In situ droplet-based on-tissue chemical derivatization for lipid isomer characterization using LESA.

In this work, we present an in situ droplet-based derivatization method for fast tissue lipid profiling at multiple isomer levels. On-tissue derivatization for isomer characterization was achieved in a droplet delivered by the TriVersa NanoMate LESA pipette. The derivatized lipids were then extracted and analyzed by the automated chip-based liquid extraction surface analysis (LESA) mass spectrometry (MS) followed by tandem MS to produce diagnostic fragment ions to reveal the lipid isomer structures. Three reactions, i.e., mCPBA epoxidation, photocycloaddition catalyzed by the photocatalyst Ir[dF(CF3)ppy]2(dtbbpy)PF6, and Mn(II) lipid adduction, were applied using the droplet-based derivatization to provide lipid characterization at carbon-carbon double-bond positional isomer and sn-positional isomer levels. Relative quantitation of both types of lipid isomers was also achieved based on diagnostic ion intensities. This method provides the flexibility of performing multiple derivatizations at different spots in the same functional region of an organ for orthogonal lipid isomer analysis using a single tissue slide. Lipid isomers were profiled in the cortex, cerebellum, thalamus, hippocampus, and midbrain of the mouse brain and 24 double-bond positional isomers and 16 sn-positional isomers showed various distributions in those regions. This droplet-based derivatization of tissue lipids allows fast profiling of multi-level isomer identification and quantitation and has great potential in tissue lipid studies requiring rapid sample-to-result turnovers.

Safety and Efficacy of Post-Dilation in Percutaneous Coronary Intervention Using Polymer-Free Ultrathin Strut Sirolimus-Probucol Coated Drug-Eluting Stents.

Background and Objectives: Polymer-free ultrathin strut sirolimus- and probucol-eluting stents (PF-SES) are recognized as safe and effective in diverse patient populations, although the implications of post-dilation during stent implantation remain underexamined. Materials and Methods: In this study, patients implanted with PF-SES at Gachon University Gil Medical Center between December 2014 and February 2018 were evaluated. Major adverse cardiovascular events (MACE), encompassing nonfatal myocardial infarction (MI), nonfatal stroke, and cardiovascular death were identified as primary outcomes, with secondary outcomes including target vessel revascularization (TVR), target lesion revascularization (TLR), and in-stent restenosis (ISR). Results: Of the 384 initial patients, 299 were considered eligible for analysis. The groups, delineated by those undergoing post-dilation (143 patients) and those not (156 patients), exhibited comparable rates of primary outcomes [hazard ratio (HR), 2.17; 95% confidence interval (CI), 0.40 to 11.87; p = 0.37]. The outcomes remained consistent irrespective of the post-dilation status and were similarly unaffected in multivariate analyses (HR, 2.90; 95% CI, 0.52 to 16.34; p = 0.227). Conclusions: These results suggest that the clinical outcomes of patients with post-dilation were similar to that of those without post-dilation in those with the polymer-free sirolimus- and probucol-eluting stents.

Differences in the modulation of functional connectivity by self-talk tasks between people with low and high life satisfaction.

Self-respect is a practical way to promote life satisfaction through gratifying basic psychological needs, whereas self-criticism is associated with life dissatisfaction. The goal of the present study was to investigate the effect of two positive and negative self-talks on the functional connectome with respect to life satisfaction and its relationships with basic psychological needs. Forty-eight individuals with low life satisfaction (LLS, n â€‹= â€‹24) and with high life satisfaction (HLS, n â€‹= â€‹24) were scanned using functional magnetic resonance imaging at a baseline state and during and after self-respect or self-criticism tasks. Functional connectivity analysis was conducted to identify the modulatory effects of the tasks on the self-referential, default mode, and reward-motivation networks. We found that self-respect changed only the connection between the posterior cingulate cortex (PCC) and frontoparietal network, whereas self-criticism changed almost all of the connections examined. The group x condition interaction effect of self-respect was identified only in connection between the PCC and left ventrolateral prefrontal cortex, while that of self-criticism was observed in various connections based on the ventromedial prefrontal cortex and nucleus accumbens. In respect to basic psychological needs, functional connectivity after self-criticism was significant in predicting the needs of autonomy and relatedness only in the LLS group, whereas functional connectivity after self-respect could predict the needs of autonomy and competence only in the HLS group. Overall, self-criticism produces more noticeable negative changes in the brain than the positive changes of self-respect. Individuals with low life satisfaction may be more vulnerable to be negatively affected not only by self-criticism but also self-respect than individuals with high life satisfaction. The satisfaction of basic psychological needs can play a mediating role in the effects of self-talk tasks differently concerning life satisfaction.

