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Background. Animal tissues and tissue-derived biomaterials are widely used in the field of xenotransplantation and regenerative medicine. A potential immunogenic risk that affects the safety and effectiveness of xenografts is the presence of remnant α-Gal antigen (synthesized by GGTA1 or/and iGb3S). GGTA1 knockout mice have been developed as a suitable model for the analysis of anti-Gal antibody-mediated immunogenicity. However, we are yet to establish whether GGTA1/iGb3S double knockout (G/i DKO) mice are sensitive to Gal antigen-positive xenoimplants. Methods. α-Gal antigen expression in the main organs of G/i DKO mice or bovine bone substitutes was detected via a standardized ELISA inhibition assay. Serum anti-α-Gal antibody titers of G/i DKO mice after immunization with rabbit red blood cells (RRBC) and implantation of raw lyophilized bone substitutes (Gal antigen content was 8.14 ± 3.17 × 10 12 / mg) or Guanhao Biotech bone substitutes (50% decrease in Gal antigen relative to the raw material) were assessed. The evaluation of total serum antibody, inflammatory cytokine, and splenic lymphocyte subtype populations and the histological analysis of implants and thymus were performed to systematically assess the immune response caused by bovine bone substitutes and bone substitute grafts in G/i DKO mice. Results. α-Gal epitope expression was reduced by 100% in the main organs of G/i DKO mice, compared with their wild-type counterparts. Following immunization with RRBC, serum anti-Gal antibody titers of G/i DKO mice increased from 80- to 180-fold. After subcutaneous implantation of raw lyophilized bone substitutes and Guanhao Biotech bone substitutes into G/i DKO mice, specific anti-α-Gal IgG, anti-α-Gal IgM, and related inflammatory factors (IFN-γ and IL-6) were significantly increased in the raw lyophilized bone substitute group but showed limited changes in the Guanhao Biotech bone substitute group, compared with the control. Conclusion. G/i DKO mice are sensitive to Gal antigen-positive xenogeneic grafts and can be effectively utilized for evaluating the α-Gal-mediated immunogenic risk of xenogeneic grafts. [ABSTRACT FROM AUTHOR]

Introduction: The National Comprehensive Cancer Network and the European Organization for Research and Treatment of Cancer recommend extracorporeal photopheresis (ECP) as systemic therapy for cutaneous T-cell lymphoma (CTCL). Objective: To investigate real-world use of ECP in CTCL patients in the US. Methods: Data from the Truven MarketScan® database (2010–2015) were used to create a cohort of CTCL patients receiving systemic treatment. Multivariable regressions were performed to compare health care resource utilization between ECP and propensity score-matched non-ECP patients. Results: Of the 1106 eligible patients, 117 (10.6%) received ECP, with an average treatment duration of 13.6 months. Psoriasis, organ transplant, graft versus host disease, and scleroderma were the most common comorbidities. ECP was used as monotherapy in 76 patients (65.0%) and combination in 41 patients (35.0%), mostly with interferon and/or a retinoid. Higher Charlson Comorbidity Index (2.6 vs 2.2, p <.05), rates of organ transplant (49.6% vs 7.8%, p <.001), and graft vs host disease (41.9% vs 3.4%, p <.001) were observed in ECP versus non-ECP patients. Post-matching analyses showed that ECP patients had shorter all-cause inpatient stay (6.67 vs 11.80 days, p =.001). Conclusions: Approximately 1 out of 10 CTCL patients receiving systemic treatment were on ECP treatment in the US. Post-matching analysis showed ECP was associated with a shorter hospital stay. [ABSTRACT FROM AUTHOR]

Homeotransplantation of bones for replacement therapy have been demonstrated reliably in clinical data. However, human donor bones applicable for homeotransplantation are in short supply, which facilitates the search for suitable alternatives, such as xenografts grafts. The α-Gal antigen-related immune risk of xenografts directly affects the safety and effectiveness of the biomaterials and limits their applications in the clinic. The immune risk can be prevented by depletion or breaking anti-Gal antibody prior to transplant. Therefore, how to assess the immune risk of the bone substitutes and select the reliable animal research model become extremely important. In this study, we prepared lyophilized bone substitutes (T1) and Guanghao Biotech bone substitutes (T2, animal-derived biomaterials with α-Gal antigen decreased), aimed to assess the immune risk of xenografts bone substitutes on GGTA1 knockout mice. The α-Gal antigen contents of T1 and T2 were firstly detected by ELISA method in vitro. The bone substitutes were then implanted subcutaneously into GGTA1 knockout mice for 2, 4 and 12 weeks, respectively. The total serum antibody levels, anti-α-Gal antibody levels, inflammatory cytokine and splenic lymphocyte surface molecules were detected and histology analysis of skin and thymus were performed to systematically evaluate the immune response caused by the T1 and T2 bone substitutes in mice. In vitro results showed that the amount of α-Gal epitopes in T1 bone substitutes was significantly higher than T2 bone substitutes, and the clearance rate of α-Gal antigen in T2 bone substitutes achieved about 55.6%. Results of antibody level in vivo showed that the T1 bone substitutes group possessed significantly higher total IgG, IgM, IgA and anti-α-Gal IgG levels than T2 and control group, while T2 group showed no significant changes of these indexes compared with control. In terms of inflammatory cytokines, T1 bone substitutes showed evidently higher levels of IL-4, IL-12P70 and IL-10 than T2 and control, while T2 group was comparable to control. No changes in the levels of splenic lymphocyte surface molecules were found in the three groups (T1, T2 and control group) during the experimental periods. The pathological results demonstrated that the inflammatory response in T2 group was lighter than the T1 group, which was in accordance with the inflammatory cytokines levels. The above results indicated that the process of antigen removal effectively reduced the α-Gal antigens content in T2 bone substitutes, which caused little immune response in vivo and could be used as bone healing materials. This study also demonstrated that GGTA1 knockout mice can be used as a routine tool to assess the immune risk of animal-derived biomaterials. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective To quantify the economic burden of binge-eating disorder (BED) in terms of work productivity loss, healthcare resource utilization, and healthcare costs. Methods Respondents of the US National Health and Wellness Survey 2013 were invited to participate in a follow-up internet survey to identify adults with BED using DSM-5 criteria. Work productivity loss, healthcare resource utilization, and direct and indirect costs were assessed for BED respondents and matched non-BED respondents using generalized linear models or two-part models as appropriate. Results A total of 1,720 people were included in our analysis ( N = 344 with BED; N= 1,376 without BED). BED respondents had higher levels of activity impairment than non-BED respondents (41.29% vs. 23.18%, p < .001). Employed BED respondents ( N = 178) had a greater level of work impairment than employed non-BED respondents ( N = 686) (36.83% vs. 14.41%, p = .009). Higher healthcare resource utilization in the past 6 months among BED respondents was reported than matched non-BED respondents: numbers of surgeries (0.23 vs. 0.13, p = .021), ER visits (0.26 vs. 0.15, p = .016), and physician visits (6.09 vs. 4.56, p = .002). BED respondents reported higher total direct costs than matched non-BED respondents ($20,194 vs. $14,465, p = .005). The indirect costs among employed BED respondents were also higher than those without BED ($19,327 vs. $9,032, p < .001). Discussion Individuals with BED reported significantly greater economic burden with respect to work productivity loss, level of healthcare resource utilization, and costs compared to non-BED respondents. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:523-532) [ABSTRACT FROM AUTHOR]

