A Robust Approach Assisted by Signal Quality Assessment for Fetal Heart Rate Estimation from Doppler Ultrasound Signal.

Fetal heart rate (FHR) monitoring, typically using Doppler ultrasound (DUS) signals, is an important technique for assessing fetal health. In this work, we develop a robust DUS-based FHR estimation approach complemented by DUS signal quality assessment (SQA) based on unsupervised representation learning in response to the drawbacks of previous DUS-based FHR estimation and DUS SQA methods. We improve the existing FHR estimation algorithm based on the autocorrelation function (ACF), which is the most widely used method for estimating FHR from DUS signals. Short-time Fourier transform (STFT) serves as a signal pre-processing technique that allows the extraction of both temporal and spectral information. In addition, we utilize double ACF calculations, employing the first one to determine an appropriate window size and the second one to estimate the FHR within changing windows. This approach enhances the robustness and adaptability of the algorithm. Furthermore, we tackle the challenge of low-quality signals impacting FHR estimation by introducing a DUS SQA method based on unsupervised representation learning. We employ a variational autoencoder (VAE) to train representations of pre-processed fetal DUS data and aggregate them into a signal quality index (SQI) using a self-organizing map (SOM). By incorporating the SQI and Kalman filter (KF), we refine the estimated FHRs, minimizing errors in the estimation process. Experimental results demonstrate that our proposed approach outperforms conventional methods in terms of accuracy and robustness.

A Pilot Study for the Development and Evaluation of an Educational Program to Reduce Stigma Toward Cancer and Cancer Survivors: Focusing on Dating and Marriage After Cancer Diagnosis.

The marriage rate of cancer survivors is lower than that of the general population and their siblings. This appears to be attributable to negative images and stigma in society regarding cancer and cancer survivors. In order to improve images and decrease stigma regarding cancer and cancer survivors, this study aimed to develop an educational program that primarily focuses on dating and marriage after cancer diagnosis. The education program was conducted for university students, and among 67 participants who attended the education program, 61 participants completed a self-report questionnaire both before and after the program. The questionnaire included measures to assess reluctance to date or marry a cancer survivor, attitudes toward marriage and having children, and level of empathy. Scores on most items assessing reluctance decreased after the program; however, only three items showed a significant decrease: reluctance to date a cancer survivor if cancer recurred or metastasized, and reluctance if one's family objects to dating a cancer survivor. Both before and after the program, disease severity was the main cause for reluctance to date. In addition, empathetic concern was associated with reduced reluctance to date or marry a cancer survivor, while conservative attitudes toward marriage were associated with greater reluctance which was a result of familial concerns regarding such relationships. Some of the reluctance could be attributable to sociocultural values in Asia, where the choice of romantic partner is likely to be subject to familial influence.

Prediction of lower-grade glioma molecular subtypes using deep learning.

INTRODUCTION: It is useful to know the molecular subtype of lower-grade gliomas (LGG) when deciding on a treatment strategy. This study aims to diagnose this preoperatively. METHODS: A deep learning model was developed to predict the 3-group molecular subtype using multimodal data including magnetic resonance imaging (MRI), positron emission tomography (PET), and computed tomography (CT). The performance was evaluated using leave-one-out cross validation with a dataset containing information from 217 LGG patients. RESULTS: The model performed best when the dataset contained MRI, PET, and CT data. The model could predict the molecular subtype with an accuracy of 96.6% for the training dataset and 68.7% for the test dataset. The model achieved test accuracies of 58.5%, 60.4%, and 59.4% when the dataset contained only MRI, MRI and PET, and MRI and CT data, respectively. The conventional method used to predict mutations in the isocitrate dehydrogenase (IDH) gene and the codeletion of chromosome arms 1p and 19q (1p/19q) sequentially had an overall accuracy of 65.9%. This is 2.8 percent point lower than the proposed method, which predicts the 3-group molecular subtype directly. CONCLUSIONS: A deep learning model was developed to diagnose the molecular subtype preoperatively based on multi-modality data in order to predict the 3-group classification directly. Cross-validation showed that the proposed model had an overall accuracy of 68.7% for the test dataset. This is the first model to double the expected value for a 3-group classification problem, when predicting the LGG molecular subtype.

