Plasma Factor XIII Activity in Patients with Disseminated Intravascular Coagulation

The objective of this study was to investigate the correlation between factor XIII (FXIII) activity and disseminated intravascular coagulation (DIC) parameters and also to evaluate the clinical usefulness of DIC diagnosis. Citrated plasma from eighty patients with potential DIC was analyzed for FXIII activity. The primary patient conditions (48 male and 32 female, mean age, 51 years) were malignancy (n = 29), infection (n = 25), inflammation (n = 6), heart disease (n = 3), thrombosis (n = 2), injury (n = 2), and other miscellaneous conditions (n = 13). FXIII testing was performed using the CoaLinkTM FXIII Incorporation Assay Kit (PeopleBio Inc.). Among 80 patients who were suspected to have DIC based on clinical analysis, 46 (57.5%) fulfilled the overt DIC criteria (DIC score > = 5) according to the International Society of Thrombosis and Haemostasis. FXIII levels in the plasma were significantly decreased in overt DIC compared to non-overt DIC patients (mean 75.1% and 199.7% respectively, p < 0.0001). Interestingly, we found a significant inverse correlation between DIC scores and FXIII activity. In addition, FXIII activity significantly correlated with other hemostatic markers that included platelet count, prothrombin time, activated partial thromboplastin time, fibrinogen, and D-dimer. FXIII levels were significantly lower in patients with liver or renal dysfunction. In conclusion, FXIII cross-linking activity measurements may have differential diagnostic value as well as predictive value in patients who are suspected to have DIC

Plasma Level of IL-6 and Its Relationship to Procoagulant and Fibrinolytic Markers in Acute Ischemic Stroke

Procoagulant or impaired fibrinolytic states as well as inflammatory reactions mediated by cytokines are likely involved in the pathogenesis of acute ischemic stroke. We examined the potential relationship between interleukin 6 (IL-6) and hemostatic markers. The procoagulant and fibrinolytic states were assessed in 46 patients with acute stroke by measuring plasma levels of plasminogen activator inhibitor-1 (PAI-1), thrombin-antithrombin complex (TAT), and plasminogen-antiplasmin complex (PAP). Circulating IL-6 levels were measured using ELISA (Quantikine, R&D systems, MN, USA). Circulating IL-6 (mean, 26.5 pg/mL) and PAI-1 (mean, 19.9 ng/mL) levels were higher in patients with acute stroke than in healthy subjects (mean, 3.0 pg/mL, 10.4 ng/mL, respectively). TAT levels were statistically different according to the etiologic subtypes of stroke (atherogenic, 2.5 ng/mL; lacunar 3.2 ng/mL; cardiogenic 9.9 ng/mL, p = 0.021). Neither procoagulant levels nor fibrinolytic markers significantly correlated with circulating IL-6 levels. Our findings suggest that elevated proinflammatory cytokines during the initial hours of ischemic stroke may be an independent pathogenic factor or a consequence of the thrombotic event with no relationship to the procoagulant or fibrinolytic states

Discutindo a educação ambiental no cotidiano escolar: desenvolvimento de projetos na escola formação inicial e continuada de professores

A presente pesquisa buscou discutir como a Educação Ambiental (EA) vem sendo trabalhada, no Ensino Fundamental e como os docentes desta escola compreendem e vem inserindo a EA no cotidiano escolar., em uma escola estadual do município de Tangará da Serra/MT, Brasil. Para tanto, realizou-se entrevistas com os professores que fazem parte de um projeto interdisciplinar de EA na escola pesquisada. Verificou-se que o projeto da escola não vem conseguindo alcançar os objetivos propostos por: desconhecimento do mesmo, pelos professores; formação deficiente dos professores, não entendimento da EA como processo de ensino-aprendizagem, falta de recursos didáticos, planejamento inadequado das atividades. A partir dessa constatação, procurou-se debater a impossibilidade de tratar do tema fora do trabalho interdisciplinar, bem como, e principalmente, a importância de um estudo mais aprofundado de EA, vinculando teoria e prática, tanto na formação docente, como em projetos escolares, a fim de fugir do tradicional vínculo “EA e ecologia, lixo e horta”.Facultad de Humanidades y Ciencias de la Educació

Comparison between gastrostomy feeding and self-expandable metal stent insertion for patients with esophageal cancer and dysphagia.