This paper investigates model validation under a variety of different data scenarios and clarifies how different validation metrics may be appropriate for different scenarios. In the presence of multiple uncertainty sources, model validation metrics that compare the distributions of model prediction and observation are considered. Both ensemble validation and point-by-point approaches are discussed, and it is shown how applying the model reliability metric point-by-point enables the separation of contributions from aleatory and epistemic uncertainty sources. After individual validation assessments are made at different input conditions, it may be desirable to obtain an overall measure of model validity across the entire domain. This paper proposes an integration approach that assigns weights to the validation results according to the relevance of each validation test condition to the overall intended use of the model in prediction. Since uncertainty propagation for probabilistic validation is often unaffordable for complex computational models, surrogate models are often used; this paper proposes an approach to account for the additional uncertainty introduced in validation by the uncertain fit of the surrogate model. The proposed methods are demonstrated with a microelectromechanical system (MEMS) example. [ABSTRACT FROM AUTHOR]

Toxicological studies have shown that phthalates, a class of widely used chemicals, can impair male reproductive function, but epidemiological evidence is in consistent This study aimed to investigate the associations of semen phthalate metabolites with sperm apoptosis and DNA damage in a Chinese population. We assessed sperm apoptosis markers with Annexin V/PI analysis and sperm DNA integrity with comet assay before measuring eight phthalate metabolites in semen by high-performance liquid chromatography and tandem mass spectrometry (HPLC-MS/MS ) among 463 men from Wuhan, China. We found a suggestive do se-response relationship between semen mono-(2-ethylhexyl) phthalate (MEHP) and an increased percentage of Annexin V7PF sperm (p for trend of <0.10). We also observed that semen monomethyl phthalate (MMP) and monoethyl phthalate (MEP) were associated with significant dose-related increases in tail length of the comet (both p for trend of < 0.01). In conclusion, our data indicate that semen MEHP is associated with increased sperm apoptosis and that semen MMP and MEP are associated with increased sperm DNA damage in a Chinese population. [ABSTRACT FROM AUTHOR]

In the Kennedy and O'Hagan framework for Bayesian calibration of physics models, selection of an appropriate prior form for the model discrepancy function is a challenging issue due to the lack of physics knowledge regarding model inadequacy. Aiming to address the uncertainty arising from the selection of a particular prior, this paper first conducts a study on possible formulations of the model discrepancy function. A first-order Taylor series expansion-based method is developed to investigate the potential redundancy caused by adding a discrepancy function to the original physics model. Further, we propose a three-step (calibration, validation, and combination) approach in order to inform the decision on the construction of model discrepancy priors. In the validation step, a reliability-based metric is used to evaluate posterior model predictions in the validation domain. The validation metric serves as a quantitative measure of how well the discrepancy formulation captures the missing physics in the model. In the combination step, the posterior distributions of model parameters and discrepancy corresponding to different priors are combined into a single distribution based on the probabilistic weights derived from the validation step. The combined distribution acknowledges the uncertainty in the prior formulation of model discrepancy function. [ABSTRACT FROM AUTHOR]

Abstract: This paper develops new insights into quantitative methods for the validation of computational model prediction. Four types of methods are investigated, namely classical and Bayesian hypothesis testing, a reliability-based method, and an area metric-based method. Traditional Bayesian hypothesis testing is extended based on interval hypotheses on distribution parameters and equality hypotheses on probability distributions, in order to validate models with deterministic/stochastic output for given inputs. Formulations and implementation details are outlined for both equality and interval hypotheses. Two types of validation experiments are considered—fully characterized (all the model/experimental inputs are measured and reported as point values) and partially characterized (some of the model/experimental inputs are not measured or are reported as intervals). Bayesian hypothesis testing can minimize the risk in model selection by properly choosing the model acceptance threshold, and its results can be used in model averaging to avoid Type I /II errors. It is shown that Bayesian interval hypothesis testing, the reliability-based method, and the area metric-based method can account for the existence of directional bias, where the mean predictions of a numerical model may be consistently below or above the corresponding experimental observations. It is also found that under some specific conditions, the Bayes factor metric in Bayesian equality hypothesis testing and the reliability-based metric can both be mathematically related to the p-value metric in classical hypothesis testing. Numerical studies are conducted to apply the above validation methods to gas damping prediction for radio frequency (RF) micro-electro-mechanical-system (MEMS) switches. The model of interest is a general polynomial chaos (gPC) surrogate model constructed based on expensive runs of a physics-based simulation model, and validation data are collected from fully characterized experiments. [Copyright &y& Elsevier]

TSL-1 is a fraction of the aqueous extract from the tender leaf of Toona sinensis Roem,a nutritious vegetable. The pandemic influenza A (H1N1) virus is a recently described, rapidly contagious respiratory pathogen which can cause acute respiratory distress syndrome (ARDS) and poses a major public health threat. In this study, we found that TSL-1 inhibited viral yields on MDCK plaque formation by pandemic influenza A (H1N1) virus on infected A549 cells with high selectivity index. Meanwhile, TSL-1 also suppressed viral genome loads in infected A549 cells, quantified by qRT-PCR. This study further demonstrated that TSL-1 inhibited pandemic influenza A (H1N1) virus activity through preventing attachment of A549 cells but not penetration. TSL-1 inhibited viral attachment through significant downregulation of adhesion molecules and chemokines (VCAM-1, ICAM-1, E-selectin, IL-8, and fractalkine) compared to Amantadine. Our results suggest that TSL-1 may be used as an alternative treatment and prophylaxis against pandemic influenza A (H1N1) virus. [ABSTRACT FROM AUTHOR]

Abstract: Polysorbate 80 coated temozolomide-loaded PLGA-based superparamagnetic nanoparticles (P80-TMZ/SPIO-NPs) were successfully synthesized and characterized as drug carriers and diagnosis agent for malignant brain glioma. The mean size of P80-TMZ/SPIO-NPs was 220nm with narrow hydrodynamic particle size distribution. The superparamagnetic characteristic of P80-TMZ/SPIO-NPs was proved by vibration simple magnetometer. P80-TMZ/SPIO-NPs exhibited high drug loading and encapsulation efficiency as well as good sustained drug release performance for 15 days. MTT assay demonstrated the antiproliferative effect of P80-TMZ/SPIO-NPs for C6 glioma cells. Significant cellular uptake of P80-TMZ/SPIO-NPs was evaluated in C6 glioma cells by fluorescence microscopy, Prussian blue staining, and atomic absorption spectrophotometer (AAS) for qualitative and quantitative study, respectively. MRI scanning analyses in vitro indicated that P80-TMZ/SPIO-NPs could be used as a good MRI contrast agent. Polysorbate 80 coated temozolomide-loaded PLGA-based superparamagnetic nanoparticles could be able to promise a multifunctional theragnostic carrier of brain cancer. [Copyright &y& Elsevier]