The Protective Role of Resilience in Attenuating Emotional Distress and Aggression Associated with Early-life Stress in Young Enlisted Military Service Candidates.

Early life stress (ELS) may induce long-lasting psychological complications in adulthood. The protective role of resilience against the development of psychopathology is also important. The purpose of this study was to investigate the relationships among ELS, resilience, depression, anxiety, and aggression in young adults. Four hundred sixty-one army inductees gave written informed consent and participated in this study. We assessed psychopathology using the Korea Military Personality Test, ELS using the Childhood Abuse Experience Scale, and resilience with the resilience scale. Analyses of variance, correlation analyses, and hierarchical multiple linear regression analyses were conducted for statistical analyses. The regression model explained 35.8%, 41.0%, and 23.3% of the total variance in the depression, anxiety, and aggression indices, respectively. We can find that even though ELS experience is positively associated with depression, anxiety, and aggression, resilience may have significant attenuating effect against the ELS effect on severity of these psychopathologies. Emotion regulation showed the most beneficial effect among resilience factors on reducing severity of psychopathologies. To improve mental health for young adults, ELS assessment and resilience enhancement program should be considered.

Exploratory Clinical Trial of a Depression Diagnostic Software That Integrates Stress Biomarkers and Composite Psychometrics.

OBJECTIVE: This study evaluated the clinical effectiveness of Minds.NAVI, a depression screening kit combining psychometric measures and stress hormone biomarkers, in a prospective clinical trial. The objective was to assess its potential as a depression screening tool and investigate the associations between psychological assessments, salivary hormone staging, and depression severity. METHODS: Thirty-five participants with major depressive disorder and 12 healthy controls (HCs) were included. The Minds.NAVI software, utilizing the PROtective and Vulnerable factors battEry Test (PROVE) and salivary cortisol/dehydroepiandrosterone (DHEA) analysis, was employed. The PROVE test is a comprehensive self-report questionnaire that assesses depressive symptoms, suicide risk, attachment style, adverse childhood experiences, mentalization capacity, and resilience. In addition, salivary cortisol and DHEA levels were measured to evaluate the functional stage of the hypothalamic-pituitary-adrenal (HPA) axis. RESULTS: Minds.NAVI exhibited 100% sensitivity, 91.7% specificity, and 97.9% accuracy in distinguishing depression from HCs within an exploratory small group. Salivary stress hormone phases showed changes with depression stage (p=0.030), and the proportion of patients with "adrenal exhaustion stage" was higher in the moderate/severe depression group (p=0.038). Protective/vulnerable factors differed significantly between controls and depressed groups (p<0.001). Cortisol awakening response inversely correlated with depressive symptom severity (r=-0.31, p=0.034). CONCLUSION: This study suggested possible clinical effectiveness of Minds.NAVI, a depression screening tool that integrates psychometric measures and stress hormone biomarkers. The findings support the potential association between depression, chronic stress, and HPA axis hyporesponsiveness.

Everyday conversation requires cognitive inference: neural bases of comprehending implicated meanings in conversations.

In ordinary conversations, literal meanings of an utterance are often quite different from implicated meanings and the inference about implicated meanings is essentially required for successful comprehension of the speaker's utterances. Inference of finding implicated meanings is based on the listener's assumption that the conversational partner says only relevant matters according to the maxim of relevance in Grice's theory of conversational implicature. To investigate the neural correlates of comprehending implicated meanings under the maxim of relevance, a total of 23 participants underwent an fMRI task with a series of conversational pairs, each consisting of a question and an answer. The experimental paradigm was composed of three conditions: explicit answers, moderately implicit answers, and highly implicit answers. Participants were asked to decide whether the answer to the Yes/No question meant 'Yes' or 'No'. Longer reaction time was required for the highly implicit answers than for the moderately implicit answers without affecting the accuracy. The fMRI results show that the left anterior temporal lobe, left angular gyrus, and left posterior middle temporal gyrus had stronger activation in both moderately and highly implicit conditions than in the explicit condition. Comprehension of highly implicit answers had increased activations in additional regions including the left inferior frontal gyrus, left medial prefrontal cortex, left posterior cingulate cortex and right anterior temporal lobe. The activation results indicate involvement of these regions in the inference process to build coherence between literally irrelevant but pragmatically associated utterances under the maxim of relevance. Especially, the left anterior temporal lobe showed high sensitivity to the level of implicitness and showed increased activation for highly versus moderately implicit conditions, which imply its central role in inference such as semantic integration. The right hemisphere activation, uniquely found in the anterior temporal lobe for highly implicit utterances, suggests its competence for integrating distant concepts in implied utterances under the relevance principle.

