Interpersonal Sensitivity as a Mediator of the Effect of Childhood Parenting Quality on Depressive Symptoms.

ABSTRACT: The aim of this study was to analyze whether interpersonal sensitivity mediates the effect of qualitative parenting characteristics experienced during childhood on the appraisal of life experiences and depression severity during adulthood in adult community volunteers. A total of 404 Japanese adult volunteers answered the following four self-report questionnaires: Parental Bonding Instrument, Interpersonal Sensitivity Measure, Life Experiences Survey, and Patient Health Questionnaire-9. Structural equation modeling was performed to analyze whether childhood parenting quality increases depressive symptom severity through interpersonal sensitivity, which then affects the appraisal of recent life events. In the two structural equation models, inadequate care and excessive overprotection received during childhood were associated with the negative evaluation of life experiences and depression severity in adulthood through high interpersonal sensitivity. Our findings indicate interpersonal sensitivity as a mediator of the effect of inadequate care and excessive overprotection experienced in childhood on the negative evaluation of life experiences and depression severity in adulthood.

Self-efficacy modulates the neural correlates of craving in male smokers and ex-smokers: an fMRI study.

The regulation of cue-induced craving for cigarettes is a key factor in smoking cessation. Outcomes of smoking cessation have been linked to self-efficacy, faith in one's own ability, in smokers. However, no study has examined the neural basis of self-efficacy during the control of craving. We examined whether self-efficacy can affect the neural response to smoking cues in smokers and ex-smokers using functional magnetic resonance imaging. During scanning, participants were instructed (1) to view smoking-related images passively, (2) to view the smoking-related images with a strategy focused on self-efficacy to control cue-induced craving or (3) to view neutral images. In smokers, the self-efficacy strategy significantly reduced self-reported craving. This strategy was related to increased activation in the rostral medial prefrontal cortex (rmPFC) and the pregenual anterior cingulate cortex in smokers compared with ex-smokers. Furthermore, smokers showed increased effective connectivity between rmPFC and hippocampus and between pregenual anterior cingulate cortex and parahippocampus gyrus when employing the self-efficacy strategy compared with ex-smokers. The magnitude of the rmPFC-hippocampus connectivity was positively correlated with self-reported self-efficacy. Our findings suggest that in smokers, self-efficacy is related to activation and connectivity in brain regions involved in regulating craving and self-assessment. The current study provides evidence for understanding the vunderlying cognitive and neurobiological mechanisms involved in the control of craving to smoke cigarettes.

Localization and osteoblastic differentiation potential of neural crest-derived cells in oral tissues of adult mice.

In embryos, neural crest cells emerge from the dorsal region of the fusing neural tube and migrate throughout tissues to differentiate into various types of cells including osteoblasts. In adults, subsets of neural crest-derived cells (NCDCs) reside as stem cells and are considered to be useful cell sources for regenerative medicine strategies. Numerous studies have suggested that stem cells with a neural crest origin persist into adulthood, especially those within the mammalian craniofacial compartment. However, their distribution as well as capacity to differentiate into osteoblasts in adults is not fully understood. To analyze the precise distribution and characteristics of NCDCs in adult oral tissues, we utilized an established line of double transgenic (P0-Cre/CAG-CAT-EGFP) mice in which NCDCs express green fluorescent protein (GFP) throughout their life. GFP-positive cells were scattered like islands throughout tissues of the palate, gingiva, tongue, and buccal mucosa in adult mice, with those isolated from the latter shown to form spheres, typical cell clusters composed of stem cells, under low-adherent conditions. Furthermore, GFP-positive cells had markedly increased alkaline phosphatase (a marker enzyme of osteoblast differentiation) activity and mineralization as shown by alizarin red staining, in the presence of bone morphogenetic protein (BMP)-2. These results suggest that NCDCs reside in various adult oral tissues and possess potential to differentiate into osteoblastic cells. NCDCs in adults may be a useful cell source for bone regeneration strategies.

