Percolation-induced gel-gel phase separation in a dilute polymer network.

Cosmic large-scale structures, animal flocks and living tissues can be considered non-equilibrium organized systems created by dissipative processes. Replicating such properties in artificial systems is still difficult. Herein we report a dissipative network formation process in a dilute polymer-water mixture that leads to percolation-induced gel-gel phase separation. The dilute system, which forms a monophase structure at the percolation threshold, spontaneously separates into two co-continuous gel phases with a submillimetre scale (a dilute-percolated gel) during the deswelling process after the completion of the gelation reaction. The dilute-percolated gel, which contains 99% water, exhibits unexpected hydrophobicity and induces the development of adipose-like tissues in subcutaneous tissues. These findings support the development of dissipative structures with advanced functionalities for distinct applications, ranging from physical chemistry to tissue engineering.

Latent metabolic bone disease, skeletal dysplasia and other conditions related to low bone formation among 38 patients with subtrochanteric femoral fractures: a retrospective observational study.

Subtrochanteric femoral fracture is rare and intractable due to the possible association with low bone formation. Retrospective analysis of 38 patients with subtrochanteric femoral fractures revealed that four patients suffered from disorders related to low bone formation and there were specific treatments for two of them. PURPOSE: The main aim of this study was to detect latent metabolic bone diseases and skeletal dysplasia associated with low bone formation among patients with morphologic atypical femoral fracture (AFF). A second aim was to evaluate the frequency of recognized risk factors, such as antiresorptive agents, glucocorticoids, and age. METHODS: Clinical information was retrospectively analyzed among 38 Japanese patients who were admitted to the Department of Orthopedic Surgery and Spinal Surgery and the Division of Emergency and Critical Care Medicine at the University of Tokyo Hospital with diagnoses of subtrochanteric fractures between February 2012 and March 2022. RESULTS: Among 38 patients (including 30 females), 21 patients were aged 75 and over. Ten patients had past oral glucocorticoid use, and 18 had past antiresorptive agent use. Two patients were diagnosed with hypophosphatemic osteomalacia after the development of fractures. One patient was suspected to be a carrier of a loss-of-function variant of alkaline phosphatase, biomineralization associated (ALPL), and one other patient had previously been genetically diagnosed with pycnodysostosis. Among four patients with a diagnosis or suspicion of these metabolic bone diseases and skeletal dysplasia, four had past clinical fractures, two had past subtrochanteric femoral fractures, and two had subtrochanteric femoral fractures on both sides. CONCLUSION: If clinicians encounter patients with morphologic AFF, latent diseases related to low bone formation should be carefully differentiated because appropriate treatment may prevent delayed union and recurrent fractures. Additionally, it may be desirable to exclude these bone diseases in advance before initiating long-term use of antiresorptive agents in osteoporotic patients by screening with serum alkaline phosphatase levels to reduce the risk of morphologic AFF.

Inflammatory diseases causing joint and bone destruction: rheumatoid arthritis and hemophilic arthropathy.

Various diseases and conditions cause joint disorders. Osteoarthritis (OA) is characterized by the degeneration of articular cartilage, synovitis, and anabolic changes in surrounding bone tissues. In contrast, rheumatoid arthritis (RA) and hemophilic arthropathy (HA) display marked destruction of bone tissues caused by synovitis. RA is a representative autoimmune disease. The primary tissue of RA pathogenesis is the synovial membrane and involves various immune cells that produce catabolic cytokines and enzymes. Hemophilia is a genetic disorder caused by a deficiency in blood clotting factors. Recurrent intra-articular bleeding leads to chronic synovitis through excessive iron deposition and results in the destruction of affected joints. Although the triggers for these two joint diseases are completely different, many cytokines and enzymes are common in the pathogenesis of both RA and HA. This review focuses on the similarities between joint and bone destruction in RA and HA. The insights may be useful in developing better treatments for hemophilia patients with arthropathy and osteoporosis by leveraging advanced therapeutics for RA.

Bispectral EEG (BSEEG) Algorithm Captures High Mortality Risk Among 1,077 Patients: Its Relationship to Delirium Motor Subtype.

