbour more positive views regarding their health. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

ZMYND8 expression in breast cancer cells blocks T-lymphocyte surveillance to promote tumor growth

Alexandros G.Sfakianakis shared this article with you from Inoreader ZMYND8 expression in breast cancer cells blocks T-lymphocyte surveillance to promote tumor growth Μέσω Cancer Research Online First Articles Emerging studies indicate that DNA damage in cancer cells triggers antitumor immunity, but its intrinsic regulatory mechanism in breast cancer cells remains poorly understood. Here, we show that ZMYND8 is upregulated and inhibits micronucleus formation and DNA damage in breast cancer cells. Loss of ZMYND8 triggered activation of the DNA sensor cyclic guanosine monophosphate-adenosine monophosphate synthase in micronuclei, leading to further activation of the downstream signaling effectors stimulator of interferon genes and NF-kappaB, but not TANK-binding kinase 1 and interferon regulatory factor 3, thereby inducing the expression of interferon-beta and interferon-stimulated genes (ISGs) in breast cancer cells in vitro and tumors in vivo. ZMYND8 knockout (KO) in breast cancer cells promoted infiltration of CD4+ and CD8+ T cells leading to tumor inhibition in syngeneic mouse models, which was significantly attenuated by treatment of anti-CD4/CD8 depleting antibodies or anti-IFNAR 1 antibody and in immunodeficient Rag1 KO mice. In human breast tumors, ZMYND8 was negatively correlated with ISGs, CD4, CD8A, CD8B, and the tumor-lymphocyte infiltration phenotype. Collectively, these findings demonstrate that maintenance of genome stability by ZMYND8 causes breast cancer cells to evade cytotoxic T-lymphocyte surveillance which leads to tumor growth. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The microbiome and cancer: creating friendly neighborhoods and removing the foes within

Alexandros G.Sfakianakis shared this article with you from Inoreader The microbiome and cancer: creating friendly neighborhoods and removing the foes within Μέσω Cancer Research Online First Articles The human body is colonized by the microbial cells that are estimated to be as abundant as human cells, yet their genome is roughly 100 times the human genome, providing significantly more genetic diversity. The past decade has observed an explosion of interest in examining the existence of microbiota in the human body and understanding its role in various diseases including inflammatory bowel disease, neurologic diseases, cardiovascular disorders, and cancer. Many studies have demonstrated differential community composition between normal tissue and cancerous tissue, paving the way for investigations focused on deciphering the cause-and-effect relationships between specific microbes and initiation and progression of various cancers. Also, evolving are the strategies to alter tumor-associated dysbiosis and move it towards eubiosis with holistic approaches to change the entire neighborhood or to neutralize pathogenic strains. In this review, we discuss important pathogenic bacte ria and the underlying mechanisms by which they impact cancer progression. We summarize key microbiota alterations observed in multiple tumor niches, their association with clinical stages, and their potential use in cancer diagnosis and management. Finally, we discuss microbiota-based therapeutic approaches. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Single-cell transcriptomic heterogeneity in invasive ductal and lobular breast cancer cells

Alexandros G.Sfakianakis shared this article with you from Inoreader Single-cell transcriptomic heterogeneity in invasive ductal and lobular breast cancer cells Μέσω Cancer Research Online First Articles Invasive lobular breast carcinoma (ILC), one of the major breast cancer histological subtypes, exhibits unique features compared to the well-studied ductal cancer subtype (IDC). The pathognomonic feature of ILC is loss of E-cadherin, mainly caused by inactivating mutations, but the contribution of this genetic alteration to ILC-specific molecular characteristics remains largely understudied. To profile these features transcriptionally, we conducted single-cell-RNA-sequencing on a panel of IDC and ILC cell lines, and an IDC cell line (T47D) with CRISPR-Cas9-mediated E-cadherin knock out (KO). Inspection of intra-cell line heterogeneity illustrated genetically and transcriptionally distinct subpopulations in multiple cell lines and highlighted rare populations of MCF7 cells highly expressing an apoptosis-related signature, positively correlated with a pre-adaptation signature to estrogen deprivation. Investigation of E-cadherin KO-induced alterations showed transcriptomic membran ous systems remodeling, elevated resemblance to ILCs in regulon activation, and increased sensitivity to IFN-γ mediated growth inhibition via activation of IRF1. This study reveals single cell transcriptional heterogeneity in breast cancer cell lines and provides a resource to identify drivers of cancer progression and drug resistance. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Radiomic detection of EGFR mutations in NSCLC

