A high-stability fiber amplifier source for the fiber opticgyroscope

We demonstrate an erbium-doped fiber amplifier (EDFA) source for the fiber gyroscope with an overall mean wavelength stability of four parts per million. This source, which amplifies the gyroscope signal before detection, is shown to be more stable than a similar single-pass source in a standard configuration. The effects of varying the fiber temperature, pump power, pump wavelength, gyroscope feedback power and signal polarization state on the output mean wavelength are individually explored. Experimental results are in excellent agreement with simulations     

TcdB of Clostridioides difficile Mediates RAS-Dependent Necrosis in Epithelial Cells

A Clostridioides difficile infection (CDI) is the most common nosocomial infection worldwide. The main virulence factors of pathogenic C. difficile are TcdA and TcdB, which inhibit small Rho-GTPases. The inhibition of small Rho-GTPases leads to the so-called cytopathic effect, a reorganization of the actin cytoskeleton, an impairment of the colon epithelium barrier function and inflammation. Additionally, TcdB induces a necrotic cell death termed pyknosis in vitro independently from its glucosyltransferases, which are characterized by chromatin condensation and ROS production. To understand the underlying mechanism of this pyknotic effect, we conducted a large-scale phosphoproteomic study. We included the analysis of alterations in the phosphoproteome after treatment with TcdA, which was investigated for the first time. TcdA exhibited no glucosyltransferase-independent necrotic effect and was, thus, a good control to elucidate the underlying mechanism of the glucosyltransferase-independent effect of TcdB. We found RAS to be a central upstream regulator of the glucosyltransferase-independent effect of TcdB. The inhibition of RAS led to a 68% reduction in necrosis. Further analysis revealed apolipoprotein C-III (APOC3) as a possible crucial factor of CDI-induced inflammation in vivo.     

Solid lipid nanoparticles of anticancer drug andrographolide: formulation,in vitro and in vivo studies

Diterpenoidal anti-cancer drug andrographolide (AD) was encapsulated into solid lipid nanoparticle (SLN) because of poor aqueous solubility and high lipophilicity. AD-SLNs were prepared by solvent injection method and characterized for droplet size, surface morphology, zeta potential, etc. In vitro drug release was carried out by dialysis-membrane method. A pharmacokinetic study was performed by UPLC/Q-TOF-MS method to determine the maximum plasma concentration (C_max), area under the curve (AUC), etc. There was an improvement in C_max and AUC of AD-SLNs when compared with AD, thereby enhancing the bioavailability of AD. The t_max was increased than that of AD suspension, indicating the sustained release pattern of AD-SLNs. The antitumor activity was carried out on Balb/c mice showing better results with AD-SLNs as compared to AD. Thus, the AD-loaded SLNs would be useful for delivering poorly water-soluble AD with enhanced bioavailability and improved antitumor activity.     

Short communication: Repeatability of β-hydroxybutyrate measurements in capillary blood obtained from the external vulvar skin

The primary objective of this study was to evaluate the repeatability of measurements of β-hydroxybutyrate (BHB) concentrations in capillary blood obtained from minimal-invasive puncturing of different sites at the external vulva skin of dairy cows. A total of 240 multiparous cows sampled once within 21 d in milk were enrolled in the study. Capillary blood samples were obtained from the right and left labium of the external vulva skin and additionally from a site close to the first puncture. Samples were analyzed by using an electronic hand-held device [FreeStyle Precison Neo (FSP-Neo), Abbott GmbH & Co., Wiesbaden, Germany)]. Additionally, samples from a coccygeal vessel were analyzed as reference in a laboratory. Mean deviations (± standard deviation) between the 3 capillary sampling sites ranged from 0.01 ± 0.14 (left vs. right labium) to 0.02 ± 0.13 mmol/L (left or right labium vs. additional site). The BHB concentrations in capillary blood compared with the reference showed a mean deviation of 0.14 ± 0.18 mmol/L. The Spearman correlation coefficient between BHB concentrations in capillary blood and coccygeal blood was 85.4%. Mixed model analyses showed no significant effect of sampling site or squeezing the skin during sampling procedures on the differences toward the reference. Based on laboratory BHB concentrations of ≥1.2 and ≥1.4 mmol/L, respectively, the prevalence of hyperketonemia was 10.4 (n = 25) and 5.0% (n = 12). Thresholds to detect hyperketonemia with the FSP-Neo were optimized by receiver operating characteristic analyses. Based on a laboratory BHB concentration of ≥1.2 mmol/L thresholds were determined as 1.1 (left labium, 2nd puncture) and 1.0 mmol/L (right labium), with sensitivities between 94 and 99% and specificities between 89 and 97%. Based on a serum BHB concentration of 1.4 mmol/L, receiver operating characteristic analyses resulted in optimized cutoffs of 1.4 mmol/L for all sampling sites at the vulva, with sensitivities of 100% and specificities between 96 and 99%. In conclusion, vulvar capillary blood is suitable for accurate measuring of BHB concentrations by using the FSP-Neo. After adjusting the thresholds, the FSP-Neo provides very good test characteristics independent of the capillary sampling site or squeezing the skin and allows a practical and reliable screening tool for dairy cows.     