OBJECTIVE: Delirium is dangerous and a predictor of poor patient outcomes. We have previously reported the utility of the bispectral EEG (BSEEG) with a novel algorithm for the detection of delirium and prediction of patient outcomes including mortality. The present study employed a normalized BSEEG (nBSEEG) score to integrate the previous cohorts to combine their data to investigate the prediction of patient outcomes. We also aimed to test if the BSEEG method can be applicable regardless of age, and independent of delirium motor subtypes. METHODS: We calculated nBSEEG score from raw BSEEG data in each cohort and classified patients into BSEEG-positive and BSEEG-negative groups. We used log-rank test and Cox proportional hazards models to predict 90-day and 1-year outcomes for the BSEEG-positive and -negative groups in all subjects and motor subgroups. RESULTS: A total of 1,077 subjects, the BSEEG-positive group showed significantly higher 90-day (hazard ratio 1.33 [95% CI 1.16-1.52] and 1-year (hazard ratio 1.22 [95% CI 1.06-1.40] mortality rates than the negative group after adjustment for covariates such as age, sex, CCI, and delirium status. Among patients with different motor subtypes of delirium, the hypoactive group showed significantly higher 90-day (hazard ratio 1.41 [95% CI 1.12-1.76] and 1-year mortality rates (hazard ratio 1.32 [95% CI 1.05-1.67], which remained significant after adjustment for the same covariates. CONCLUSION: We found that the BSEEG method is capable of capturing patients at high mortality risk.

Oral Iron Absorption of Ferric Citrate Hydrate and Hepcidin-25 in Hemodialysis Patients: A Prospective, Multicenter, Observational Riona-Oral Iron Absorption Trial.

Oral ferric citrate hydrate (FCH) is effective for iron deficiencies in hemodialysis patients; however, how iron balance in the body affects iron absorption in the intestinal tract remains unclear. This prospective observational study (Riona-Oral Iron Absorption Trial, R-OIAT, UMIN 000031406) was conducted at 42 hemodialysis centers in Japan, wherein 268 hemodialysis patients without inflammation were enrolled and treated with a fixed amount of FCH for 6 months. We assessed the predictive value of hepcidin-25 for iron absorption and iron shift between ferritin (FTN) and red blood cells (RBCs) following FCH therapy. Serum iron changes at 2 h (ΔFe2h) after FCH ingestion were evaluated as iron absorption. The primary outcome was the quantitative delineation of iron variables with respect to ΔFe2h, and the secondary outcome was the description of the predictors of the body's iron balance. Generalized estimating equations (GEEs) were used to identify the determinants of iron absorption during each phase of FCH treatment. ΔFe2h increased when hepcidin-25 and TSAT decreased (-0.459, -0.643 to -0.276, p = 0.000; -0.648, -1.099 to -0.197, p = 0.005, respectively) in GEEs. FTN increased when RBCs decreased (-1.392, -1.749 to -1.035, p = 0.000) and hepcidin-25 increased (0.297, 0.239 to 0.355, p = 0.000). Limiting erythropoiesis to maintain hemoglobin levels induces RBC reduction in hemodialysis patients, resulting in increased hepcidin-25 and FTN levels. Hepcidin-25 production may prompt an iron shift from RBC iron to FTN iron, inhibiting iron absorption even with continued FCH intake.

Conditional inactivation of the L-type amino acid transporter LAT1 in chondrocytes models idiopathic scoliosis in mice.

