The role of global vulnerability for mental and substance use disorders.

Social exclusion and poverty are associated with increased mental health issues. In addition, the current political and civil conflicts worldwide are also considered as leading factors to mental disorders and substance use disorders. The Compassion, Assertive action, Pragmatism and Evidence (CAPE) index comprises nine country-level measures and highlights the need for assistance in countries with a high degree of vulnerability. Several findings from previous studies reported a broad relationship between CAPE indices and increased levels of mental disorders and substance use. In this paper, we identified the prevalence of mental disorders and substance use disorders among those countries reporting higher (i.e., highest CAPE Index scores) as well as lower (i.e., highest Quality of Life Index scores) vulnerability. We extracted prevalence data from the Institute for Health Metrics and Evaluation global database in 2019. There was a lower prevalence of mental (12.5%) and substance use (1.7%) disorders in highly vulnerable countries than less vulnerable ones (15.1% and 3.5%, respectively). These findings suggest an urgent need for early detection of mental and substance use disorders in vulnerable countries: increasing mental health literacy among non-specialized health professionals in these regions may greatly improve the level of detection and treatment.

Generation of glucocorticoid resistant SARS-CoV-2 T-cells for adoptive cell therapy

Adoptive cell therapy with viral-specific T cells has been successfully used to treat life-threatening viral infections, supporting the application of this approach against COVID-19. We expanded SARS-CoV-2 T-cells from the peripheral blood of COVID-19-recovered donors and non-exposed controls using different culture conditions. We observed that the choice of cytokines modulates the expansion, phenotype and hierarchy of antigenic recognition by SARS-CoV-2 T-cells. Culture with IL-2/4/7 but not other cytokine-driven conditions resulted in >1000 fold expansion in SARS-CoV-2 T-cells with a retained phenotype, function and hierarchy of antigenic recognition when compared to baseline (pre-expansion) samples. Expanded CTLs were directed against structural SARS-CoV-2 proteins, including the receptor-binding domain of Spike. SARS-CoV-2 T-cells could not be efficiently expanded from the peripheral blood of non-exposed controls. Since corticosteroids are used for the management of severe COVID-19, we developed an efficient strategy to inactivate the glucocorticoid receptor gene (NR3C1) in SARS-CoV-2 CTLs using CRISPR-Cas9 gene editing.

Optimal path to epigenetic switching.

We use large deviation methods to calculate rates of noise-induced transitions between states in multistable genetic networks. We analyze a synthetic biochemical circuit, the toggle switch, and compare the results to those obtained from a numerical solution of the master equation.