Alexandros G.Sfakianakis shared this article with you from Inoreader Radiomic detection of EGFR mutations in NSCLC Μέσω Cancer Research Online First Articles Radiomics is defined as the use of automated or semi-automated post-processing and analysis of multiple features derived from imaging exams. Extracted features might generate models able to predict the molecular profile of solid tumors. The aim of this study was to develop a predictive algorithm to define the mutational status of epidermal growth factor receptor (EGFR) in treatment-naïve patients with advanced non-small cell lung cancer (NSCLC). Computed tomography (CT)-scans from 109 treatment-naïve NSCLC patients (21 EGFR-mutant and 88 EGFR-wild type) underwent radiomics analysis in order to develop a machine learning model able to recognize EGFR-mutant from EGFR-WT patients via CT scans. A "test-retest" approach was used to identify stable radiomics features. The accuracy of the model was tested on an external validation set from another Institution and on a dataset from the Cancer Imaging Archive (TCIA). The machine learning model that considered both radiomic and clinica l features (gender and smoking status) reached a diagnostic accuracy of 88.1% in our dataset with an AUC at the ROC curve of 0.85, while the accuracy in the datasets from TCIA and the external Institution were 76.6% and 83.3%, respectively. Furthermore, 17 distinct radiomics features detected at baseline CT scan were associated with subsequent development of T790M during treatment with an EGFR inhibitor. In conclusion, our machine learning model was able to identify EGFR-mutant patients in multiple validation sets with globally good accuracy, especially after data optimization. More comprehensive training sets might result in further improvement of radiomics-based algorithms. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Ear Cartilage Reconstruction Combining Induced Pluripotent Stem Cell-Derived Cartilage and Three-Dimensional Shape-Memory Scaffold

Alexandros G.Sfakianakis shared this article with you from Inoreader Ear Cartilage Reconstruction Combining Induced Pluripotent Stem Cell-Derived Cartilage and Three-Dimensional Shape-Memory Scaffold Μέσω Tissue Engineering Part A - Table of Contents Tissue Engineering Part A, Ahead of Print. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Facial Nerve Repair by Muscle-Vein Conduit in Rats: Functional Recovery and Muscle Reinnervation

Alexandros G.Sfakianakis shared this article with you from Inoreader Facial Nerve Repair by Muscle-Vein Conduit in Rats: Functional Recovery and Muscle Reinnervation Μέσω Tissue Engineering Part A - Table of Contents Tissue Engineering Part A, Ahead of Print. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Glycosyltransferase ST6Gal-I promotes the epithelial to mesenchymal transition in pancreatic cancer cells [Cell Biology]

Alexandros G.Sfakianakis shared this article with you from Inoreader Glycosyltransferase ST6Gal-I promotes the epithelial to mesenchymal transition in pancreatic cancer cells [Cell Biology] Μέσω JBC Papers in Press ST6Gal-I, an enzyme upregulated in numerous malignancies, adds α2-6-linked sialic acids to select membrane receptors, thereby modulating receptor signaling and cell phenotype. In this study, we investigated ST6Gal-I's role in epithelial to mesenchymal transition (EMT) using the Suit2 pancreatic cancer cell line, which has low endogenous ST6Gal-I and limited metastatic potential, along with two metastati c Suit2-derived subclones, S2-013 and S2-LM7AA, which have upregulated ST6Gal-I. RNA-Seq results suggested that the metastatic subclones had greater activation of EMT-related gene networks than parental Suit2 cells, and forced overexpression (OE) of ST6Gal-I in the Suit2 line was sufficient to activate EMT pathways. Accordingly, we evaluated expression of EMT markers and cell invasiveness (a key phenotypic feature of EMT) in Suit2 cells with or without ST6Gal-I OE, as well as S2-013 and S2-LM7AA cells with or without ST6Gal-I knockdown (KD). Cells with high ST6Gal-I expression displayed enrichment in mesenchymal markers (N-cadherin, slug, snail, fibronectin) and cell invasiveness, relative to ST6Gal-I-low cells. Contrarily, epithelial markers (E-cadherin, occludin) were suppressed in ST6Gal-I-high cells. To gain mechanistic insight into ST6Gal-I's role in EMT, we examined the activity of EGFR, a known EMT driver. ST6Gal-I-high cells had greater α2-6 sialylation and activation of EGFR than ST6Gal-I-low cells. The EGFR inhibitor, erlotinib, neutralized ST6Gal-I-dependent differences in EGFR activation, mesenchymal marker expression and invasiveness in Suit2 and S2-LM7AA, but not S2-013, lines. Collectively, these results advance our understanding of ST6Gal-I's tumor-promoting function by highlighting a role for ST6Gal-I in EMT, which may be mediated, at least in part, by α2-6-sialylated EGFR. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Human genetic variants disrupt RGS14 nuclear shuttling and regulation of LTP in hippocampal neurons [Neurobiology]