Scoliosis, usually diagnosed in childhood and early adolescence, is an abnormal lateral curvature of the spine. L-type amino acid transporter 1 (LAT1), encoded by solute carrier transporter 7a5 (Slc7a5), plays a crucial role in amino acid sensing and signaling in specific cell types. We previously demonstrated the pivotal role of LAT1 on bone homeostasis in mice, and the expression of LAT1/SLC7A5 in vertebral cartilage of pediatric scoliosis patients; however, its role in chondrocytes on spinal homeostasis and implications regarding the underlying mechanisms during the onset and progression of scoliosis, remain unknown. Here, we identified LAT1 in mouse chondrocytes as an important regulator of postnatal spinal homeostasis. Conditional inactivation of LAT1 in chondrocytes resulted in a postnatal-onset severe thoracic scoliosis at the early adolescent stage with normal embryonic spinal development. Histological analyses revealed that Slc7a5 deletion in chondrocytes led to general disorganization of chondrocytes in the vertebral growth plate, along with an increase in apoptosis and a decrease in cell proliferation. Furthermore, loss of Slc7a5 in chondrocytes activated the general amino acid control (GAAC) pathway but inactivated the mechanistic target of rapamycin complex 1 (mTORC1) pathway in the vertebrae. The spinal deformity in Slc7a5-deficient mice was corrected by genetic inactivation of the GAAC pathway, but not by genetic activation of the mTORC1 pathway. These findings suggest that the LAT1-GAAC pathway in chondrocytes plays a critical role in the maintenance of proper spinal homeostasis by modulating cell proliferation and survivability.

Risk and resilience in trajectories of post-traumatic stress symptoms among first responders after the 2011 Great East Japan Earthquake: 7-year prospective cohort study.

BACKGROUND: First responders to disasters are at risk of developing post-traumatic stress disorder (PTSD). The trajectories of post-traumatic stress symptom severity differ among individuals, even if they are exposed to similar events. These trajectories have not yet been reported in non-Western first responders. AIMS: We aimed to explore post-traumatic stress symptom severity trajectories and their risk factors in first responders to the 2011 Great East Japan Earthquake (GEJE) - a historically large earthquake that resulted in a tsunami and a nuclear disaster. METHOD: A total of 55 632 Japan Ground Self-Defense Force (JGSDF) personnel dispatched to the GEJE were enrolled in this 7-year longitudinal cohort study. PTSD symptom severity was measured using the Impact of Event Scale-Revised. Trajectories were identified using latent growth mixture models (LGMM). Nine potential risk factors for the symptom severity trajectories were analysed using multinomial logistic regression. RESULTS: Five symptom severity trajectories were identified: 'resilient' (54.8%), 'recovery' (24.6%), 'incomplete recovery' (10.7%), 'late-onset' (5.7%), and 'chronic' (4.3%). The main risk factors for the four non-resilient trajectories were older age, personal disaster experiences and working conditions. These working conditions included duties involving body recovery or radiation exposure risk, longer deployment length, later or no post-deployment leave and longer post-deployment overtime. CONCLUSIONS: The majority of first responders to GEJE were resilient and developed few or no PTSD symptoms. A substantial minority experienced late-onset and chronic symptom severity trajectories. The identified risk factors can inform policies for prevention, early detection and intervention in individuals at risk of developing symptomatic trajectories.

Regulation of osteoarthritis development by ADAM17/Tace in articular cartilage.

INTRODUCTION: A disintegrin and metalloproteinase 17 (Adam17), also known as TNFα-converting enzyme (Tace), is a membrane-anchored protein involved in shedding of TNF, IL-6 receptor, ligands of epidermal growth factor receptor (EGFR), and Notch receptor. This study aimed to examine the role of Adam17 in adult articular cartilage and osteoarthritis (OA) pathophysiology. MATERIALS AND METHODS: Adam17 expression was examined in mouse knee joints during OA development. We analyzed OA development in tamoxifen-inducible chondrocyte-specific Adam17 knockout mice of a resection of the medial meniscus and medial collateral ligament (medial) model, destabilization of the medial meniscus (DMM) model, and aging model. We analyzed downstream pathways by in vitro experiments, and further performed intra-articular administration of an Adam17 inhibitor TAPI-0 for surgically induced mouse OA. RESULTS: Adam17 expression in mouse articular cartilage was increased by OA progression. In all models, Adam17 knockout mice showed ameliorated progression of articular cartilage degradation. Adam17 knockout decreased matrix metallopeptidase 13 (Mmp13) expression in both in vivo and in vitro experiments, whereas Adam17 activation by phorbol-12-myristate-13-acetate (PMA) increased Mmp13 and decreased aggrecan in mouse primary chondrocytes. Adam17 activation enhanced release of soluble TNF and transforming growth factor alpha, a representative EGF ligand, from mouse primary chondrocytes, while it did not change release of soluble IL-6 receptor or nuclear translocation of Notch1 intercellular domain. Intra-articular administration of the Adam17 inhibitor ameliorated OA progression. CONCLUSIONS: This study demonstrates regulation of OA development by Adam17, involvement of EGFR and TNF pathways, and the possibility of Adam17 as a therapeutic target for OA.