Effects of Peer Victimization in Childhood and Trait Anxiety on Job Stress in Adulthood.

Background: The experience of peer victimization in childhood increases the risk of developing anxiety disorders and depression, risk of suicide, as well as sensitivity to stress, in adulthood. Various personality traits are known to be associated with these effects. However, the influence of trait anxiety on job stress has not yet been reported. In the present study, we tested the hypothesis that the experience of peer victimization in childhood and trait anxiety influence job stress in adulthood. Methods: A questionnaire survey, including State-Trait Anxiety Inventory, Childhood Victimization Rating Scale, and Brief Job Stress Questionnaire, was administered to 566 adult workers. The interrelationship between multiple variables was analyzed by multiple regression analysis and path analysis. Results: In the path model, childhood peer victimization had a positive direct effect on trait anxiety and the psychological and physical stress response (PPSR). Trait anxiety had a positive direct effect on job stressors and PPSR, and job stressors had a positive direct effect on PPSR. Regarding indirect effects, childhood peer victimization had a significant adverse effect on job stressors and PPSR via trait anxiety. Conclusion: Our results showed that childhood peer victimization has a negative impact on job stress in adulthood, which is influenced by trait anxiety. Interventions to address peer victimization in childhood and trait anxiety may reduce job stress in adulthood, and thus contribute to improved occupational mental health and productivity in the workplace.

Effects of Subjective Social Status and Self-Esteem in the Association Between Childhood Abuse and Adulthood Anxiety.

Background: Subjective social status influences anxiety, but at present, the mechanism is not fully understood. It has been reported that negative childhood experiences, such as abuse, can influence depressive symptoms through subjective social status and personality traits, such as self-esteem. A similar mechanism is presumed to underlie anxiety symptoms in adulthood. Therefore, we hypothesized that subjective social status and self-esteem are intermediate factors in the indirect effects of childhood abuse on state anxiety in adulthood, and analyzed the indirect effects via these factors using a path analysis. Subjects and Methods: Child Abuse and Trauma Scale, Subjective Social Status, Rosenberg Self-Esteem Scale, and State-Trait Anxiety Inventory Form Y questionnaires were administered in a self-report format to 404 adult volunteers from January 2014 to August 2014. In addition, a path analysis was conducted to determine whether subjective social status and self-esteem are associated with the indirect effects of childhood abuse on anxiety symptoms in adulthood. Results: Childhood abuse did not directly affect state anxiety in adulthood, but affected state anxiety via subjective social status and self-esteem. Subjective social status affected state anxiety via self-esteem. This model explained 25.2% of the variation in state anxiety in adult volunteers. Conclusion: The present study demonstrated that childhood abuse affects anxiety in adulthood through subjective social status and self-esteem. Therefore, interventions that enhance subjective social status and self-esteem for adults who experienced childhood abuse may help reduce their anxiety.

Effects of childhood experiences of parental attitude, depressive rumination, and sleep disturbances on adulthood depressive symptoms.

Aim: Various factors are thought to be involved in the development of depression, but the mechanisms are not yet clear. Although several reports have demonstrated that parental attitude experienced in childhood, depressive rumination, and sleep disturbances each influence depressive symptoms, and the association between two of these four variables, to our knowledge, no reports to date have investigated the association among the four variables. Methods: A questionnaire survey was administered to 576 adults who agreed to participate in this study between April 2017 and April 2018. Questionnaires assessed parental attitudes experienced in childhood, depressive rumination, sleep disturbances, and depressive symptoms in adulthood. The associations among the four variables were tested by structural equation modeling. Results: Regarding the direct effects, the parental attitude of "care" had a negative influence on depressive rumination and depressive symptoms, whereas "overprotection" had a positive influence on depressive rumination. Depressive rumination had a positive influence on sleep disturbance and depressive symptoms, whereas sleep disturbances had a positive influence on depressive symptoms. Regarding indirect effects, depressive rumination mediated the association between parental attitudes and sleep disturbances or depressive symptoms. Furthermore, sleep disturbances mediated the association between depressive rumination and depressive symptoms. Care and overprotection showed opposite effects. The goodness of fit of this model was high. Conclusion: The results of this study demonstrated that there were associations among the four variables. Clinical assessment and intervention of depressive rumination and sleep disturbances that are closely associated with previous parental attitudes may lead to an improvement of depressive symptoms.