Laser Speckle Contrast Imaging for Intraoperative Quantitative Assessment of Intestinal Blood Perfusion During Colorectal Surgery: A Prospective Pilot Study.

BACKGROUND: The main limitation of perfusion assessment with indocyanine green fluorescence angiography during colorectal surgery is that the surgeon assesses the quality of perfusion subjectively. The ideal intestinal viability test must be minimally invasive, objective, and reproducible. We evaluated the quantitativity and reproducibility of laser speckle contrast imaging for perfusion assessment during colorectal surgery. METHODS: This was a prospective, nonrandomized, pilot study of 8 consecutive patients who underwent elective left-sided colorectal resection. Laser speckle perfusion images at the site of proximal transection of the bowel were obtained intraoperatively. We tested the hypothesis that laser speckle contrast imaging was able to quantitatively identify areas of diminished intestinal perfusion after devascularization and assessed the reproducibility of this method. RESULTS: All surgical procedures were uneventful and blood flow measurements were successfully made in all patients. None of the patients developed postoperative complications related to the anastomosis and stoma. Data analyses were successfully optimized to perform quantitative regional perfusion assessments in all cases. The bowel tissue blood flows of the anal side region adjacent to the transection line were significantly lower than those of the oral side region adjacent to the transection line after ligation of marginal vessels ( P = .012). Interrater reliability was high (intraclass correlation coefficients = 0.989), and a Bland-Altman plot showed few differences of mean flux data between 2 investigators. CONCLUSION: Laser speckle contrast imaging is feasible for real-time assessment of bowel perfusion with quantitativity and excellent reproducibility during colorectal surgery without administration of any contrast agents.

Integrin α9 on lymphatic endothelial cells regulates lymphocyte egress.

Sphingosine 1-phosphate (S1P) plays a role in lymphocyte egress from lymphoid organs. However, it remains unclear how S1P production and secretion are regulated. We show that under inflammatory conditions, α9 integrin, which is closely associated with activated ß1 integrin, and its ligand, tenascin-C, colocalize on medullary and cortical sinuses of draining lymph nodes (dLNs), which is a gate for lymphocyte exit, and that inhibition of lymphocyte egress is evident by blockade of α9 integrin-mediated signaling at dLNs. Based on in vitro analysis using lymphatic endothelial cells obtained from mice embryos, we suggested the possibility that stimulation of lymphatic endothelial cells by tenascin-C enhances S1P secretion in an α9 integrin-dependent manner without affecting S1P synthesis and/or degradation. Blockade of α9 integrin-mediated signaling reduced lymphocyte egress from dLNs in several models, including experimental autoimmune encephalomyelitis, where it improved clinical scores and pathology. Therefore, manipulating α9 integrin function may offer a therapeutic strategy for treating various inflammatory disorders.

[The stress symptoms and posttraumatic growth of dispatched firefighters following the Great East Japan Earthquake].

This study investigated posttraumatic stress symptoms and posttraumatic growth among 534 fire fighters who were dispatched to the disaster area following the Great East Japan Earthquake. Specifically, we investigated the effect of acute stress symptoms and social support from peers and family on posttraumatic stress symptoms, depression, and posttraumatic growth one year after being dispatched. We found that dispatched fire fighters experienced posttraumatic growth as well as posttraumatic stress symptoms following disaster work. Moreover, social support from peers was positively associated with professional growth as a disaster worker, whereas social support from family positively associated with gratitude. These results imply that it is useful to take into consideration supporting the posttraumatic growth of fire fighters as an opportunity for professional growth with respect to stress management programs as well as relieving posttraumatic symptoms with early intervention.

[Effects of empathy on fund-raising activities on behalf of victims of the 2011 Great East Japan Earthquake, focusinig on the residents in the South Kanto area].

