BackgroundIn the treatment of major depression, antidepressants are effective but not curative. Cognitive behavioral therapy (CBT) is also effective, alone or in combination with pharmacotherapy, but accessibility is a problem.ObjectiveThe aim is to evaluate the effectiveness of a smartphone CBT app as adjunctive therapy among patients with antidepressant-resistant major depression.MethodsA multisite, assessor-masked, parallel-group randomized controlled trial was conducted in 20 psychiatric clinics and hospitals in Japan. Participants were eligible if they had a primary diagnosis of major depression and were antidepressant-refractory after taking one or more antidepressants at an adequate dosage for four or more weeks. After a 1-week run-in in which participants started the medication switch and had access to the welcome session of the app, patients were randomized to medication switch alone or to medication switch plus smartphone CBT app via the centralized Web system. The smartphone app, called Kokoro-app (“kokoro” means “mind” in Japanese), included sessions on self-monitoring, behavioral activation, and cognitive restructuring presented by cartoon characters. The primary outcome was depression severity as assessed by masked telephone assessors with the Patient Health Questionnaire-9 (PHQ-9) at week 9. The secondary outcomes included the Beck Depression Inventory-II (BDI-II) and Frequency, Intensity, and Burden of Side Effects Ratings (FIBSER).ResultsIn the total sample (N=164), 81 participants were allocated to the smartphone CBT in addition to medication change and 83 to medication change alone. In the former group, all but one participant (80/81, 99%) completed at least half, and 71 (88%) completed at least six of eight sessions. In the intention-to-treat analysis, patients allocated the CBT app scored 2.48 points (95% CI 1.23-3.72, P<.001; standardized mean difference 0.40) lower on PHQ-9 than the control at week 9. The former group also scored 4.1 points (95% CI 1.5-6.6, P=.002) lower on BDI-II and 0.76 points (95% CI –0.05 to 1.58, P=.07) lower on FIBSER. In the per-protocol sample (comfortable with the smartphone app, still symptomatic, and adherent to medication with mild or less side effects after run-in), the intervention group (n=60) scored 1.72 points (95% CI 0.25-3.18, P=.02) lower on PHQ-9, 3.2 points (95% CI –0.01 to 6.3, P=.05) lower on BDI-II, and 0.75 points (95% CI 0.03-1.47, P=.04) lower on FIBSER than the control (n=57). The treatment benefits were maintained up to week 17.ConclusionsThis is the first study to demonstrate the effectiveness of a smartphone CBT in the treatment of clinically diagnosed depression. Given the merits of the mobile mental health intervention, including accessibility, affordability, quality control, and effectiveness, it is clinically worthwhile to consider adjunctive use of a smartphone CBT app when treating patients with antidepressant-resistant depression. Research into its effectiveness in wider clinical contexts is warranted.Trial RegistrationJapanese Clinic...

We evaluated the therapeutic efficacy of topical administration of SN50, an inhibitor of nuclear factor-kappaB, in a corneal alkali burn model in mice. An alkali burn was produced with 1 N NaOH in the cornea of C57BL/6 mice under general anesthesia. SN50 (10 microg/microl) or vehicle was topically administered daily for up to 12 days. The eyes were processed for histological or immunohistochemical examination after bromodeoxyuridine labeling or for semi-quantification of cytokine mRNA. Topical SN50 suppressed nuclear factor-kappaB activation in local cells and reduced the incidence of epithelial defects/ulceration in healing corneas. Myofibroblast generation, macrophage invasion, activity of matrix metalloproteinases, basement membrane destruction, and expression of cytokines were all decreased in treated corneas compared with controls. To elucidate the role of tumor necrosis factor (TNF)-alpha in epithelial cell proliferation, we performed organ culture of mouse eyes with TNF-alpha, SN50, or an inhibitor of c-Jun N-terminal kinase (JNK) and examined cell proliferation in healing corneal epithelium in TNF-alpha-/- mice treated with SN50. An acceleration of epithelial cell proliferation by SN50 treatment was found to depend on TNF-alpha/JNK signaling. In conclusion, topical application of SN50 is effective in treating corneal alkali burns in mice.

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Both acid and alkaline invertases were present in immature juice sacs of satsuma mandarin (Citrus‘Unshu Marcovitch”) fruit, in which sugar content was low. Maturing and mature juice sacs, in which sugar content increased steadily with time, were characterized by the presence of alkaline invertase and the absence of acid invertase. When the immature juice sacs were homogenized with 0.2 M sodium phosphate‐citrate buffer (pH 8.0), almost all of the acid invertase activity was found in the solubilized fraction, whereas almost all of the alkaline invertase activity was present in the insoluble fraction. The distribution of alkaline invertase between the solubilized and insoluble fractions changed with the development of fruit. The acid invertase had a molecular weight of 69,000, optimum pH of 4.8–5.3, and Km value for sucrose of 7.3 mM. The alkaline invertase had a molecular weight of 200,000, pH optimum of 7.2–7.7, and Km value of 35.7 mM. The hydrolysing activities of both enzymes for raffinose were considerably less than those for sucrose. The alkaline invertase had lower activity for raffinose than the acid invertase.