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Objectives: Individuals with bipolar disorder commonly report cognitive impairment which is associated with several psychosocial factors (e.g., mood symptoms). Within this study, we investigated the relationship between these psychosocial factors and the perception of cognitive impairment in individuals with bipolar disorder. Methods: We measured the relationship between subjective cognitive impairment and mood symptoms, quality of life, age, gender, bipolar disorder subtype, anxiety and sleep disturbance in 140 individuals with bipolar disorder with a mixed linear regression model. Our primary outcome measures were obtained via National Institute of Health (NIH)-sponsored PROMIS cognition scores. Results: Results from the model suggest that both the PROMIS Cognitive Function and Cognitive Function-Abilities scores were significantly negatively correlated with sleep disturbance and depression symptoms (p≤0.05). PROMIS Cognitive Function was also significantly negatively correlated with anxiety (p≤0.05). Limitations: Limitations of this study include the absence of a healthy control group, limited demographic diversity, and cross-sectional study design. Conclusions: Perceived cognitive impairment in individuals with bipolar disorder is associated with increased sleep disturbance, depression, and anxiety. Future studies with objective cognitive measures combined with PROMIS self-report scores might further clarify the expression of cognitive impairment in bipolar disorder.

The second messenger, cAMP has potent immunosuppressive and anti-inflammatory actions. These have been attributed, in part, to the ability of cAMP-induced signals to interfere with the function of the proinflammatory transcription factor Nuclear Factor-kappa B (NF-κB). However, the mechanisms underlying the modulation of NF-κB activity by cAMP remain unclear. Here we demonstrate an important role for cAMP-mediated increase in nuclear actin monomer levels in inhibiting NF-κB activity. Elevated cAMP or forced expression of a nuclear localised polymerisation defective actin mutant (NLS-ActinR62D) inhibited basal and TNFα induced mRNA levels of NF-κB-dependent genes and NF-κB-dependent reporter gene activity. Elevated cAMP or NLS-ActinR62D did not affect NF-κB nuclear translocation but did reduce total cellular and nuclear RelA/p65 levels. Preventing the cAMP-induced increase in nuclear actin monomer, either by expressing a nuclear localised active mutant of the actin polymerising protein mDIA, silencing components of the nuclear actin import complex IPO9 and CFL1 or overexpressing the nuclear export complex XPO6, rescued RelA/p65 levels and NF-κB reporter gene activity in forskolin-stimulated cells. Elevated cAMP or NLS-ActinR62D reduced the half-life of RelA/p65, which was reversed by the proteasome inhibitor MG132. Accordingly, forskolin stimulated association of RelA/p65 with ubiquitin affinity beads, indicating increased ubiquitination of RelA/p65 or associated proteins. Taken together, our data demonstrate a novel mechanism underlying the anti-inflammatory effects of cAMP and highlight the important role played by nuclear actin in the regulation of inflammation.

Background Digital testing services for sexually transmitted and blood-borne infections (STBBIs), such as GetCheckedOnline, experience significant user drop-offs. For example, 32% of GetCheckedOnline users needing testing at account creation do not test, constituting missed opportunities. We explored the influence of users’ expectations and experiences of GetCheckedOnline's web design and implementation on missed opportunities. Methods This interpretive description purposively sampled 14 GetCheckedOnline users who created accounts between April 2022 and February 2023, indicated needed testing at account creation but did not test. We conducted semi-structured interviews and cognitive walkthroughs of GetCheckedOnline on Zoom, exploring participants’ expectations and experiences, including problems using the service. Interviews were audio recorded, transcribed verbatim, and analyzed using reflexive thematic analyses. Results Three themes were identified: (a) transitioning between GetCheckedOnline and laboratory services is a major testing barrier; (b) users’ appraisal of their health and social contexts is a determinant of testing through GetCheckedOnline; and (c) tailoring GetCheckedOnline's design and implementation to accommodate varying user needs can promote equitable testing. Health equity issues occurred along sociodemographic gradients as the GetCheckedOnline-laboratory transition was more onerous for older users. Users’ appraisal of their testing needs which varied by age and gender, and their assessment of time, and travel requirements for testing in remote communities influenced testing. Learning about GetCheckedOnline from healthcare providers improved testing compared with learning about the service through Google search which raised trust concerns regarding GetCheckedOnline's authenticity. Suggested improvements to promote health equity include personalized education, mail-in testing options, and simpler seamless web experiences. Conclusions To promote equitable access to digital STBBI testing services such as GetCheckedOnline, we can adapt web-design and implementation to suit user needs and contexts, ensuring simplicity and options for testing that reduce user burdens.