Evaluating the Feasibility of a Multiplayer Role-Playing Game as a Behavioral Health Intervention in Adolescent Patients With Chronic Physical or Mental Conditions: Protocol for a Cohort Study.

BACKGROUND: Numerous studies have revealed that adolescents with chronic physical or mental conditions (CPMCs) are at an increased risk for depression and anxiety, with serious direct and indirect negative effects on treatment adherence, family functioning, and health-related quality of life. As game-based approaches are effective interventions in treating anxiety and depression, we propose to explore the use of a multiplayer role-playing game (RPG) as a potential intervention for social isolation, anxiety, and depression. OBJECTIVE: The objectives of this study were to (1) determine the feasibility of using Masks, a multiplayer RPG, as an intervention for social isolation, anxiety, and depression in adolescents with CPMCs; (2) evaluate the viability of the research process; and (3) gauge participation in and engagement with RPG-based interventions. METHODS: This study is a remote synchronous game-based intervention for adolescents with CPMCs aged 14-19 years. Eligible participants completed a web-based baseline survey to assess anxiety, depression, and social isolation and to identify their gaming habits. After completing the baseline survey, they participated in 5 moderated Masks game sessions. In Masks, players assume the roles of young superheroes; select their character types, superpowers; and perform actions determined by the game's rule system and dice rolls. All game sessions were played using Discord, a communication platform commonly used by gaming communities. Games were led and moderated by game masters (GMs). After each game session, participants completed surveys to assess changes in anxiety, depression, and social isolation, and their attitude toward the game and the user experience. The participants also completed an exit survey after all 5 game sessions (modified version of the Patient Health Questionnaire and the Generalized Anxiety Disorder Questionnaire, and 17 open-ended questions). The GMs rated each game session and reported on gameplay, player behavior, comfort, and engagement levels of the players. RESULTS: As of March 2020, six participants were recruited for the pilot study to participate in moderated web-based game sessions of Masks; 3 completed all game sessions and all required assessments. Although the number of participants was too low to draw generalizable conclusions, self-reported clinical outcomes did seem to indicate a positive change in depression, anxiety, and social isolation symptoms. Qualitative analysis of postgame survey data from participants and GMs indicated high levels of engagement and enjoyment. Furthermore, the participants provided feedback about improved mood and engagement related to weekly participation in Masks. Lastly, responses to the exit survey showed interest in future RPG-related studies. CONCLUSIONS: We established a workflow for gameplay and evaluated a research protocol for evaluating the impact of RPG participation on isolation, anxiety, and depression symptoms in adolescents with CPMCs. Preliminary data collected from the pilot study support the validity of the research protocol and the use of RPG-based interventions in larger clinical studies. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/43987.

A hypolipoprotein sepsis phenotype indicates reduced lipoprotein antioxidant capacity, increased endothelial dysfunction and organ failure, and worse clinical outcomes.

OBJECTIVE: Approximately one-third of sepsis patients experience poor outcomes including chronic critical illness (CCI, intensive care unit (ICU) stay > 14 days) or early death (in-hospital death within 14 days). We sought to characterize lipoprotein predictive ability for poor outcomes and contribution to sepsis heterogeneity. DESIGN: Prospective cohort study with independent replication cohort. SETTING: Emergency department and surgical ICU at two hospitals. PATIENTS: Sepsis patients presenting within 24 h. METHODS: Measures included cholesterol levels (total cholesterol, high density lipoprotein cholesterol [HDL-C], low density lipoprotein cholesterol [LDL-C]), triglycerides, paraoxonase-1 (PON-1), and apolipoprotein A-I (Apo A-I) in the first 24 h. Inflammatory and endothelial markers, and sequential organ failure assessment (SOFA) scores were also measured. LASSO selection assessed predictive ability for outcomes. Unsupervised clustering was used to investigate the contribution of lipid variation to sepsis heterogeneity. MEASUREMENTS AND MAIN RESULTS: 172 patients were enrolled. Most (~ 67%, 114/172) rapidly recovered, while ~ 23% (41/172) developed CCI, and ~ 10% (17/172) had early death. ApoA-I, LDL-C, mechanical ventilation, vasopressor use, and Charlson Comorbidity Score were significant predictors of CCI/early death in LASSO models. Unsupervised clustering yielded two discernible phenotypes. The Hypolipoprotein phenotype was characterized by lower lipoprotein levels, increased endothelial dysfunction (ICAM-1), higher SOFA scores, and worse clinical outcomes (45% rapid recovery, 40% CCI, 16% early death; 28-day mortality, 21%). The Normolipoprotein cluster patients had higher cholesterol levels, less endothelial dysfunction, lower SOFA scores and better outcomes (79% rapid recovery, 15% CCI, 6% early death; 28-day mortality, 15%). Phenotypes were validated in an independent replication cohort (N = 86) with greater sepsis severity, which similarly demonstrated lower HDL-C, ApoA-I, and higher ICAM-1 in the Hypolipoprotein cluster and worse outcomes (46% rapid recovery, 23% CCI, 31% early death; 28-day mortality, 42%). Normolipoprotein patients in the replication cohort had better outcomes (55% rapid recovery, 32% CCI, 13% early death; 28-day mortality, 28%) Top features for cluster discrimination were HDL-C, ApoA-I, total SOFA score, total cholesterol level, and ICAM-1. CONCLUSIONS: Lipoproteins predicted poor sepsis outcomes. A Hypolipoprotein sepsis phenotype was identified and characterized by lower lipoprotein levels, increased endothelial dysfunction (ICAM-1) and organ failure, and worse clinical outcomes.

The response of Escherichia coli to the alkylating agents chloroacetaldehyde and styrene oxide.

DNA damage is ubiquitous and can arise from endogenous or exogenous sources. DNA-damaging alkylating agents are present in environmental toxicants as well as in cancer chemotherapy drugs and are a constant threat, which can lead to mutations or cell death. All organisms have multiple DNA repair and DNA damage tolerance pathways to resist the potentially negative effects of exposure to alkylating agents. In bacteria, many of the genes in these pathways are regulated as part of the SOS reponse or the adaptive response. In this work, we probed the cellular responses to the alkylating agents chloroacetaldehyde (CAA), which is a metabolite of 1,2-dichloroethane used to produce polyvinyl chloride, and styrene oxide (SO), a major metabolite of styrene used in the production of polystyrene and other polymers. Vinyl chloride and styrene are produced on an industrial scale of billions of kilograms annually and thus have a high potential for environmental exposure. To identify stress response genes in E. coli that are responsible for tolerance to the reactive metabolites CAA and SO, we used libraries of transcriptional reporters and gene deletion strains. In response to both alkylating agents, genes associated with several different stress pathways were upregulated, including protein, membrane, and oxidative stress, as well as DNA damage. E. coli strains lacking genes involved in base excision repair and nucleotide excision repair were sensitive to SO, whereas strains lacking recA and the SOS gene ybfE were sensitive to both alkylating agents tested. This work indicates the varied systems involved in cellular responses to alkylating agents, and highlights the specific DNA repair genes involved in the responses.