The effectiveness of unguided internet cognitive behavioural therapy for mixed anxiety and depression.

Clinician-guided internet-delivered cognitive behavioral therapy (iCBT) is an effective treatment for depression and anxiety disorders. However, few studies have examined the effectiveness of completely unguided iCBT. The current research investigated adherence to, and the effects of two brief unguided iCBT programs on depression and anxiety symptom severity, and psychological distress. Study 1 evaluated a four-lesson transdiagnostic iCBT program for anxiety and depression (N = 927). Study 2 then evaluated a three-lesson version of the same program (N = 5107) in order to determine whether reducing the duration of treatment would influence adherence and treatment effects. Cross-tabulations and independent t-tests were used to examine the extent to which users adhered and remitted with treatment. Linear mixed models were used to evaluate the effects of treatment in the entire sample, and stratified by gender and completer-type (e.g., users who completed some but not all lessons vs. those who completed all lessons of treatment). Among those who began treatment, 13.83% completed all four lessons in Study 1. Shortening the course to three lessons did not improve adherence (e.g., 13.11% in Study 2). In both studies, users, on average, experienced moderate to large effect size reductions in anxiety and depressive symptom severity, as well as psychological distress. This pattern of results was robust across gender and for those who did and did not complete treatment. Approximately two-thirds of those who completed treatment experienced remission. These data show that unguided iCBT programs, which have the capacity to attract large numbers of individuals with clinically significant symptoms of depression and anxiety, and psychological distress, can produce significant improvements in wellbeing.

Fine-tuning of voltage sensitivity of the Kv1.2 potassium channel by interhelix loop dynamics.

Many proteins function by changing conformation in response to ligand binding or changes in other factors in their environment. Any change in the sequence of a protein, for example during evolution, which alters the relative free energies of the different functional conformations changes the conditions under which the protein will function. Voltage-gated ion channels are membrane proteins that open and close an ion-selective pore in response to changes in transmembrane voltage. The charged S4 transmembrane helix transduces changes in transmembrane voltage into a change in protein internal energy by interacting with the rest of the channel protein through a combination of non-covalent interactions between adjacent helices and covalent interactions along the peptide backbone. However, the structural basis for the wide variation in the V50 value between different voltage-gated potassium channels is not well defined. To test the role of the loop linking the S3 helix and the S4 helix in voltage sensitivity, we have constructed a set of mutants of the rat Kv1.2 channel that vary solely in the length and composition of the extracellular loop that connects S4 to S3. We evaluated the effect of these different loop substitutions on the voltage sensitivity of the channel and compared these experimental results with molecular dynamics simulations of the loop structures. Here, we show that this loop has a significant role in setting the precise V50 of activation in Kv1 family channels.