Objectives: To evaluate the feasibility and usability of stroke survivor participation in an 8-week virtual environment intervention that provides opportunities for social support exchanges, social network interactions, and recovery education. Materials and methods: A single-group, pre- and post-test measure design was used. Descriptive statistics were used to examine enrollment and retention rates, proportion of questionnaires completed, and virtual environment process data (e.g., number of log-ins) and usability scores. Changes in pre- and post-intervention questionnaire (e.g., usability, social support, depression, anxiety, loneliness, and self-efficacy) scores were explored using Wilcoxon signed-rank tests and paired t-test. Results: Fifteen (65 %) of the eligible stroke survivors enrolled (60 % white, 27 % black), 12 (80 %) had an ischemic stroke, ages ranged from 33 to 74 years (mean 44 years), and mean months since stroke was 33 +/- 23. Retention and questionnaire completion rates were both 93 % (n = 14). Survivors logged into the virtual environment a total of 122 times, logged an average of 49 min/log-in, and 12 (80 %) attended support groups and social activities. Median usability score indicated lower than average usability. Improvement trends in social support, loneliness, and depressive symptoms were found, but significant changes in mean questionnaire scores were not found. Conclusions: Overall, the results suggest that using a virtual environment to foster social support exchanges, social network interactions, and recovery education after stroke is feasible. Similar to other chronic disease populations, stroke survivor adoption of a virtual environment likely requires ongoing technical assistance, repetition of instructions, and opportunities for practice to reinforce engagement. Trial registration: NCT05487144.

Abstract Mania and bipolar spectrum disorders (or BSDs) are serious and recurrent psychological disorders with significant occupational, social, and mortality costs. BSDs are characterized by episodic and prolonged mood episodes that range between abnormally and persistently elevated mood phases (mania) and frequently periods of dysphoria mood (depression). This first part of this chapter aims to provide an overview of the phenomenology and assessment of BSDs, review associated psychobiological processes across cognitive, affective, neural, and circadian rhythm dimensions, and consider the influence of context and social environment on BSDs. The second part of this chapter synthesizes empirically supported interventions to prevent and treat BSDs and highlights future directions that focus on increasing diversity and representation of marginalized communities and addressing stigma about BSDs and related psychiatric disorders.

Substance misuse is a major burden for not only patients but the healthcare system. Understanding how substance misuse alters a patient’s genome, proteome, and neurocircuitry is an important step toward identifying targets for treatments. In this exploratory study, we performed a proteomic analysis of postmortem brain from individuals with substance misuse disorder (n=29), including alcohol (n=11) and opioid misuse disorder (n=12), or comorbidity with both disorders (n=6), compared to controls (n=12). The results demonstrate that these substances affect both common and different biological pathways compared to controls. Alcohol misuse affects primarily protein translation, rRNA processing, and energy metabolism pathways, while opioid influences G-protein signaling, protein translation, rRNA processing, energy metabolism, and angiogenesis pathways. Alcohol and opioid misuse combined appears to have a synergistic effect on protein expression of the TCA cycle, respiratory transport, mitochondrial function, LGI-ADAM interactions, interleukin signaling, neuronal system changes, and actin polymerization. These findings offer new insights into how substance misuse leads to protein alterations and how combined substance misuse leads to different protein changes compared to single substance misuse.

A possible accelerated biological aging in patients with substance use disorders (SUD) is considered one of the main contributors to the adverse outcomes in SUD, such as premature mortality. So far, the evaluation of epigenetic clocks, which are accurate estimators of biological aging based on DNA methylation changes, has been limited to blood tissue in patients with SUD. Thus, the impact of epigenetic aging in the brain of individuals with SUD remains unknown.

Opioid abuse can cause brain alterations, including neuroinflammation and increased risk for ischemic stroke. Cancer studies show that opioids affect angiogenesis and endothelial cell proliferation. However, human brain studies are scarce, and the molecular mechanisms of opioid-induced neurotoxicity are unclear. This study comprehensively interrogated the transcriptomic and proteomic profiles of the dorsolateral prefrontal cortex (BA9) in subjects with opioid use disorder (OUD), to investigate the molecular effects of opioid abuse in the human brain.