Moderation by better sleep of the association among childhood maltreatment, neuroticism, and depressive symptoms in the adult volunteers: A moderated mediation model.

BACKGROUND: Previously, we demonstrated that childhood maltreatment could worsen depressive symptoms through neuroticism. On the one hand, some studies report that sleep disturbances are related to childhood maltreatment and neuroticism and worsens depressive symptoms. But, to our knowledge, no reports to date have shown the interrelatedness between childhood maltreatment, neuroticism, and depressive symptoms, and sleep disturbance in the one model. We hypothesized that sleep disturbance enhances the influence of maltreatment victimization in childhood or neuroticism on adulthood depressive symptoms and the mediation influence of neuroticism between maltreatment victimization in childhood and adulthood depressive symptoms. SUBJECTS AND METHODS: Total 584 Japanese volunteer adults recruited through convenience sampling from 4/2017 to 4/2018 were assessed regarding their characteristics of demographics, history of childhood maltreatment, sleep disturbance, neuroticism, and depressive symptoms with questionnaires self-administered. Survey data were analyzed using simple moderation models and a moderating mediation model. RESULTS: The interaction of sleep disturbance with childhood maltreatment or neuroticism on depressive symptoms was significantly positive. Furthermore, the moderating effect of sleep disturbance on the indirect effect of childhood maltreatment to depressive symptoms through neuroticism was significantly positive. LIMITATIONS: Because this was a cross-sectional study, a causal relationship could not be confirmed. CONCLUSIONS: Our findings indicate that individuals with milder sleep disturbance experience fewer depressive symptoms attributable to neuroticism and childhood maltreatment. Additionally, people with less sleep disturbance have fewer depressive symptoms arising from neuroticism owing to childhood maltreatment. Therefore, improvement of sleep disturbance will buffer the aggravating effect of childhood maltreatment, neuroticism caused by various factors, and neuroticism resulting from childhood maltreatment on depressive symptoms.

Effects of Inappropriate Nurturing Experiences, Depressive Rumination, and Trait Anxiety on Depressive Symptoms.

Background: Prior research has shown that inappropriate childhood nurturing experiences (low care and high overprotection), trait anxiety, and depressive rumination are risk factors for depression. However, no studies to date have analyzed the overall association between these factors and depressive symptoms. In the present study, we hypothesized that depressive rumination mediates the impacts of inappropriate childhood nurturing experiences on depressive symptoms, and that these mediating effects are moderated by trait anxiety, and tested these hypotheses in adult volunteers. Methods: The subjects were adult volunteers who were investigated between April 2017 and April 2018. A self-report questionnaire on demographic data, childhood nurturing experiences, trait anxiety, depressive rumination, and depressive symptoms was distributed to conduct the survey, and written informed consent and valid responses were obtained from 585 subjects. Mediation and moderated-mediation analyses were performed by SPSS 28 and macro PROCESS 4.0 software. This study was approved by the Ethics Committee of Tokyo Medical University. Results: Parental care showed a significant negative indirect effect on depressive symptoms via its effect on depressive rumination (p < 0.01), whereas parental overprotection showed the opposite effect (p < 0.01). Furthermore, the mediation effect of depressive rumination on depressive symptoms was increased by trait anxiety (p < 0.05). Conclusion: Our present study demonstrated that the main factor affecting depressive symptoms is inappropriate childhood nurturing experiences, which indirectly enhance depression by intensifying depressive rumination, and that depressive rumination and trait anxiety mutually reinforce each other to enhance depressive symptoms. These findings may be useful for the prevention of depressive symptoms. Large-scale prospective studies are needed to confirm the causal associations among these factors in the future.

