RESUMO
BACKGROUND: Individuals with inflammatory bowel disease (IBD) experience cycles of aggressive physical symptoms including abdominal pain, diarrhea, and fatigue. These acute symptoms regress and return, and chronic symptoms and complications often linger. The nature of the disease can also cause individuals to experience psychological distress including symptoms of anxiety and depression; however, unlike the physical symptoms of IBD, these psychological symptoms often remain untreated. OBJECTIVE: This study aims to evaluate the feasibility, acceptability, and effectiveness of virtual mindfulness-based stress reduction (v-MBSR) for adults with IBD. METHODS: IBD patients with self-reported anxiety or depression were recruited from clinics in Alberta, Canada to participate in an 8-week v-MSBR intervention. Eligible patients participated in v-MBSR delivered by psychiatrists using a videoconferencing platform. Primary feasibility outcomes included trial uptake, adherence, attendance, and attrition rates. Secondary effectiveness outcomes included measures of anxiety, depression, quality of life (QoL), and mindfulness. Effectiveness data were collected at 3 time points: baseline, at intervention completion, and 6 months after completion. To further assess feasibility and acceptability, participants were invited to participate in a semistructured interview after completing v-MBSR. RESULTS: A total of 16 of the 64 (25%) referred patients agreed to participate in v-MBSR with the most common reason for decline being a lack of time while 7 of the 16 (43.8%) participants completed the program and experienced encouraging effects including decreased anxiety and depression symptoms and increased health-related QoL with both improvements persisting at 6-month follow-up. Participants described improved coping strategies and disease management techniques as benefits of v-MBSR. CONCLUSIONS: Patients with IBD were interested in a psychiatrist-led virtual anxiety management intervention, but results demonstrate v-MBSR may be too time intensive for some patients with IBD patients. v-MBSR was acceptable to those who completed the intervention, and improvements to anxiety, depression, and QoL were promising and sustainable. Future studies should attempt to characterize the patients with IBD who may benefit most from interventions like v-MBSR.
RESUMO
Ultraviolet light (UV)-induced DNA damage is repaired primarily by the nucleotide excision repair (NER) pathway. Gadd45 is a multifunctional protein that regulates NER. Gadd45-deficient keratinocytes fail to repair UV-induced DNA damage, but the mechanism by which Gadd45 stimulates repair of UV-induced DNA damage is unknown. p21WAF1/Cip1 (p21) is a well-characterized downstream target of p53 that binds to Gadd45 and proliferating cell nuclear antigen (PCNA). The role of p21 in NER is somewhat controversial, however, recent studies appear to suggest that it inhibits DNA repair by inhibiting PCNA activity. Since a physical interplay exists between p21, Gadd45 and PCNA, we hypothesized that Gadd45 promoted DNA repair via p21. Initially, we examined p21 protein expression in Gadd45-deficient and proficient mice and found a higher base level of p21 protein in Gadd45-deficient keratinocytes and in most other tissues. With these results, we next speculated on the role played by p21 in Gadd45 regulated NER, by exposing keratinocytes from wild-type, single and double knockout (Gadd45 and p21) mice to UV, and measuring the responses. We confirmed that Gadd45-deficient keratinocytes were defective in UV-induced NER, but interestingly Gadd45/p21-null keratinocytes had normal NER in response to UV. Furthermore, Gadd45/p21-null keratinocytes were more resistant to UV-induced cell death than Gadd45-deficient keratinocytes. These results support the hypothesis that Gadd45 enhances NER by negatively regulating basal p21 expression in keratinocytes.