Previous diffusion-weighted imaging studies had been suggested white matter (WM) impairment among participants with cocaine addiction. Here we evaluated the potential neurotoxic effects of cocaine use in the WM of prefrontal cortex Brodmann area 9 (BA9) of patients with cocaine use disorder (CUD) and in healthy controls (HCs).

ABSTRACT IMPACT: This project will use human neuron models and bioinformatics techniques to elucidate mechanisms of cocaine neurotoxicity, which will allow treatments to be developed for minimizing or preventing neurological damage caused by cocaine abuse and overdose. OBJECTIVES/GOALS: The goals of this project are to identify genes and gene networks altered by cocaine exposure in neurons (short term), and to use these pathways to understand mechanisms of cocaine neurotoxicity for the establishment of therapeutic targets (long term). METHODS/STUDY POPULATION: To study the molecular effects of cocaine, we generated preliminary proteomics and next-generation RNA sequencing (RNAseq) data from human postmortem prefrontal cortex (Broadmann area 9 or BA9) of 12 cocaine overdose subjects and 17 controls. Future directions for this project include RNAseq analysis of neuronal nuclei sorted from human postmortem BA9 and a human induced pluripotent stem cell-derived neuron (hiPSN) model of cocaine exposure from the same postmortem subjects from whom we have brain samples. RESULTS/ANTICIPATED RESULTS: We found alterations in neuronal synaptic protein levels and gene expression, including the serotonin transporter SLC6A4, and synaptic proteins SNAP25, SYN2, SYNGR3. Pathway analysis of our results revealed alterations in specific pathways involved with neuronal function including voltage-gated calcium channels, and GABA receptor signaling. In the future, we expect to see an enhancement in neuron-specific gene expression signatures in our sorted neuronal nuclei and our hiPSN model of cocaine exposure. The hiPSN model will help elucidate which effects are due to acute versus chronic exposure of cocaine. DISCUSSION/SIGNIFICANCE OF FINDINGS: Transcriptomic signatures found with this analysis can help us understand mechanisms of cocaine neurotoxicity in human neurons. With this work and future proposed studies, we can discover targetable molecular pathways to develop drugs that can reduce or reverse cocaine-related impairment.

White matter (WM) abnormalities in patients with cocaine use disorder (CUD) have been studied; however, the reported effects on the human brain are heterogenous and most results have been obtained from male participants. In addition, biological data supporting the imaging findings and revealing possible mechanisms underlying the neurotoxic effects of chronic cocaine use (CU) on WM are largely restricted to animal studies. To evaluate the neurotoxic effects of CU in the WM, we performed an in vivo diffusion tensor imaging assessment of male and female cocaine users ( n = 75) and healthy controls (HC) ( n = 58). Moreover, we performed an ex vivo large-scale proteomic analysis using liquid chromatography-tandem mass spectrometry in postmortem brains of patients with CUD ( n = 8) and HC ( n = 12). Compared with the HC, the CUD group showed significant reductions in global fractional anisotropy (FA) ( p < 0.001), and an increase in global mean (MD) and radial diffusion (RD) (both p < 0.001). The results revealed that FA, RD, and MD alterations in the CUD group were widespread along the major WM tracts, after analysis using the tract-based special statistics approach. Global FA was negatively associated with years of CU ( p = 0.0421) and female sex ( p < 0.001), but not with years of alcohol or nicotine use. Concerning the fibers connecting the left to the right prefrontal cortex, Brodmann area 9 (BA9), the CUD group presented lower FA ( p = 0.006) and higher RD ( p < 0.001) values compared with the HC group. A negative association between the duration of CU in life and FA values in this tract was also observed ( p = 0.019). Proteomics analyses in BA9 found 11 proteins differentially expressed between cocaine users and controls. Among these, were proteins related to myelination and neuroinflammation. In summary, we demonstrate convergent evidence from in vivo diffusion tensor imaging and ex vivo proteomics analysis of WM disruption in CUD.

