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Tumour-promoting inflammation is a hallmark of cancer, and chronic inflammatory disease increases the risk of cancer. In this context, MYD88, a downstream signalling molecule of Toll-like receptors that initiates inflammatory signalling cascades, has a critical role in tumour development in mice and its gene mutation was found in human cancers. In inflammation-induced colon cancer, tumour suppressor p53 mutations have also been detected with high frequency as early events. However, the molecular mechanism of MYD88-induced cancer development is poorly understood. Here, we demonstrated that MYD88 induced the protein accumulation of the transcription factor HIF-1α through NF-κB in p53-deficient cells. HIF-1α accumulation was not caused by enhanced protein stability but by NF-κB-mediated transcriptional activation, the enhanced translation of HIF-1α and JNK activation. In contrast, MYD88-induced mRNA expressions of HIF-1α and HIF-1-target genes were attenuated in the presence of p53. Furthermore, constitutively active forms of MYD88 induced tumour-initiating cell (TIC) generation in p53-deficient cells, as determined by tumour xenografts in nude mice. TIC generating activity was diminished by the suppression of NF-κB or HIF-1α. These results indicate that MYD88 signals induce the generation of TICs through the NF-κB-HIF-1α activation cascade in p53-deficient cells and suggest this molecular mechanism underlies inflammation-induced cancer development.

This study aimed to identify occupational therapy intervention strategies, specific to Japan, for promoting occupational participation in the early stage of psychiatric hospitalization. Online focus group discussions were conducted with 13 occupational therapists with clinical experience in Japanese psychiatric wards. The transcripts were analyzed using reflexive thematic analysis. Four themes emerged as strategies that Japanese occupational therapists use (or consider necessary) to foster occupational participation in early psychiatric inpatient care: (1) \"Identifying client occupations\"; (2) \"Enhancing motivation for occupational participation\", primarily through educational interventions; (3) \"Providing opportunities for occupational experiences that facilitate change\"; and (4) \"Addressing difficulties in occupational participation arising from mental disorders\". Although therapists must contend with the distinctive challenges of an early stage of hospitalization, these strategies represent ongoing iterative efforts to support clients. The findings underscore the need to deepen clients' understanding of occupations, boost motivation through early educational engagement, elicit change through actual occupational experiences, and mitigate barriers caused by mental disorders so that meaningful occupational participation can take place. Taken together, these results suggest that occupation-focused interventions can leverage occupational therapists' expertise and contribute to recovery-oriented practices in Japan, even within the limited timeframe of early hospitalization.

In mental health occupational therapy, occupation-focused practice is recognized as crucial for supporting clients' quality of life and facilitating their recovery. However, evidence supporting the effectiveness of group-based, occupation-focused interventions for individuals with mental disorders during the early stages of hospitalization remains limited. This study aimed to develop and evaluate the effectiveness of a group occupational therapy program designed to promote occupational participation among individuals with mental disorders during the early stages of hospitalization. A multi-center, open-label, randomized controlled trial was conducted. Participants were block-randomized in a 1:1 ratio by sex into an intervention group (novel program + standard occupational therapy) or a control group (standard occupational therapy only). The developed program was designed to identify clients' occupations, clarify challenges in daily life, enhance motivation for occupational participation, and explore strategies to address barriers to occupational performance. It was implemented once a week over four sessions. Outcomes included the Japanese version of the Intrinsic Motivation Inventory (primary outcome), the Occupational Self-Assessment Short Form, the Occupational Questionnaire (OQ), the General Self-Efficacy Scale, and the Life Assessment Scale for the Mentally Ill (LASMI), all assessed pre- and post-intervention. Program evaluation questionnaires and qualitative feedback were collected from the intervention group. Analyses used hierarchical Bayesian linear models with weakly informative priors and the NUTS algorithm to estimate time-by-group interaction effects. A total of 13 participants were analyzed (intervention group: 10, control group: 3). Posterior estimates indicated meaningful interaction effects, suggesting that the intervention group showed greater improvements in interpersonal relationships and work on the LASMI, as well as in interest in occupation on the OQ, compared to the control group. Additionally, a potential positive effect was observed for the daily living subscale of the LASMI. Qualitative feedback highlighted participants' awareness of meaningful occupations, reactivated motivation, and transformative changes in occupational participation and interpersonal relationships. The study's findings suggest that occupation-focused group interventions may enhance motivation, specifically, interest in meaningful occupations related to occupational participation and improve community living functions during early psychiatric hospitalization. The results support the clinical value of such programs as recovery-oriented practices in acute mental health care. Further large-scale studies are required to verify reproducibility, given the small sample size.