Abstract: This paper presents a Bayesian probabilistic methodology to integrate model-based fatigue damage prognosis (FDP) with online and offline structural health monitoring (SHM) data. The prognosis uses fracture mechanics-based fatigue crack growth modeling, along with quantification of various sources of uncertainty, including natural variability, data uncertainty and model errors. These uncertainty sources are connected using a Bayesian network and a probabilistic sensitivity analysis is performed to assess the uncertainty contributions from these sources. The cycle-by-cycle simulation of fatigue crack growth is expedited via the use of a surrogate modeling technique (Gaussian process model) to replace computationally expensive finite element analysis. Real-time monitoring data of external variable amplitude loading history is used to construct a Bayesian autoregressive integrated moving average (ARIMA) model to predict and update the loading. On-ground crack inspection data is used to quantify the uncertainty in the initial and current size of an existing crack, using the Bayesian approach. Three possible cases of inspection results are considered: (1) crack is not detected; (2) crack is detected but not measured; (3) crack is detected and measured. Different scenarios of data availability (load monitoring data and inspection data) are considered for the prognosis of an individual component in a fleet. A numerical example, surface cracking in a rotorcraft mast under service loading, is implemented to illustrate the proposed methodology. The results of prognosis are validated using Bayesian hypothesis testing. [Copyright &y& Elsevier]

Abstract: Theragnostics polymer nanoparticles (NPs) loaded simultaneously with anticancer drug docetaxel (Dtxl) and superparamagnetic iron oxide (SPIO) nanocrystals were developed for both cancer therapy and ultrasensitive MRI. These multifunctional polymer vesicles were formed by carboxy-terminated poly(lactic-co-glycolic) acid using a single emulsion evaporation method. The active tumor-targeting single chain prostate stem cell antigen antibodies (scAbPSCA) were conjugated on the surface of polymer vesicles by using functional poly(ethylene glycol). The diameter of NPs was about 147 nm and the SPIO and drug encapsulation efficacy was 23% and 6.02%, respectively. Vibration simple magnetometer and X-ray diffraction proved that the superparamagnetic behavior of SPIO was not changed during NPs formation and modification. The NPs exhibited a triphasic drug release pattern in vitro over 30 days. Enhanced cellular uptake ability and antiproliferative effect of the targeted NPs in prostate cancer PC3 cell line by using the confocal laser scanning microscopy and cytotoxicity assay were observed. Moreover, the Prussian blue staining and the MRI assay in vitro demonstrated that the NPs have a high SPIO clustering effect. Therefore, these stable and tumor-targeting polymer NPs could be promising multifunctional vesicles for simultaneous targeting imaging, drug delivery and real time monitoring of therapeutic effect. [Copyright &y& Elsevier]

Abstract: Accurate characterization and prediction of loading, while properly accounting for uncertainty, are essential for probabilistic fatigue damage prognosis. Three different techniques – rainflow counting, the Markov chain method, and autoregressive moving average (ARMA) modeling – are investigated for stochastic characterization and reconstruction of the fatigue load history. The ARMA method is extended in this paper by introducing random coefficients and probabilistic weights, to account for the uncertainty in the selection of the model, inherent variability in loading, and uncertainty due to sparse data. A continuous model updating approach based on real-time monitoring data is developed and applied to all the three techniques mentioned above. The relation between prediction accuracy and updating interval is evaluated quantitatively. A quantitative model validation approach using Bayesian hypothesis testing is proposed to assess the confidence in load prediction from all the three methods. [Copyright &y& Elsevier]

Abstract: This paper presents a methodology for uncertainty quantification and model validation in fatigue crack growth analysis. Several models – finite element model, crack growth model, surrogate model, etc. – are connected through a Bayes network that aids in model calibration, uncertainty quantification, and model validation. Three types of uncertainty are included in both uncertainty quantification and model validation: (1) natural variability in loading and material properties; (2) data uncertainty due to measurement errors, sparse data, and different inspection results (crack not detected, crack detected but size not measured, and crack detected with size measurement); and (3) modeling uncertainty and errors during crack growth analysis, numerical approximations, and finite element discretization. Global sensitivity analysis is used to quantify the contribution of each source of uncertainty to the overall prediction uncertainty and to identify the important parameters that need to be calibrated. Bayesian hypothesis testing is used for model validation and the Bayes factor metric is used to quantify the confidence in the model prediction. The proposed methodology is illustrated using a numerical example of surface cracking in a cylindrical component. [Copyright &y& Elsevier]

Abstract: A probabilistic methodology is proposed in this paper to estimate the equivalent initial flaw size (EIFS) distribution accounting for various sources of variability, uncertainty and error, for mechanical components with complicated geometry and multi-axial variable amplitude loading conditions. A Bayesian approach is used to calibrate the distribution of EIFS, where the likelihood function is constructed from model-based fatigue crack growth analysis and inspection results. The variability, uncertainties and errors in the above procedures are quantified, and the distribution of EIFS is calibrated by explicitly accounting for the various sources of uncertainty. Three types of uncertainty are considered: (1) natural variability in loading and material properties; (2) data uncertainty, due to crack detection uncertainty, measurement errors, and sparse data; (3) modeling uncertainty and errors during crack growth analysis, numerical approximations, and finite element discretization. A Monte Carlo simulation-based approach is developed for uncertainty quantification in the crack growth analysis and for constructing the likelihood function of EIFS. The proposed methodology is illustrated by a numerical example. [ABSTRACT FROM AUTHOR]