On-Site Stimulation of Dendritic Cells by Cancer-Derived Extracellular Vesicles on a Core-Shell Nanowire Platform.

Extracellular vesicles (EVs) contain a subset of proteins, lipids, and nucleic acids that maintain the characteristics of the parent cell. Immunotherapy using EVs has become a focus of research due to their unique features and bioinspired applications in cancer treatment. Unlike conventional immunotherapy using tumor fragments, EVs can be easily obtained from bodily fluids without invasive actions. We previously fabricated nanowire devices that were specialized for EV collection, but they were not suitable for cell culturing. In this study, we fabricated a ZnO/Al2O3 core-shell nanowire platform that could collect more than 60% of the EVs from the cell supernatant. Additionally, we could continue to culture dendritic cells (DCs) on the platform as an artificial lymph node to investigate cell maturation into antigen-presenting cells. Finally, using this platform, we reproduced a series of on-site immune processes that are among the pivotal immune functions of DCs and include such processes as antigen uptake, antigen presentation, and endocytosis of cancer-derived EVs. This platform provides a new ex vivo tool for EV-DC-mediated immunotherapies.

Depressive rumination and trait anxiety mediate the effects of childhood victimization on adulthood depressive symptoms in adult volunteers.

BACKGROUND: Prior studies have reported that childhood victimization experiences substantially augment the risk of depression and suicide in adulthood. Several of our previous studies suggested that childhood experiences of victimization interact with the quality of parenting experienced in childhood, childhood experiences of abuse, neuroticism, and other factors to influence depressive symptoms in adulthood. In this study, it was hypothesized that "childhood victimization" worsens "trait anxiety" and "depressive rumination", and that "trait anxiety" and "depressive rumination" are mediators that worsen "depressive symptoms in adulthood". SUBJECTS AND METHODS: The following self-administered questionnaires were completed by 576 adult volunteers: Patient Health Questionnaire-9, State-Trait Anxiety Inventory form Y, Ruminative Responses Scale, and Childhood Victimization Rating Scale. Statistical analyses were performed by Pearson correlation coefficient analysis, t-test, multiple regression analysis, path analysis, and covariance structure analysis. RESULTS: Path analysis demonstrated that the direct effect was statistically significant for the paths from childhood victimization to trait anxiety, depressive rumination, and depressive symptom severity. Moreover, the indirect effect of childhood victimization on depressive rumination mediated by trait anxiety was statistically significant. The indirect effects of childhood victimization on depressive symptom severity mediated by trait anxiety and depressive rumination were statistically significant. Furthermore, the indirect effect of childhood victimization on depressive symptom severity mediated by both trait anxiety and depressive rumination was statistically significant. CONCLUSIONS: We found that childhood victimization directly and adversely influenced each of the above factors, and indirectly worsened adulthood depressive symptoms with trait anxiety and depressive ruminations as mediating factors. The present study is the first to clarify these mediation effects. Therefore, the results of this study suggest the importance of preventing childhood victimization and the importance of identifying and addressing childhood victimization in patients with clinical depression.

Interpersonal sensitivity mediates the effects of perceived parenting styles on state anxiety and negative assessment of life events in adult volunteers from the community.

Aim: The association of parenting experiences in childhood with anxiety symptoms in adulthood has yet to be clarified. We hypothesized that interpersonal sensitivity (IPS) mediates the impacts of parenting experiences in childhood on anxiety symptoms and negative assessment of life events in adulthood. Methods: An observational cross-sectional study was carried out from January 2014 to August 2014 on 853 adults. Participants provided their demographic information and answered the following four self-administered questionnaires: Parental Bonding Instrument (PBI), Interpersonal Sensitivity Measure (IPSM), Life Experiences Survey (LES), and State-Trait Anxiety Inventory Form Y (STAI-Y). The data of a total of 404 participants who agreed to take part in this study were analyzed. Results: Multiple regression analysis with the State Anxiety subscale of STAI-Y as the dependent variable identified the following five out of the 15 independent variables as being statistically significant: IPSM total, LES positive and negative, PBI paternal overprotection, and employment status. This model explains 17.8% of the State Anxiety subscale score. In the structural equation models, the Care subscale showed significant indirect negative effects on State Anxiety subscale and LES negative score through a decrease in IPSM total score (ß = -0.061 and -0.042, respectively). The former indirect effect accounted for 31.6%, and the latter accounted for 56.8% of the total effects. In contrast, Overprotection subscale had opposite effects to Care subscale. Conclusion: These results suggest that parenting experiences in childhood are related to adult anxiety symptoms and the negative assessment of life events indirectly through IPS.

