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.

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.

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.

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.

Non-invasive Fetal ECG Signal Quality Assessment based on Unsupervised Learning Approach.

The non-invasive fetal electrocardiogram (FECG) derived from abdominal surface electrodes has been widely used for fetal heart rate (FHR) monitoring to assess fetal well-being. However, the accuracy of FECG-based FHR estimation heavily depends on the quality of FECG signal itself, which can generally be affected by several interference sources such as maternal heart activities and fetal movements. Hence, FECG signal quality assessment (SQA) is an essential task to improve the accuracy of FHR estimation by removing or interpolating low-quality FECG signals. In recent research, various SQA methods based on supervised learning have been proposed. Although these methods could perform accurate SQA, they require large labeled datasets. Nevertheless, the labeled datasets for the FECG SQA are very limited. In this paper, to address this limitation, we propose an unsupervised learning-based SQA method for identifying high and low-quality FECG signal segments. Specifically, a fully convolutional network (FCN)-based autoencoder (AE) is trained for reconstructing a spectrogram derived from FECG. An AE-based feature related to reconstruction error is then calculated to identify high and low-quality FECG segments. In addition, entropy-based features, statistical features, and ECG signal quality indices (SQIs) are also extracted. The high and low-quality segments are identified by feeding the extracted features into self-organizing map (SOM). The experimental results showed that our proposal achieved an accuracy of 98% in high and low-quality signal classification.

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.

Post-Traumatic Stress Disorder among Children Involved in Traffic Accidents and Their Parents in Japan.

BACKGROUND: Children who survive traffic accidents, and their parents, may develop post-traumatic stress disorder (PTSD) or related symptoms (depression or anxiety), which can hinder the children's development and the parents' ability to provide effective care. In Japan, the PTSD incidence rate after traffic accidents and its related factors remain unclarified. METHODS: The participants were 79 children and 104 parents. The children were aged 3-18 years when injured. From August through December 2015, participants completed a self-reported questionnaire survey that comprised the 15-item Post-traumatic Stress Symptoms for Children and the Japanese version of the Impact of Event Scale-Revised. The children's Injury Severity Score (ISS) was also obtained from their medical records. Correlation analysis, analysis of variance, and multiple regression analysis were conducted. RESULTS: Among the children and parents, 10.1% and 22.1%, respectively, were deemed to be at high risk of PTSD. Their stress scores were significantly positively correlated with each other and negatively correlated with the children's age at the time of the accident. Parents who witnessed their children's accidents and those whose children were hospitalized were more stressed. Neither the children's nor the parents' risk for PTSD was associated with ISS or the amount of time since the accident. CONCLUSIONS: A system that simultaneously works with children and parents to support both parties' psychological recovery is required. To ensure psychological care post-injury, it is necessary to evaluate PTSD risk, regardless of injury severity. Implementing preventive and early interventions can prove more valuable than awaiting natural recovery.

The Impact of Cancer on Romantic Relationships and Marriage Postdiagnosis Among Young Adult Cancer Survivors in Japan: A Qualitative Study.

Purpose: This study explored the impact of cancer on romantic relationships and marriage postdiagnosis among adolescents and young adults (AYAs) who had been diagnosed with cancer in Japan. Methods: Semistructured interviews were conducted with 24 AYA cancer survivors, regardless of cancer type, who were unmarried and aged 15-39 at the time of cancer diagnosis. For theme and category generation, the authors coded the interview transcripts independently through inductive thematic analysis. Results: The analysis yielded 11 themes. The most common impact on romantic partnership was "fertility and parenthood concerns" (45.8%), followed by "disclosure of cancer history" (37.5%), and finally by "recurrence, metastasis, and poor health" (25.0%). Conclusions: Although the impacts of cancer that were identified in this study were mostly consistent with earlier findings, certain impacts seem to stem from traditional family perceptions in East Asia. Because men are traditionally seen as the family successors, unlike women, they are primarily concerned about fertility and parenthood. This causes a parental influence on romantic and marital choices. The fact that there exists a parental influence in partner selection from the parents of both men and women indicates that cultural factors in East Asia/Japan influence romantic and/or marriage postdiagnosis.

Case Report: Nutritional Examination of Weight Loss Treatment Using Kampo.

Loss of appetite is a common symptom in patients with dementia, and if weight loss or difficulty eating occurs without subjective symptoms, the patient can easily become malnourished. There is also a close relationship between dementia and physical frailty, such as weight loss and muscle weakness, and thus early intervention to address frailty in patients with dementia is important. In this study, 3 patients with dementia who complained of loss of appetite and weight loss showed increases in body weight and muscle mass after taking Ninjin'yoeito. Ninjin'yoeito was found to be a potentially effective treatment option for physical frailty in patients with dementia.

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.

Clinical efficacy of bowel perfusion assessment during laparoscopic colorectal resection using laser speckle contrast imaging: A matched case-control study.

INTRODUCTION: Disadvantages of bowel perfusion assessment with indocyanine green fluorescence angiography include the need for a fluorophore and the subjective nature of the assessment. This study was performed to evaluate the clinical efficacy of bowel perfusion assessment using laser speckle contrast imaging (LSCI) during laparoscopic colorectal surgery. METHODS: The study population comprised the first 27 consecutive patients who underwent laparoscopic left-sided colorectal resection with intraoperative perfusion assessment using LSCI. The operative outcomes of these patients were compared with those of a matched group of patients without perfusion assessment. We analyzed the flux data expressed in laser speckle perfusion units. RESULTS: After propensity score matching, we found no significant between-group differences in the patients' characteristics with the exception of the cancer stage. No patients undergoing LSCI perfusion assessment developed anastomotic leakage, but five (18.5%) patients in the control group did, at a significantly higher rate in male patients (P = .042). There were no significant differences in other operative outcomes. The laser speckle perfusion unit values after ligating marginal vessels were significantly lower than before ligation (P < .01). CONCLUSIONS: With respect to anastomotic leakage, LSCI may improve patient outcomes after colorectal surgery. This technique appears to be a superior tool with the advantages of measurement repeatability and quantitativity and no need for a fluorophore.

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.

Osteopontin is indispensable for activation of astrocytes in injured mouse brain and primary culture.

OBJECTIVES: Osteopontin (OPN) is an inflammatory cytokine inducer involved in cell proliferation and migration in inflammatory diseases or tumors. To investigate the function of OPN in astrocyte activation during brain injury, we compared OPN-deficient (OPN/KO) with wild-type (WT) mouse brains after stab wound injury and primary culture of astrocytes. METHODS: Primary cultures of astrocytes were prepared from either WT or OPN/KO postnatal mouse brains. Activation efficiency of astrocytes in primary culture was accessed using Western blotting by examining the protein levels of glial fibrillary acidic protein (GFAP) and tenascin-C (TN-C), which are markers for reactive astrocytes, following lipopolysaccharide (LPS) stimulation. Furthermore, the stab wound injury on the cerebral cortex as a brain traumatic injury model was used, and activation of astrocytes and microglial cells was investigated using immunofluorescent analysis on fixed brain sections. RESULTS: Primary cultures of astrocytes prepared from WT or OPN/KO postnatal mouse brains showed that only 25% of normal shaped astrocytes in a flask were produced in OPN/KO mice. The expression levels of both GFAP and TN-C were downregulated in the primary culture of astrocytes from OPN/KO mice compared with that from WT mice. By the immunofluorescent analysis on the injured brain sections, glial activation was attenuated in OPN/KO mice compared with WT mice. DISCUSSION: Our data suggest that OPN is essential for proper astrocytic generation in vitro culture prepared from mouse cerebral cortex. OPN is indispensable for astrocyte activation in the mouse brain injury model and in LPS stimulated primary culture. ABBREVIATIONS: AQP4: aquaporin 4; BBB: blood brain barrier; BrdU: bromo-deoxy uridine; CNS: central nervous system; GFAP: glial fibllirary acidic protein; IgG: immunoglobulin G; LPS: lipopolysaccharide; OPN: osteopontin; OPN/KO: osteopontin-deficient; TN-C: tenascin-C.

Standardization of Brief Inventory of Social Support Exchange Network (BISSEN) in Japan.

