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The proceedings contain 96 papers. The topics discussed include: practical pharmacotherapy for opioid use disorder in the age of fentanyl;can COVID-19 cause acute psychosis in pediatric patients? a case report;a survey of bullying experiences in a child and adolescent psychiatric clinic population;acute emergence of suicidal thoughts following Lemborexant initiation: an adverse reaction case report;assessing the unmet clinical need and opportunity for digital therapeutic intervention in schizophrenia: perspective from people with schizophrenia;rapid antidepressant effects and MADRS item improvements with AXS-05 (DEXTROMETHORPHAN-BUPROPION), an oral NMDA receptor antagonist in major depressive disorder: results from two randomized double-blind, controlled trials;targeting lncRNA NEAT1 impedes Alzheimers disease progression via MicroRNA-193a mediated CREB/BDNF and NRF2/NQO1 pathways;and impact of AXS-05 (DEXTROMETHORPHAN-BUPROPION), an Oral NMDA receptor antagonist, on Anhedonic symptoms in major depressive disorder.
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Introduction: COVID19 can cause neutrophilic inflammation and reaction oxygen species (ROS) production, leading to acute lung injury and mortality. AMPK is a key regulator of cellular energy with profound effects on neutrophil function. This study aims to investigate the role of AMPK activity in neutrophils during COVID-19 and pneumonia caused by pathogens other than SARS-CoV-2. Method(s): Patients hospitalised due to pneumonia or COVID-19 were recruited from Ninewells Hospital (Dundee, UK). Blood was sampled at day 1, 8, and 15. ROS production, phospho-AMPK (pAMPK), and NQO1 were stained in neutrophils, and then analysed by flow cytometry. The endogenous AMPK inhibitor, resistin, was quantified by ELISA, in serum (day 1, 8, 15). WHO clinical scale and CURB65 score were utilised to define severity. Result(s): 133 patients were enrolled (mean age 63.6 years). Resistin was not different between pneumonia and COVID-19 on day1. However, day 1 resistin was higher in severe disease defined by CURB65 Score (p=0.0220) and WHO score (p=0.0184). Resistin reduced over time at day 1 (mean 63.1pg/mL;n=121) to day 15 (mean 59.5pg/mL;n=66)(p=0.0002). Zymosan stimulation significantly increases neutrophil ROS production (p<0.0001), and significantly decreases NQO1 (p<0.0001), but caused no changes with pAMPK. There were no changes in these markers over time. pAMPK significantly correlated with NQO1 in unstimulated neutrophils (p=0.0388), but not when stimulated with zymosan. There were no associations between resistin and pAMPK, and no difference in these markers between pneumonia and COVID-19 groups. Conclusion(s): Our study suggests resistin as a marker of severity and disease course in COVID-19, independent of neutrophil AMPK signalling.
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The COVID pandemic caused an increase in virtual meetings & work from home scenarios that resulted in people spending increased time in front of computer screens & electronic devices. Studies have shown that blue light can produce cytotoxic effects, primarily through the production of reactive oxygen species & increased inflammation. However, the topic has been controversial with some studies claiming no adverse effects of blue light on the skin. Methods for testing the effects of blue light using in vitro testing models are lacking. Our work was conducted in order to develop a reproducible, validated testing method for assessing the effects of blue light on the skin. We designed a custom blue-light box that can be used to generate blue light at 460 nm wavelength. We performed a series of studies to optimize the dose and timing of the exposure & skin-culture conditions. Our work demonstrates that 6 hours of daily blue light for 5 consecutive days (total 30 J/cm2) produced a dose-and-time dependent decrease in skin health in 3D full thickness in vitro skin tissues. In addition, gene expression data showed an increase in the expression of genes that regulate inflammation and oxidative stress pathways (IL1A, IL6, CXCL8, COX2, CYP1B1, & NQO1) & a decrease in the expression of genes that maintain skin barrier and integrity (KRT1, KRT10, LOR, DSC and Collagen). Genes regulating skin aging & hydration including MMP1 & FLG were also regulated by exposure to blue light. Enzyme-linked immunoassays were performed to confirm changes in specific proteins. Exposure to blue light significantly increased 8-hydroxy-2' -deoxyguanosine, a marker for oxidative stress, & MMP1, markers for photoaging. Immunohistochemistry staining was performed to confirm changes in Collagen, Filaggrin & NQO1 protein expression in skin tissue. Our results showed that consistent blue light exposure produced skin damage via alterations in key biological pathways. This work provides a new, reproducible in vitro testing method for assessing the effects of blue light on human skin using gene expression, protein ELISA and IHC staining.