To protect the audiosensory organ from tissue damage from the immune system, the inner ear is separated from the circulating immune system by the blood-labyrinth barrier, which was previously considered an immune-privileged site. Recent studies have shown that macrophages are distributed in the cochlea, especially in the spiral ligament, spiral ganglion, and stria vascularis; however, the direct pathogen defence mechanism used by audiosensory receptor hair cells (HCs) has remained obscure. Here, we show that HCs are protected from pathogens by surrounding accessory supporting cells (SCs) and greater epithelial ridge (GER or Kölliker’s organ) cells (GERCs). In isolated murine cochlear sensory epithelium, we established Theiler’s murine encephalomyelitis virus, which infected the SCs and GERCs, but very few HCs. The virus-infected SCs produced interferon (IFN)-α/β, and the viruses efficiently infected the HCs in the IFN-α/β receptor-null sensory epithelium. Interestingly, the virus-infected SCs and GERCs expressed macrophage marker proteins and were eliminated from the cell layer by cell detachment. Moreover, lipopolysaccharide induced phagocytosis of the SCs without cell detachment, and the SCs phagocytosed the bacteria. These results reveal that SCs function as macrophage-like cells, protect adjacent HCs from pathogens, and provide a novel anti-infection inner ear immune system.

Although sensorineural hearing loss (SHL) is relatively common, its cause has not been identified in most cases. Previous studies have suggested that viral infection is a major cause of SHL, especially sudden SHL, but the system that protects against pathogens in the inner ear, which is isolated by the blood-labyrinthine barrier, remains poorly understood. We recently showed that, as audiosensory receptor cells, cochlear hair cells (HCs) are protected by surrounding accessory supporting cells (SCs) and greater epithelial ridge (GER or Kölliker’s organ) cells (GERCs) against viral infections. Here, we found that virus-infected SCs and GERCs induce HC death via production of the tumour necrosis factor-related apoptosis-inducing ligand (TRAIL). Notably, the HCs expressed the TRAIL death receptors (DR) DR4 and DR5, and virus-induced HC death was suppressed by TRAIL-neutralizing antibodies. TRAIL-induced HC death was not caused by apoptosis, and was inhibited by necroptosis inhibitors. Moreover, corticosteroids, the only effective drug for SHL, inhibited the virus-induced transformation of SCs and GERCs into macrophage-like cells and HC death, while macrophage depletion also inhibited virus-induced HC death. These results reveal a novel mechanism underlying virus-induced HC death in the cochlear sensory epithelium and suggest a possible target for preventing virus-induced SHL.

Background. Social withdrawal is predominantly seen among adults with depression. However, a dearth of reviews exists that explore nonpharmacological treatments, especially occupational therapy (OT) interventions and their effect in promoting social participation. The aim of this research was to review what intervention programs are conducted to support the social participation of adults with depression and their effectiveness. Method. A systematic review was performed wherein relevant articles were searched in PubMed, CINAHL, Wiley Online Library, PsycINFO, and OTseeker databases and AJOT, BJOT, SJOT, and OTMH journals. Only English articles published from January 2010 to December 2018, which tackled intervention for adults aged 20–60 years with depression, were considered. Ten out of 918 studies met the screening criteria. Result. Among the ten studies, the effective intervention programs were categorized as either occupation-based intervention (OBI) or cognitive behavioral therapy-based intervention (CBT-BI). These programs sought the following outcomes: behavioral change in social participation (n=4), reduction of depression or depressive symptoms (n=13), life satisfaction (n=4), and quality of life (QoL) (n=1). Studies showed moderate (n=3) to strong (n=7) level of certainty, whereas they also revealed high to unclear (n=3) and low (n=7) risk of bias. Conclusion. Both OBI such as animal-assisted therapy and CBT-BI such as behavioral change program and health education have a strong level of certainty and low risk of bias in promoting social participation by supporting positive behavioral change and reducing depressive symptoms. Furthermore, the sport and exercise program of OBI was popular in encouraging participation and engagement with other people. Other programs were suggested for combined interventions to support social participation, life satisfaction, and QoL.

