ABSTRACT
BACKGROUND: To safeguard the most vulnerable individuals during the COVID-19 pandemic, numerous governments enforced measures such as stay-at-home orders, social distancing, and self-isolation. These social restrictions had a particularly negative effect on older adults, as they are more vulnerable and experience increased loneliness, which has various adverse effects, including increasing the risk of mental health problems and mortality. Chatbots can potentially reduce loneliness and provide companionship during a pandemic. However, existing chatbots do not cater to the specific needs of older adult populations. OBJECTIVE: We aimed to develop a user-friendly chatbot tailored to the specific needs of older adults with anxiety or depressive disorders during the COVID-19 pandemic and to examine their perspectives on mental health chatbot use. The primary research objective was to investigate whether chatbots can mitigate the psychological stress of older adults during COVID-19. METHODS: Participants were older adults belonging to two age groups (≥65 years and <65 years) from a psychiatric outpatient department who had been diagnosed with depressive or anxiety disorders by certified psychiatrists according to the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5) criteria. The participants were required to use mobile phones, have internet access, and possess literacy skills. The chatbot's content includes monitoring and tracking health data and providing health information. Participants had access to the chatbot for at least 4 weeks. Self-report questionnaires for loneliness, depression, and anxiety were administered before and after chatbot use. The participants also rated their attitudes toward the chatbot. RESULTS: A total of 35 participants (mean age 65.21, SD 7.51 years) were enrolled in the trial, comprising 74% (n=26) female and 26% (n=9) male participants. The participants demonstrated a high utilization rate during the intervention, with over 82% engaging with the chatbot daily. Loneliness significantly improved in the older group ≥65 years. This group also responded positively to the chatbot, as evidenced by changes in University of California Los Angeles Loneliness Scale scores, suggesting that this demographic can derive benefits from chatbot interaction. Conversely, the younger group, <65 years, exhibited no significant changes in loneliness after the intervention. Both the older and younger age groups provided good scores in relation to chatbot design with respect to usability (mean scores of 6.33 and 6.05, respectively) and satisfaction (mean scores of 5.33 and 5.15, respectively), rated on a 7-point Likert scale. CONCLUSIONS: The chatbot interface was found to be user-friendly and demonstrated promising results among participants 65 years and older who were receiving care at psychiatric outpatient clinics and experiencing relatively stable symptoms of depression and anxiety. The chatbot not only provided caring companionship but also showed the potential to alleviate loneliness during the challenging circumstances of a pandemic.
ABSTRACT
The recognition of ubiquitylated substrates is an essential element of ubiquitin/26S proteasome-mediated proteolysis (UPP), which is mediated directly by the proteasome subunit RPN10 and/or RPN13, or indirectly by ubiquitin receptors containing ubiquitin-like and ubiquitin-associated domains. By pull-down and mutagenesis assays, we detected cross-species divergence of the major recognition pathways. RPN10 plays a major role in direct recognition in Arabidopsis and yeast based on the strong affinity for the long and K48-linked ubiquitin chains. In contrast, both the RPN10 and RPN13 homologs play major roles in humans. For indirect recognition, the RAD23 and DSK2 homologs (except for the human DSK2 homolog) are major receptors. The human RAD23 homolog is targeted to the 26S proteasome by the RPN10 and RPN13 homologs. In comparison, Arabidopsis uses UIM1 and UIM3 of RPN10 to bind DSK2 and RAD23, respectively. Yeast uses UIM in RPN10 and LRR in RPN1. Overall, multiple proteasome subunits are responsible for the direct and/or indirect recognition of ubiquitylated substrates in yeast and humans. In contrast, a single proteasome subunit, RPN10, is critical for both the direct and indirect recognition pathways in Arabidopsis. In agreement with these results, the accumulation of ubiquitylated substrates and severe pleiotropic phenotypes of vegetative and reproductive growth are associated with the loss of RPN10 function in an Arabidopsis T-DNA insertion mutant. This implies that the targeting and proteolysis of the critical regulators involved are affected. These results support a cross-species mechanistic and functional divergence of the major recognition pathways for ubiquitylated substrates of UPP.