Self-expandable metal stent (SEMS) insertion and percutaneous gastrostomy (PG) feeding are commonly used for patients with esophageal cancer and dysphagia. This study aimed to compare outcomes between SEMS insertion and PG feeding for them.We retrospectively analyzed 308 patients with esophageal cancer who underwent fully covered SEMS insertion (stent group) or PG (gastrostomy group) for dysphagia due to tumor. Patients with other causes of dysphagia, such as radiation-induced or postoperative stricture, were excluded from the study. Clinical outcomes were compared between the two groups, including overall survival and need for additional intervention and postprocedural nutritional status.At baseline, the stent group (n = 169) had more stage IV patients, less cervical cancers, and received radiotherapy and esophagectomy less often than the gastrostomy group (n = 64). The Kaplan-Meier curves showed higher overall survival in the gastrostomy group than in the stent group. Multivariate analysis revealed that PG was associated with better survival compared with SEMS insertion (hazard ratio 0.541, 95% confidence interval 0.346-0.848, p = 0.007). In addition, the gastrostomy group needed additional intervention less often (3.1% vs. 21.9%, p < 0.001) and experienced less decrease in serum albumin levels (-0.15 ± 0.56 g/dL vs. -0.39 ± 0.58 g/dL, p = 0.011) than the stent group after procedure.Our data suggested that, compared with SEMS insertion, PG is associated with better overall survival in patients with esophageal cancer and dysphagia. Stabilized nutritional status by PG may play a role in improving patient survival

Machine Learning Model to Stratify the Risk of Lymph Node Metastasis for Early Gastric Cancer: A Single-Center Cohort Study

Stratification of the risk of lymph node metastasis (LNM) in patients with non-curative resection after endoscopic resection (ER) for early gastric cancer (EGC) is crucial in determining additional treatment strategies and preventing unnecessary surgery. Hence, we developed a machine learning (ML) model and validated its performance for the stratification of LNM risk in patients with EGC. We enrolled patients who underwent primary surgery or additional surgery after ER for EGC between May 2005 and March 2021. Additionally, patients who underwent ER alone for EGC between May 2005 and March 2016 and were followed up for at least 5 years were included. The ML model was built based on a development set (70%) using logistic regression, random forest (RF), and support vector machine (SVM) analyses and assessed in a validation set (30%). In the validation set, LNM was found in 337 of 4428 patients (7.6%). Among the total patients, the area under the receiver operating characteristic (AUROC) for predicting LNM risk was 0.86 in the logistic regression, 0.85 in RF, and 0.86 in SVM analyses; in patients with initial ER, AUROC for predicting LNM risk was 0.90 in the logistic regression, 0.88 in RF, and 0.89 in SVM analyses. The ML model could stratify the LNM risk into very low (<1%), low (<3%), intermediate (<7%), and high (≥7%) risk categories, which was comparable with actual LNM rates. We demonstrate that the ML model can be used to identify LNM risk. However, this tool requires further validation in EGC patients with non-curative resection after ER for actual application

Fetal mesenchymal stem cells derived from human umbilical cord sustain primitive characteristics during extensive expansion

Stem cells of fetal origin lie between embryonic and adult stem cells in terms of potentiality. Because of the ethical controversy surrounding embryonic stem cells and the relatively inferior quality of adult stem cells, the use of fetal stem cells would be an attractive option in future therapeutic applications. Here, we have investigated primitive characteristics of human umbilical-cord-derived fetal mesenchymal stem cells (UC fMSCs) during extensive expansion. We have successfully isolated and cultured UC fMSCs from all UC samples, but with two early fungal contaminations. UC fMSCs proliferated without significant evidence of morphological changes, and the average cumulative population-doubling level was over 25 for about 3 months. UC fMSCs showed the positive expression of several CD markers, known to be related to MSCs, including CD73 (SH-3, 4), CD90 (Thy-1), CD105 (SH-2), CD117 (c-kit), and CD166 (ALCAM). They demonstrated primitive properties throughout the expansion period: multilineage differentiation potentials examined by functional assays, a variety of pluripotent stem cell markers including Nanog, Oct-4, Sox-2, Rex-1, SSEA-3, SSEA-4, Tra-1-60, and Tra-1-81, minimal evidence of senescence as shown by beta-galactosidase staining, and the consistent expression of telomerase activity. These results suggest that UC fMSCs have more primitive properties than adult MSCs, which might make them a useful source of MSCs for clinical applications

Evolution of the Tumor Microenvironment toward Immune-Suppressive Seclusion during Brain Metastasis of Breast Cancer: Implications for Targeted Therapy.