Roles of childhood maltreatment, personality traits, and life stress in the prediction of severe premenstrual symptoms.

BACKGROUND: About 3% to 8% of women of fertile age are thought to have premenstrual dysphoric disorder (PMDD), which is regarded as a serious form of premenstrual syndrome (PMS), although the details of this common condition remain unclear. The aim of this study was to analyze the interrelations of childhood maltreatment, personality traits, and life stress in the etiology of PMS/PMDD. METHODS: A total of 240 adult female volunteers from a community in Japan were investigated, using the following 5 questionnaires: Patient Health Quesstionaire-9, Child Abuse and Trauma Scale, Temperament and Character Inventory (TCI), Life Experiences Survey, and premenstrual dysphoric disorder (PMDD) scale. The questionnaire data were subjected to path analyses to clarify the association between childhood maltreatment and the severity of premenstrual symptoms, mediated by personality traits and life stress. RESULTS: The 2 path analysis models showed that high harm avoidance (HA) on the TCI and low self-directedness (SD) on the TCI had significant direct effects on the severity of premenstrual symptoms. Moreover, childhood maltreatment was associated with the severity of premenstrual symptoms, both directly and indirectly through personality traits. CONCLUSION: Our findings suggest that HA on the TCI might be a risk factor for severe premenstrual symptoms among general women and furthermore that SD on the TCI may be a protective factor. In addition, childhood maltreatment is associated with severe premenstrual symptoms both directly and indirectly through personality traits.

Effects of the Interaction between Affective Temperaments and BIS/BAS on Depressive Symptoms in Individuals with Major Depressive Disorder.

Depressive symptoms (DepS) associated with major depressive disorder (MDD) are influenced by affective temperaments (ATs), behavioral inhibition system (BIS), and behavioral activation system (BAS). However, the effect of interactions between ATs and BIS/BAS on DepS in MDD remains poorly understood. Herein, we aimed to investigate the effects of these interactions. The Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Auto-questionnaire (TEMPS-A), BIS/BAS questionnaire, and Patient Health Questionnaire-9 (PHQ-9) were used to evaluate ATs, BIS/BAS, and DepS, respectively, in 90 participants with MDD. Data were analyzed using hierarchical multiple regression analysis to assess the interaction effect. The interaction (ß = 0.199, p < 0.05) between depressive temperament (DepT) (ß = 0.319, p < 0.01) and BIS scores (ß = 0.300, p < 0.01) exhibited a significant positive effect on DepS (ΔR2 = 0.038, p < 0.05). However, the interaction between ATs and BAS scores did not exhibit a significant effect on DepS. Our findings suggest that interactions between BIS sensitivity and DepT worsen DepS in individuals with MDD. Hence, to manage DepS associated with BIS sensitivity and DepT, evaluating their interaction may be useful in daily clinical practice. This study presents important insights into MDD psychopathology.

Long Working Hours Indirectly Affect Psychosomatic Stress Responses via Complete Mediation by Irregular Mealtimes and Shortened Sleep Duration: A Cross-Sectional Study.