Abstract: Docetaxel (Dtxl) remains the preferred choice of improving the survival of patients with hormone refractory prostate cancer (HRPC), but many patients suffer from modest drug response and significant toxicity. In the present study, we investigated the efficiency of novel Dtxl loaded-[1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-carboxy(polyethylene glycol)]2000 (DSPE-PEG-COOH) stabilized-oleic acid (OA) coated hydroxyapatite (HA) nanoparticles (Dtxl-NPs) and gained insights into the molecular mechanism of the apoptosis induced by these novel Dtxl-loaded nanoparticles. The drug encapsulation efficiency of Dtxl was 83.6% and the sustained drug release was observed over 30days. The Dtxl-NPs exhibited significantly more cytotoxicity in both prostate cancer cell lines (PC3 and DU145) compared with Dtxl in vitro and increased the Dtxl-induced apoptosis in the PC3 cells. Cell cycle analysis showed that the PC3 cells treated with Dtxl-NPs exhibited significant arrest in the G2-M phase but a higher sub-G0/G1 population when compared with Dtxl. The enhanced apoptosis induced by Dtxl-NPs in the PC3 cells was associated with the changes in mitochondrial membrane potential (MMP) and seemed to involve the activation of caspase-2. The kinetic studies of caspases demonstrated an early activation of caspase-2 in Dtxl-NPs-induced apoptosis in PC3 cells, which differs from Dtxl-induced apoptosis. The inhibition of caspase-2 activation by small interfering RNA (siRNA) knockdown resulted in the significant inhibition of Dtxl-NPs-induced disruption of MMP and Dtxl-NPs-induced apoptosis, indicating that the activation of caspase-2 was the critical event before the mitochondrial depolarization in the PC3 cells. Our findings showed that nanoparticles, more than simple drug carriers, may play an active role in mediating the biological effects. [ABSTRACT FROM AUTHOR]

Abstract: This paper presents several efficient statistical inference techniques to calibrate the equivalent initial flaw size (EIFS) of fatigue cracks for mechanical components with complicated geometry and multi-axial, variable amplitude loading. Finite element analysis is used to address the complicated geometry and calculate the stress intensity factors. Multi-modal stress intensity factors due to multi-axial loading are combined to calculate an equivalent stress intensity factor using a characteristic plane approach. During cycle-by-cycle integration of the crack growth law, a Gaussian process surrogate model is used to replace the expensive finite element analysis, resulting in rapid computation. Experimental data (crack size after a particular number of loading cycles) and statistical methods are used to calibrate the EIFS. The methods of least squares and maximum likelihood method are extended to evaluate the entire probability distribution of EIFS. Bayesian techniques are also implemented for this purpose. A fast numerical integration technique is developed as an efficient alternative to the expensive Markov Chain Monte Carlo sampling approach in the Bayesian analysis. An application problem of cracking in a cylindrical structure is used to illustrate the proposed methods. [Copyright &y& Elsevier]

Background. Asthma significantly impacts human life and health as a chronic disease. Traditional treatments for asthma have several limitations. Artificial intelligence aids in cancer treatment and may also accelerate our understanding of asthma mechanisms. We aimed to develop a new clinical diagnosis model for asthma using artificial neural networks (ANN). Methods. Datasets (GSE85566, GSE40576, and GSE13716) were downloaded from Gene Expression Omnibus (GEO) and identified differentially expressed CpGs (DECs) enriched by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Random forest (RF) and ANN algorithms further identified gene characteristics and built clinical models. In addition, two external validation datasets (GSE40576 and GSE137716) were used to validate the diagnostic ability of the model. Results. The methylation analysis tool (ChAMP) considered DECs that were up-regulated (n =121) and down-regulated (n =20). GO results showed enrichment of actin cytoskeleton organization and cell-substrate adhesion, shigellosis, and serotonergic synapses. RF (random forest) analysis identified 10 crucial DECs (cg05075579, cg20434422, cg03907390, cg00712106, cg05696969, cg22862094, cg11733958, cg00328720, and cg13570822). ANN constructed the clinical model according to 10 DECs. In two external validation datasets (GSE40576 and GSE137716), the Area Under Curve (AUC) for GSE137716 was 1.000, and AUC for GSE40576 was 0.950, confirming the reliability of the model. Conclusion. Our findings provide new methylation markers and clinical diagnostic models for asthma diagnosis and treatment. [ABSTRACT FROM AUTHOR]

A moisture detection of single rice grains using a slim and small open-ended coaxial probe is presented. The coaxial probe is suitable for the nondestructive measurement of moisture values in the rice grains ranging from from 9.5% to 26%. Empirical polynomial models are developed to predict the gravimetric moisture content of rice based on measured reflection coefficients using a vector network analyzer. The relationship between the reflection coefficient and relative permittivity were also created using a regression method and expressed in a polynomial model, whose model coefficients were obtained by fitting the data from Finite Element-based simulation. Besides, the designed single rice grain sample holder and experimental set-up were shown. The measurement of single rice grains in this study is more precise compared to the measurement in conventional bulk rice grains, as the random air gap present in the bulk rice grains is excluded. [ABSTRACT FROM AUTHOR]

Melatonin promotes bone formation and prevents bone degradation via receptor-dependent or receptor-independent actions. The aim of this study is to encapsulate melatonin into poly (lactic-co-glycolic acid) (PLGA) microspheres (PLGA-MEL-MS) and create a melatonin sustained release system, then to evaluate its effect on the osteogenesis of human mesenchymal stem cells (hMSCs) in vitro. PLGA-MEL-MS were prepared by single emulsion solvent evaporation technique. Scanning electron microscopy demonstrated the incorporation of melatonin did not disturb the conventional generation of PLGA microspheres in size and morphology. In vitro drug release assay showed that PLGA-MEL-MS exhibited a biphasic drug release pattern: a low initial burst release effect with approximately 40% drug release at the first 3 days and a relatively retarded and continuous release with about 85% drug release over the 25 days. Cell proliferation assay demonstrated that PLGA-MEL-MS had no apparent effect on proliferation of human MSCs. In an osteogenesis assay, PLGAMEL- MS obviously enhanced alkaline phosphatase (ALP) mRNA expression and increased ALP activity compared to that in the control group. Meanwhile, several markers of osteoblast differentiation were also significantly upregulated, including runx2, osteopontin, and osteocalcin. Furthermore, quantificational alizarin red-based assay demonstrated that PLGA-MEL-MS significantly enhanced calcium deposit of hMSCs compared to the controls. Therefore, this simple melatonin sustained release system can control released melatonin to generate a microenvironment with a relatively stable concentration of melatonin for a period of time to support osteogenic differentiation of hMSCs in vitro. This suggests that this system may be used as bone growth stimulator in bone healing in vivo. [ABSTRACT FROM AUTHOR]

Abstract: Folate (FOL) mediated poly–lactide-co-glycolide–polyethylene glycol nanoparticles (FOL–PEG–PLGA NPs) bearing paclitaxel (PTX) were prepared for the effective delivery of drug to endometrial carcinoma. The average size, zeta potential and encapsulation efficiency of FOL-targeted NPs were found to be around 220nm, −30.43mV and 95.6%. Cellular uptake was observed. The accumulation of FOL-targeted NPs depends on dual effects of passive and active targeting. The FOL-targeted PTX NPs showed a greater cytotoxicity against HEC-1A cancer cells in vitro and in vivo, which might be induced by apoptosis. H&E staining did not showed apparent tissue damage to liver and kidney of the mice after injecting NPs intravenously. These results suggest that the novel FOL–PEG–PLGA NPs could be a potential delivery system with excellent therapeutic efficacy for targeting the drugs to cancer cells. [Copyright &y& Elsevier]