Inflammatory Arthritis and Bone Metabolism Regulated by Type 2 Innate and Adaptive Immunity.

While type 2 immunity has traditionally been associated with the control of parasitic infections and allergic reactions, increasing evidence suggests that type 2 immunity exerts regulatory functions on inflammatory diseases such as arthritis, and also on bone homeostasis. This review summarizes the current evidence of the regulatory role of type 2 immunity in arthritis and bone. Key type 2 cytokines, like interleukin (IL)-4 and IL-13, but also others such as IL-5, IL-9, IL-25, and IL-33, exert regulatory properties on arthritis, dampening inflammation and inducing resolution of joint swelling. Furthermore, these cytokines share anti-osteoclastogenic properties and thereby reduce bone resorption and protect bone. Cellular effectors of this action are both T cells (i.e., Th2 and Th9 cells), but also non-T cells, like type 2 innate lymphoid cells (ILC2). Key regulatory actions mediated by type 2 cytokines and immune cells on both inflammation as well as bone homeostasis are discussed.

Loss of Mob1a/b in mice results in chondrodysplasia due to YAP1/TAZ-TEAD-dependent repression of SOX9.

Hippo signaling is modulated in response to cell density, external mechanical forces, and rigidity of the extracellular matrix (ECM). The Mps one binder kinase activator (MOB) adaptor proteins are core components of Hippo signaling and influence Yes-associated protein 1 (YAP1) and transcriptional co-activator with PDZ-binding motif (TAZ), which are potent transcriptional regulators. YAP1/TAZ are key contributors to cartilage and bone development but the molecular mechanisms by which the Hippo pathway controls chondrogenesis are largely unknown. Cartilage is rich in ECM and also subject to strong external forces - two upstream factors regulating Hippo signaling. Chondrogenesis and endochondral ossification are tightly controlled by growth factors, morphogens, hormones, and transcriptional factors that engage in crosstalk with Hippo-YAP1/TAZ signaling. Here, we generated tamoxifen-inducible, chondrocyte-specific Mob1a/b-deficient mice and show that hyperactivation of endogenous YAP1/TAZ impairs chondrocyte proliferation and differentiation/maturation, leading to chondrodysplasia. These defects were linked to suppression of SOX9, a master regulator of chondrogenesis, the expression of which is mediated by TEAD transcription factors. Our data indicate that a MOB1-dependent YAP1/TAZ-TEAD complex functions as a transcriptional repressor of SOX9 and thereby negatively regulates chondrogenesis.

Increased mortality in patients with standard EEG findings of 'diffuse slowing'.

BACKGROUND: We aimed to confirm the association between slow brain wave activity typically described as "diffuse slowing" on standard electroencephalogram (EEG) and patient outcomes, including mortality. METHODS: This retrospective study was conducted with patient chart data from March 2015 to March 2017 at a tertiary care academic hospital in the midwestern United States. In total, 1,069 participants age ≥55 years on an inpatient floor or ICU received a standard 24-hour EEG. The primary outcome was all-cause mortality at 30, 90, 180, and 365 days. Secondary outcomes were time to discharge, and discharge to home. RESULTS: Having diffuse slowing on standard EEG was significantly associated with 30-, 90-, 180-, and 365-day mortality compared with patients who had normal EEG findings, after controlling for age, sex, and Charlson Comorbidity Index score. When controlling for these factors, patients with diffuse slowing had a significant longer time to discharge and were significantly less likely to discharge to home. Our findings showed that a standard EEG finding of diffuse slowing for inpatients age ≥55 years is associated with poor outcomes, including greater mortality. CONCLUSIONS: This study suggested that the finding of diffuse slowing on EEG may be an important clinical marker for predicting mortality in geriatric inpatients.