BACKGROUND: Long working hours are detrimental to physical and mental health. However, the association between long working hours and psychosomatic symptoms have remained controversial, possibly because of the existence of mediators between working hours and psychosomatic stress responses. We hypothesized that lifestyle habits, regarding sleep and mealtimes, act as mediators, and analyzed the associations between long working hours, sleep duration, mealtime regularity, and psychosomatic stress responses in office workers. METHODS: From April 2017 to March 2018, an online cross-sectional survey regarding overtime work hours, work-related stress, sleep, and eating habits was conducted with employees of 17 companies located in Tokyo, Japan. Answers were obtained from 3559 employees, and 3100 provided written consent for the academic use of their answers, and were included in the analysis. A path analysis was conducted to assess the effect of overtime work on psychosomatic stress via shortened sleep or irregular mealtimes. RESULTS: Overtime work hours had no direct effect on psychosomatic stress responses and depressive symptoms. However, overtime work hours affected sleep duration and the regularity of mealtimes. The effects of overtime work hours on psychosomatic stress responses and depressive symptoms were completely mediated by sleep duration and the regularity of mealtimes. CONCLUSION: Long working hours do not affect mental health directly; however, shortened sleep duration and irregular mealtimes mediate the effect of long working hours on psychosomatic stress responses and depressive symptoms.

Moderating and Mediating Effects of Resilience Together with Neuroticism on Depressive Symptoms in Adult Volunteers.

Background: Parenting quality experienced in childhood affects depressive symptoms in adulthood, and neuroticism and resilience are attracting attention as personality traits that mediate the effects of parental rearing quality experienced in childhood on adulthood depressive symptoms. However, the interaction between neuroticism and resilience remains unclear. In this study, we hypothesized that resilience and neuroticism are mediators between parental rearing quality experienced in childhood and depressive symptoms in adulthood, and furthermore, that resilience and neuroticism interact with each other in their effects on depressive symptoms. To test these hypotheses, we conducted structural equation modeling and hierarchical multiple regression analysis including interactions in adult volunteers. Methods: A self-administered questionnaire survey was conducted on 528 adult volunteers recruited at Tokyo Medical University for 1 year from April 2017 to April 2018. The Parental Bonding Instrument (PBI), Eysenck Personality Questionnaire-revised short version, Connor-Davidson Resilience Scale, and Patient Health Questionnaire-9 were used as questionnaires, and their scores were analyzed using structure equation modeling. The interaction between resilience and neuroticism was analyzed using hierarchical multiple regression analysis. Results: Structural equation modeling showed that parenting quality (care and overprotection) experienced in childhood had a significant indirect effect on the severity of depressive symptoms in adulthood, mediated by both neuroticism and resilience. Among the subscores of the PBI, "care" showed opposite effects to "overprotection". Structural equation modeling of "care" and "overprotection" explained 36.9% and 36.6% of the variability in depressive symptoms in adulthood, respectively. Hierarchical multiple regression analysis showed that the negative interaction between neuroticism and resilience had a significant effect on depressive symptom severity in adulthood. Conclusion: The results of this study show that resilience and neuroticism are mediators of the effects from parental child-rearing to depressive symptoms in adulthood. Furthermore, resilience antagonizes the effect of neuroticism on adulthood depressive symptoms.

Childhood Victimization and Neuroticism Mediate the Effects of Childhood Abuse on Adulthood Depressive Symptoms in Volunteers.

BACKGROUND: When assessing patients with depressive and anxiety disorders in psychiatric clinical practice, it is common to encounter children and adolescents who have experienced abuse and victimization. To date, it has been clarified that experiences of "childhood abuse" and "childhood victimization" lead to "neuroticism", and that neuroticism leads to "adult depressive symptoms". In this study, we analyzed how these four factors are interrelated. SUBJECTS AND METHODS: The following self-administered questionnaire surveys were conducted in 576 adult volunteers: Patient Health Questionnaire-9, Eysenck Personality Questionnaire-revised shortened version, Child Abuse and Trauma Scale, and Childhood Victimization Rating Scale. For statistical analysis, Pearson correlation coefficient analysis, t-test, multiple regression analysis, and covariance structure analysis (path analysis) were performed. RESULTS: Path analysis showed that the indirect effects of childhood abuse and childhood victimization on depressive symptoms through neuroticism were statistically significant. In addition, the indirect effects of childhood abuse on neuroticism through childhood victimization were statistically significant. Finally, the indirect effects of childhood abuse on depressive symptoms through the combined paths of childhood victimization and neuroticism were statistically significant. CONCLUSION: Our results suggest that "childhood abuse (A)" induces changes in the personality trait of "neuroticism (C)" with "childhood victimization (B)" as a mediator, and that these adversities affect the expression of "depressive symptoms in adulthood (D)" through "neuroticism (C)" as a mediator. In other words, to our knowledge, this is the first study to clarify that these four factors are not only individually associated with each other but also cause a chain reaction of A to B to C to D.