Introduction. Depression in adulthood decreases social participation in the workplace, family, and community, which further results in decreased work performance and cessation and social isolation. There is a high statistic of outpatient consultation and readmission of Thais with depression, yet the mental health support for remission in community life and social participation remains limited and unclear. Further, due to the lack of mental health professional resources, particularly occupational therapists, there is much to be known regarding how such therapists work to support the development of social participation in Thai adults with depression. Objective. This research was aimed at understanding the process of how occupational therapists work to redevelop the social participation of community-dwelling Thai adults with depression. Method. The grounded theory methodology was used in this study. Data were collected through interviews and nonparticipatory observations of 14 participants who had experience providing mental health care in community services. The constant comparative analysis method was employed. Result. Three concepts illustrated a proactive community occupational therapy service for depression (PCOTS-D), namely, integrating depression care in community occupational therapy service (COTS), supporting meaningful participation, and forming collaborative networks. The PCOTS-D supported the reconnection of social participation by leading from proactive depression care service to COTS and then working to support meaningful participation toward the patient’s self-management and building collaborative networks with inter- and intraprofessional teams simultaneously. Conclusion. The PCOTS-D presented a holistic view of working with community-dwelling Thai adults with depression by considering the importance of the community and researchers’ network to redevelop social participation, promote health and recovery, build teams in depression care, and encourage research evidence to enhance the supportive advocacy policy for Thai people with depression.

Anti‐proinflammatory cytokine therapies against interleukin (IL)‐6, tumor necrosis factor (TNF)‐α, and IL‐1 are major advancements in treating inflammatory diseases, especially rheumatoid arthritis. Such therapies are mainly performed by injection of antibodies against cytokines or cytokine receptors. We initially found that the glycolytic inhibitor 2‐deoxy‐d‐glucose (2‐DG), a simple monosaccharide, attenuated cellular responses to IL‐6 by inhibiting N‐linked glycosylation of the IL‐6 receptor gp130. Aglycoforms of gp130 did not bind to IL‐6 or activate downstream intracellular signals that included Janus kinases. 2‐DG completely inhibited dextran sodium sulfate‐induced colitis, a mouse model for inflammatory bowel disease, and alleviated laminarin‐induced arthritis in the SKG mouse, an experimental model for human rheumatoid arthritis. These diseases have been shown to be partially dependent on IL‐6. We also found that 2‐DG inhibited signals for other proinflammatory cytokines such as TNF‐α, IL‐1β, and interferon ‐γ, and accordingly, prevented death by another inflammatory disease, lipopolysaccharide (LPS) shock. Furthermore, 2‐DG prevented LPS shock, a model for a cytokine storm, and LPS‐induced pulmonary inflammation, a model for acute respiratory distress syndrome of coronavirus disease 2019 (COVID‐19). These results suggest that targeted therapies that inhibit cytokine receptor glycosylation are effective for treatment of various inflammatory diseases. The glycolytic inhibitor 2‐deoxy‐D‐glucose attenuated cellular responses to proinflammatory cytokines by inhibiting N‐linked glycosylation of their receptors and alleviated the signs and symptoms of mouse models for inflammatory bowel disease, rheumatoid arthritis, cytokine storm, and acute respiratory distress syndrome.