Increased mortality in patients with standard EEG findings of 'diffuse slowing'.

BACKGROUND: We aimed to confirm the association between slow brain wave activity typically described as "diffuse slowing" on standard electroencephalogram (EEG) and patient outcomes, including mortality. METHODS: This retrospective study was conducted with patient chart data from March 2015 to March 2017 at a tertiary care academic hospital in the midwestern United States. In total, 1,069 participants age ≥55 years on an inpatient floor or ICU received a standard 24-hour EEG. The primary outcome was all-cause mortality at 30, 90, 180, and 365 days. Secondary outcomes were time to discharge, and discharge to home. RESULTS: Having diffuse slowing on standard EEG was significantly associated with 30-, 90-, 180-, and 365-day mortality compared with patients who had normal EEG findings, after controlling for age, sex, and Charlson Comorbidity Index score. When controlling for these factors, patients with diffuse slowing had a significantly longer time to discharge and were significantly less likely to discharge to home. Our findings showed that a standard EEG finding of diffuse slowing for inpatients age ≥55 years is associated with poor outcomes, including greater mortality. CONCLUSIONS: This study suggested that the finding of diffuse slowing on EEG may be an important clinical marker for predicting mortality in geriatric inpatients.

Mechanisms of synovial joint and articular cartilage development.

Articular cartilage is formed at the end of epiphyses in the synovial joint cavity and permanently contributes to the smooth movement of synovial joints. Most skeletal elements develop from transient cartilage by a biological process known as endochondral ossification. Accumulating evidence indicates that articular and growth plate cartilage are derived from different cell sources and that different molecules and signaling pathways regulate these two kinds of cartilage. As the first sign of joint development, the interzone emerges at the presumptive joint site within a pre-cartilage tissue. After that, joint cavitation occurs in the center of the interzone, and the cells in the interzone and its surroundings gradually form articular cartilage and the synovial joint. During joint development, the interzone cells continuously migrate out to the epiphyseal cartilage and the surrounding cells influx into the joint region. These complicated phenomena are regulated by various molecules and signaling pathways, including GDF5, Wnt, IHH, PTHrP, BMP, TGF-ß, and FGF. Here, we summarize current literature and discuss the molecular mechanisms underlying joint formation and articular development.

Correction to: Adamts17 is involved in skeletogenesis through modulation of BMP­Smad1/5/8 pathway.

In the published article, the Fig. 4a was published incorrectly.

Adamts17 is involved in skeletogenesis through modulation of BMP-Smad1/5/8 pathway.

Fibrillin microfibrils are ubiquitous elements of extracellular matrix assemblies that play crucial roles in regulating the bioavailability of growth factors of the transforming growth factor beta superfamily. Recently, several "a disintegrin and metalloproteinase with thrombospondin motifs" (ADAMTS) proteins were shown to regulate fibrillin microfibril function. Among them, ADAMTS17 is the causative gene of Weill-Marchesani syndrome (WMS) and Weill-Marchesani-like syndrome, of which common symptoms are ectopia lentis and short stature. ADAMTS17 has also been linked to height variation in humans; however, the molecular mechanisms whereby ADAMTS17 regulates skeletal growth remain unknown. Here, we generated Adamts17-/- mice to examine the role of Adamts17 in skeletogenesis. Adamts17-/- mice recapitulated WMS, showing shorter long bones, brachydactyly, and thick skin. The hypertrophic zone of the growth plate in Adamts17-/- mice was shortened, with enhanced fibrillin-2 deposition, suggesting increased incorporation of fibrillin-2 into microfibrils. Comprehensive gene expression analysis of growth plates using laser microdissection and RNA sequencing indicated alteration of the bone morphogenetic protein (BMP) signaling pathway after Adamts17 knockout. Consistent with this, phospho-Smad1 levels were downregulated in the hypertrophic zone of the growth plate and in Adamts17-/- primary chondrocytes. Delayed terminal differentiation of Adamts17-/- chondrocytes, observed both in primary chondrocyte and primordial metatarsal cultures, and was prevented by BMP treatment. Our data indicated that Adamts17 is involved in skeletal formation by modulating BMP-Smad1/5/8 pathway, possibly through inhibiting the incorporation of fibrillin-2 into microfibrils. Our findings will contribute to further understanding of disease mechanisms and will facilitate the development of therapeutic interventions for WMS.