Oxide Nanowire Microfluidic Devices for Capturing Single-stranded DNAs.

Since DNA analysis is the fundamental process for most applications in biomedical fields, capturing DNAs with high efficiency is important. Here, we used several oxide nanowire microfluidic devices to capture CpG-rich single-stranded DNAs (ssDNAs) in different pH solutions. All the oxide nanowires exhibited the highest capture efficiency around pH 7 with good capture efficiency shown by each metal oxide; ZnO/ZnO core/shell NWs (71.6%), ZnO/Al2O3 core/shell NWs (86.3%) and ZnO/SiO2 core/shell NWs (86.7%). ZnO/Al2O3 core/shell NWs showed the best performance for capturing ssDNAs under varying pH, which suggests its suitability for application in diverse biological fluids. The capturing efficiencies were attributed to the interactions from phosphate backbones and nucleobases of ssDNAs to each nanowire surface. This finding provides a useful platform for highly efficient capture of the target ssDNAs, and these results can be extended for future studies of cancer-related genes in complex biological fluids.

Tissue-scale tensional homeostasis in skin regulates structure and physiological function.

Tensional homeostasis is crucial for organ and tissue development, including the establishment of morphological and functional properties. Skin plays essential roles in waterproofing, cushioning and protecting deeper tissues by forming internal tension-distribution patterns, which involves aligning various cells, appendages and extracellular matrices (ECMs). The balance of traction force is thought to contribute to the formation of strong and pliable physical structures that maintain their integrity and flexibility. Here, by using a human skin equivalent (HSE), the horizontal tension-force balance of the dermal layer was found to clearly improve HSE characteristics, such as the physical relationship between cells and the ECM. The tension also promoted skin homeostasis through the activation of mechano-sensitive molecules such as ROCK and MRTF-A, and these results compared favourably to what was observed in tension-released models. Tension-induced HSE will contribute to analyze skin physiological functions regulated by tensional homeostasis as an alternative animal model.

Controlling Nutritional Status (CONUT) Score is Associated with Overall Survival in Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib: A Multicenter Cohort Study.

We aimed to investigate the impact of the controlling nutritional status (CONUT) score, an immuno-nutritional biomarker, on the prognosis of patients with hepatocellular carcinoma (HCC) treated with lenvatinib (LEN). This retrospective study enrolled 164 patients with HCC and treated with LEN (median age 73 years, Barcelona Clinic Liver Cancer (BCLC) stage B/C 93/71). Factors associated with overall survival (OS) were evaluated using multivariate and decision tree analyses. OS was calculated using the Kaplan-Meier method and analyzed using the log-rank test. Independent factors for OS were albumin-bilirubin grade 1, BCLC stage B, and CONUT score <5 (hazard ratio (HR) 2.9, 95% confidence interval (CI) 1.58-5.31, p < 0.001). The CONUT score was the most important variable for OS, with OS rates of 70.0% and 29.0% in the low and high CONUT groups, respectively. Additionally, the median survival time was longer in the low CONUT group than in the high CONUT group (median survival time not reached vs. 11.3 months, p < 0.001). The CONUT score was the most important prognostic variable, rather than albumin-bilirubin grade and BCLC stage, in patients with HCC treated with LEN. Accordingly, immuno-nutritional status may be an important factor in the management of patients with HCC treated with LEN.