Search

Abstract Objective To study structure-specific solubilization effect of Sulfobutyl ether-β-cyclodextrin (SBE-β-CD) on Remdesivir (RDV) and to understand the experimental clathration with the aid of quantum mechanics (QM), molecular docking and molecular dynamics (MD) calculations. Methods The experiment was carried out by phase solubility method at various pH and temperatures, while the concentration of Remdesivir in the solution was determined by HPLC. The complexation mechanism and the pH dependence of drug loading were investigated following a novel procedure combining QM, MD and molecular docking, based on accurate pKa predictions. Results The phase solubility and solubilization effect of RDV in SBE-β-CD were explored kinetically and thermodynamically for each assessed condition. An optimal drug / SBE-β-CD feeding molar ratio was determined stoichiometrically for RDV solubility in pH1.7 solution. The supersaturated solubility was examined over time after pH of the solution was adjusted from 1.7 to 3.5. A possible hypothesis was raised to elucidate the experimentally observed stabilization of supersaturation based on the proposed RDV Cation A /SBE-β-CD pocket conformations. Conclusion The computational explorations conformed to the experimentally determined phase solubilization and well elucidated the mechanism of macroscopic clathration between RDV and SBE-β-CD from the perspective of microscopic molecular calculations. Graphical Abstract

In this study, we describe the use of a sodium cholate suspension-dialysis method to adsorb the redox enzyme glucose oxidase (GOX) onto single-walled carbon nanotubes (SWNT). By this method, solutions of dispersed and debundled SWNTs were prepared that remained stable for 30 days and which retained 75% of the native enzymatic activity. We also demonstrate that GOX-SWNT conjugates can be assembled into amperometric biosensors with a poly[(vinylpyridine)Os[(bipyridyl).sub.2][Cl.sup.2+/3+]] redox polymer (PVP-Os) through a layer-by-layer (LBL) self-assembly process. Incorporation of SWNT-enzyme conjugates into the LBL films resulted in current densities as high as 440 [micro]A/[cm.sup.2], which were a 2-fold increase over the response of films without SWNTs. We also demonstrate that the adsorption pH of the redox polymer solution and the dispersion quality of SWNTs were important parameters in controlling the electrochemical and enzymatic properties of the LBL films.

Control of polymorphism of the enantiotropic p-aminobenzoic acid at either the α or β polymorphwhile maintaining high yield was achieved by mixed suspension mixedproduct removal (MSMPR) cascade design. A systematic approach wasdeveloped to identify the operational window of the process variables,stage temperature and residence time, in which the stringent polymorphpurity criterion (>95 wt %) and high yield were met. The comprehensiveunderstanding of the polymorphism of the model compound, p-aminobenzoic acid, was the key for the identification of the operationalwindow. On the basis of single-stage MSMPR experiments, three temperatureregimesthermodynamic control, energy barrier control, andkinetic competitionwere identified, and the interplay betweenthe crystallization kinetics and the thermodynamics in each regimewas elucidated. Experimental studies also demonstrated the first polymorphspecific MSMPR for enantiotropic systems. Single-stage MSMPRs at lowtemperature, e.g., 5 °C, were found to be β polymorph-specificat steady states across multiple operating conditions. Two-stage MSMPRwas designed to alter the polymorphism at the 5 °C stage fromβ polymorph-specific to α polymorph-specific. The firststage temperature was selected in the thermodynamic control regime(30 °C) at which the steady state polymorphism was α-specific.Feeding continuously to the second stage, the α crystals generatedat the first stage increased the total surface area and thereby thesecondary nucleation and mass deposition rates of the α polymorphin the 5 °C stage. This in turn increased the α polymorphfrom 0 wt % to at least 75 wt %, proving that it is feasible to controlthe polymorphism via design of the MSMPR cascade. [ABSTRACT FROM AUTHOR]

Abstract: SrAl2O4:Eu2+ phosphors with various content of Bi2O3 flux were synthesized and analyzed. It was observed that the crystallinity and the particle size of the phosphors were increased with the addition of Bi2O3 flux. These phenomena are considered to be caused via the melting of the Bi2O3 flux particles during the synthesis of the phosphors. The melted Bi2O3 flux increased the mobility and homogeneity of solid reactants, thereby enhancing the photoluminescence intensity of the phosphors. SrAl2O4:Eu2+ phosphors with Bi2O3 as the flux exhibited a broad green emission with a peak at 520nm. The highest photoluminescence emission intensity was observed when 5mol% Bi2O3 flux was added into the phosphors. The emission is due to 4f65d→4f7 (8S7/2) transitions of the Eu2+ ions. Moreover, Bi2O3 flux extended the application of the ultraviolet excited phosphors toward the blue-light excited phosphors. Nevertheless, the influence of Bi2O3 on the afterglow and the emission color of SrAl2O4:Eu2+ phosphors were not significant. This research indicated that Bi2O3 flux is effective flux for synthesizing SrAl2O4:Eu2+ phosphors. [Copyright &y& Elsevier]

The capability index C"pk is designed for an in-control process with asymmetric tolerances. In this article, the density function of the natural estimator is derived. The expression is in terms of finite sum and only involves standard normal distribution. Four ensemble estimators for C"pk are proposed. A simulation study is conducted due to the complexity of the mean-squared error of the estimators. The comparisons among estimators are based on the mean-squared error, standard error and absolute bias of estimators. Furthermore, the ability for an estimator to reach a given capability level is also considered. [ABSTRACT FROM AUTHOR]

The capability index C"pk is designed for an in-control process with asymmetric tolerances. In this article, the density function of the natural estimator is derived. The expression is in terms of finite sum and only involves standard normal distribution. Four ensemble estimators for C"pk are proposed. A simulation study is conducted due to the complexity of the mean-squared error of the estimators. The comparisons among estimators are based on the mean-squared error, standard error and absolute bias of estimators. Furthermore, the ability for an estimator to reach a given capability level is also considered. [ABSTRACT FROM AUTHOR]

Abstract Background Kocuria, established by Stackebrandt et al., previously was classified into Micrococcus. Only two species, K. rosea and K. kristinae are reported to be associated as pathogenic and found with catheter-related bacteremia and acute cholecystitis. Case presentation We herein report the first case of brain abscess caused by Kocuria varians, a gram-positive microorganism, in a 52-year-old man. Hematogenous spread is the probable pathogenesis. Conclusions This report presents a case of Kocuria varians brain abscess successfully treated with surgical excision combined with antimicrobial therapy. In addition, Vitek 2 system has been used to identify and differentiate between coagulase-negative staphylococcus.

Background: Mycoplasma pneumoniae is a pneumonia-causing pathogen commonly found in pediatric patients in Taiwan. Recently, macrolide-resistant (MR) strains have been emerging globally. The prevalence of pneumonia due to MR-M. pneumoniae (hereafter, MPP) in northern Taiwan before 2017 has been reported to be 12.3-24%. The prevalence of MR-MPP within a specific location can vary. Hence, we investigated the prevalence of MR-MPP in southern Taiwan., Methods: Eighty-one children with PCR-confirmed MPP were enrolled between July 2016 and June 2019. They were assigned to macrolide-sensitive (MS) and MR groups based on their PCR results, and their clinical manifestations and laboratory data were compared., Results: The proportions of patients with MS-MPP and MR-MPP varied with time. The average ratio of the proportion of MR-MPP was 54.3% in this study. Patients with MR-MPP had lower neutrophil counts, higher lymphocyte counts, and higher platelet counts than those with MS-MPP. In contrast with the 40% of the MR-MPP group that still had a fever after three days of azithromycin treatment, only 11.8% of the MS-MPP group still had a fever., Conclusion: Our study provided valuable epidemiological survey information for children with MR-MPP in southern Taiwan. The prevalence of MR-MPP was different from that reported in previous studies in northern Taiwan. Specific MR strains should be considered in children with MPP if they still have a fever after three days of macrolide treatment., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021. Published by Elsevier B.V.)

Mycoplasma pneumoniae is a common pathogen that causes community-acquired pneumonia. In the past, M. pneumoniae was sensitive to macrolide antibiotics, and M. pneumoniae pneumonia (MPP) was usually a benign and self-limiting disease. However, despite use of the appropriate antibiotics, persistent fever and clinical deterioration may occur, leading to severe disease. Two major complicated conditions that may be clinically encountered are macrolide-resistant MPP and refractory MPP. Regarding the epidemics in Taiwan, before 2017, the mean rate of macrolide resistance was below 30%. Notably, since 2018, the prevalence of macrolide-resistant MPP in Taiwan has increased rapidly. Macrolide-resistant MPP shows persistent fever and/or no radiological regression to macrolide antibiotics and may even progress to severe and complicated pneumonia. Tetracyclines (doxycycline or minocycline) or fluoroquinolones are alternative treatments for macrolide-resistant MPP. Refractory MPP is characterized by an excessive immune response against the pathogen. In this context, corticosteroids have been suggested as an immunomodulator for downregulating the overactive host immune reaction. Overuse of macrolides may contribute to macrolide resistance, and thereafter, an increase in macrolide-resistant MPP. Delayed effective antimicrobial treatment is associated with prolonged and/or more severe disease. Thus, the appropriate prescription of antibiotics, as well as the rapid and accurate diagnosis of MPP, is important. The exact starting point, dose, and duration of the immunomodulator are yet to be established. We discuss these important issues in this review., Competing Interests: Declaration of competing interest The authors declare that there are no competing financial interests related to this work., (Copyright © 2020. Published by Elsevier B.V.)