Objective and background: Integrated PET and CT (PET/CT) is accurate in detecting hilar-mediastinal metastases. However, it has a moderate positive predictive value, necessitating pathological verification, especially in situations in which the result would make a difference to treatment. This study aimed to evaluate the performance of transbronchial needle aspiration (TBNA) for hilar-mediastinal lesions suspicious on PET/CT. Methodology: A retrospective study was conducted on 19 patients with a total of 25 positive hilar-mediastinal lymph nodes localized on PET/CT. Standard TBNA technique with rapid on-site cytopathology was performed. Results: The mean short-axis diameter of the positive lymph nodes identified on PET/CT was 9.9 ± 3.0 mm. The sensitivity, specificity and diagnostic accuracy of PET/CT-guided TBNA were 81.8%, 100% and 84%, respectively. The number of needle passes to successful lymph node aspiration or a diagnosis of cancer was 2.36 ± 0.49. Nine of the 25 positive lymph nodes (36%) on PET/CT were smaller than 1.0 cm. The accuracy and sensitivity of TBNA for these subcentimetre nodes was 88.9% and 87.5%, respectively. TBNA replaced surgical sampling in 15 patients (78.9%) with positive lymph nodes on PET/CT. In seven non-small cell lung cancer patients, diagnosis and staging were possible in the one procedure. No complications were encountered. Conclusion: PET/CT can identify small malignant lymph nodes that can then be successfully biopsied by TBNA with on-site cytopathology. [ABSTRACT FROM AUTHOR]

Explores the role of tumor susceptibility gene TSG101 in thyroid tumorigenesis. Information on the screening of human papillary thyroid carcinomas (PTC) by immunohistochemical staining and in situ hybridization analysis on paraffin-embedded tissues; Demonstration of the specificity of anti-TSG101 antiserum; Detection of increased TSG101 expression in PTC specimens by immunohistochemistry; Overexpression of TSG101 protein not caused by mutation of C-terminal steadiness box.

In the field of implantable medical devices, the antibacterial extracellular matrix (ECM) biologic scaffold, which is constructed by modifying biomaterials with antibacterial peptides, has excellent potential. An antibacterial peptide–modified ECM scaffold was formed with chitosan (CS), antimicrobial peptide (AMP), and ECM scaffold. Chitosan has a firm positive-charge surface and can combine with the ECM scaffold material to form a positive-charge layer on the surface. The surface potential was characterized using a surface potential map. Infrared spectroscopy and scanning electron microscopy (SEM) were used to observe the scaffold surface characteristics and cell morphology. Fluorescence staining and MTS assay kit were used to assess cytotoxicity and biocompatibility. To evaluate the antibacterial and repairing effects on the infected wounds in vivo, a subcutaneous antibacterial test of rabbit back was conducted. The antibacterial peptide–modified ECM scaffold was successfully formed and presented an excellent three-dimensional micro-surface porous structure. The antibacterial peptide–modified ECM scaffold could be effectively-prepared by surface modification and activation. Fluorescence staining tests showed good cell adhesion, proliferation ability, and cell affinity. The in vivo experiment indicated that the antibacterial ECM scaffold had antibacterial and healing-promotion abilities. • Solution to the problem of antibiotic resistance in extracellular matrix scaffold implantation. • Surface features of antimicrobial peptide modified extracellular matrix scaffold. • A potential material for tissue damage repair and indicated a new research thought for the extracellular matrix scaffold. • Extracellular matrix scaffold coated with different concentrations of CS present various biocompatibility. [ABSTRACT FROM AUTHOR]

Background Glioblastoma (GBM) is associated with poor prognosis, large morbidity burden, and limited treatment options. This analysis evaluated real-world treatment patterns, overall survival, resource use, and costs among Medicare patients with GBM. Methods This retrospective observational study evaluated Medicare patients age 66 years or older with newly diagnosed GBM using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data from 2007 through 2013. Patients were followed from diagnosis to death or end of follow-up. An algorithm defined treatment patterns as lines of therapy (LOTs). The Kaplan-Meier method was used to estimate overall survival for the full sample as well as by LOT, surgical resection, Charlson Comorbidity Index (CCI), tumor size, and age. Resource use and costs during the follow-up period were reported in terms of total and per-patient-per-month (PPPM) estimates. Results A total of 4308 patients with GBM were identified (median age, 74 years; CCI of 0, 52%). The most commonly used first LOT was temozolomide (82%), whereas chemotherapy + bevacizumab was most prevalent for second-line (42%) and third-line (58%) therapy. The median overall survival was 5.9 months for resected patients and 3 months for unresected patients, with considerable heterogeneity depending on patient characteristics. A great proportion of patients had claims for an ICU admission (86.2%), skilled nursing facility (76.9%), and home health (56.0%) in the postdiagnosis period. The cumulative mean cost was $95 377 per patient and $18 053 PPPM, mostly attributed to hospitalizations. Conclusions Limited treatment options, poor survival, and economic burden emphasize the need for novel interventions to improve care for Medicare patients with GBM. [ABSTRACT FROM AUTHOR]

Objective: The present study was to compare the incidence of septal defect (SD) in patients with atrial fibrillation (AF) who received radiofrequency ablation or cryoablation. Methods: A total of 293 AF patients were performed with radiofrequency ablation and cryoablation. Cardiac ultrasonography was performed to calculate left atrial diameter (LAD), left atrial ejection fraction (LAEF%), strain rate (SR), left ventricular systolic (SRs), left ventricular diastolic (SRe), and left atrial systole (SRa) before surgery, 3 months and 1 year after surgery. The patients were followed up to observe statin and angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) medication, AF recurrence, 6-min walk test, stroke, any symptoms caused by arrhythmia, and re-hospitalization. Results: The levels of LAD and SD were higher, while SRe and SRa were lower in the cryoablation group in the comparison with the radiofrequency ablation group after surgery (P<0.05). LAEF was lower in the cryoablation group than the radiofrequency ablation group after 3 months (P<0.05). After 1-year follow-up, no right-to-left shunt occurred in all patients with SD. The AF recurrence rate in SD group was higher than that in the normal group (P<0.05). The use of statin and the application of ACEI/ARB were protective factors, whereas hypertension, LAD, left atrial operation time, and surgical plan were risk factors. Conclusion: SD affects left atrial function and increases the risk of AF recurrence. Hypertension, LAD, and left atrial operation time are risk factors for SD, whereas statin and ACEI/ARB drugs can reduce SD. [ABSTRACT FROM AUTHOR]