Relationship of early-life stress and resilience to military adjustment in a young adulthood population.

PURPOSE: Early-life stress (ELS) may mediate adjustment problems while resilience may protect individuals against adjustment problems during military service. We investigated the relationship of ELS and resilience with adjustment problem factor scores in the Korea Military Personality Test (KMPT) in candidates for the military service. METHODS: Four hundred and sixty-one candidates participated in this study. Vulnerability traits for military adjustment, ELS, and resilience were assessed using the KMPT, the Korean Early-Life Abuse Experience Questionnaire, and the Resilience Quotient Test, respectively. Data were analyzed using multiple linear regression analyses. RESULTS: The final model of the multiple linear regression analyses explained 30.2 % of the total variances of the sum of the adjustment problem factor scores of the KMPT. Neglect and exposure to domestic violence had a positive association with the total adjustment problem factor scores of the KMPT, but emotion control, impulse control, and optimism factor scores as well as education and occupational status were inversely associated with the total military adjustment problem score. CONCLUSIONS: ELS and resilience are important modulating factors in adjusting to military service. We suggest that neglect and exposure to domestic violence during early life may increase problem with adjustment, but capacity to control emotion and impulse as well as optimistic attitude may play protective roles in adjustment to military life. The screening procedures for ELS and the development of psychological interventions may be helpful for young adults to adjust to military service.

Intervertebral disc organ-on-a-chip: an innovative model to study monocyte extravasation during nucleus pulposus degeneration.

Degenerative cascades of the intervertebral disc (IVD) are characterized by the presence of immune cells like monocytes, macrophages, and leukocytes, which contribute to inflammation. Previous in vitro studies on monocyte chemotaxis in the presence of chemical or mechanical stimulation were unable to establish the effects of endogenous stimulating factors from resident IVD cells, or fully understand macrophage and monocyte differentiation pathways in IVD degeneration. Our study simulates monocyte extravasation using a fabricated microfluidic chemotaxis IVD organ-on-a-chip (IVD organ chip), which models the geometry of IVD, chemoattractant diffusion, and infiltration of immune cells. Additionally, the fabricated IVD organ chip mimics stepwise monocyte infiltration and differentiation into macrophages in the degenerative nucleus pulposus (NP) induced by IL-1ß. We find that naïve NP cells do not recruit THP-1 monocyte-like cells, but degenerative NP cells recruit and accumulate macrophages through chemo-gradient channels. Furthermore, the differentiated and migrated THP-1 cells show phagocytic activity around inflammatory NP cells. Our in vitro model of monocyte chemotaxis with degenerative NP on an IVD organ chip depicts the sequential processes of monocyte migration/infiltration, monocyte-to-macrophage differentiation, and accumulation. Using this platform to gain a deeper understanding of monocyte infiltration and differentiation processes can provide insights into the pathophysiology of the immune response in degenerative IVD.

Long-term clinical outcomes for patients with uncrossable patent foramen ovale.

Introduction: Patent foramen ovale (PFO) closure is performed in selected patients with cryptogenic stroke to prevent recurrence. The prognosis of patients with uncrossable PFO after failed guidewire or catheter passage during the procedure remains unknown. We compared the long-term prognosis between uncrossable PFO and successful PFO closure in patients with high-grade PFO shunts. Methods: We analyzed patients who underwent PFO closure for stroke or transient ischemic attack (TIA) prevention at Gachon University Gil Medical Center between April 2010 and March 2022. The primary outcome was a composite of recurrent stroke or TIA. Secondary outcomes included stroke, TIA, all-cause death, and a composite of stroke, TIA, and all-cause death. Results: Of 286 patients, 245 were included in the analysis after excluding those with transseptal puncture technique usage or concurrent atrial septal defect. Among them, 82 had uncrossable PFO, and 163 underwent successful PFO closure. Large shunts were more prevalent in the PFO closure group compared to the uncrossable PFO group (62.0% vs. 34.1%, P < 0.001), and resting shunts were also more common in the PFO closure group (17.8% vs. 2.4%, P < 0.001). Stroke or TIA occurred in 2 patients (2.4%) in the uncrossable PFO group and 8 patients (4.9%) in the PFO closure group (hazard ratio, 1.44; 95% confidence interval, 0.30-6.81; P = 0.647). Additionally, no disparities in the occurrence of stroke or TIA were found in subgroups divided by baseline characteristics, RoPE score, or shunt grade. Conclusion: Clinical outcomes for patients with uncrossable PFO seem similar to those with successful PFO closure.

