Risk of death in patients with post-traumatic cerebrospinal fluid leakage—Analysis of 1773 cases

AbstractBackgroundPost-traumatic cerebrospinal fluid (CSF) leakage is one of the most troublesome conditions associated with head trauma. CSF fistulae, meningitis/central nervous infection, or even death may accompany it. Few studies have discussed post-traumatic CSF leakage as a risk factor in mortality following head trauma. We conducted this cohort study to examine the issue.MethodsWe reviewed the records in the Taiwan Traumatic Brain Injury (TBI) Registry System between 1993 and 2008. The study group included patients with acute TBI and post-traumatic CSF leakage, and the control group included cases with TBI but without CSF leakage, selected randomly at a 5:1 ratio with respect to the study group. The demographic data, Glasgow Coma Scale, brain computerized tomography, association of skull fractures and intracranial lesions, and 1-year mortality rates between these two cohorts were reviewed meticulously and analyzed statistically.ResultsOf 174,236 cases, 1773 with post-traumatic CSF leakage were included in the study group, and 8865 cases in the control group. Of the total 10,638 sampled cases, 406 (3.8%) died during the 1-year follow-up period, 159 (9.0%) cases in the CSF leakages group, and 247 (2.8%) in the control group. The patients with CSF leakage had a significantly higher mortality rate within 1 year (adjusted hazard ratio = 1.44, p < 0.001) than those without. We divided the CSF leakage group into three subgroups: otorrhea (n = 568), rhinorrhea (n = 302), and tension pneumocephalus (n = 903). The mortality rates were 8.5% (48/568) in the otorrhea subgroup, 10.9% (33/302) in the rhinorrhea subgroup, and 8.6% (78/903) in the tension pneumocephalus subgroup. The cases with CSF rhinorrhea had a significantly higher mortality rate than the other two subgroups (p < 0.05). All three subgroups had significantly higher mortality rates than the control group during the 1-year follow-up period (adjusted hazard ratios = 2.29, 1.35, and 1.32 in the rhinorrhea, tension pneumocephalus, and otorrhea subgroups, respectively).ConclusionPost-traumatic CSF leakages had higher mortality rates than those without CSF leakages in TBI cases, and the cases with CSF rhinorrhea had worse outcomes compared with CSF leakages with pneumocephalus or otorrhea

Investigation of Hepatoprotective Activity of Induced Pluripotent Stem Cells in the Mouse Model of Liver Injury

To date liver transplantation is the only effective treatment for end-stage liver diseases. Considering the potential of pluripotency and differentiation into tridermal lineages, induced pluripotent stem cells (iPSCs) may serve as an alternative of cell-based therapy. Herein, we investigated the effect of iPSC transplantation on thioacetamide- (TAA-) induced acute/fulminant hepatic failure (AHF) in mice. Firstly, we demonstrated that iPSCs had the capacity to differentiate into hepatocyte-like cells (iPSC-Heps) that expressed various hepatic markers, including albumin, α-fetoprotein, and hepatocyte nuclear factor-3β, and exhibited biological functions. Intravenous transplantation of iPSCs effectively reduced the hepatic necrotic area, improved liver functions and motor activity, and rescued TAA-treated mice from lethal AHF. 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate cell labeling revealed that iPSCs potentially mobilized to the damaged liver area. Taken together, iPSCs can effectively rescue experimental AHF and represent a potentially favorable cell source of cell-based therapy

Purification and Characterization of Hemagglutinating Proteins from Poker-Chip Venus (Meretrix lusoria) and Corbicula Clam (Corbicula fluminea)

Hemagglutinating proteins (HAPs) were purified from Poker-chip Venus (Meretrix lusoria) and Corbicula clam (Corbicula fluminea) using gel-filtration chromatography on a Sephacryl S-300 column. The molecular weights of the HAPs obtained from Poker-chip Venus and Corbicula clam were 358 kDa and 380 kDa, respectively. Purified HAP from Poker-chip Venus yielded two subunits with molecular weights of 26 kDa and 29 kDa. However, only one HAP subunit was purified from Corbicula clam, and its molecular weight was 32 kDa. The two Poker-chip Venus HAPs possessed hemagglutinating ability (HAA) for erythrocytes of some vertebrate animal species, especially tilapia. Moreover, HAA of the HAP purified from Poker-chip Venus was higher than that of the HAP of Corbicula clam. Furthermore, Poker-chip Venus HAPs possessed better HAA at a pH higher than 7.0. When the temperature was at 4°C–10°C or the salinity was less than 0.5‰, the two Poker-chip Venus HAPs possessed better HAA compared with that of Corbicula clam