DNA modification is a naturally occurring DNA modification in prokaryotic and eukaryotic organisms and is involved in several biological processes. Although genome-wide methylation has been studied in many insects, the understanding of global and genomic DNA methylation during insect early embryonic development, is lacking especially for insect diapause. In this study, we analyzed the relationship between DNA methylomes and transcriptomes in diapause-destined eggs compared to diapause-terminated eggs in the silkworm, Bombyx mori (B. mori). The results revealed that methylation was sparse in this species, as previously reported. Moreover, methylation levels in diapause-terminated eggs (HCl-treated) were 0.05% higher than in non-treated eggs, mainly due to the contribution of CG methylation sites. Methylation tends to occur in the coding sequences and promoter regions, especially at transcription initiation sites and short interspersed elements. Additionally, 364 methylome- and transcriptome-associated genes were identified, which showed significant differences in methylation and expression levels in diapause-destined eggs when compared with diapause-terminated eggs, and 74% of methylome and transcriptome associated genes showed both hypermethylation and elevated expression. Most importantly, Kyoto Encyclopaedia of Genes and Genomes (KEGG) analyses showed that methylation may be positively associated with Bombyx mori embryonic development, by regulating cell differentiation, metabolism, apoptosis pathways and phosphorylation. Through analyzing the G2/M phase-specific E3 ubiquitin-protein ligase (G2E3), we speculate that methylation may affect embryo diapause by regulating the cell cycle in Bombyx mori. These findings will help unravel potential linkages between DNA methylation and gene expression during early insect embryonic development and insect diapause. [ABSTRACT FROM AUTHOR]

Carnosic acid (CA), a major polyphenolic diterpene present in Rosmarinus officinalis, has been reported to have multiple functions, including antitumor activity. The MTT assay, BrdU incorporation, wound healing, and colony formation were used to detect melanoma B16F10 cell growth and proliferation. Flow cytometry was used for cell cycle detection. p21 and p27 expression was detected byWestern blotting. B16F10 cell xenograftmodel was established, and treated with CA, carmustine (BCNU), or lomustine (CCNU). The present study found that CA exhibits significant growth inhibition and cell cycle arrest in melanoma B16F10 cells. We also found that CA triggers cell cycle arrest at G0/G1 phase, and enhances p21 expression. Additionally, CA can enhance BCNU- and CCNU-mediated cytotoxicity and cell cycle arrest in B16F10 cells. Finally, we found that CA inhibits tumor growth, and reduces the values of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in vivo. The present study study concluded that CA may be safe and useful as a novel chemotherapeutic agent. [ABSTRACT FROM AUTHOR]

Background: CUL4A has been known for its oncogenic properties in various human cancers. However, its role in intrahepatic cholangiocarcinoma (iCCA) has not been explored.Methods: We retrospectively investigated 105 iCCA cases from a single medical institution. Tissue microarrays were used for immunohistochemical analysis of CUL4A expression. CUL4A expression vectors were introduced in cell lines. Cell migration and invasion assays were used to compare the mobility potential of iCCA cells under basal conditions and after manipulation. Then we evaluated the effects of CUL4A on the cell growth by proliferation assay, and further checked the susceptibility to cisplatin in iCCA cells with or without CUL4A overexpression.Results: CUL4A overexpression was detected in 34 cases (32.4%). Patients with CUL4A-overexpressing tumors exhibited shortened disease-free survival (mean, 27.7 versus 90.4 months; P = 0.011). In the multivariate analysis model, CUL4A overexpression was shown to be an independent unfavorable predictor for disease-free survival (P = 0.045). Moreover, stably transfected CUL4A-overexpressing iCCA cell lines displayed an increased mobility potential and enhanced cell growth without impact on susceptibility to cisplatin.Conclusions: Our data demonstrate that overexpression of CUL4A plays an oncogenic role in iCCA and adversely affects disease-free survival. Thus, it may prove to be a powerful prognostic factor and a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Vancomycin-resistant Enterococcus (VRE) is a kind of enterococci, which shows resistance toward antibiotics. It may last for a long period of time and meanwhile transmit the vancomycin-resistant gene (vanA) to other bacteria. In the United States alone, the resistant rate of Enterococcus to vancomycin increased from a mere 0.3% to a whopping 40% in the past two decades. Therefore, timely diagnosis and control of VRE is of great need so that clinicians can prevent patients from becoming infected. Nowadays, VRE is diagnosed by antibiotic susceptibility test or molecular diagnosis assays such as matrix-assisted laser desorption ionization/time-of-flight mass spectrometry and polymerase chain reaction. However, the existing diagnostic methods have some drawbacks, for example, time-consumption, no genetic information, or high false-positive rate. This study reports an integrated microfluidic system, which can automatically identify the vancomycin resistant gene (vanA) from live bacteria in clinical samples. A new approach using ethidium monoazide, nucleic acid specific probes, low temperature chemical lysis, and loop-mediated isothermal amplification (LAMP) has been presented. The experimental results showed that the developed system can detect the vanA gene from live Enterococcus in joint fluid samples with detection limit as low as 10 colony formation units/reaction within 1 h. This is the first time that an integrated microfluidic system has been demonstrated to detect vanA gene from live bacteria by using the LAMP approach. With its high sensitivity and accuracy, the proposed system may be useful to monitor antibiotic resistance genes from live bacteria in clinical samples in the near future. [ABSTRACT FROM AUTHOR]

BACKGROUND: Metals in single spot urine samples are often used to estimate individual exposure in human studies. However, measurements in urine could vary greatly over time due to variable exposure, potentially leading to exposure misclassification. OBJECTIVE: We examined the variability of metal levels in the urine of 11 men who provided 529 samples on 8 days during a 3-month period, which corresponds to the duration of spermatogenesis. METHOD: The urinary levels of arsenic (As), cadmium (Cd), cobalt (Co), copper (Cu), lead (Pb), molybdenum (Mo), and nickel (Ni) were measured using inductively coupled plasma-mass spectrometry. We calculated the intraclass correlation coefficients (ICCs) to assess the reproducibility of metal measures and computed the sensitivity and specificity to evaluate how well spot urine samples determined the individuals' 3-month average exposure. RESULTS: Fair to good reproducibility was observed for the serial measurements of Cd (ICC = 0.53) in spot samples collected during the 3-month period, whereas the serial measurements of As, Co, Cu, Pb, Mo, and Ni showed poor reproducibility (ICCs = 0.01-0.29). Use of single spot urine samples to classify the high (top 33%) 3-month average metal levels had uniformly high specificities (0.70-0.84) but relatively low sensitivities (0.40-0.57), except for Cd (0.77). The minimum number of specimens (k) required to estimate the participant-specific mean for the seven metals within 20% of the "true" values ranged from 3 for Cd to 27 for Ni. CONCLUSIONS: The high variability observed in the urinary levels of As, Co, Cu, Pb, Mo, and Ni suggests that a single measurement provides only a brief snapshot in time of the exposure levels of an individual, which can result in a moderate degree of exposure misclassification. [ABSTRACT FROM AUTHOR]