An Active Inference Account of Touch and Verbal Communication in Therapy.

This paper offers theoretical explanations for why "guided touch" or manual touch with verbal communication can be an effective way of treating the body (e.g., chronic pain) and the mind (e.g., emotional disorders). The active inference theory suggests that chronic pain and emotional disorders can be attributed to distorted and exaggerated patterns of interoceptive and proprioceptive inference. We propose that the nature of active inference is abductive. As such, to rectify aberrant active inference processes, we should change the "Rule" of abduction, or the "prior beliefs" entailed by a patient's generative model. This means pre-existing generative models should be replaced with new models. To facilitate such replacement-or updating-the present treatment proposes that we should weaken prior beliefs, especially the one at the top level of hierarchical generative models, thereby altering the sense of agency, and redeploying attention. Then, a new prior belief can be installed through inner communication along with manual touch. The present paper proposes several hypotheses for possible experimental studies. If touch with verbal guidance is proven to be effective, this would demonstrate the relevance of active inference and the implicit prediction model at a behavioral level. Furthermore, it would open new possibilities of employing inner communication interventions, including self-talk training, for a wide range of psychological and physical therapies.

Osteopathic Care as (En)active Inference: A Theoretical Framework for Developing an Integrative Hypothesis in Osteopathy.

Osteopathy is a person-centred healthcare discipline that emphasizes the body's structure-function interrelationship-and its self-regulatory mechanisms-to inform a whole-person approach to health and wellbeing. This paper aims to provide a theoretical framework for developing an integrative hypothesis in osteopathy, which is based on the enactivist and active inference accounts. We propose that osteopathic care can be reconceptualised under (En)active inference as a unifying framework. Active inference suggests that action-perception cycles operate to minimize uncertainty and optimize an individual's internal model of the lived world and, crucially, the consequences of their behaviour. We argue that (En)active inference offers an integrative framework for osteopathy, which can evince the mechanisms underlying dyadic and triadic (e.g., in paediatric care) exchanges and osteopathic care outcomes. We propose that this theoretical framework can underpin osteopathic care across the lifespan, from preterm infants to the elderly and those with persistent pain and other physical symptoms. In situations of chronicity, as an ecological niche, the patient-practitioner dyad provides the osteopath and the patient with a set of affordances, i.e., possibilities for action provided by the environment, that through shared intentionally, can promote adaptations and restoration of productive agency. Through a dyadic therapeutic relationship, as they engage with their ecological niche's affordances-a structured set of affordances shared by agents-osteopath and patient actively construct a shared sense-making narrative and realise a shared generative model of their relation to the niche. In general, touch plays a critical role in developing a robust therapeutic alliance, mental state alignment, and biobehavioural synchrony between patient and practitioner. However, its role is particularly crucial in the fields of neonatology and paediatrics, where it becomes central in regulating allostasis and restoring homeostasis. We argue that from an active inference standpoint, the dyadic shared ecological niche underwrites a robust therapeutic alliance, which is crucial to the effectiveness of osteopathic care. Considerations and implications of this model-to clinical practice and research, both within- and outside osteopathy-are critically discussed.

Relationship of Resilience Factors With Biopsychosocial Markers Using a Comprehensive Home Evaluation Kit for Depression and Suicide Risk: A Real-World Data Analysis.