Multiple Lineages of Human Breast Cancer Stem/Progenitor Cells Identified by Profiling with Stem Cell Markers

Heterogeneity of cancer stem/progenitor cells that give rise to different forms of cancer has been well demonstrated for leukemia. However, this fundamental concept has yet to be established for solid tumors including breast cancer. In this communication, we analyzed solid tumor cancer stem cell markers in human breast cancer cell lines and primary specimens using flow cytometry. The stem/progenitor cell properties of different marker expressing-cell populations were further assessed by in vitro soft agar colony formation assay and the ability to form tumors in NOD/SCID mice. We found that the expression of stem cell markers varied greatly among breast cancer cell lines. In MDA-MB-231 cells, PROCR and ESA, instead of the widely used breast cancer stem cell markers CD44+/CD24-/low and ALDH, could be used to highly enrich cancer stem/progenitor cell populations which exhibited the ability to self renew and divide asymmetrically. Furthermore, the PROCR+/ESA+ cells expressed epithelial-mesenchymal transition markers. PROCR could also be used to enrich cells with colony forming ability from MB-361 cells. Moreover, consistent with the marker profiling using cell lines, the expression of stem cell markers differed greatly among primary tumors. There was an association between metastasis status and a high prevalence of certain markers including CD44+/CD24−/low, ESA+, CD133+, CXCR4+ and PROCR+ in primary tumor cells. Taken together, these results suggest that similar to leukemia, several stem/progenitor cell-like subpopulations can exist in breast cancer

HuR cytoplasmic expression is associated with increased cyclin A expression and poor outcome with upper urinary tract urothelial carcinoma

BACKGROUND: HuR is an RNA-binding protein that post-transcriptionally modulates the expressions of various target genes implicated in carcinogenesis, such as CCNA2 encoding cyclin A. No prior study attempted to evaluate the significance of HuR expression in a large cohort with upper urinary tract urothelial carcinomas (UTUCs). METHODS: In total, 340 cases of primary localized UTUC without previous or concordant bladder carcinoma were selected. All of these patients received ureterectomy or radical nephroureterectomy with curative intents. Pathological slides were reviewed, and clinical findings were collected. Immunostaining for HuR and cyclin A was performed and evaluated by using H-score. The results of cytoplasmic HuR and nuclear cyclin A expressions were correlated with disease-specific survival (DSS), metastasis-free survival (MeFS), urinary bladder recurrence-free survival (UBRFS), and various clinicopathological factors. RESULTS: HuR cytoplasmic expression was significantly related to the pT status, lymph node metastasis, a higher histological grade, the pattern of invasion, vascular and perineurial invasion, and cyclin A expression (p = 0.005). Importantly, HuR cytoplasmic expression was strongly associated with a worse DSS (p < 0.0001), MeFS (p < 0.0001), and UBRFS (p = 0.0370) in the univariate analysis, and the first two results remained independently predictive of adverse outcomes (p = 0.038, relative risk [RR] = 1.996 for DSS; p = 0.027, RR = 1.880 for MeFS). Cyclin A nuclear expression was associated with a poor DSS (p = 0.0035) and MeFS (p = 0.0015) in the univariate analysis but was not prognosticatory in the multivariate analyses. High-risk patients (pT3 or pT4 with/without nodal metastasis) with high HuR cytoplasmic expression had better DSS if adjuvant chemotherapy was performed (p = 0.015). CONCLUSIONS: HuR cytoplasmic expression was correlated with adverse phenotypes and cyclin A overexpression and also independently predictive of worse DSS and MeFS, suggesting its roles in tumorigenesis or carcinogenesis and potentiality as a prognostic marker of UTUC. High HuR cytoplasmic expression might identify patients more likely to be beneficial for adjuvant chemotherapy

The impact of the synergistic effect of SO2 and PM2.5/PM10 on obstructive lung disease in subtropical Taiwan