BACKGROUND: Previous studies have suggested that elevated exposure to disinfection by-products (DBPs) in drinking water during gestation may result in adverse birth outcomes. However, the findings of these studies remain inconclusive. OBJECTIVE: The purpose of our study was to examine the association between blood biomarkers of late pregnancy exposure to trihalomethanes (THMs) in drinking water and fetal growth and gestational age. METHODS: We recruited 1,184 pregnant women between 2011 and 2013 in Wuhan and Xiaogan City, Hubei, China. Maternal blood THM concentrations, including chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM), were measured as exposure biomarkers during late pregnancy. We estimated associations with gestational age and fetal growth indicators [birth weight, birth length, and small for gestational age (SGA)]. RESULTS: Total THMs (TTHMs; sum of TCM, BDCM, DBCM, and TBM) were associated with lower mean birth weight (-60.9 g; 95% CI: -116.2, -5.6 for the highest vs. lowest tertile; p for trend = 0.03), and BDCM and DBCM exposures were associated with smaller birth length (e.g., -0.20 cm; 95% CI: -0.37, -0.04 for the highest vs. lowest tertile of DBCM; p for trend = 0.02). SGA was increased in association with the second and third tertiles of TTHMs (OR = 2.91; 95% CI: 1.32, 6.42 and OR = 2.25; 95% CI: 1.01, 5.03; p for trend = 0.08). CONCLUSIONS: Our results suggested that elevated maternal THM exposure may adversely affect fetal growth. [ABSTRACT FROM AUTHOR]

Exposure to metals, including essential and nonessential elements, is widespread and may be associated with altered semen quality. This study aimed to examine the association between urinary metal concentrations and semen quality in a Chinese population. We measured semen quality parameters (sperm concentration, count, motility, normal morphology, and abnormal head) and 13 metals [arsenic (As), cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), lead (Pb), manganese (Mn), molybdenum (Mo), mercury (Hg), nickel (Ni), selenium (Se), and zinc (Zn)] in the urine of 394 men from an infertility clinic. Multivariable logistic and linear regressions were used to assess the relationship between the creatinine-adjusted urinary metal concentrations and semen quality parameters. We found a significant trend for decreased odds ratios (ORs) for below-reference sperm count with increasing Se quartiles (p for trend = 0.04) and a significant trend for increased sperm percent abnormal head with increasing Ni quartiles (p for trend = 0.03). These associations persisted, even when considering multiple metals. Our results suggest that Ni exposure may be associated with deteriorated sperm morphology and that Se exposure may be associated with better semen quality. However, our findings warrant further studies in a larger and general population. [ABSTRACT FROM AUTHOR]

Urinary trichloroacetic acid (TCAA) and baseline blood trihalomethanes (THMs) have been measured as biomarkers of exposure to drinking water disinfection by-products (DBPs) that have been associated with increased risk of cancers and adverse reproductive outcomes. This study aimed to identify predictors of urinary TCAA and baseline blood THMs among men in China. Urine samples, blood samples, and information on socio-demographic factors and water-use activities were collected from 2216 men who participated in a cross-sectional study of exposure to drinking water DBPs and reproductive health during 2011 to 2012. Urinary TCAA and baseline blood THMs including chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM) were analyzed. Multivariable linear regression was used to evaluate predictors of urinary TCAA and baseline blood THM concentrations. Tap water consumption was significantly associated with creatinine-adjusted urinary TCAA concentration (β = 0.23 µg/g creatinine per log10 unit; 95% CI: 0.12, 0.35). Men with surface water source had 0.13 (95% CI: 0.00, 0.27) higher mean creatinine-adjusted urinary TCAA concentrations than those with ground water source. Smoking was associated with lower concentration of creatinine-adjusted urinary TCAA. Age was significantly associated with baseline blood Br-THM (sum of BDCM, DBCM, and TBM) concentration (β = 0.01 ng/L per unit; 95% CI: 0.00, 0.02). Increased household income was associated with decreased concentrations of baseline blood BDCM and Br-THMs. Our results suggest that tap water consumption, water source, smoking, age, and household income as the primary determinants of exposure to drinking water DBPs should be considered in exposure assessment. [ABSTRACT FROM AUTHOR]

A novel three-dimensional ZnII complex, poly[aqua(μ4-5-carboxylato-1-carboxylatomethyl-2-oxidopyridinium)zinc(II)], [Zn(C8H5NO4)(H2O)] n, has been prepared by hydrothermal assembly of Zn(CH3COO)2·2H2O and 5-carboxy-1-(carboxymethyl)pyridin-1-ium-2-olate (H2ccop). The ccop2− anions bridge the ZnII cations in a head-to-tail fashion via monodentate aromatic carboxylate and phenolate O atoms to form an extended zigzag chain which runs parallel to the [011] direction. One O atom of the aliphatic carboxylate group of the ccop2− ligand coordinates to the ZnII atom of a neighbouring chain thereby producing undulating layers which lie parallel to the (01) plane. A similar parallel undulating planar structure can be obtained if a path involving the other O atom of the aliphatic carboxylate group is considered. Thus, the aliphatic carboxylate group acts in a bridging bidentate mode to give extended -Zn-O-C-O-Zn- sequences running parallel to [001] which link the layers into an overall three-dimensional framework. The three-dimensional framework can be simplified as a 4-connected sra topology with a Schläfli symbol of 42.63.8 if all the ZnII centres and ccop2− anions are regarded as tetrahedral 4-connected nodes. The three-dimensional luminescence spectrum was measured at room temperature with excitation and emission wavelengths of 344-354 and 360-630 nm, respectively, at intervals of 0.15 and 2 nm, respectively. [ABSTRACT FROM AUTHOR]

Background: Radiation-induced brain injury (RBI) is the most serious complication of primary and metastatic brain and neck malignant tumors following radiation therapy. However, at present, RBI is difficult to diagnose in the early period. Recently, studies have demonstrated that the early stage of RBI is characterized by an inflammatory reaction, and that intercellular adhesion molecule-1 (ICAM-1) is significantly up-regulated in the irradiated brain tissues.Purpose: To provide an early diagnosis of RBI using molecular magnetic resonance imaging (MRI) with microparticles of iron oxide (MPIO) targeted to ICAM-1 in the vascular endothelium of brains.Material and Methods: A monoclonal antibody against ICAM-1 was conjugated to MPIO to form the targeted MRI contrast agent ICAM-MPIO. The adhesion of ICAM-MPIO to endothelial cells was quantified by optical imaging and MRI. Sprague-Dawley rats were irradiated to establish an animal model of the early period of RBI. ICAM-MPIO and free-MPIO were injected via tail vein, respectively. T(2) signal intensity and T(2) values of the irradiated brains and normal brains were subsequently evaluated by MRI.Results: In vitro, the adhesion of ICAM-MPIO to the activated endothelial cells was 5 ± 0.5-fold greater than to the non-stimulated cells, which could be detected by optical imaging and MRI (R(2) = 1.0, P < 0.01). In vivo, ICAM-MPIO caused a marked negative MRI contrast effect in irradiated brains. As compared with brains without irradiation, the specific contrast effect increased more than seven-fold after administration of ICAM-MPIO (F = 751.495, P < 0.05).Conclusion: MPIO coated with monoclonal antibody of ICAM-1 could be used for detecting the early period of RBI by optical imaging and MRI. [ABSTRACT FROM AUTHOR]