OBJECTIVES/GOALS: The goal of this project is to identify new therapeutic targets and biomarkers to treat or prevent cocaine toxicity by investigating proteomic, transcriptomic and epigenetic signatures of cocaine exposure in human subjects. METHODS/STUDY POPULATION: Cocaine is a highly addictive neurotoxic substance, and it is estimated that 1.9 million Americans are current users of cocaine. To study the molecular effects of cocaine, we generated preliminary proteomics and next-generation RNA sequencing (RNAseq) data from human postmortem dorsolateral prefrontal cortex (Broadmann area 9 or BA9) of 12 cocaine-exposed subjects and 17 controls. Future directions for this project include RNAseq and DNA methylation analysis of neuronal nuclei sorted from human postmortem BA9 and a human induced pluripotent stem cell-derived neuron (hiPSN) model of cocaine exposure from the same postmortem subjects from whom we have brain samples. RESULTS/ANTICIPATED RESULTS: We found alterations in neuronal synaptic protein levels and gene expression, including the serotonin transporter SLC6A4, and synaptic proteins SNAP25, SYN2, SYNGR3. Pathway analysis of our results revealed alterations in specific pathways involved with neuronal function including voltage-gated calcium channels, and GABA receptor signaling. In the future, we expect to see an enhancement in neuron-specific gene expression signatures in our sorted neuronal nuclei and our hiPSN model of cocaine exposure. The hiPSN model will help elucidate which effects are due to acute versus chronic exposure of cocaine. DISCUSSION/SIGNIFICANCE OF IMPACT: Neuronal signatures found with this analysis can help us understand mechanisms of cognitive decline in long-term cocaine users as well as the acute effects on the brain of cocaine taken in overdose. With this work and future proposed studies, we can discover novel clinical biomarkers for cocaine neurotoxicity in patients with cocaine use disorder and determine readouts for future therapeutic development on cocaine addiction and overdose.

Meeting the demand for food in arid and water-scarce regions can be economically and environmentally challenging. Uncertainties related to climate change and global warming exacerbates technical challenges for efficient food production. Protected agriculture in the form of greenhouses grow different types of crops in a controlled microclimate offering better conditions for healthy and profitable production. Moreover, CO2 enrichment has also been proven to increase crop yields at low costs, and can be supplied from burning carbon-based resources and transferring the carbon recovered through pipeline networks or tanks. However, the sustenance of CO2 supply to greenhouses requires compliance with the global sustainability standards, and as such there is a need for economically viable and environmentally-friendly networks for the supply of CO2 required by the greenhouses. The objective of this study is to design an optimum supply chain network for a sustainable supply of CO2 to greenhouses. The framework developed is based on an optimisation model solved using integer linear programing (ILP) aiming to minimise the economic cost associated with the operations of the entire supply chain network serving greenhouses. An environmental assessment is also conducted in quantifying the CO2 offset related to the CO2 utilisation in agricultural greenhouse applications. The proposed model was implemented for a case study based in Qatar, comprising of a set of hypothetical greenhouses placed at various locations; a source of CO2 from a biomass based power plant, a distribution centre, and existing pipeline and roadway networks. GIS optimisation models previously developed for the Qatar case study provide locations for greenhouses, pipeline and road transportation routes for CO2 fertilisation as inputs for the proposed supply chain model. The demand for resources, CO2 transport networks, and the distances between the source and greenhouses were assumed to be the constraints impacting the design of the supply chain network. The results obtained indicate the optimal CO2 supply quantities to the greenhouses following a proposed network of pipelines and road routes, with a minimum associated cost of transportation of approximately 0,09$/kg of CO2.

Our previous work shows that young and old adults with bipolar disorder (BD) display poor reward-associated decision making (RDM). RDM in youth with BD is a largely unexplored research area. This study uses a component-wise gradient (CGB) machine learning algorithm to identify cognitive measures that can accurately differentiate youth with BD from a healthy comparison group.

The heterogeneity within psychiatric disorders has complicated the identification of susceptibility genes. One way to address this issue is to explore core characteristics such as ‘impulsivity’.