Objectives: Adverse childhood experiences (ACEs) are fundamental factors in developing depression with increased suicide risk. Resilience is considered an important protective factor that can prevent trauma survivors from developing depression. We developed a home evaluation kit for a comprehensive assessment of bio-psycho-social factors related to depression and suicide. This kit contained a psycho-social evaluation battery, named the Protective and Vulnerable factors battery questionnaire (PROVE) comprising depressive symptoms and suicide risk, as well as various depression-related psychosocial factors, such as ACE, resilience, mentalization capacity, and attachment, via online survey tools. Furthermore, salivary cortisol levels were used as biological indicators to assess the hypothalamus-pituitary-adrenal axis function. Methods: Real-world data analysis was made out of data collected from participants who visited CHEEU Counseling center or Gangnam Severance hospital for mental health check-ups. The participants were put into three mental state groups (green-normal, yellow-borderline, and red-risk) depending on the result of PROVE battery. The difference between psychosocial factors and salivary cortisol indicators by the group was identified by analysis of covariance with sex and age as covariates. Linear regression analysis was conducted to find a significant association of resilience score with other bio-psycho-social variables, such as ACE, attachment, mentalization, or post-awakening cortisol concentrations (area under the curve with respect to ground, AUCg). A partial correlation analysis was performed to evaluate the relationship of AUCg with psychosocial factors. Results: Depression-related psycho-social indicators were significantly different among groups. Insecure attachment and the mentalization problem are negatively influencing factors to resilience. Furthermore, the severity of depression in participants with ACE was also influenced by mentalization problems. AUCg was different according to the PROVE group, presence of ACE, or resilience level. In addition, AUCg showed a positive correlation with resilience score but negative correlations with depressive symptoms, ACE, mentalization problems, and anxiety or avoidance attachment. Conclusion: This study suggests that there are some key factors negatively affecting resilience: insecure attachment and mentalization problems. In groups with ACE, a mentalization problem was suggested as a factor that can increase depressive symptoms. AUCg was associated with resilience as well as several other vulnerable factors of depression, showing its potential as a promising biomarker.

Transforming growth factor-ß induces epithelial to mesenchymal transition and suppresses the proliferation and transdifferentiation of cultured human pancreatic duct cells.

Pancreatic duct cells are considered a potential source of ß-cell regeneration, and transforming growth factor-ß (TGF-ß) has been suggested to perform an important role in these processes, but the underlying mechanism of the signal pathways, especially in humans, remains poorly understood. To evaluate the role of TGF-ß1, pancreatic duct cells were isolated from three brain-dead organ donors. Pancreatic cell clusters harvested after islet isolation were dispersed to single cells and cultured in monolayers, then treated with TGF-ß1. We analyzed the characteristics of the cultured cells, the TGF-ß1 intracellular signaling pathway, the proliferation, and transdifferentiation rates of the duct cells. We also evaluated the genes and protein expression patterns after TGF-ß1 treatment. After TGF-ß1 treatment, typical morphologic changes representative of EMT were observed and Erk1/2, JNK, and AKT phosphorylation, Ras downstream effectors, were increased. ß cell-specific transcription factors including PDX-1, Beta2/NeuroD, Ist-1, and NGN3 were markedly suppressed and the rate of transdifferentiation into ß cells was also suppressed. Genomic and proteomic analyses suggested that TGF-ß1 induces marked changes in a variety of structural genes and proteins associated with EMT. In conclusion, TGF-ß1 induces EMT in cultured human pancreatic duct cells, but suppresses its proliferation and transdifferentiation into ß cells. Our results are the first report of TGF-ß1 effects for EMT and ductal cell transdifferentiation and proliferation at the protein level in human pancreatic duct cells.

Differences in basic psychological needs-related resting-state functional connectivity between individuals with high and low life satisfaction.

Basic psychological needs including autonomy, competence, and relatedness can be affected by the level of life satisfaction. The current research aimed to elucidate differences in the association of these needs and functional connectivity of reward processing and emotion regulation between individuals with high and low life satisfaction. A total of 83 young adults were divided into the high life satisfaction (HLS) and low life satisfaction (LLS) groups and were scanned for 5-min resting-state fMRI. A seed-to-voxel analysis was performed using the seeds of the nucleus accumbens (NAcc), medial orbitofrontal cortex, subgenual anterior cingulate cortex (sgACC), insula, and amygdala. Analysis of covariance was conducted to test differences in the association of basic psychological needs and functional connectivity between the two groups. Connectivity strengths between the NAcc and right ventromedial prefrontal cortex and between the sgACC and left ventromedial prefrontal cortex were higher in the HLS group as the autonomy and relatedness scores increased, respectively, whereas in the LLS group as they decreased. Connectivity strengths between the NAcc and right midcingulate cortex and between the sgACC and left fusiform gyrus were higher in the HLS group as the competence and relatedness scores decreased, respectively, but in the LLS group as they increased. These findings suggest that individuals' perceived life satisfaction affects the relationship between the neural mechanism for reward processing and emotion regulation and basic psychological needs support. Psychological need satisfactions seem to have an emotional impact by acting as a contradictory brain mechanism between individuals with high and low life satisfaction.

