The bitter end: T2R bitter receptor agonists elevate nuclear calcium and induce apoptosis in non-ciliated airway epithelial cells.

Bitter taste receptors (T2Rs) localize to airway motile cilia and initiate innate immune responses in retaliation to bacterial quorum sensing molecules. Activation of cilia T2Rs leads to calcium-driven NO production that increases cilia beating and directly kills bacteria. Several diseases, including chronic rhinosinusitis, COPD, and cystic fibrosis, are characterized by loss of motile cilia and/or squamous metaplasia. To understand T2R function within the altered landscape of airway disease, we studied T2Rs in non-ciliated airway cell lines and primary cells. Several T2Rs localize to the nucleus in de-differentiated cells that typically localize to cilia in differentiated cells. As cilia and nuclear import utilize shared proteins, some T2Rs may target to the nucleus in the absence of motile cilia. T2R agonists selectively elevated nuclear and mitochondrial calcium through a G-protein-coupled receptor phospholipase C mechanism. Additionally, T2R agonists decreased nuclear cAMP, increased nitric oxide, and increased cGMP, consistent with T2R signaling. Furthermore, exposure to T2R agonists led to nuclear calcium-induced mitochondrial depolarization and caspase activation. T2R agonists induced apoptosis in primary bronchial and nasal cells differentiated at air-liquid interface but then induced to a squamous phenotype by apical submersion. Air-exposed well-differentiated cells did not die. This may be a last-resort defense against bacterial infection. However, it may also increase susceptibility of de-differentiated or remodeled epithelia to damage by bacterial metabolites. Moreover, the T2R-activated apoptosis pathway occurs in airway cancer cells. T2Rs may thus contribute to microbiome-tumor cell crosstalk in airway cancers. Targeting T2Rs may be useful for activating cancer cell apoptosis while sparing surrounding tissue.

Effectiveness of youth psychotherapy delivered remotely: A meta-analysis.

Reports on remote psychotherapies for youth (e.g., technology-based treatment) suggest it is acceptable, feasible, and useful in overcoming logistical barriers to treatment. But how effective is remote care? To find out, PsycINFO and PubMed were searched from 1960 through 2020, supplemented by journal searches and reference trails, to identify randomized controlled trials of youth psychotherapy for anxiety (including obsessive-compulsive disorder and trauma), depression, attention-deficit/hyperactivity disorder (ADHD), or conduct problems, in which all therapeutic contact occurred remotely. Articles (N = 37) published from 1988 through 2020, reporting 43 treatment-control group comparisons, were identified. Robust variance estimation was used to account for effect size dependencies and to synthesize overall effects and test candidate moderators. Pooled effect size was .47 (95% confidence interval [CI: .26, .67], p < .001) at posttreatment, .44 (95% CI [.12, .76], p < .05) at follow-up-comparable to effects reported in meta-analyses of in-person youth psychotherapy. Effects were significantly (a) larger for remote psychotherapies supported by therapeutic provider contact (.64) than for those accessed by youths, with only logistical support (.22), (b) larger for treatments with phone contact (.65) than for those without (.25), (c) larger for treatment of anxiety (.62) and conduct problems (.78) than ADHD (-.03), and (d) smaller for therapies involving attention/working memory training (-.18) than for those without (.60). Among studies with therapeutic contact, effects were significantly larger when therapists facilitated skill-building (e.g., practicing exposures or problem solving [.68]) than when therapists did not (.18). These findings support the effectiveness of remote psychotherapies for youths, and they highlight moderators of treatment benefit that warrant attention in future research. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Can Artificial Intelligence Improve Psychotherapy Research and Practice?

Leonard Bickman's article on the future of artificial intelligence (AI) in psychotherapy research paints an encouraging picture of the progress to be made in this field. We support his perspective, but we also offer some cautionary notes about the boost AI can provide. We suggest that AI is not likely to transform psychotherapy research or practice to the degree seen in pharmacology and medicine because the factors that contribute to treatment response in these realms differ so markedly from one another, and in ways that do not favor advances in psychotherapy. Despite this limitation, it seems likely that AI will have a beneficial impact, improving empirical analysis through data-driven model development, tools for addressing the limitations of traditional regression methods, and novel means of personalizing treatment. In addition, AI has the potential to augment the reach of the researcher and therapist by expanding our ability to gather data and deliver interventions beyond the confines of the lab or clinical office.