Alexandros G.Sfakianakis shared this article with you from Inoreader Human genetic variants disrupt RGS14 nuclear shuttling and regulation of LTP in hippocampal neurons [Neurobiology] Μέσω JBC Papers in Press The human genome contains vast genetic diversity as naturally occurring coding variants, yet the impact of these variants on protein function and physiology is poorly understood. RGS14 is a multifunctional signaling protein that suppresses synaptic plasticity in dendritic spines of hippocampal neurons. RGS14 also is a nucleocytoplasmic shuttling protein, suggesting that balanced nuclear import/export and d endritic spine localization are essential for RGS14 functions. We identified genetic variants L505R (LR) and R507Q (RQ) located within the nuclear export sequence (NES) of human RGS14. Here we report that RGS14 encoding LR or RQ profoundly impacts protein functions in hippocampal neurons. RGS14 membrane localization is regulated by binding Gαi-GDP, whereas RGS14 nuclear export is regulated by Exportin 1 (XPO1). Remarkably, LR and RQ variants disrupt RGS14 binding to Gαi1-GDP and XPO1, nucleocytoplasmic equilibrium, and capacity to inhibit LTP. Variant LR accumulates irreversibly in the nucleus, preventing RGS14 binding to Gαi1, localization to dendritic spines, and inhibitory actions on LTP induction, while variant RQ exhibits a mixed phenotype. When introduced into mice by CRISPR/Cas9, RGS14-LR protein expression was detected predominantly in the nuclei of neurons within hippocampus, central amygdala, piriform cortex, and striatum, brain regions associated with learning and syna ptic plasticity. Whereas mice completely lacking RGS14 exhibit enhanced spatial learning, mice carrying variant LR exhibit normal spatial learning, suggesting that RGS14 may have distinct functions in the nucleus independent from those in dendrites and spines. These findings show that naturally occurring genetic variants can profoundly alter normal protein function, impacting physiology in unexpected ways. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

From pathogen to a commensal: modification of the Microbacterium nematophilum-Caenorhabditis elegans interaction during chronic infection by the absence of host insulin signalling [RESEARCH ARTICLE]

Alexandros G.Sfakianakis shared this article with you from Inoreader From pathogen to a commensal: modification of the Microbacterium nematophilum-Caenorhabditis elegans interaction during chronic infection by the absence of host insulin signalling [RESEARCH ARTICLE] Μέσω Biology Open current issue Maria Gravato-Nobre, Jonathan Hodgkin, and Petros Ligoxygakis The nematode worm Caenorhabditis elegans depends on microbes in decaying vegetation as its food source. To survive in an environment rich in opportunistic pathogens, C. elegans has evolved an epithelial defence system where surface-exposed tissues such as epidermis, pharynx, intestine, vulva and hindgut have the capacity of eliciting appropriate immune defences to acute gut infection. However, it is unclear how the worm responds to chronic intestinal infections. To this end, we have surveyed C. elegans mutants that are involved in inflammation, immunity and longevity to find their phenotypes during chronic infection. Worms that grew in a monoculture of the natural pathogen Microbacterium nematophilum (CBX102 strain) had a reduced lifespan and vigour. This was independent of intestinal colonisation as both CBX102 and the derived avirulent strain UV336 were early persistent colonisers. In contrast, the long-lived daf-2 mutant was resi stant to chronic infection, showing reduced colonisation and higher vigour. In fact, UV336 interaction with daf-2 resulted in a host lifespan extension beyond OP50, the Escherichia coli strain used for laboratory C. elegans culture. Longevity and vigour of daf-2 mutants growing on CBX102 was dependent on the FOXO orthologue DAF-16. Our results indicate that the interaction between host genotype and strain-specific bacteria determines longevity and health for C. elegans. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

De-Ritis Ratio Is Associated with Mortality after Cardiac Arrest

Alexandros G.Sfakianakis shared this article with you from Inoreader De-Ritis Ratio Is Associated with Mortality after Cardiac Arrest Μέσω Hindawi Publishing Corporation Introduction. The aim of our study was to explore the associations of the aspartate transaminase/alanine transaminase (De-Ritis) ratio with outcomes after cardiac arrest (CA). Methods. This retrospective study included 374 consecutive adult cardiac arrest patients. Information on the study population was obtained from the Dryad Digital Repository. Patients were divided into tertiles based on their De-Ritis ratio. The logistic regression hazard analysis was used to assess the independent relationship between the De-Ritis ratio and mortality. The Kaplan-Meier method and log-rank test were used to estimate the survival of different groups. Receiver operating characteristic (ROC) curve analysis was utilized to compare the prognostic ability of biomarkers. A model combining the De-Ritis ratio was established, and its performance was evaluated using the Akaike information criterion (AIC). Results. Of the 374 patients who were included in the study, 194 patients (51.9%) died in the intensive care unit (ICU), 213 patients (57.0%) died during hospitalization, and 226 patients (60.4%) had an unfavorable neurologic outcome. Logistic regression analysis including potentially confounding factors showed that the De-Ritis ratio was independently associated with mortality, yielding a more than onefold risk of ICU mortality (OR 1.455; 95% CI 1.088-1.946; ) and hospital mortality (OR 1.378; 95% CI 1.031-1.842; ). Discriminatory performance assessed by ROC curves showed an area under the curve of 0.611 (95% CI 0.553-0.668) for ICU mortality and 0.625 (0.567-0.682) for hospital mortality. Further, the likelihood ratio test (LRT) analysis showed that the model combining the De-Ritis ratio had a smaller AIC and higher likelihood ratio score than the model without the De-Ritis ratio. The Kaplan-Meier curves sho wed that the CA patients in the De-Ritis ratio tertile 3 group clearly had a significantly higher incidence of ICU mortality ().Conclusion. An elevated De-Ritis ratio on admission was significantly associated with ICU mortality and hospital mortality after CA. Assessment of the De-Ritis ratio might help identify groups at high risk for mortality. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.