Outcomes of an interdisciplinary return to work intervention including occupational therapy for mood and adjustment disorders: A single-arm clinical trial.

BACKGROUND: Mood and adjustment disorders are two major causes of long-term sick leave among employees, leading to large social losses. Therefore, a return to work (RTW) intervention was attempted, targeting patients with mood and adjustment disorders. OBJECTIVE: This study aimed to investigate the outcome of an interdisciplinary RTW intervention including occupational therapy implemented within the Japanese healthcare framework. METHODS: An interdisciplinary RTW intervention including occupational therapy was conducted five times a week for approximately three months, targeting individuals with mood and adjustment disorders who took a leave of absence. Their mental symptoms, cognitive functioning, job performance, temperament, social adaptation, psychosocial state, and readiness to RTW before and after the intervention were evaluated. Full-time RTW ratios at 3, 6, 12, 18, and 24 months from baseline were followed up and compared with those of prior studies. RESULTS: A total of 30 individuals completed the intervention. After the intervention, participants' psychological symptoms, cognitive function, vocational aptitude, temperament, social adaptation, psychosocial state, and readiness to RTW improved (p≤0.001-0.0279). The ratios of RTW at 3, 6, 12, 18, and 24 months from the baseline were 6.7%, 46.7%, 73.3%, 77.8%, and 82.6%, respectively, reflecting a higher pattern than prior reports. CONCLUSIONS: The interdisciplinary RTW intervention including occupational therapy has the potential to improve not only depressive symptoms but also cognitive functioning, job performance, social adaptation, and readiness to RTW. They can also raise RTW ratios.

Asymmetric configurations and N-terminal rearrangements in connexin26 gap junction channels.

Gap junction channels are unique in that they possess multiple mechanisms for channel closure, several of which involve the N terminus as a key component in gating, and possibly assembly. Here, we present electron crystallographic structures of a mutant human connexin26 (Cx26M34A) and an N-terminal deletion of this mutant (Cx26M34Adel2-7) at 6-Å and 10-Å resolutions, respectively. The three-dimensional map of Cx26M34A was improved by data from 60° tilt images and revealed a breakdown of the hexagonal symmetry in a connexin hemichannel, particularly in the cytoplasmic domain regions at the ends of the transmembrane helices. The Cx26M34A structure contained an asymmetric density in the channel vestibule ("plug") that was decreased in the Cx26M34Adel2-7 structure, indicating that the N terminus significantly contributes to form this plug feature. Functional analysis of the Cx26M34A channels revealed that these channels are predominantly closed, with the residual electrical conductance showing normal voltage gating. N-terminal deletion mutants with and without the M34A mutation showed no electrical activity in paired Xenopus oocytes and significantly decreased dye permeability in HeLa cells. Comparing this closed structure with the recently published X-ray structure of wild-type Cx26, which is proposed to be in an open state, revealed a radial outward shift in the transmembrane helices in the closed state, presumably to accommodate the N-terminal plug occluding the pore. Because both Cx26del2-7 and Cx26M34Adel2-7 channels are closed, the N terminus appears to have a prominent role in stabilizing the open configuration.