Background: Concerns have been raised about how the transmission of emerging infectious diseases from patients to healthcare workers (HCWs) and vice versa could be recognized and prevented in a timely manner. An effective strategy to block transmission of pandemic H1N1 (2009) influenza in HCWs is important. Methodology/Principal Findings: An infection control program was implemented to survey and prevent nosocomial outbreaks of H1N1 (2009) influenza at a 2,600-bed, tertiary-care academic hospital. In total, 4,963 employees at Kaohsiung Chang Gung Memorial Hospital recorded their temperature and received online education on control practices for influenza infections. Administration records provided vaccination records and occupational characteristics of all HCWs. Early recognition of a pandemic H1N1 (2009) influenza case was followed by a semi-structured questionnaire to analyze possible routes of patient contact, household contact, or unspecified contact. Surveillance spanned August 1, 2009 to January 31, 2010; 51 HCWs were confirmed to have novel H1N1 (2009) influenza by quantitative real-time reverse transcription polymerase chain reaction. Prevalence of patient contact, household contact, or unspecified contact infection was 13.7% (7/ 51), 13.7% (7/51), and 72.5% (37/51), respectively. The prevalence of the novel H1N1 infection was significantly lower among vaccinated HCWs than among unvaccinated HCWs (p,0.001). Higher viral loads in throat swabs were found in HCWs with patient and household contact infection than in those with unspecified contact infection (4.15 vs. 3.53 copies/mL, log10, p = 0.035). Conclusion: A surveillance system with daily temperature recordings and online education for HCWs is important for a low attack rate of H1N1 (2009) influenza transmission before H1N1 (2009) influenza vaccination is available, and the attack rate is further decreased after mass vaccination. Unspecified contact infection rates were significantly higher than that of patient contact and household contact infection, highlighting the need for public education of influenza transmission in addition to hospital infection control. [ABSTRACT FROM AUTHOR]

Pandemic (H1N1) 2009 virus causes severe illness, including pneumonia, which leads to hospitalization and even death. To characterize the kinetic changes in viral load and identify factors of influence, we analyzed variables that could potentially influence the viral shedding time in a hospital-based cohort of 1,052 patients. Viral load was inversely correlated with number of days after the onset of fever and was maintained at a high level over the first 3 days. Patients with pneumonia had higher viral loads than those with bronchitis or upper respiratory tract infection. Median viral shedding time after the onset of symptoms was 9 days. Patients <13 years of age had a longer median viral shedding time than those ≥13 years of age (11 days vs. 7 days). These results suggest that younger children may require a longer isolation period and that patients with pneumonia may require treatment that is more aggressive than standard therapy for pandemic (H1N1) 2009 virus. [ABSTRACT FROM AUTHOR]

Abstract: Diglycidyl ether of 4,4′-dihydroxybiphenol (BPDGE) is a liquid crystalline epoxy. The biphenyl epoxy (diglycidyl ether of 3,3′,5,5′-tetramethyl-4,4′-biphenyl, TMBPDGE) has found great applications in plastic encapsulated semiconductor packaging. Phenol novolac (PN) was used as curing agent. The reaction kinetics of BPDGE/PN and TMBPDGE/PN systems in the presence of triphenylphosphine (TPP) were characterized by an isoconversional method under dynamic conditions using differential scanning calorimetry (DSC) measurements. The results showed that the curing of epoxy resins involves different reaction stages and the values of activation energy are dependent on the degree of conversion. The effects of curing temperature on their phase structure have been investigated with polarized optical microscopy and Wide-angle X-ray diffraction. With proper curing process, BPDGE showed a nematic phase when cured with PN. [Copyright &y& Elsevier]

Bowens disease (BD), a carcinoma in situ of the skin, has been identified as an early lesion in arsenic carcinogenesis. Patients with arsenic-induced Bowens disease (As-BD) showed both cutaneous and systemic immune dysfunctions. We set out to evaluate the interactions between keratinocytes and lymphocytes in the context of As-BD carcinogenesis. Our results showed that As-BD lesions demonstrated a significant dermal CD4+ cell, an essential regulator of proper tumor immunity, undergoing apoptosis. In addition, it was found that the As-BD patients have lower percentage of peripheral CD4+ cells as compared with control subjects. However, the CD4+ cells from As-BD patients were less susceptible to arsenic-induced apoptosis, due to reduced tumor necrosis factor receptor 1 expression. Interestingly, arsenic was found to induce Fas expression on CD4+ cells and increase the soluble Fas ligand (sFasL) production from keratinocytes. This sFasL-containing keratinocyte supernatant was able to induce comparable CD4+ cell apoptosis for both patients and controls. Using immunofluorescent staining, increased FasL was observed in keratinocytes of As-BD lesions and Fas was expressed among infiltrating CD4+ cells. Our findings suggested that systemically, the percentage of CD4+ cells was decreased in the peripheral blood of As-BD patients. These residual CD4+ cells were less susceptible to arsenic-induced apoptosis. However, once infiltrated into the As-BD lesions, the selective CD4+ cell apoptosis might be mediated by FasL from keratinocytes. This additional tumor-anti-immune phenomenon present in the cutaneous environment provides a reasonable explanation for frequent occurrence of arsenic cancers in the skin. [ABSTRACT FROM AUTHOR]

Acute intermittent porphyria (AIP) is a rare metabolic disorder characterized by mutations of the porphobilinogen deaminase gene. Clinical manifestations of AIP are caused by the neurotoxic effects of increased porphyrin precursors, although the underlying pathophysiology of porphyric neuropathy remains unclear. To further investigate the neurotoxic effect of porphyrins, excitability measurements (stimulus-response, threshold electrotonus, current–threshold relationship and recovery cycle) of peripheral motor axons were undertaken in 20 AIP subjects combined with the results of genetic screening, biochemical and conventional nerve conduction studies. Compared with controls, excitability measurements from five latent AIP patients were normal, while 13 patients who experienced acute porphyric episodes without clinical neuropathy (AIPWN) showed clear differences in their responses to hyperpolarizing currents (e.g. reduced hyperpolarizing I/V slope, P < 0.01). Subsequent mathematical simulation using a model of human axons indicated that this change could be modelled by a reduction in the hyperpolarization-activated, cyclic nucleotide-dependent current (IH). In contrast, in one patient tested during an acute neuropathic episode, axons of high threshold with reduced superexcitability, consistent with membrane depolarization and reminiscent of ischemic changes. It is proposed that porphyrin neurotoxicity causes a subclinical reduction in IH in AIPWN axons, whereas porphyric neuropathy may develop when reduced activity of the Na+/K+ pump results in membrane depolarization. [ABSTRACT FROM AUTHOR]