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Abstract The stigma of mental illness is a form of negative judgmental knowledge and is a barrier to individual seeking treatment. Contact-based educational interventions with first-person perspective (1PP) combined with immersive virtual reality (IVR) is promising as an anti-stigma intervention. This study aims to investigate the effectiveness of 1PP anti-stigma IVR intervention compared to video in enhancing depression knowledge and reducing stigma, as well as to examine the corresponding depression knowledge brain activity change using functional magnetic resonance imaging (fMRI). Participants engaged in a 1PP anti-stigma intervention using both IVR and conventional video, focusing on the daily life and recovery of a patient with mild depression. The change in depression knowledge, stigma-related behavioral, and brain activity using fMRI were measured at pre- and post-interventions. Depression knowledge improved for both interventions; however, only the IVR intervention reduced stigma. In the IVR intervention, depression knowledge score was positively associated with neural response in the right superior frontal gyrus activation, indicative of empathic concern. Conversely, the video intervention correlated with increased activity in the right anterior insula, suggesting a distress-related response. The findings demonstrate that the immersive nature of IVR can reduce stigma more effectively than video intervention. This effectiveness is underpinned by the change in depression knowledge on neural activity, with IVR fostering empathy-related behavioral responses. The results highlight the potential of IVR in enhancing empathic understanding and reducing stigma towards mental illness, emphasizing the need for further exploration into immersive technologies for mental health education.

Abstract Astrocytes, which can be obtained from neural stem cells (NSCs) by adding serum and/or recombinant proteins in culture media or by passaging NSCs repeatedly, are expected to be applicable in regenerative medicine for the treatment of neurodegenerative diseases. However, astrocytes obtained using existing methods are costly and have poor quality. The stiffness of culture surfaces has been reported to affect astrocytic differentiation of adult NSCs. However, the influence of surface stiffness on astrocytic differentiation of embryonic NSCs has not yet been reported. In this study, we showed that astrocytic differentiation of embryonic NSCs was increased on soft surfaces (1 kPa and 12 kPa) compared with the NSCs on stiff surfaces (2.8 GPa) in serum-free condition. Furthermore, di-phosphorylated myosin regulatory light chain (PP-MRLC) was decreased in embryonic NSCs cultured on the soft surfaces than the cells on the stiff surfaces. Additionally, astrocytic differentiation of embryonic NSCs was induced by a Ras homolog associated kinase (ROCK) inhibitor, which decreased PP-MRLC in NSCs. These results suggest that decreasing the PP-MRLC of embryonic NSCs on soft surfaces or treating NSCs with a ROCK inhibitor is a good method to prepare astrocytes for application in regenerative medicine.

We previously reported that Lys175 in the region of the active site of chymotrypsin (Csin) could be site-selectively modified by using an N-hydroxy succinimide (NHS) ester of the peptidyl derivative containing 1-amino-2-ethylphenylphosphonate diphenyl ester [NHS-Suc-Ala-Ala-PheP(OPh)2]. In this study, the Lys175-selective modification method was expanded to incorporate functional groups into Lys 175 in Csin. Two types of peptidyl phosphonate derivatives with the dansyl group (Dan) as a functional molecule, Dan-β-Ala-[Asp(NHS) or Glu(NHS)]-Ala-Ala-(R)-PheP(OPh)2 (DanD and DanE, respectively), were synthesized, and their action was evaluated when modifying Lys175 in Csin. Ion-exchange chromatography (IEC), fluorescence spectroscopy, and LC-MS/MS were used to analyze the products from the reaction of Csin with DanD or DanE. By IEC and LC-MS/MS, the results showed that DanE reacted with Csin more effectively than DanD to produce the modified Csin (DanMCsin) bearing Dan at Lys175. DanMCsin exhibited an enzymatic activity corresponding to 1/120 of Csin against Suc-Ala-Ala-Phe-pNA. In addition, an effect of Lys175 modification on the access of the proteinaceous Bowman–Birk inhibitor to the active site of DanMCsin was investigated. In conclusion, by using a peptidyl derivative containing 1-amino-2-ethylphenylphosphonate diphenyl ester, we demonstrated that a functional group could be incorporated into Lys175 in Csin.