Background: Mycoplasma pneumoniae is one of the major pathogens causing community-acquired pneumonia in children. Although usually self-limited, Mycoplasma pneumoniae pneumonia (MPP) may lead to complicated morbidity that can even be life-threatening. Upon MPP infection, alveolar macrophage becomes attracted and activated and will induce subsequent cytokine and chemokine reaction. Refractory Mycoplasma pneumoniae pneumonia (RMPP) is manifested by clinical or radiological deterioration despite proper antibiotic therapy. RMPP is characterized with excessive inflammation and may need subsequent glucocorticoid treatment., Aim: The aim of this study was to investigate the change of plasma chemokines in non-refractory Mycoplasma pneumoniae pneumonia (NRMPP) and RMPP before and after antibiotic or methylprednisolone treatment., Method: A total of 42 children with MPP were enrolled in this study. Plasma specimens were collected at admission and one to two weeks after antibiotic or methylprednisolone treatment with declined fever. Plasma specimens were then indicated to chemokines detection., Results: Mycoplasma pneumoniae pneumonia altered the chemokine profile through the observation of decreased plasma M1 related chemokines (CCL2, CCL8 and CXCL10) and increased M2 related chemokines (CCL17 and CCL22) after treatment.When the patients were divided into RMPP and NRMPP groups and the chemokines before treatment were compared, the RMPP group showed higher CXCL10 but lower CCL3 and CCL11 than the NRMPP group., Conclusion: Unique changes in macrophage related chemokines is observed in the course of MPP infection. NRMPP and RMPP infection in children showed distinct manifestation in chemokine profiles., (Copyright © 2020. Published by Elsevier B.V.)

Introduction: Phthalates are substances that are added to plastic products to increase their plasticity. These substances are released easily into the environment and can act as endocrine disruptors. Epidemiological studies in children have showed inconsistent findings regarding the relationship between prenatal or postnatal exposure to phthalates and the risk of allergic disease. Our hypothesis is that prenatal exposure to phthalates may contribute to the development of allergies in children. Material and methods: The objective of this study was to determine the associations between urinary phthalate metabolite concentrations in pregnant women, maternal atopic diathesis, maternal lifestyle, and cord blood IgE. Pregnant mothers and paired newborns (n = 101) were enrolled from an antenatal clinic. The epidemiologic data and the clinical information were collected using standard questionnaires and medical records. The maternal blood and urine samples were collected at 24-28 weeks gestation, and cord blood IgE, IL-12p70, IL-4, and IL-10 levels were determined from the newborns at birth. The link between phthalates and maternal IgE was also assessed. To investigate the effects of phthalates on neonatal immunity, cord blood mononuclear cells (MNCs) were used for cytokine induction in another in vitro experiment. Results: We found that maternal urine monoethyl phthalate (MEP) (a metabolite of di-ethyl phthalate (DEP)) concentrations are positively correlated with the cord blood IgE of the corresponding newborns. The cord blood IL-12p70 levels of mothers with higher maternal urine MEP groups (high DEP exposure) were lower than mothers with low DEP exposure. In vitro experiments demonstrated that DEP could enhance IL-4 production of cord blood MNCs rather than adult MNCs. Conclusion: Prenatal DEP exposure is related to neonatal IgE level and alternation of cytokines relevant to Th1/Th2 polarization. This suggests the existence of a link between prenatal exposure to specific plasticizers and the future development of allergies.

Few studies have addressed the risk of infection in transfusion-naïve thalassemia patients. We aimed to investigate whether transfusion-naïve thalassemia population has higher hospitalization rates for lower airway infection-related diseases than non-thalassemia population in children. A nationwide population-based retrospective cohort study was conducted using detailed medical records of the Taiwan National Health Insurance Research Database. Transfusion-naïve thalassemia patients were compared with a matched cohort at a ratio of 1:4. Data of the selected patients were adjusted for age, sex, and related comorbidities. We recorded the frequency of admissions or outpatient clinic visits for patients with a diagnosis of pneumonia or acute bronchitis/bronchiolitis. Based on our results, the hospitalization rates and incidence rate ratios of bronchitis/bronchiolitis and pneumonia for transfusion-naïve thalassemia children were all higher than those for non-thalassemia controls. Therefore, we conclude that transfusion-naïve thalassemia children are more likely to experience lower airway infections and have a higher probability of hospitalization for these conditions., (Copyright © 2020 Tsai, Tsai, Yang, Lee, Sheen, Lee, Tsai, Chen, Chang, Niu and Yu.)

Acute lower respiratory infection is the leading cause of child death in developing countries. Current strategies to reduce this problem include early detection and appropriate treatment. Better diagnostic and therapeutic strategies are still needed in poor countries. Artificial-intelligence chest X-ray scheme has the potential to become a screening tool for lower respiratory infection in child. Artificial-intelligence chest X-ray schemes for children are rare and limited to a single lung disease. We need a powerful system as a diagnostic tool for most common lung diseases in children. To address this, we present a computer-aided diagnostic scheme for the chest X-ray images of several common pulmonary diseases of children, including bronchiolitis/bronchitis, bronchopneumonia/interstitial pneumonitis, lobar pneumonia, and pneumothorax. The study consists of two main approaches: first, we trained a model based on YOLOv3 architecture for cropping the appropriate location of the lung field automatically. Second, we compared three different methods for multi-classification, included the one-versus-one scheme, the one-versus-all scheme and training a classifier model based on convolutional neural network. Our model demonstrated a good distinguishing ability for these common lung problems in children. Among the three methods, the one-versus-one scheme has the best performance. We could detect whether a chest X-ray image is abnormal with 92.47% accuracy and bronchiolitis/bronchitis, bronchopneumonia, lobar pneumonia, pneumothorax, or normal with 71.94%, 72.19%, 85.42%, 85.71%, and 80.00% accuracy, respectively. In conclusion, we provide a computer-aided diagnostic scheme by deep learning for common pulmonary diseases in children. This scheme is mostly useful as a screening for normal versus most of lower respiratory problems in children. It can also help review the chest X-ray images interpreted by clinicians and may remind possible negligence. This system can be a good diagnostic assistance under limited medical resources.

In the real world, dynamic changes in air pollutants and meteorological factors coexist simultaneously. Studies identifying the effects of individual pollutants on acute exacerbation (AE) of asthma may overlook the health effects of the overall combination. A comprehensive study examining the influence of air pollution and meteorological factors is required. Asthma AE data from emergency room visits were collected from the Taiwan National Health Insurance Research Database. Complete monitoring data for air pollutants (SO 2 ; NO 2 ; O 3 ; CO; PM 2.5 ; PM 10 ) and meteorological factors were collected from the Environmental Protection Agency monitoring stations. A bi-directional case-crossover analysis was used to investigate the effects of air pollution and meteorological factors on asthma AE. Among age group divisions, a 1 °C temperature increase was a protective factor for asthma ER visits with OR = 0.981 (95% CI, 0.971-0.991) and 0.985 (95% CI, 0.975-0.994) for pediatric and adult patients, respectively. Children, especially younger females, are more susceptible to asthma AE due to the effects of outdoor air pollution than adults. Meteorological factors are important modulators for asthma AE in both asthmatic children and adults. When studying the effects of air pollution on asthma AE, meteorological factors should be considered., Competing Interests: The authors declare no conflict of interest.

Obesity during pregnancy increases the risk of cardiovascular problems, diabetes, asthma, and cognitive impairments, affecting the offspring. It is important to reduce the negative effects of obesity and high-fat (HF) diet during pregnancy. We employed a rat model of maternal HF diet to evaluate the possible de-programming effects of resveratrol in rodent male offspring with maternal HF diet/obesity. Male rat offspring were randomized into four groups: maternal control diet/postnatal control diet, maternal HF diet/postnatal control diet, maternal control diet plus maternal resveratrol treatment/postnatal control diet, and maternal HF diet plus maternal resveratrol treatment/postnatal control diet. Maternal HF diet during pregnancy plus lactation resulted in retroperitoneal adiposity in the male offspring. Maternal resveratrol treatment re-programmed maternal HF exposure-induced visceral adiposity. Offspring that received prenatal HF diet showed higher leptin/soluble leptin receptor (sOB-R) ratio than offspring that received prenatal control diet. Maternal resveratrol treatment ameliorated maternal HF exposure-induced increase in leptin/sOB-R ratio and altered the expression of genes for crucial fatty acid synthesis enzymes in the offspring. Thus, maternal resveratrol administration reduces retroperitoneal adiposity in rat offspring exposed to prenatal HF diet/obesity and could be used to ameliorate negative effects of maternal HF diet in the offspring.

A method for the non-covalent attachment of proteins to single-walled carbon nanotubes (SWNTs) is described. In this method, the protein is adsorbed to SWNTs that are suspended using sodium cholate, a surfactant and bile salt. The sodium cholate is then removed by dialysis with retention of the protein on the SWNTs. This method has resulted in good protein loadings and good retention of protein activity.