Wettability of Surface Oxyfluorinated Polypropylene Fibres and Its Effect on Interfacial Bonding with Cementitious Matrix

The surface of high molecular weight polypropylene monofilament fibre was modified using a oxyfluorination method. The oxyfluorination treatment level was varied and a hydrolysis post-treatment was also applied. Contact angles of oxyfluorinated, hydro-lyzed oxyfluorinated and unmodified polypropylene fibres were obtained by dynamic contact angle (DCA) measurement using three liquids of known dispersion, acid and base surface free energy components. The surface free energies were then calculated according to the acid-base theory developed by Good, van Oss and Chaudhury. Surface oxyfluorination largely increased the acid and base components of the fibres' surface free energy compared with unmodified polypropylene fibres. The oxyfluorinated and unmodified polypropylene fibre surfaces were observed by Scanning Electronic Microscopy and Photoacoustic Infrared Spectroscopy. It was found that the surface oxyfluorination largely increases the roughness of the polypropylene surfaces and the carbonyl group content increases as the treatment level increases. The interfacial shear bond strengths between the cementitious matrix and the polypropylene fibres treated under various conditions were determined by embedded fibre pull-out tests. Results showed that the fibre surface oxyfluorination treatments increase the interfacial bond strengths. The correlations between the shear bond strengths and surface free energy components were established. Results showed that fibre/concrete interfacial bonding was best correlated with the acid component of surface free energy of polypropylene fibres.     

Fibroblast Growth Factor 21 Response in a Preclinical Alcohol Model of Acute-on-Chronic Liver Injury

Background and Aims: Fibroblast growth factor (FGF) 21 has recently been shown to play a potential role in bile acid metabolism. We aimed to investigate the FGF21 response in an ethanol-induced acute-on-chronic liver injury (ACLI) model in Abcb4^−/− mice with deficiency of the hepatobiliary phospholipid transporter. Methods: Total RNA was extracted from wild-type (WT, C57BL/6J) and Abcb4⁻/⁻ (KO) mice, which were either fed a control diet (WT-Cont and KO-Cont groups; n = 28/group) or ethanol diet, followed by an acute ethanol binge (WT-EtOH and KO-EtOH groups; n = 28/group). A total of 58 human subjects were recruited into the study, including patients with alcohol-associated liver disease (AALD; n = 31) and healthy controls (n = 27). The hepatic and ileal expressions of genes involved in bile acid metabolism, plasma FGF levels, and bile acid and its precursors 7α- and 27-hydroxycholesterol (7α- and 27-OHC) concentrations were determined. Primary mouse hepatocytes were isolated for cell culture experiments. Results: Alcohol feeding significantly induced plasma FGF21 and decreased hepatic Cyp7a1 levels. Hepatic expression levels of Fibroblast growth factor receptor 1 (Fgfr1), Fgfr4, Farnesoid X-activated receptor (Fxr), and Small heterodimer partner (Shp) and plasma FGF15/FGF19 levels did not differ with alcohol challenge. Exogenous FGF21 treatment suppressed Cyp7a1 in a dose-dependent manner in vitro. AALD patients showed markedly higher FGF21 and lower 7α-OHC plasma levels while FGF19 did not differ. Conclusions: The simultaneous upregulation of FGF21 and downregulation of Cyp7a1 expressions upon chronic plus binge alcohol feeding together with the invariant plasma FGF15 and hepatic Shp and Fxr levels suggest the presence of a direct regulatory mechanism of FGF21 on bile acid homeostasis through inhibition of CYP7A1 by an FGF15-independent pathway in this ACLI model. Lay Summary: Alcohol challenge results in the upregulation of FGF21 and repression of Cyp7a1 expressions while circulating FGF15 and hepatic Shp and Fxr levels remain constant both in healthy and pre-injured livers, suggesting the presence of an alternative FGF15-independent regulatory mechanism of FGF21 on bile acid homeostasis through the inhibition of Cyp7a1.     

Prosthetic valve endocarditis: superiority of surgical valve replacement versus medical therapy only

The objective of our study was to assess the long-term outcome of patients with prosthetic valve endocarditis. We used a multicenter, prospective, observational study design. Six university teaching hospitals with high volume cardiothoracic surgery participated. Seventy-four patients with prosthetic valve endocarditis as defined by explicit, objective criteria were selected for participation. All patients were followed up prospectively for 1 year. Thirty-one percent and 69% had development of endocarditis within 60 days of valve insertion ("early") and after 60 days ("late"), respectively. The most common causes were Staphylococcus epidermidis (40%), Staphylococcus aureus (20%), streptococcal species (18%), and aerobic gram-negative bacilli (11%). Physical signs of endocarditis (new or changing murmur, stigmata, emboli) were seen in 58%. At 6 months and 12 months, mortality was 46% and 47%, respectively. Surgical replacement of the infected valve led to significantly lower mortality (23%) as compared with medical therapy alone (56%), as assessed by both univariate and multivariate analyses (p < 0.05). Improved outcome was seen for the surgical group even when controlling for severity of illness at time of diagnosis. From these findings we conclude that accurate assessment of outcome in prosthetic valve endocarditis requires long-term follow-up of at least 6 months following diagnosis. Surgical therapy warrants greater scrutiny; evaluation in controlled clinical trials is appropriate.