Breast cancer (BC) is the second most common solid malignant tumor that metastasizes to the brain. Despite emerging therapies such as immunotherapy, whether the tumor microenvironment (TME) in breast cancer brain metastasis (BCBM) has potential as a target of new treatments is unclear. Expression profiling of 770 genes in 12 pairs of primary BC and matched brain metastasis (BM) samples was performed using the NanoString nCounter PanCancer IO360TM Panel. Immune cell profiles were validated by immunohistochemistry (IHC) in samples from 50 patients with BCBM. Pathway analysis revealed that immune-related pathways were downregulated. Immune cell profiling showed that CD8+ T cells and M1 macrophages were significantly decreased, and M2 macrophages were significantly increased, in BM compared to primary BC samples (p = 0.001, p = 0.021 and p = 0.007, respectively). CCL19 and CCL21, the top differentially expressed genes, were decreased significantly in BM compared to primary BC (p &lt; 0.001, both). IHC showed that the CD8+ count was significantly lower (p = 0.027), and the CD163+ and CD206+ counts were higher, in BM than primary BC (p &lt; 0.001, both). A low CD8+ T cell count, low CD86+ M1 macrophage count, and high M2/M1 macrophage ratio were related to unfavorable clinical outcomes. BC exhibits an immunosuppressive characteristic after metastasis to the brain. These findings will facilitate establishment of a treatment strategy for BCBM based on the TME of metastatic cancer

Contact-ID, a tool for profiling organelle contact sites, reveals regulatory proteins of mitochondrial associated membrane formation

The mitochondria-associated membrane (MAM) has emerged as a cellular signaling hub regulating various cellular processes. However, its molecular components remain unclear owing to lack of reliable methods to purify the intact MAM proteome in a physiological context. Here, we introduce Contact-ID, a split-pair system of BioID with strong activity, for identification of the MAM proteome in live cells. Contact-ID specifically labeled proteins proximal to the contact sites of the endoplasmic reticulum (ER) and mitochondria, and thereby identified 115 MAM-specific proteins. The identified MAM proteins were largely annotated with the outer mitochondrial membrane (OMM) and ER membrane proteins with MAM-related functions: e.g., FKBP8, an OMM protein, facilitated MAM formation and local calcium transport at the MAM. Furthermore, the definitive identification of biotinylation sites revealed membrane topologies of 85 integral membrane proteins. Contact-ID revealed regulatory proteins for MAM formation and could be reliably utilized to profile the proteome at any organelle???membrane contact sites in live cells

Evolution of the Tumor Microenvironment toward Immune-Suppressive Seclusion during Brain Metastasis of Breast Cancer: Implications for Targeted Therapy

Breast cancer (BC) is the second most common solid malignant tumor that metastasizes to the brain. Despite emerging therapies such as immunotherapy, whether the tumor microenvironment (TME) in breast cancer brain metastasis (BCBM) has potential as a target of new treatments is unclear. Expression profiling of 770 genes in 12 pairs of primary BC and matched brain metastasis (BM) samples was performed using the NanoString nCounter PanCancer IO360TM Panel. Immune cell profiles were validated by immunohistochemistry (IHC) in samples from 50 patients with BCBM. Pathway analysis revealed that immune-related pathways were downregulated. Immune cell profiling showed that CD8+ T cells and M1 macrophages were significantly decreased, and M2 macrophages were significantly increased, in BM compared to primary BC samples (p = 0.001, p = 0.021 and p = 0.007, respectively). CCL19 and CCL21, the top differentially expressed genes, were decreased significantly in BM compared to primary BC (p &lt; 0.001, both). IHC showed that the CD8+ count was significantly lower (p = 0.027), and the CD163+ and CD206+ counts were higher, in BM than primary BC (p &lt; 0.001, both). A low CD8+ T cell count, low CD86+ M1 macrophage count, and high M2/M1 macrophage ratio were related to unfavorable clinical outcomes. BC exhibits an immunosuppressive characteristic after metastasis to the brain. These findings will facilitate establishment of a treatment strategy for BCBM based on the TME of metastatic cancer