The effects of positive or negative self-talk on the alteration of brain functional connectivity by performing cognitive tasks.

Self-talk can improve cognitive performance, but the underlying mechanism of such improvement has not been investigated. This study aimed to elucidate the effects of self-talks on functional connectivity associated with cognitive performance. We used the short form of Progressive Matrices Test (sRPM) to measure differences in performance improvements between self-respect and self-criticism. Participants were scanned using functional magnetic resonance imaging in the following order: baseline, during-sRPM1, post-sRPM1, self-respect or self-criticism, during-sRPM2, and post-sRPM2. Analysis was conducted to identify the self-talks' modulatory effects on the reward-motivation, default mode, and central-executive networks. Increase in sRPM2 score compared to sRPM1 score was observed only after self-criticism. The self-talk-by-repetition interaction effect was not found for during-sRPM, but found for post-sRPM; decreased nucleus accumbens-based connectivity was shown after self-criticism compared with self-respect. However, the significant correlations between the connectivity change and performance change appeared only in the self-respect group. Our findings showed that positive self-talk and negative self-talk differently modulate brain states concerning cognitive performance. Self-respect may have both positive and negative effects due to enhanced executive functions and inaccurate confidence, respectively, whereas self-criticism may positively affect cognitive performance by inducing a less confident state that increases internal motivation and attention.

In vitro model of distinct catabolic and inflammatory response patterns of endothelial cells to intervertebral disc cell degeneration.

To evaluate dominant cell-to-cell paracrine interactions, including those of human annulus fibrosus (AF), nucleus pulposus (NP), and endothelial cells (ECs), in the production of inflammatory mediators and catabolic enzymes, ECs was cultured in soluble factors derived from AF or NP cells (AFCM or NPCM, respectively) and vice versa. We analysed IL-6 and -8, vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-1 and -3, nerve growth factor (NGF)-ß, and brain-derived neurotrophic factors (BDNFs) with qRT-PCR and ELISA. We implement a microfluidic platform to analyse migration properties of AF and NP cells and ECs in 3D cultures. Our results show that IL-1ß-stimulated AF cells produced significantly higher levels of IL-6 and -8, VEGF, and MMP-1 than IL-1ß-stimulated NP cells. However, production of IL-6 and -8, VEGF, and MMP-3 was significantly higher in NP cells than in AF cells, under the presence of ECs conditioned medium. We observed considerable migration of NP cells co-cultured with ECs through the microfluidic platform. These results suggest that AF cells may play a major role in the initial degeneration of intervertebral disc. Furthermore, it was found that interactions between NP cells and ECs may play a significant role in the development or progression of diseases.

Effects of photobiomodulation on annulus fibrosus cells derived from degenerative disc disease patients exposed to microvascular endothelial cells conditioned medium.

Intervertebral disc (IVD) degeneration with chronic low back pain is associated with neo-vascularisation into the deeper IVD regions. During this process, endothelial cells (ECs), which are primarily responsible for angiogenesis, interact with the adjacent annulus fibrosus (AF) cells, which are the first line of defence against the invasion of vascular structures into deeper IVD regions. However, the accumulation of inflammatory and catabolic enzymes that results from this interaction promotes matrix degradation and an inflammatory response. Thus, regulating the production of these mediators and catabolic enzymes could ameliorate IVD degeneration. Photobiomodulation (PBM) therapy is a non-invasive stimulation known to have biologically beneficial effects on wound healing, tissue repair, and inflammation. Here, we examined the effects of PBM, administered at various wavelengths (645, 525, and 465 nm) and doses (16, 32, and 64 J/cm2), on EC-stimulated human AF cells. Our results show that PBM selectively inhibited the EC-mediated production of inflammatory mediators, catabolic enzymes, and neurotrophins by human AF cells in a dose- and wavelength-dependent manner. These results suggest that PBM could be a superior and advanced treatment strategy for IVD degeneration.