This study describes the Brief Inventory of Social Support Exchange Network (BISSEN) as a standardized brief inventory measuring various aspects of social support. We confirmed the reliability and validity for function and direction of support and standardized the BISSEN. For Sample 1, a stratified random sampling method was used to select 5200 residents in Japan. We conducted mail surveys and responses were retrieved from 2274 participants (collection rate 43.7%). Participants completed a questionnaire packet that included BISSEN, suicidal ideation, depression, support seeking, and Multidimensional Scale of Perceived Social Support (MSPSS). Sample 2 surveys for test-retest reliability were conducted on 23 residents at approximately two-week intervals. Participants were asked about gender, age, and BISSEN. First, we assessed the internal consistency, test-retest reliability, construct, convergent, and concurrent validity. McDonald's omega (.73-.92) and test-retest correlations (.78-.85) demonstrated adequate internal consistency and test-retest reliability. Depression, support seeking, and MSPSS were significantly correlated with all scores of BISSEN. The non-suicidal ideation group had significantly more support compared to the suicidal ideation group. Therefore, function and direction of support in BISSEN had sufficient reliability and validity. Next, we standardized BISSEN using Z-scores and percentile rank with respect to each 12 norm groups by age and gender.

[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.

Reporting of Cardiovascular Medical Device Adverse Events to Pharmaceuticals and Medical Devices Agency, Japan.

BACKGROUND: Marketing authorization holders (MAHs) are obligated to report adverse events (AEs) within 15 days (some cases 30 days) to the Pharmaceuticals and Medical Devices Agency (PMDA) of Japan. METHODS: To analyze the timeliness of AE reporting to the PMDA, 6610 reports for five categories of cardiovascular devices were retrieved. Two durations were calculated: (1) time from the date the AE occurred to that when the MAH captured it (DOC: days); and (2) time from the date of MAH capture to that of MAH report (DCR: days). Number of DOC > 15 days (DOC15) and delayed reports (DCR > 15 or 30 days) were also calculated. RESULTS: AEs included 9.2% deaths and 7.5% non-recoveries. DOC15 and delayed reports were 51.0% and 10.9%, respectively. By multivariate analysis, DOC15 was associated with foreign AE, device category, MAH, patient outcome, event category, and AE that had to be reported within 15 or 30 days (AE15/30). Delayed report was associated with device category, MAH, patient outcome, event category, and AE15/30. COMMENTS: Although Japanese MAHs complied with the obligation to report AEs, they often failed to share AEs with healthcare providers. Registry may be a potential solution, although the cooperation of healthcare providers to input data is essential.

[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.

Tumor-α9ß1 integrin-mediated signaling induces breast cancer growth and lymphatic metastasis via the recruitment of cancer-associated fibroblasts.

UNLABELLED: Tumor-derived matricellular proteins such as osteopontin (OPN) and tenascin-C (TN-C) have been implicated in tumor growth and metastasis. However, the molecular basis of how these proteins contribute to tumor progression remains to be elucidated. Importantly, these matricellular proteins are known to interact with α9ß1 integrin. Therefore, we hypothesized that tumor-derived α9ß1 integrin may contribute to tumor progression. To clarify the roles of α9ß1 integrin in tumor growth and lymphatic metastasis, we used an inhibitory anti-human α9ß1 integrin antibody (anti-hα9ß1 antibody) and a α9ß1 integrin-positive human breast cancer cell line, MDA-MB-231 luc-D3H2LN (D3H2LN), in vitro functional assays, and an in vivo orthotopic xenotransplantation model. In this study, we demonstrated that tumor, but not host α9ß1 integrin, contributes to tumor growth, lymphatic metastasis, recruitment of cancer-associated fibroblasts (CAFs), and host-derived OPN production. We also found that CAFs contributed to tumor growth, lymphatic metastasis, and host-derived OPN levels. Consistent with those findings, tumor volume was well-correlated with numbers of CAFs and levels of host-derived OPN. Furthermore, it was shown that the inoculation of D3H2LN cells into mammary fat pads with mouse embryonic fibroblasts (MEFs), obtained from wild type, but not OPN knock-out mice, resulted in enhancement of tumor growth, thus indicating that CAF-derived OPN enhanced tumor growth. These results suggested that tumor α9ß1-mediated signaling plays a pivotal role in generating unique primary tumor tissue microenvironments, which favor lymphatic metastasis and tumor growth. KEY MESSAGES: Tumor α9ß1 integrin promotes lymphatic metastasis through enhancing invasion. Tumor α9ß1 integrin promotes tumor growth through CAFs. Tumor α9ß1 integrin enhances the recruitment of CAFs into the primary tumor. Tumor cells induce the production of OPN by CAFs in the primary tumor. CAF-derived OPN promotes tumor growth.

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.

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.