Fund-raising activities on behalf of victims of the 2011 Great East Japan Earthquake during the year after the earthquake were investigated in residents of the South Kanto area (N = 749), which is adjacent to the disaster area. The percentage of people that raised funds was 67.4%. We investigated the effects of the following on fundraising activities: demographic variables (sex, age, and educational background), trait empathy (empathic concern, perspective taking, and personal distress), former experience with fund-raising activities, effects of similarity to victims (e.g., experienced inconveniences because of the disaster, or had problems returning home), and psychological closeness to victims (e.g, have family members or acquaintances that suffered from the disaster, or that once lived in the disaster area). The results indicated that fund-raising activities were affected by former experience with fund-raising, similarity to victims, psychological closeness to victims, empathic concern, and being female. The relationship between fund-raising activities for victims and empathy are discussed.

Network analysis for motives in suicide cases: a cross-sectional study.

AIM: Suicide victims have various distresses or motives. There are few studies on how these motives toward suicide relate with each other. We used network analyses to extract the structures of correlations among the motives for suicide. METHODS: We obtained datasets of suicide victims from 2007-2009 in Japan in cooperation with Ibaraki Prefectural Police Headquarters. The data were analyzed by network centrality measures and a structural analysis by block modeling. RESULTS: Among the motives, depression and physical illness showed relatively high scores of 'degree centrality', whereas depression and unemployment showed relatively high scores of 'betweenness centrality'. Structural analysis by block modeling resulted in eight blocks. The most important block comprised eight motives, including conflict between parent and child, marital conflict, economic hardship, and overloaded with debt. CONCLUSION: Depression and physical illness were important and priority areas for completed suicides, although these two motives had different influences on suicide behaviors. Furthermore, structural analysis revealed the important role of a block, including some familial and financial motives, which induced hopelessness. Our results suggest that it might be useful to consider the common ways in which motivations for suicide are tied together when suicide intervention is launched from a social model point of view.

An Examination of the Association Between Psychosocial Aspects of Fertility Issues and Demographic Characteristics of Unmarried Adolescent and Young Adult Cancer Survivors.

Purpose: The purpose of this study was to examine the association between fertility issues and demographic characteristics of unmarried adolescent and young adult cancer survivors. Methods: We conducted a survey among cancer survivors who were 15-39 years old and unmarried at the time of cancer diagnosis and 20-45 years old at the time of the survey. Views on fertility issues, originally developed based on the results of a qualitative study conducted with the same inclusion criteria, were used to assess thoughts and feelings regarding fertility issues. Results: Through exploratory factor analysis of the 128 respondents who either had children or desired children, two factors related to fertility issues were identified: "anxiety related to the possibility of not being able to have children" and "pressure from others to have children." Multiple regression analysis was performed to examine the association between these factors and demographic characteristics. The analysis revealed that being male and having a partner were significant predictors for both factors for views on fertility issues. Additionally, younger age at the time of diagnosis was a significant predictor for the first factor. Conclusions: Greater fertility issues among unmarried cancer survivors were associated with younger age at diagnosis, having a partner, and being male. Surprisingly, contrary to previous findings, male cancer survivors experienced more significant fertility problems than women. This result may be attributed to the well-established gender roles in Japan, where men are predominantly considered the heirs and inheritors of the family.

RNA Analysis of Circulating Leukocytes in Patients with Alzheimer's Disease.

Background: One of the key symptoms of Alzheimer's disease (AD) is the impairment of short-term memory. Hippocampal neurogenesis is essential for short-term memory and is known to decrease in patients with AD. Impaired short-term memory and impaired neurogenesis are observed in aged mice alongside changes in RNA expression of gap junction and metabolism-related genes in circulating leukocytes. Moreover, after penetrating the blood-brain barrier via the SDF1/CXCR4 axis, circulating leukocytes directly interact with hippocampal neuronal stem cells via gap junctions. Objective: Evaluation of RNA expression profiles in circulating leukocytes in patients with AD. Methods: Patients with AD (MMSE≧23, n = 10) and age-matched controls (MMSE≧28, n = 10) were enrolled into this study. RNA expression profiles of gap junction and metabolism-related genes in circulating leukocytes were compared between the groups (jRCT: 1050210166). Results: The ratios of gap junction and metabolism-related genes were significantly different between patients with AD and age-matched controls. However, due to large inter-individual variations, there were no statistically significant differences in the level of single RNA expression between these groups. Conclusions: Our findings suggest a potential connection between the presence of circulating leukocytes and the process of hippocampal neurogenesis in individuals with AD. Analyzing RNA in circulating leukocytes holds promise as a means to offer novel insights into the pathology of AD, distinct from conventional markers.

Syndecan-4 prevents cardiac rupture and dysfunction after myocardial infarction.

RATIONALE: Syndecan-4 (Syn4), a cell-surface heparan sulfate proteoglycan, has been detected in the infarct region after myocardial infarction (MI), but its functional significance has not been elucidated. OBJECTIVE: We examined whether and how Syn4 regulates the cardiac healing process after MI. METHODS AND RESULTS: Although the heart in Syn4-deficient (Syn4(-/-)) mice was morphologically and functionally normal, Syn4(-/-) mice exhibited impaired heart function and increased mortality rate as a result of cardiac ruptures after MI. Cardiac ruptures in Syn4(-/-) mice were associated with reduced inflammatory reaction and impaired granulation tissue formation during the early phase of MI, as evidenced by reduced numbers of leukocytes, fibroblasts, myofibroblasts, macrophages, and capillary vessels, along with reduced extracellular matrix protein deposition in the infarct region after MI. Transforming growth factor-ß1-dependent cell signaling was preserved, whereas cell migration, fibronectin-induced cell signaling, and differentiation into myofibroblasts were defective in Syn4(-/-) cardiac fibroblasts. We also found that Syn4 was involved in basic fibroblast growth factor-dependent endothelial cell signaling, cell proliferation, and tube formation. Finally, overexpression of the shed form of Syn4 before MI creation led to an increase in mortality due to cardiac rupture via its action as a dominant-negative inhibitor of endogenous Syn4 signaling, which suggested a protective role of Syn4 signaling in MI. CONCLUSIONS: These results suggest that Syn4 plays an important role in the inflammatory response and granulation tissue formation, thereby preventing cardiac rupture and dysfunction after MI.

Impaired mental health among the bereaved spouses of cancer patients.

OBJECTIVE: Few cancer physicians routinely provide bereavement follow-up in clinical practice. The purpose of this study was to identify the prevalence of impaired mental health among the bereaved spouses over several years and explore the indicators for early detection of high-risk spouses during end-of life (EOL) care. METHODS: A cross-sectional mail survey was conducted for the bereaved spouses of patients who had died at the National Cancer Center Hospital of Japan. Bereaved spouses with potential psychiatric disorders were identified by the cut-off score of the 28-item General Health Questionnaire. Associated factors of potential psychiatric disorders were explored by logistic regression analysis. RESULTS: A total of 821 spouses experiencing bereavement from 7 months to 7 years returned the questionnaires. Overall mean prevalence of potential psychiatric disorders was 44% (360/821). Bereaved spouses 'under 55 years' (71%) or '2 years after bereavement' (59%) revealed a significantly higher prevalence (p < 0.01). Associated factors during EOL care were several characteristics such as 'spouses' history of psychiatric disorder (odds ratio (OR) = 3.19), 'patients' with stomach cancer (OR = 1.87), and 'patients' using psychiatric consultation services (OR = 1.52) as well as spouses' dissatisfaction with EOL care such as 'physicians' treatment of physical symptoms' (OR = 3.44) and 'time spent communicating with patients' (OR = 1.55). CONCLUSIONS: Nearly half the bereaved spouses showed potential psychiatric disorders even 7 years after bereavement. Patients' psychological distress, spouses' history of psychiatric disorder, and dissatisfaction with EOL care were indicators of high-risk spouses.

Interleukin-17A deficiency accelerates unstable atherosclerotic plaque formation in apolipoprotein E-deficient mice.

OBJECTIVE: Interleukin(IL)-17A, an inflammatory cytokine, has been implicated in atherosclerosis, in which inflammatory cells within atherosclerotic plaques express IL-17A. However, its role in the development of atheroscelrosis remains to be controversial. METHODS AND RESULTS: To directly examine the role of IL-17A in atherosclerosis, we generated apolipoprotein E (ApoE)/IL-17A double-deficient (ApoE(-/-)IL-17A(-/-)) mice. Mice were fed with high-fat diet (HFD) for either 8 or 16 weeks, both starting at ages of 6 to 8 weeks. We found that splenic CD4(+) T-cells produced high amounts of IL-17A in ApoE(-/-) mice after HFD feeding for 8 weeks. Atherosclerosis was significantly accelerated in HFD-fed ApoE(-/-)IL-17A(-/-) mice compared with ApoE(-/-) mice. Splenic CD4(+) T-cells of ApoE(-/-)IL-17A(-/-) mice after HFD feeding for 8 weeks, but not for 16 weeks, exhibited increased interferon gamma and decreased IL-5 production. Importantly, formation of vulnerable plaque as evidenced by reduced numbers of vascular smooth muscle cells and reduced type I collagen deposition in the plaque was detected in ApoE(-/-)IL-17A(-/-) mice after HFD feeding for 8 weeks. CONCLUSIONS: These results suggest that IL-17A regulates the early phase of atherosclerosis development after HFD feeding and plaque stability, at least partly if not all by modulating interferon gamma and IL-5 production from CD4(+) T-cells.

Osteopontin modulates the generation of memory CD8+ T cells during influenza virus infection.

The adaptive immune system generates memory cells, which induce a rapid and robust immune response following secondary Ag encounter. Memory CD8(+) T cells are a critical component of protective immunity against infections and cancers. Therefore, understanding the mechanism whereby memory CD8(+) T cells are generated and maintained is important for inducing effective memory CD8(+) T cell response. Recent studies have demonstrated that the inflammatory cytokine IL-12 favors the generation of terminal effector CD8(+) T cells rather than memory precursor effector CD8(+) T cells by regulating the expression of the transcription factor T-bet. In this study, we report that the inflammatory cytokine osteopontin (Opn) modulates memory CD8(+) T cell generation during influenza virus infection. Although Opn wild-type and Opn knockout (KO) mice had similar numbers of virus-specific effector CD8(+) T cells, virus-specific effector CD8(+) T cells generated in Opn KO mice showed low levels of T-bet expression and an increased memory precursor cell population compared with cells generated in Opn wild-type mice. This resulted in the persistently increased number of memory CD8(+) T cells in Opn KO mice. Studies with bone marrow-derived dendritic cells demonstrated that Opn deficiency in bone marrow-derived dendritic cells results in low levels of IL-12 production in response to the stimulation with influenza virus. Thus, we hypothesize that Opn modulates the generation of memory precursor effector CD8(+) T cells by regulating cytokine milieu during the acute phase of virus infection. This finding may provide new insight into the role of Opn in adaptive immune response.

α9ß1 integrin-mediated signaling serves as an intrinsic regulator of pathogenic Th17 cell generation.

The interaction between matricellular proteins such as tenascin-C (TN-C) and osteopontin (OPN) and integrins has been implicated in the pathology of rheumatoid arthritis in which Th17 cells are recognized as primary pathogenic cells. The differentiation of Th17 cells is tightly regulated by cytokines derived from APCs, receiving various signals including TLR stimuli. In this study, we used a collagen-induced arthritis model and found that increased numbers of α(9) integrin-positive conventional dendritic cells and macrophage were detectable in the draining lymph node (dLN) shortly following first immunization, and these cells produced both TN-C and OPN, ligands for α(9) integrin. α(9) integrin-mediated signaling, induced by TN-C and OPN, promoted the production of Th17-related cytokines by conventional dendritic cells and macrophages in synergy with TLR2 and 4 signaling. This led to the Th17 cell differentiation and arthritis development. Moreover, Th17 cells generated under blocking of α(9) integrin-mediated signaling showed low level of CCR6 expression and impaired migration ability toward CCL20. Thus, we have identified α(9) integrin-mediated signaling by TN-C and OPN as a novel intrinsic regulator of pathogenic Th17 cell generation that contributes to the development of rheumatoid arthritis.

CSF-1-dependent red pulp macrophages regulate CD4 T cell responses.

The balance between immune activation and suppression must be regulated to maintain immune homeostasis. Tissue macrophages (MΦs) constitute the major cellular subsets of APCs within the body; however, how and what types of resident MΦs are involved in the regulation of immune homeostasis in the peripheral lymphoid tissues are poorly understood. Splenic red pulp MΦ (RPMs) remove self-Ags, such as blood-borne particulates and aged erythrocytes, from the blood. Although many scattered T cells exist in the red pulp of the spleen, little attention has been given to how RPMs prevent harmful T cell immune responses against self-Ags. In this study, we found that murine splenic F4/80(hi)Mac-1(low) MΦs residing in the red pulp showed different expression patterns of surface markers compared with F4/80(+)Mac-1(hi) monocytes/MΦs. Studies with purified cell populations demonstrated that F4/80(hi)Mac-1(low) MΦs regulated CD4(+) T cell responses by producing soluble suppressive factors, including TGF-ß and IL-10. Moreover, F4/80(hi)Mac-1(low) MΦs induced the differentiation of naive CD4(+) T cells into functional Foxp3(+) regulatory T cells. Additionally, we found that the differentiation of F4/80(hi)Mac-1(low) MΦs was critically regulated by CSF-1, and in vitro-generated bone marrow-derived MΦs induced by CSF-1 suppressed CD4(+) T cell responses and induced the generation of Foxp3(+) regulatory T cells in vivo. These results suggested that splenic CSF-1-dependent F4/80(hi)Mac-1(low) MΦs are a subpopulation of RPMs and regulate peripheral immune homeostasis.

[Patterns of coping strategies after bereavement among spouses of cancer patients].

The purposes of this study were (1) to identify healthy and unhealthy patterns of coping strategies after bereavement among spouses of cancer patients and 2) to explore the characteristics of patients and spouses associated with these patterns of coping strategies. The participants were 821 bereaved individuals whose spouses had died at the National Cancer Center Hospital East. Three patterns of coping strategies after bereavement were found: "Distraction Focused" (healthy), "Continuing Bonds Focused" (unhealthy), and "General Coping" (almost healthy). Two strategies for improving the unhealthy coping patterns of "Continuing Bonds Focused" were (1) enhancing "Distraction" and reducing "Continuing Bonds" for achieving "Distraction Focused" (healthy) and (2) enhancing both "Distraction" and "Social Sharing/Reconstruction" for achieving "General Coping" (almost healthy). The patients' characteristics associated with the bereaved spouses' coping strategy of "Continuing Bonds Focused" were "under 65 years", "history of psychiatric consultation", "duration of last hospital admission was less than one week", and "time since cancer diagnosis to death was less than one year". These four characteristics of the deceased patients were considered to be risk factors for spouses who would utilize unhealthy coping patterns after bereavement.

Unsupervised Learning-Based Non-Invasive Fetal ECG Muti-Level Signal Quality Assessment.

OBJECTIVE: To monitor fetal health and growth, fetal heart rate is a critical indicator. The non-invasive fetal electrocardiogram is a widely employed measurement for fetal heart rate estimation, which is extracted from the electrodes placed on the surface of the maternal abdomen. The qualities of the fetal ECG recordings, however, are frequently affected by the noises from various interference sources. In general, the fetal heart rate estimates are unreliable when low-quality fetal ECG signals are used for fetal heart rate estimation, which makes accurate fetal heart rate estimation a challenging task. So, the signal quality assessment for the fetal ECG records is an essential step before fetal heart rate estimation. In other words, some low-quality fetal ECG signal segments are supposed to be detected and removed by utilizing signal quality assessment, so as to improve the accuracy of fetal heart rate estimation. A few supervised learning-based fetal ECG signal quality assessment approaches have been introduced and shown to accurately classify high- and low-quality fetal ECG signal segments, but large fetal ECG datasets with quality annotation are required in these methods. Yet, the labeled fetal ECG datasets are limited. Proposed methods: An unsupervised learning-based multi-level fetal ECG signal quality assessment approach is proposed in this paper for identifying three levels of fetal ECG signal quality. We extracted some features associated with signal quality, including entropy-based features, statistical features, and ECG signal quality indices. Additionally, an autoencoder-based feature is calculated, which is related to the reconstruction error of the spectrograms generated from fetal ECG signal segments. The high-, medium-, and low-quality fetal ECG signal segments are classified by inputting these features into a self-organizing map. MAIN RESULTS: The experimental results showed that our proposal achieved a weighted average F1-score of 90% in three-level fetal ECG signal quality classification. Moreover, with the acceptable removal of detected low-quality signal segments, the errors of fetal heart rate estimation were reduced to a certain extent.