Development and Validation of a Virtual Reality-Based Training Program for Promoting Subjective Well-Being.

OBJECTIVE: Enhancing subjective well-being is an effective way to improve mental health. This study aimed to validate a virtual realitybased interactive feedback program as an intervention tool for promoting subjective well-being. METHODS: Thirty-six males participated in this program, consisting of three tasks constructed based on the theories of positive psychology: 'Experience-based problem recognition task', 'Future self-based success story expression task', and 'Strength expression task'. Participants rated visual analog scores associated with each of the tasks' contents. The concurrent validity of task scores was evaluated by correlations with the psychological scale scores. RESULTS: The total task score was positively correlated with scores of Mental Health Continuum-Short Form (MHC-SF) emotional wellbeing and psychological well-being, Rosenberg's Self-Esteem Scale, Dispositional Hope Scale agency dimension and pathways dimension, and Life Orientation Test Revised, but not with MHC-SF social well-being scores. After controlling for the effects of the other task scores, the task scores had linear relationships with certain psychological assessments. CONCLUSION: Since the task scores are closely related to indicators of well-being, self-esteem, hope, and optimism, the program contents are well associated with certain aspects of subjective well-being and thus may be available for training that improves subjective well-being through interactive feedback.

Feasibility of a virtual reality-based interactive feedback program for modifying dysfunctional communication: a preliminary study.

BACKGROUND: Functional communication is vital in many areas of daily life, and modifying dysfunctional communication has been emphasized in various social areas, including family and school. The present preliminary study addressed the feasibility of a virtual reality (VR)-based interactive feedback program for the modification of dysfunctional communication. METHODS: Thirty-seven healthy young males completed psychological assessments associated with functional communication and participated in the VR-based program, consisting of the three tasks of 'exploring the communication style,' 'practicing functional communication,' and 'expressing empathy.' Behavioral parameters were recorded based on the participants' choices among available options and the visual analog scale scores that resulted in responses to questions in the tasks. RESULTS: Participants completed the program without dropping-out and reported 10.76 (SD, 9.66) in the Simulator Sickness Questionnaire and 106.97 (SD, 16.66) in the Presence Questionnaire. In exploring the communication style, there was no difference between the dysfunction level-with family and dysfunction level-with a friend, but only the dysfunction level-with family showed significant correlations with the level of communication with parents. In practicing functional communication, the communication scores with the placating, blaming, and computing styles significantly increased according to the repetition of trials. In expressing empathy, the empathetic feeling score was negatively correlated with the perspective-taking score, whereas the emotional intensity score was positively correlated with the level of differentiation of the self. CONCLUSION: These results suggest that the program may have a tolerable level of cybersickness, an adequate level of presence, an improvement in the behavioral parameters that may reflect the important aspects of communication, and a proper reflection of psychological states or interpersonal characteristics. The use of this program can be an important starting point for the development of a more convenient method for delivering VR programs designed to modify dysfunctional communication, which can further increase computerized dissemination.

Electrical impulse effects on degenerative human annulus fibrosus model to reduce disc pain using micro-electrical impulse-on-a-chip.

Electrical stimulation of cells and tissues for therapeutic benefit is a well-established method. Although animal studies can emulate the complexity of an organism's physiology, lab-on-a-chip platforms provide a suitable primary model for follow-up animal studies. Thus, inexpensive and easy-to-use platforms for in vitro human cell studies are required. In the present study, we designed a micro-electrical impulse (micro-EI)-on-a-chip (micro-EI-chip), which can precisely control electron density and adjust the frequency based on a micro-EI. The micro-EI-chip can stimulate cells at various micro-EI densities (0-500 mV/mm) and frequencies (0-300 Hz), which enables multiple co-culture of different cell types with or without electrical stimulation. As a proof-of-concept study, a model involving degenerative inflamed human annulus fibrosus (hAF) cells was established in vitro and the effects of micro-EI on inflamed hAF cells were evaluated using the micro-EI-chip. Stimulation of the cells (150 mV/mm at 200 Hz) inhibited the secretion of inflammatory cytokines and downregulated the activities of extracellular matrix-modifying enzymes and matrix metalloproteinase-1. These results show that micro-EI stimulation could affect degenerative diseases based on inflammation, implicating the micro-EI-chip as being useful for basic research of electroceuticals.