Evaluation of the Severity of Major Depression Using a Voice Index for Emotional Arousal.

Recently, the relationship between emotional arousal and depression has been studied. Focusing on this relationship, we first developed an arousal level voice index (ALVI) to measure arousal levels using the Interactive Emotional Dyadic Motion Capture database. Then, we calculated ALVI from the voices of depressed patients from two hospitals (Ginza Taimei Clinic (H1) and National Defense Medical College hospital (H2)) and compared them with the severity of depression as measured by the Hamilton Rating Scale for Depression (HAM-D). Depending on the HAM-D score, the datasets were classified into a no depression (HAM-D < 8) and a depression group (HAM-D ≥ 8) for each hospital. A comparison of the mean ALVI between the groups was performed using the Wilcoxon rank-sum test and a significant difference at the level of 10% (p = 0.094) at H1 and 1% (p = 0.0038) at H2 was determined. The area under the curve (AUC) of the receiver operating characteristic was 0.66 when categorizing between the two groups for H1, and the AUC for H2 was 0.70. The relationship between arousal level and depression severity was indirectly suggested via the ALVI.

General psychological distress among Japan Self-Defense Forces personnel dispatched on United Nations peacekeeping operations and their spouses.

AIM: The importance of family care during international deployment is emphasized within military organizations, but mental health interactions between deployed personnel and their spouses have not yet been assessed. This study addressed this gap by examining couples' mental health throughout a deployment period. METHODS: The mental health of 324 spousal dyads of Japan Self-Defense Forces personnel dispatched for a half-year United Nations Disengagement Observer Force mission was examined, using longitudinal data derived from a survey at four time points: one-month pre-deployment, initial deployment, middle deployment, and immediately after homecoming. The 30-item General Health Questionnaire was used to evaluate general psychological distress, with high scores (≥7) indicating adverse mental health. RESULTS: The spouses' general psychological distress was significantly higher compared with the deployed personnel (P < 0.001). The high general psychological distress of personnel was significantly related to that of their spouses (odds ratio = 2.24; 95% confidence interval, 1.32-3.80), and vice versa (odds ratio = 2.38; 95% confidence interval 1.39-4.08). CONCLUSION: Mental health care will be beneficial for not only deployed personnel but also their spouses.

Differential effects of voluntary wheel running and toy rotation on the mRNA expression of neurotrophic factors and FKBP5 in a post-traumatic stress disorder rat model with the shuttle-box task.

Life-threatening experiences can result in the development of post-traumatic stress disorder. We have developed an animal model for post-traumatic stress disorder (PTSD) using a shuttle box in rats. In this paradigm, the rats were exposed to inescapable foot-shock stress (IS) in a shuttle box, and then an avoidance/escape task was performed in the same box 2 weeks after IS. A previous study using this paradigm revealed that environmental enrichment (EE) ameliorated avoidance/numbing-like behaviors, but not hyperarousal-like behaviors, and EE also elevated hippocampal brain-derived neurotrophic factor (BDNF) expression. However, the differential effects of EE components, i.e., running wheel (RW) or toy rotation, on PTSD-like behaviors has remained unclear. In this experiment, we demonstrated that RW, toy rotation, and EE (containing RW and toy rotation) ameliorated avoidance/numbing-like behaviors, induced learning of avoidance responses, and improved depressive-like behaviors in traumatized rats. The RW increased the hippocampal mRNA expression of neurotrophic factors, especially BDNF and glial-cell derived neurotrophic factor. Toy rotation influenced FK506 binding protein 5 mRNA expression, which is believed to be a regulator of the hypothalamic-pituitary-adrenal (HPA)-axis system, in the hippocampus and amygdala. This is the first report to elucidate the differential mechanistic effects of RW and toy rotation. The former appears to exert its effects via neurotrophic factors, while the latter exerts its effects via the HPA axis. Further studies will lead to a better understanding of the influence of environmental factors on PTSD.

Local cyclical compression modulates macrophage function in situ and alleviates immobilization-induced muscle atrophy.

Physical inactivity gives rise to numerous diseases and organismal dysfunctions, particularly those related to aging. Musculoskeletal disorders including muscle atrophy, which can result from a sedentary lifestyle, aggravate locomotive malfunction and evoke a vicious circle leading to severe functional disruptions of vital organs such as the brain and cardiovascular system. Although the significance of physical activity is evident, molecular mechanisms behind its beneficial effects are poorly understood. Here, we show that massage-like mechanical interventions modulate immobilization-induced pro-inflammatory responses of macrophages in situ and alleviate muscle atrophy. Local cyclical compression (LCC) on mouse calves, which generates intramuscular pressure waves with amplitude of 50 mmHg, partially restores the myofiber thickness and contracting forces of calf muscles that are decreased by hindlimb immobilization. LCC tempers the increase in the number of cells expressing pro-inflammatory proteins, tumor necrosis factor-α and monocyte chemoattractant protein-1 (MCP-1), including macrophages in situ The reversing effect of LCC on immobilization-induced thinning of myofibers is almost completely nullified when macrophages recruited from circulating blood are depleted by administration of clodronate liposomes. Furthermore, application of pulsatile fluid shear stress, but not hydrostatic pressure, reduces the expression of MCP-1 in macrophages in vitro Together with the LCC-induced movement of intramuscular interstitial fluid detected by µCT analysis, these results suggest that mechanical modulation of macrophage function is involved in physical inactivity-induced muscle atrophy and inflammation. Our findings uncover the implication of mechanosensory function of macrophages in disuse muscle atrophy, thereby opening a new path to develop a novel therapeutic strategy utilizing mechanical interventions.

The relationship between dispositional empathy, psychological distress, and posttraumatic stress responses among Japanese uniformed disaster workers: a cross-sectional study.

BACKGROUND: Disaster workers suffer from psychological distress not only through the direct experience of traumatic situations but also through the indirect process of aiding disaster victims. This distress, called secondary traumatic stress, is linked to dispositional empathy, which is the tendency for individuals to imagine and experience the feelings and experiences of others. However, the association between secondary traumatic stress and dispositional empathy remains understudied. METHODS: To examine the relationship between dispositional empathy and mental health among disaster workers, we collected data from 227 Japan Ground Self-Defense Force personnel who engaged in international disaster relief activities in the Philippines following Typhoon Yolanda in 2013. The Impact of Event Scale-Revised and the Kessler Psychological Distress Scale were used to evaluate posttraumatic stress responses (PTSR) and general psychological distress (GPD), respectively. Dispositional empathy was evaluated through the Interpersonal Reactivity Index, which consists of four subscales: Perspective Taking, Fantasy, Empathic Concern, and Personal Distress. Hierarchial linear regression analyses were performed to identify the variables related to PTSR and GPD. RESULTS: High PTSR was significantly associated with high Fantasy (identification tendency, ß = 0.21, p < .01), high Personal Distress (the self-oriented emotional disposition of empathy, ß = 0.18, p < .05), and no experience of disaster relief activities (ß = 0.15, p < .05). High GPD was associated with high Personal Distress (ß = 0.28, p < .001), marital status (married, ß = 0.22, p < .01), being female (ß = 0.18, p < .01), medical unit (ß = 0.18, p < .05), and no experience of disaster relief activities (ß = 0.13, p < .05). CONCLUSIONS: Among Japanese uniformed disaster workers, high PTSR was associated with two subtypes of dispositional empathy: the self-oriented emotional disposition of empathy and high identification tendency, whereas high GPD was associated with high identification tendency. Educational interventions that aim to mitigate these tendencies might be able to relieve the psychological distress of disaster workers.