Syndecan-4 deficiency limits neointimal formation after vascular injury by regulating vascular smooth muscle cell proliferation and vascular progenitor cell mobilization.

OBJECTIVE: Syndecan-4 (Syn4) is a heparan sulfate proteoglycan and works as a coreceptor for various growth factors. We examined whether Syn4 could be involved in the development of neointimal formation in vivo. METHODS AND RESULTS: Wild-type (WT) and Syn4-deficient (Syn4-/-) mice were subjected to wire-induced femoral artery injury. Syn4 mRNA was upregulated after vascular injury in WT mice. Neointimal formation was attenuated in Syn4-/- mice, concomitantly with the reduction of Ki67-positive vascular smooth muscle cells (VSMCs). Basic-fibroblast growth factor- or platelet-derived growth factor-BB-induced proliferation, extracellular signal-regulated kinase activation, and expression of cyclin D1 and Bcl-2 were impaired in VSMCs from Syn4-/- mice. To examine the role of Syn4 in bone marrow (BM)-derived vascular progenitor cells (VPCs) and vascular walls, we generated chimeric mice by replacing the BM cells of WT and Syn4-/- mice with those of WT or Syn4-/- mice. Syn4 expressed by both vascular walls and VPCs contributed to the neointimal formation after vascular injury. Although the numbers of VPCs were compatible between WT and Syn4-/- mice, mobilization of VPCs from BM after vascular injury was defective in Syn4-/- mice. CONCLUSIONS: Syn4 deficiency limits neointimal formation after vascular injury by regulating VSMC proliferation and VPC mobilization. Therefore, Syn4 may be a novel therapeutic target for preventing arterial restenosis after angioplasty.

Psychological states and coping strategies after bereavement among spouses of cancer patients: a quantitative study in Japan.

PURPOSE: The purposes of this study were (1) to characterize psychological states and coping strategies after bereavement among spouses of cancer patients in Japan and (2) to explore the factors associated with psychological states in oncology settings. METHODS: In March 2009, questionnaires to assess spouses' psychological states, coping strategies, and mental health states (GHQ-28) were sent after patients died at the National Cancer Center of Japan. To address the first purpose, exploratory factor analysis, gender comparison, and calculation of correlation with age, time since bereavement, and mental health states were conducted. Hierarchical regression analysis was conducted to address the second purpose. RESULTS: A total of 821 spouses experiencing bereavement for 7 months to 7 years participated in the study. Psychological states revealed three factor structures: "Anxiety/Depression/Anger", "Yearning", and "Acceptance/Future-Oriented Feelings". Coping strategies also revealed three factor structures: "Distraction", "Continuing Bonds", and "Social Sharing/Reconstruction". Coping strategies represented 18 % to 34 % of each factor associated with psychological states, whereas the characteristics of bereaved spouses and deceased patients represented 6 % and less than 6 %, respectively. More "Distraction and Social Sharing/Reconstruction" and less "Continuing Bonds" were significantly associated coping strategies for achieving "Acceptance/Future-Oriented Feelings" (p < 0.01). CONCLUSIONS: Both psychological states and coping strategies after bereavement revealed three factor structures. Coping strategies was the primary, bereaved spouses' characteristics was the secondary, and deceased patients' characteristics was the tertiary factor associated with psychological states. Enhancing "Distraction" and "Social Sharing/Reconstruction", and reducing "Continuing Bonds" might be promising strategies for achieving positive psychological states of the bereaved.