BackgroundChronic Obstructive lung diseases (COPD) are complex conditions influenced by various environmental, lifestyle, and genetic factors. Ambient air pollution has been identified as a potential risk factor, causing 4.2 million deaths worldwide in 2016, accounting for 25% of all COPD-related deaths and 26% of all respiratory infection-related deaths. This study aims to evaluate the associations among chronic lung diseases, air pollution, and meteorological factors.MethodsThis cross-sectional study obtained data from the Taiwan Biobank and Taiwan Air Quality Monitoring Database. We defined obstructive lung disease as patients with FEV1/FVC &lt; 70%. Descriptive analysis between spirometry groups was performed using one-way ANOVA and the chi-square or Fisher’s exact test. A generalized additive model (GAM) was used to evaluate the relationship between SO2 and PM2.5/PM10 through equations and splines fitting.ResultsA total of 2,635 participants were enrolled. Regarding environmental factors, higher temperature, higher relative humidity, and lower rainfall were risk factors for obstructive lung disease. SO2 was positively correlated with PM10 and PM2.5, with correlation coefficients of 0.53 (p &lt; 0.0001) and 0.52 (p &lt; 0.0001), respectively. Additionally, SO2 modified the relative risk of obstructive impairment for both PM10 [β coefficient (β) = 0.01, p = 0.0052] and PM2.5 (β = 0.01, p = 0.0155). Further analysis per standard deviation (per SD) increase revealed that SO2 also modified the relationship for both PM10 (β = 0.11, p = 0.0052) and PM2.5 (β = 0.09, p = 0.0155). Our GAM analysis showed a quadratic pattern for SO2 (per SD) and PM10 (per SD) in model 1, and a quadratic pattern for SO2 (per SD) in model 2. Moreover, our findings confirmed synergistic effects among temperature, SO2 and PM2.5/PM10, as demonstrated by the significant associations of bivariate (SO2 vs. PM10, SO2 vs. PM2.5) thin-plate smoothing splines in models 1 and 2 with obstructive impairment (p &lt; 0.0001).ConclusionOur study showed high temperature, humidity, and low rainfall increased the risk of obstructive lung disease. Synergistic effects were observed among temperature, SO2, and PM2.5/PM10. The impact of air pollutants on obstructive lung disease should consider these interactions

Women with endometriosis have higher comorbidities: Analysis of domestic data in Taiwan

AbstractEndometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases. Concerning malignant tumors, we identified four studies on the links between endometriosis and ovarian cancer, one on breast cancer, two on endometrial cancer, one on colorectal cancer, and one on other malignancies, as well as one on associations between endometriosis and irritable bowel syndrome, one on links with migraine headache, three on links with pelvic inflammatory diseases, four on links with infertility, four on links with obesity, four on links with chronic liver disease, four on links with rheumatoid arthritis, four on links with chronic renal disease, five on links with diabetes mellitus, and five on links with cardiovascular diseases (hypertension, hyperlipidemia, etc.). The data available to date support that women with endometriosis might be at risk of some chronic illnesses and certain malignancies, although we consider the evidence for some comorbidities to be of low quality, for example, the association between colon cancer and adenomyosis/endometriosis. We still believe that the risk of comorbidity might be higher in women with endometriosis than that we supposed before. More research is needed to determine whether women with endometriosis are really at risk of these comorbidities

Changes in Plasma Membrane Surface Potential of PC12 Cells as Measured by Kelvin Probe Force Microscopy

The plasma membrane of a cell not only works as a physical barrier but also mediates the signal relay between the extracellular milieu and the cell interior. Various stimulants may cause the redistribution of molecules, like lipids, proteins, and polysaccharides, on the plasma membrane and change the surface potential (Φs). In this study, the Φss of PC12 cell plasma membranes were measured by atomic force microscopy in Kelvin probe mode (KPFM). The skewness values of the Φss distribution histogram were found to be mostly negative, and the incorporation of negatively charged phosphatidylserine shifted the average skewness values to positive. After being treated with H2O2, dopamine, or Zn2+, phosphatidylserine was found to be translocated to the membrane outer leaflet and the averaged skewness values were changed to positive values. These results demonstrated that KPFM can be used to monitor cell physiology status in response to various stimulants with high spatial resolution

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms