Granulocyte Colony-Stimulating Factor Improves Endothelial Progenitor Cell-Mediated Neovascularization in Mice with Chronic Kidney Disease.

Patients with chronic kidney disease (CKD) have a higher prevalence of peripheral arterial disease (PAD), and endothelial progenitor cells (EPCs) play a pivotal role. We examined the impact of granulocyte colony-stimulating factor (G-CSF) on EPC function in response to tissue ischemia. Eight-week-old male C57BL/6J male mice were divided into sham operation and subtotal nephrectomy (SNx) groups, received hindlimb ischemic operation after seven weeks, then randomly received G-CSF or PBS intervention for four weeks with weekly follow-ups. SNx mice had significantly reduced limb reperfusion, decreased plasma EPC mobilization, and impaired angiogenesis in ischemic hindlimbs compared to the control group. However, G-CSF increased IL-10 and reversed these adverse changes. Additionally, ischemia-associated protein expressions, including IL-10, phospho-STAT3, VEGF, and phospho-eNOS, were significantly downregulated in the ischemic hindlimbs of SNx mice versus control, but these trends were reversed by G-CSF. Furthermore, in cultured EPCs, G-CSF significantly attenuated the decrease in EPC function initiated by indoxyl sulfate through IL-10. Overall, we discovered that G-CSF can improve EPC angiogenic function through a hypoxia/IL-10 signaling cascade and impede neovascular growth in response to ischemia of SNx mice. Our results highlight G-CSF's potential to restore angiogenesis in CKD patients with PAD via EPC-based methods.

Prothrombin Complex Concentrate for Trauma Induced Coagulopathy: A Systematic Review and Meta-Analysis.

BACKGROUND: Optimal management for trauma-induced coagulopathy (TIC) is a clinical conundrum. In conjunction with the transfusion of fresh-frozen plasma (FFP), additional administration of prothrombin complex concentrate (PCC) was proposed to bring about further coagulative benefit. However, investigations evaluating the efficacy as well as corresponding side effects were scarce and inconsistent. The aim of this study was to systematically review current literature and to perform a meta-analysis comparing FFP+PCC with FFP alone. METHODS: Web search followed by manual interrogation was performed to identify relevant literatures fulfilling the following criteria, subjects as TIC patients taking no baseline anticoagulants, without underlying coagulative disorders, and reported clinical consequences. Those comparing FFP alone with PCC alone were excluded. Comprehensive Meta-analysis software was utilized, and statistical results were delineated with odd ratio (OR), mean difference (MD), and 95% confidence interval (CI). I2 was calculated to determine heterogeneity. The primary endpoint was set as all-cause mortality, while the secondary endpoint consisted of international normalized ratio (INR) correction, transfusion of blood product, and thrombosis rate. RESULTS: One hundred and sixty-four articles were included for preliminary evaluation, 3 of which were qualified for meta-analysis. A total of 840 subjects were pooled for assessment. Minimal heterogeneity was present in the comparisons (I2 < 25%). In the PCC + FFP cohort, reduced mortality rate was observed (OR: 0.631; 95% CI: 0.450-0.884, p = 0.007) after pooling. Meanwhile, INR correction time was shorter under PCC + FFP (MD: -608.300 mins, p < 0.001), whilst the rate showed no difference (p = 0.230). The PCC + FFP group is less likely to mandate transfusion of packed red blood cells (p < 0.001) and plasma (p < 0.001), but not platelet (p = 0.615). The incidence of deep vein thrombosis was comparable in the two groups (p = 0.460). CONCLUSIONS: Compared with FFP only, PCC + FFP demonstrated better survival rate, favorable clinical recovery and no elevation of thromboembolism events after TIC.

Morphing pasta and beyond.

Morphing structures are often engineered with stresses introduced into a flat sheet by leveraging structural anisotropy or compositional heterogeneity. Here, we identify a simple and universal diffusion-based mechanism to enable a transient morphing effect in structures with parametric surface grooves, which can be realized with a single material and fabricated using low-cost manufacturing methods (e.g., stamping, molding, and casting). We demonstrate from quantitative experiments and multiphysics simulations that parametric surface grooving can induce temporary asynchronous swelling or deswelling and can transform flat objects into designed, three-dimensional shapes. By tuning the grooving pattern, we can achieve both zero (e.g., helices) and nonzero (e.g., saddles) Gaussian curvature geometries. This mechanism allows us to demonstrate approaches that could improve the efficiency of certain food manufacturing processes and facilitate the sustainable packaging of food, for instance, by creating morphing pasta that can be flat-packed to reduce the air space in the packaging.

Propolin C Inhibited Migration and Invasion via Suppression of EGFR-Mediated Epithelial-to-Mesenchymal Transition in Human Lung Cancer Cells.

Controlling lung cancer cell migration and invasion via epithelial-to-mesenchymal transition (EMT) through the regulation of epidermal growth factor receptor (EGFR) signaling pathway has been demonstrated. Searching biological active phytochemicals to repress EGFR-regulated EMT might prevent lung cancer progression. Propolis has been used as folk medicine in many countries and possesses anti-inflammatory, antioxidant, and anticancer activities. In this study, the antimigration and anti-invasion activities of propolin C, a c-prenylflavanone from Taiwanese propolis, were investigated on EGFR-regulated EMT signaling pathway. Cell migration and invasion activities were dose-dependently suppressed by noncytotoxic concentration of propolin C. Downregulations of vimentin and snail as well as upregulation of E-cadherin expressions were through the inhibition of EGFR-mediated phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) and extracellular signal-regulated kinase (ERK) signaling pathway in propolin C-treated cells. In addition, EGF-induced migration and invasion were suppressed by propolin C-treated A549 lung cancer cells. No significant differences in E-cadherin expression were observed in EGF-stimulated cells. Interestingly, EGF-induced expressions of vimentin, snail, and slug were suppressed through the inhibition of PI3K/Akt and ERK signaling pathway in propolin C-treated cells. Inhibition of cell migration and invasion by propolin C was through the inhibition of EGF/EGFR-mediated signaling pathway, followed by EMT suppression in lung cancer.

Higher disappearance rate of anti-HBs in Taiwanese freshers neonatally vaccinated with recombinant yeast hepatitis B vaccine.

BACKGROUND & AIM: The aim of this study was to compare the long-term efficacy of infant recombinant yeast hepatitis B vaccine (Recombinant group) and infant plasma-derived one (Plasma group) in Taiwanese freshers. METHODS: Recruited were a total of 38 377 freshmen who underwent university entrance health examinations from 2003 to 2015. Subjects were assigned into two groups-plasma type and recombinant type, according to the national neonatal hepatitis B immunization program. The seroprevalences of hepatitis B surface antigen, antibody against hepatitis B surface antigen, and antibody against hepatitis B core antigen in each group and gender were calculated. Multivariate logistic regression analysis was performed to compare the efficacy of two groups. RESULTS: The HBsAg-positive rates in the plasma group and recombinant group were 1.5% and 0.3% respectively. The anti-HBs positive rates were 43.6% and 30.9%. The hepatitis B viral natural infection rates were 3.6% and 1.3%. Taking those who were born in July 1986-April 1992 as baseline group after adjustment for gender and age at hepatitis B markers checkup time, the efficacy of recombinant group in decreasing HBsAg positive rate, and decreasing hepatitis B virus natural infection rate was 71.0% (95% C.I.: 59.0-79.0%, P<.001) and 65.0% (95% C.I. 58.0-71.0%, P<.001) respectively. On the contrary, the seroprevalence of anti-HBs positive rate in recombinant group was 39.0% (95% C.I.: 36.0-42.0%, P<.001) lower than that of plasma group. (P<.001). CONCLUSION: Higher disappearance rate of anti-HBs was noted in recombinant group than in plasma group when the subjects reached their youth and young adulthood in Taiwan.

Influence of non-alcoholic fatty liver disease on autonomic changes evaluated by the time domain, frequency domain, and symbolic dynamics of heart rate variability.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular atherosclerosis independent of classical risk factors. This study investigated the influence of NAFLD on autonomic changes, which is currently unknown. METHODS: Subjects without an overt history of cardiovascular disease were enrolled during health checkups. The subjects diagnosed for NAFLD using ultrasonography underwent 5-min heart rate variability (HRV) measurements that was analyzed using the following indices: (1) the time domain with the standard deviation of N-N (SDNN) intervals and root mean square of successive differences between adjacent N-N intervals (rMSSD); (2) the frequency domain with low frequency (LF) and high frequency (HF) components; and (3) symbolic dynamics analysis. Routine blood biochemistry data and serum leptin levels were analyzed. Homeostasis model assessment of insulin resistance (HOMA-IR) was measured. RESULTS: Of the 497 subjects (mean age, 46.2 years), 176 (35.4%) had NAFLD. The HRV indices (Ln SDNN, Ln rMSSD, Ln LF, and Ln HF) were significantly decreased in the NAFLD group (3.51 vs 3.62 ms, 3.06 vs 3.22 ms, 5.26 vs 5.49 ms(2), 4.49 vs 5.21 ms(2), respectively, all P<0.05). Ln SDNN was significantly lower in the NAFLD group after adjustment for age, sex, hypertension, dyslipidemia, metabolic syndrome, body mass index, smoking, estimated glomerular filtration rate, HOMA-IR, and leptin (P<0.05). In the symbolic dynamic analysis, 0 V percentage was significantly higher in the NAFLD group (33.8% vs 28.7%, P = 0.001) and significantly correlated with linear HRV indices (Ln SDNN, Ln rMSSD, and Ln HF). CONCLUSIONS: NAFLD is associated with decreased Ln SDNN and increased 0 V percentage. The former association was independent of conventional cardiovascular risk factors and serum biomarkers (insulin resistance and leptin). Further risk stratification of autonomic dysfunction with falls or cardiovascular diseases by these HRV parameters is required in patients with NAFLD.

Predominance of genetic diagnosis and imaging results as predictors in determining the speech perception performance outcome after cochlear implantation in children.

OBJECTIVE: To investigate the roles of genetic diagnosis and imaging studies, as well as other prognostic factors, in predicting outcomes in children with cochlear implant. DESIGN: Prospective cohort study. SETTING: Tertiary referral center. PARTICIPANTS: Sixty-seven consecutive children with sensorineural hearing impairment who had at least 3 years of experience with cochlear implant. INTERVENTIONS: Imaging of the inner ear was done with high-resolution computed tomography, and mutations were screened in 3 genes commonly associated with pediatric hearing impairment: GJB2, SLC26A4, and the mitochondrial 12S ribosomal RNA gene. Speech perception performance was compared according to genetic diagnosis and imaging data. A general linear model was constructed to demonstrate the predictive values of specific genetic and imaging results after adjusting for other factors. Main Outcome Measure Recognition scores on speech perception tests. RESULTS: Twenty-two children (33%) showed genetic mutations: 18 with SLC26A4 and 4 with GJB2 mutations. According to imaging findings, 33 children (49%) showed inner ear malformations: 9 with a narrow internal auditory canal and 24 with other malformations. All children with SLC26A4 or GJB2 mutations exhibited excellent speech recognition scores, whereas a narrow internal auditory canal was associated with poorer outcomes (P < .001 in all recognition scores). The general linear model confirmed that both a narrow internal auditory canal (P < .001) and SLC26A4 mutations (P = .04) correlated with speech perception outcome. CONCLUSIONS: Genetic diagnosis and imaging results are the 2 predominant factors determining the outcome in children with cochlear implants. In pediatric candidates for cochlear implantation, both genetic examination and imaging studies should be included in the battery of preoperative evaluations.

Seroprevalence of hepatitis B viral markers among freshmen--20 years after mass hepatitis B vaccination program in Taiwan.

BACKGROUND/PURPOSE: The nationwide hepatitis B vaccination program in Taiwan was well known for its efficacy in reducing the carrier rate of hepatitis B and the morbidity and mortality of hepatitis B-related diseases among children. The aim of this study was to investigate the seroprevalence of hepatitis B 20 years after this program was implemented. METHODS: A total of 7592 freshmen from one university in Northern Taiwan participated in this study during their school entry health exam in September 2003 and September 2004. Basic data including gender, birthday, family history and vaccination history of hepatitis B by self-reported questionnaire were collected. Hepatitis B serum markers, including hepatitis B surface antigen, antibody against hepatitis B surface antigen, and antibody against hepatitis B core antigen were all checked. The differences in the seroprevalence of hepatitis B between two groups of subjects born before July 1984 and after July 1984 were examined. Multiple logistic analyses were performed for identifying the odds ratio (OR) of family history and other variables for each hepatitis B serum marker. RESULTS: Subjects born after July 1984 were found to have a lower rate of hepatitis B surface antigen of 2.2% (95% confidence interval [CI], 1.8-2.6%) vs. 7.4% (95% CI, 5.9-8.9%), and core antibody against hepatitis B of 6.7% (95% CI, 6.0-7.3%) vs. 23.5% (95% CI, 21.1-25.9%), but a higher rate of surface antibody against hepatitis B of 74.3% (95% CI, 73.2-75.4%) vs. 69.1% (95% CI, 66.5-71.7%) compared with those born before July 1984 (all p < 0.001). Subjects with a family history of hepatitis B had higher risk of being infected by hepatitis B (OR, 4.07; 95% CI, 3.18-5.12) and becoming carriers (OR, 7.26; 95% CI, 5.05-10.44) after adjustment for sex, age, birth year, and self-reported hepatitis B vaccination history. CONCLUSION: The seroprevalence of hepatitis B surface antigen continued to decline 20 years after neonatal hepatitis B vaccination program. It is strongly recommended that those who have a family history of hepatitis B should receive early check-up of hepatitis B status after complete vaccination or closely follow up their hepatitis B status after neonatal hepatitis B vaccination.

Lifestyle risk factors associated with fatigue in graduate students.

BACKGROUND/PURPOSE: Fatigue is not only common in clinical patients but is also prevalent in the healthy population. This study aimed to estimate the prevalence rate of fatigue and identify significant risk factors among graduate students. METHODS: Health check-ups were carried out on graduate students who were newly admitted to the National Taiwan University in this cross-sectional study. A total of 1806 attendees (response rate, 84%) agreed to participate in the fatigue survey, which used the Checklist Individual Strength questionnaire (CIS-20). The modified Baecke's questionnaire was used to quantify the intensity of physical activity. RESULTS: The prevalence rates of fatigue were 45.8% for males and 48.9% for females. Regular meal (odds ratio [OR], 0.69) and exercise habits (OR, 0.68), insomnia (OR, 2.23), greater amount of sleeping time (OR, 0.7), identity (doctorate vs. master students; OR, 0.61), and chronic disease history (OR, 1.61) were statistically significant predictors for fatigue. Intensity of physical activity was a protective factor (ORs, 0.72, 0.50 and 0.36 in the 2nd, 3rd and top quartiles vs. 1st quartile; p < 0.001). CONCLUSION: A high prevalence rate of fatigue among the graduate students was demonstrated. The risk factors among young adults are not only related to current chronic disease and insomnia but are also attributed to the lack of physical activity.