Preliminary evaluation of translated and culturally adapted internet-delivered cognitive therapy for social anxiety disorder: multicenter, single-arm trial in japan

Background: Internet-delivered cognitive therapy for social anxiety disorder (iCT-SAD), which is a therapist-guided modular web-based treatment, has shown strong efficacy and acceptability in English-language randomized controlled trials in the United Kingdom and Hong Kong. However, it is not yet known whether iCT-SAD can retain its efficacy following linguistic translation and cultural adaptation of treatment contents and implementation in other countries such as Japan. Objective: This study aimed to examine the preliminary efficacy and acceptability of the translated and culturally adapted iCT-SAD in Japanese clinical settings. Methods: This multicenter, single-arm trial recruited 15 participants with social anxiety disorder. At the time of recruitment, participants were receiving usual psychiatric care but had not shown improvement in their social anxiety and required additional treatment. iCT-SAD was provided in combination with usual psychiatric care for 14 weeks (treatment phase) and for a subsequent 3-month follow-up phase that included up to 3 booster sessions. The primary outcome measure was the self-report version of the Liebowitz Social Anxiety Scale. The secondary outcome measures examined social anxiety–related psychological processes, taijin kyofusho (the fear of offending others), depression, generalized anxiety, and general functioning. The assessment points for the outcome measures were baseline (week 0), midtreatment (week 8), posttreatment (week 15; primary assessment point), and follow-up (week 26). Acceptability was measured using the dropout rate from the treatment, the level of engagement with the program (the rate of module completion), and participants’ feedback about their experience with the iCT-SAD. Results: Evaluation of the outcome measures data showed that iCT-SAD led to significant improvements in social anxiety symptoms during the treatment phase (P<.001; Cohen d=3.66), and these improvements were maintained during the follow-up phase. Similar results were observed for the secondary outcome measures. At the end of the treatment phase, 80% (12/15) of participants demonstrated reliable improvement, and 60% (9/15) of participants demonstrated remission from social anxiety. Moreover, 7% (1/15) of participants dropped out during treatment, and 7% (1/15) of participants declined to undergo the follow-up phase after completing the treatment. No serious adverse events occurred. On average, participants completed 94% of the modules released to them. Participant feedback was positive and highlighted areas of strength in treatment, and it included further suggestions to improve suitability for Japanese settings. Conclusions: Translated and culturally adapted iCT-SAD demonstrated promising initial efficacy and acceptability for Japanese clients with social anxiety disorder. A randomized controlled trial is required to examine this more robustly

Deletion of CDKAL1 Affects Mitochondrial ATP Generation and First-Phase Insulin Exocytosis

A variant of the CDKAL1 gene was reported to be associated with type 2 diabetes and reduced insulin release in humans; however, the role of CDKAL1 in β cells is largely unknown. Therefore, to determine the role of CDKAL1 in insulin release from β cells, we studied insulin release profiles in CDKAL1 gene knockout (CDKAL1 KO) mice.Total internal reflection fluorescence imaging of CDKAL1 KO β cells showed that the number of fusion events during first-phase insulin release was reduced. However, there was no significant difference in the number of fusion events during second-phase release or high K(+)-induced release between WT and KO cells. CDKAL1 deletion resulted in a delayed and slow increase in cytosolic free Ca(2+) concentration during high glucose stimulation. Patch-clamp experiments revealed that the responsiveness of ATP-sensitive K(+) (K(ATP)) channels to glucose was blunted in KO cells. In addition, glucose-induced ATP generation was impaired. Although CDKAL1 is homologous to cyclin-dependent kinase 5 (CDK5) regulatory subunit-associated protein 1, there was no difference in the kinase activity of CDK5 between WT and CDKAL1 KO islets.We provide the first report describing the function of CDKAL1 in β cells. Our results indicate that CDKAL1 controls first-phase insulin exocytosis in β cells by facilitating ATP generation, K(ATP) channel responsiveness and the subsequent activity of Ca(2+) channels through pathways other than CDK5-mediated regulation

Measurement of work-related psychological injury with depressive symptoms

Abstract Objective This study aimed to measure the level of psychological injury caused by work-related stress as well as the severity of depression among workers. Method First, we conducted an online survey and recruited 500 workers diagnosed with depression or adjustment disorder to investigate what type of stress they experienced within six months before onset. Second, we conducted another online survey and recruited 767 participants who experienced some form of work-related stress. All the participants were classified into four groups by whether or not they were diagnosed with depression and whether or not they quit their jobs due to work-related stress. We used the Impact of Event Scale-Revised (IES-R) to measure psychological injury caused by work-related stressful events and the Patient Health Questionnaire (PHQ)-9 to assess the severity of depression. Results In study 1, 62.4% of workers diagnosed with depression or adjustment disorder experienced work-related stress within six months before onset. In study 2, the IES-R mean scores were 40.7 (SD = 23.1) for Group A (workers with depression and quit their jobs) and 36.67 (SD = 23.4) for Group B (workers with depression but stayed at their jobs), with both exceeding the cut-off point (24/25) of PTSD (Post-Traumatic Stress Disorder), while the mean score of Group C (workers who did not have depression but quit their jobs because of work-related stress) was 20.74 (SD = 21.2), and it was 13.89 (SD = 17.4) for Group D (workers who had work-related stress but stayed at their jobs), with both of them below the cut-off point of PTSD. The total scores of IES-R of Group A and Group B were significantly higher than those of Group C and Group D(p < 0.001). There was a significant positive correlation between the scores of IES-R and PHQ-9 for all four groups (r = 0.708). Conclusions This study suggests that it is necessary to measure not only depressive symptoms but also the level of psychological injury resulting from stressful events in the workplace to assess workers with depression

Anthocyanidins-enriched bilberry extracts inhibit 3T3-L1 adipocyte differentiation via the insulin pathway

Abstract Background Obesity and metabolic syndrome are important public concerns, and there is increasing demand for effective therapeutic strategies. Flavonoids are expected to improve the risk factors associated with metabolic syndrome. Anthocyanidins are a kind of flavonoids; well known for their anti-oxidative, anti-inflammatory and anti-tumor properties. However, their effects on adipocytes and molecular systems are not well defined. In this study, we examined the effects of anthocyanidins-enriched bilberry extracts on adipocyte differentiation. Methods Utilizing 3T3-L1 cell line, we investigated that bilberry extracts and anthocyanidins induced inhibition of lipid accumulation during adipogenesis. To identify what is the most important bilberry mediated-effect, we analyzed the expressions of key transcriptional factors associated with adipocyte differentiation by Real Time (RT)-PCR. From the results of RT-PCR, we hypothesized that bilberry extracts and anthocyanidins blocks insulin signal, we determined the phosphorylation of tyrosine residues of insulin receptor substrate 1 (IRS1) protein by western blotting analysis. In addition, we compared the whole-genome expression profiles of early stage of adipocyte differentiation under four different growth conditions (DMSO, bilberry, two anthocyanidins) by microarray analyses and Gene Set Enrichment Analysis (GSEA). Results Exposure to bilberry extracts and anthocyanidins during adipocyte differentiation inhibited 3T3-L1 differentiation. During this period, bilberry extracts and anthocyanidin significantly decreased a key adipocyte differentiation-associated marker, peroxisome proliferator-activated receptor- γ (Ppar γ ) and sterol regulatory element-binding protein 1c (Srebp1c). Western blotting analysis showed that bilberry extracts and anthocyanidin decreased the phosphorylation of tyrosine residues of IRS1. In addition, microarray experiments and GSEA data revealed significantly altered expression of the known genes of the insulin pathway in cells treated with bilberry extracts or anthocyanidins in the early differentiation stages. Conclusions Our data demonstrate that anthocyanidin enriched bilberry extracts strongly inhibit the adipocyte differentiation via the insulin pathway. Furthermore, bilberry extracts might be used as a potential complementary treatment for the obese patients with metabolic syndrome.</p

Novel murine model of congenital diabetes: The insulin hyposecretion mouse

Abstract Aims/Introduction Diabetic animal models have made an enormous contribution to our understanding of the etiology of diabetes and the development of new medications. The aim of the present study was to develop and characterize a novel, non‐obese murine strain with spontaneous diabetes – the insulin hyposecretion (ihs) mouse. Materials and Methods During the development of the ICGN.B6‐Tns2WT strain as the control for the ICGN‐Tns2nph congenital nephrotic strain, diabetic mice were discovered and named ihs mice. Intraperitoneal insulin tolerance test, oral glucose tolerance test and an insulin secretion experiment by the pancreas perfusion system were carried out on ihs mice. The pancreatic islets were examined histologically, and the mRNA expression of pancreatic β‐cell‐specific genes or genes associated with monogenic diabetes was examined by RT‐qPCR. Results The ihs mice showed several distinctive diabetes‐related characteristics: (i) the onset of diabetes was observed only in the male mice; (ii) there were no differences in insulin content between the ihs and control mice; (iii) impaired insulin secretion was elicited by glucose, potassium chloride and sulfonylureas; (iv) there was a significant reduction of relative β‐cell volume with no signs of inflammation or fibrosis; (v) they showed a normal glycemic response to exogenous insulin; and (vi) the mice were not obese. Conclusions The ihs mouse provides a novel murine model of congenital diabetes that shows insulin secretion failure. This model allows not only an analysis of the progression of diabetes, but also the identification of unknown genes involved in insulin secretion

Genetic locus responsible for diabetic phenotype in the insulin hyposecretion (ihs) mouse.

Diabetic animal models have made significant contributions to understanding the etiology of diabetes and to the development of new medications. Our research group recently developed a novel diabetic mouse strain, the insulin hyposecretion (ihs)mouse. The strain involves neither obesity nor insulitis but exhibits notable pancreatic β-cell dysfunction, distinguishing it from other well-characterized animal models. In ihs mice, severe impairment of insulin secretion from pancreas has been elicited by glucose or potassium chloride stimulation. To clarify the genetic basis of impaired insulin secretion, beginning with identifying the causative gene, genetic linkage analysis was performed using [(C57BL/6 × ihs) F1 × ihs] backcross progeny. Genetic linkage analysis and quantitative trait loci analysis for blood glucose after oral glucose loading indicated that a recessively acting locus responsible for impaired glucose tolerance was mapped to a 14.9-Mb region of chromosome 18 between D18Mit233 and D18Mit235 (the ihs locus). To confirm the gene responsible for the ihs locus, a congenic strain harboring the ihs locus on the C57BL/6 genetic background was developed. Phenotypic analysis of B6.ihs-(D18Mit233-D18Mit235) mice showed significant glucose tolerance impairment and markedly lower plasma insulin levels during an oral glucose tolerance test. Whole-genome sequencing and Sanger sequencing analyses on the ihs genome detected two ihs-specific variants changing amino acids within the ihs locus; both variants in Slc25a46 and Tcerg1 were predicted to disrupt the protein function. Based on information regarding gene functions involving diabetes mellitus and insulin secretion, reverse-transcription quantitative polymerase chain reaction analysis revealed that the relative abundance of Reep2 and Sil1 transcripts from ihs islets was significantly decreased whereas that of Syt4 transcripts were significantly increased compared with those of control C57BL/6 mice. Thus, Slc25a46, Tcerg1, Syt4, Reep2 and Sil1 are potential candidate genes for the ihs locus. This will be the focus of future studies in both mice and humans

Clinical Effectiveness and Cost-effectiveness of Videoconference-Based Integrated Cognitive Behavioral Therapy for Chronic Pain: Randomized Controlled Trial

BackgroundCognitive behavioral therapy is known to improve the management of chronic pain. However, the components of this therapy are still being investigated and debated. ObjectiveThis study aimed to examine the effectiveness of an integrated cognitive behavioral therapy program with new components (attention-shift, memory work, video feedback, and image training) delivered via videoconferencing. MethodsThis study was unblinded and participants were recruited and assessed face-to-face in the outpatient department. We conducted a randomized controlled trial for chronic pain to compare 16 weekly videoconference-based cognitive behavioral therapy (vCBT) sessions provided by a therapist with treatment as usual (TAU). Thirty patients (age range, 22-75 years) with chronic pain were randomly assigned to either vCBT (n=15) or TAU (n=15). Patients were evaluated at week 1 (baseline), week 8 (midintervention), and week 16 (postintervention). The primary outcome was the change in pain intensity, which was recorded using the numerical rating scale at 16 weeks from the baseline. Secondary outcomes were pain severity and pain interference, which were assessed using the Brief Pain Inventory. Additionally, we evaluated disability, pain catastrophizing cognition, depression, anxiety, quality of life, and cost utility. ResultsIn the eligibility assessment, 30 patients were eventually randomized and enrolled; finally, 15 patients in the vCBT and 14 patients in the TAU group were analyzed. Although no significant difference was found between the 2 groups in terms of changes in pain intensity by the numerical rating scale scores at week 16 from baseline (P=.36), there was a significant improvement in the comprehensive evaluation of pain by total score of Brief Pain Inventory (–1.43, 95% CI –2.49 to –0.37, df=24; P=.01). Further, significant improvement was seen in pain interference by using the Brief Pain Inventory (–9.42, 95% CI –14.47 to –4.36, df=25; P=.001) and in disability by using the Pain Disability Assessment Scale (–1.95, 95% CI –3.33 to –0.56, df=24; P=.008) compared with TAU. As for the Medical Economic Evaluation, the incremental cost-effectiveness ratio for 1 year was estimated at 2.9 million yen (about US $25,000) per quality-adjusted life year gained. ConclusionsThe findings of our study suggest that integrated cognitive behavioral therapy delivered by videoconferencing in regular medical care may reduce pain interference but not pain intensity. Further, this treatment method may be cost-effective, although this needs to be further verified using a larger sample size. Trial RegistrationUniversity Hospital Medical Information Network UMIN000031124; https://tinyurl.com/2pr3xsz