BackgroundPublic stigma against depression contributes to low employment rates among individuals with depression. Contact-based educational (CBE) interventions have been shown to reduce this public stigma. ObjectiveWe investigated the ability of our Virtual Reality Antistigma (VRAS) app developed for CBE interventions to reduce the stigma of depression. MethodsSixteen medical students were recruited and randomized 1:1 to the intervention group, who used the VRAS app (VRAS group), and the control group, who watched a video on depression. The depression stigma score was assessed using the Depression Stigma Scale (DSS) and Attitudinal Social Distance (ASD) questionnaire at pre- and postintervention. Feasibility was assessed in both groups and usability was assessed only in the VRAS group after the intervention. A qualitative study was performed on the acquisition of knowledge about stigma in both groups based on participants’ answers to open-ended questions and interviews after the intervention. ResultsThe feasibility score was significantly higher in the VRAS group (mean 5.63, SD 0.74) than in the control group (mean 3.88, SD 1.73; P=.03). However, no significant differences were apparent between the VRAS and control groups for the DSS (VRAS: mean 35.13, SD 5.30; control: mean 35.38, SD 4.50; P=.92) or ASD (VRAS: mean 12.25, SD 3.33; control: mean 11.25, SD 1.91; P=.92). Stigma scores tended to decrease; however, the stigma-reducing effects of the VRAS app were not significant for the DSS (pre: mean 33.00, SD 4.44; post: mean 35.13, SD 5.30; P=.12) or ASD (pre: mean 13.25, SD 3.92; post: mean 12.25, SD 3.33; P=.12). Qualitative analysis suggested that the VRAS app facilitated perspective-taking and promoted empathy toward the patient. ConclusionsThe CBE intervention using virtual reality technology (VRAS app) was as effective as the video intervention. The results of the qualitative study suggested that the virtual reality intervention was able to promote perspective-taking and empathy toward patients. Trial RegistrationUniversity Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) UMIN000043020; https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000049109

Background: In neurosurgery, it is important to inspect the spatial correspondence between the preoperative medical image (virtual space), and the intraoperative findings (real space) to improve the safety of the surgery. Navigation systems and related modalities have been reported as methods for matching this correspondence. However, because of the influence of the brain shift accompanying craniotomy, registration accuracy is reduced. In the present study, to overcome these issues, we developed a spatially accurate registration method of medical fusion 3-dimensional computer graphics and the intraoperative brain surface photograph, and its registration accuracy was measured. Methods: The subjects included 16 patients with glioma. Nonrigid registration using the landmarks and thin-plate spline methods was performed for the fusion 3-dimensional computer graphics and the intraoperative brain surface photograph, termed mixed-reality computer graphics. Regarding the registration accuracy measurement, the target registration error was measured by two neurosurgeons, with 10 points for each case at the midpoint of the landmarks. Results: The number of target registration error measurement points was 160 in the 16 cases. The target registration error was 0.72 ± 0.04 mm. Aligning the intraoperative brain surface photograph and the fusion 3-dimensional computer graphics required ∼10 minutes on average. The average number of landmarks used for alignment was 24.6. Conclusions: Mixed-reality computer graphics enabled highly precise spatial alignment between the real space and virtual space. Mixed-reality computer graphics have the potential to improve the safety of the surgery by allowing complementary observation of brain surface photographs and fusion 3-dimensional computer graphics.

γ-secretase inhibitors (GSI) are drugs developed to decrease amyloid-β peptide (Aβ) production by inhibiting intramembranous cleavage of β-amyloid protein precursor (βAPP). However, a large phase 3 trial of semagacestat, a potential non-transition state analog (non-TSA) GSI, in patients with Alzheimer’s disease (AD) was terminated due to unexpected aggravation of cognitive deficits and side effects. Here, we show that some semagacestat effects are clearly different from a phenotype caused by a loss of function of presenilins, core proteins in the γ-secretase complex. Semagacestat increases intracellular byproduct peptides, produced along with Aβ through serial γ-cleavage of βAPP, as well as intracellular long Aβ species, in cell-based and in vivo studies of AD model mice. Other potential non-TSA GSIs, but not L685,458, a TSA GSI, have similar effects. Furthermore, semagacestat inhibits release of de novo intramembranous γ-byproducts to the soluble space. Thus, semagacestat is a pseudo-GSI, and therefore, the semagacestat clinical trial did not truly test the Aβ hypothesis.

BACKGROUND:As a consequence of indoor occupations and reduced exposure to sunlight, concerns have been raised that vitamin D deficiency is widespread in developed countries. Vitamin D is known to be associated with increased risks of morbidity and mortality in various diseases. OBJECTIVE:To investigate the serum vitamin D status and its relation with life-style factors in pregnant Japanese women. METHODS:Among a cohort for 3,327 pregnant women who participated in an the adjunct study of the Japan Environment and Children's Study during 2011-2013, in which data were obtained on various life-style factors, including both dietary intake of vitamin D and frequency of UV exposure, this study consisted of 1,592 pregnant women, from whom 2,030 serum samples were drawn in Jan, Apr, Jul, and Oct, and the association between serum 25(OH)D level and life-style factors were analyzed using linear mixed models. RESULTS:Serum 25(OH)D levels were less than 20ng/mL in 1,486 of 2,030 samples (73.2%). There was an obvious seasonal change, with serum 25(OH)D levels of less than 20 ng/mL in 89.8% and 47.8% of samples in spring (April) and autumn (October), respectively. Both the frequency spent under sunlight and dietary intake of vitamin D were significantly associated with serum 25(OH)D level. An increase in sunlight exposure of more than 15 min for 1 to 2 days per week in non-winter, or dietary intake of 2 μg/day of vitamin D resulted in an elevation of 1 ng/mL in serum 25(OH)D levels. CONCLUSION:These findings indicate that vitamin D deficiency is very severe in Japanese pregnant women, especially those rarely exposed to sunlight. The benefits of UV rays should also be informed of when its risk is alerted, and clinicians should propose the adequate UV exposure level.

BackgroundVitamin D has been reported to affect both innate, and acquired immunity with immune cells such as dendritic cells having the vitamin D receptors. The co-occurrence of the high prevalence of allergic diseases and vitamin D deficiency globally documented in recent decades, has prompted a hypothesis on whether there is a reasonable association between them.ObjectiveTo investigate the association between serum vitamin D deficiency and allergic symptoms.MethodsHistorical cohort. On a cohort study for the association between desert dust exposure and allergic symptoms in 3,327 pregnant women during spring and fall in 2011-2013 in Japan conducted as an adjunct study to the Japan Environment and Children's Study, we promptly acquired subjects' daily allergic symptom scores by sending a web-based questionnaire to each participant on some days. Of the 29,434 answers provided by 3,327 participating pregnant women, we extracted 13,356 answers from 1,475 pregnant women that were answered within a 3-month period after blood samplings. And we measured 25(OH)D levels on those samples to investigate the association between their vitamin D deficiency (serum 25(OH)D < 20ng/mL) and the occurrence of any allergic symptom (allergic symptom score> 0) within 3 months.ResultsSerum 25(OH)D was less than 20ng/mL in 1,233 of 1,745 samples (70.7%). The adjusted odds ratio (aOR) for occurrence of any allergic symptom in deficient cases compared with non-deficient cases was 1.33 (95% CI: 1.07-1.64, p = 0.01). Further, vitamin D deficiency significantly enhanced the risk increase at desert dust events and at pollen exposure (p-values for interaction ConclusionWe confirmed the association between serum vitamin D deficiency and allergic symptoms in Japanese pregnant women.

Background: This study aimed to propose an experiential approach for understanding color vision variation using virtual reality technology. Methods: The study design was adapted from the phase 1 clinical trial for medical apps. A virtual classroom was developed in a three-dimensional space, and ten healthy university students were tested to understand color vision variations. Results: No participant interrupted the experience due to VR sickness. Most participants noted that the virtual classroom was an excellent educational tool, which could help teachers understand the problems associated with [visual analog scale (VAS): mean ± standard deviation (SD), 9.6 ± 0.6] and obtain a better understanding of (VAS: mean ± SD, 9.0 ± 1.0) color vision deficiencies. Conclusions: A pilot study was conducted on the impact of immersive virtual classroom experiences as an educational tool for color barrier-free presentations. This approach may help the participants to respond appropriately to children who suffer from this disorder. It is necessary to evaluate the impact of this approach on new teachers.

Background: This study aimed to develop an experiential approach for understanding color vision variations using virtual reality technology. Methods: A virtual classroom was developed in a three-dimensional space, and 10 university students were tested to understand color vision variations. Results: Most participants noted that the virtual classroom was an excellent educational tool, which could help teachers understand the problems associated with [visual analog scale (VAS): mean ± standard deviation (SD), 9.55 ± 1.57] and obtain a better understanding of (VAS: mean ± SD, 9.04 ± 1.0) color vision variations. Conclusions: Our results show that this approach enhanced the participants' understanding of color vision variations; thus, it may assist children who suffer from this variation. It is necessary to evaluate the effectiveness of this approach for teachers.