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Particle packed columns used for liquid chromatography (LC) can suppress a column internal band broadening (hereinafter referred to as band broadening) by packing monodisperse particles homogenously. However, a quantitative evaluation for the effects of particle shape and packed state on band broadening needs to be more investigated. In this study, we fabricated a model of particle packed bed using microfluid LC columns that have pillar array structure prepared by microfabrication technology, evaluating how structural factors inside of a column affect its band broadening. At first, microfluid LC columns was prepared using Si-quartz glass (Si-Q column) for the optimization of LC measurement system. Through the evaluation, it showed 11.6 times higher pressure tolerance compared to that of PDMS-soda lime glass (PDMS-g column). Then, an optimized LC measurement system was constructed using a microfluidic LC column made of Si-Q column, and it was confirmed that the measurement error was small enough and the LC measurement could be performed with high repeatability. Additionally, the effect of a distribution of structural size on band broadening was evaluated. It was confirmed that wide distribution of the structural size provided large band broadening in actual measurements. Comparing two columns having different structural log-normal distributions of 0 and 0.22 showed approximately 1.8 times difference in both real LC measurement. Lastly, the relationship between packed state and band broadening was evaluated. As packed state, we employed void arrangement and structural arrangement in the columns. Different location arrangements of 50 and 100 µm pillar sizes afforded different band broadening. Well-homogenized array showed approximately two times worse band broadening compared to that of delocalized array. Based on these results, the developed packed bed of particles model was able to evaluate the relation between structural factors and band broadening., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Case Presentation: A 57-year-old woman was admitted to our hospital for an abnormal chest shadow found during routine chest radiography. She had no respiratory symptoms. Her medical history included dyslipidemia, and her surgical history included conization for cervical cancer at age 38 years. She was a social drinker and ex-smoker of approximately 10 cigarettes per day (from ages 20 to 30 years); she denied recreational drug use., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Introduction: Echinocandins are frequent use antifungals in the treatment of invasive candidiasis, and it is important to update information on their efficacy and safety for optimal antifungal drug treatment. The aim of this study is to clarify whether echinocandins are superior to non-echinocandins for the treatment of invasive candidiasis., Methods: We conducted a meta-analysis of RCTs of echinocandins and non-echinocandins for adult invasive candidiasis. The MEDLINE, Web of Sciences, Cochrane Register of Controlled Trials, and ClinicalTrials.gov databases before June 2019 were used. The risk ratio (RR) and 95% confidence interval (95% CI) were calculated using the Mantel-Haenszel method random-effects model., Results: We identified 14,846 articles and screened, and five studies were included meta-analysis. The treatment success ratio for echinocandins was significantly higher than that for non-echinocandins (RR = 1.14, 95% CI 1.06-1.22, p = 0.0003). In regard to adverse events, there was no significant difference between the two treatment groups. A subgroup analysis showed that the treatment success ratio for echinocandins was significantly higher than that for azoles (RR = 1.20, 1.08-1.34, p = 0.001), whereas no significant differences were observed between echinocandins and polyenes. In safety analysis, the incidence ratio of electrolyte disorder (RR = 0.50, 0.33-0.76, p = 0.001), renal disorder (RR = 0.19, 0.09-0.40, p < 0.0001), and fever (RR = 0.46, 0.23-0.93, p = 0.03) were significantly lower in patients receiving echinocandins than in those receiving polyenes., Conclusions: This meta-analysis based on RCTs was first to show that use of echinocandins was associated with improved clinical success. Echinocandins may be useful as a first-line drug for invasive candidiasis., Competing Interests: Declaration of Competing Interest ST, SO, YI, YW, XL, YE, KT, TM, YM, and KM report no conflicts of interest. YT received research grants from Dainippon Sumitomo Pharm Co., Ltd., Astellas Pharm, Inc., and MSD Japan., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Because exclusive use of echinocandins can induce the drug-resistant strains, appropriate use of azoles and polyenes is still necessary in the treatment of candidemia. In this study, we conducted a meta-analysis of randomized controlled trials regarding the efficacy and safety of azole and polyene antifungals in the treatment of candidemia. MEDLINE and the Cochrane Register of Controlled Trials were used as reference databases, and papers published up to June 10, 2019 were searched. The search results were carefully scrutinized, duplicate references were removed, and the study was ultimately carried out using three reports. Among azole antifungals, fluconazole and voriconazole were extracted, however; only conventional amphotericin B (AMPH-B) was extracted among polyene antifungals. Treatment successes with the use of azoles and AMPH-B were compared, and findings showed that AMPH-B was significantly superior (RR = 0.90, 95% CI 0.82-1.00, p = 0.04). However, there was no significant difference in mortality (RR = 0.87, 95% CI 0.72-1.07, p = 0.19). Analysis of adverse events showed that renal disorders were significantly less common with azoles than with AMPH-B (RR = 0.26, 95% CI 0.10-0.68, p = 0.006). In conclusion, AMPH-B were superior to azoles in terms of efficacy, but had a risk of causing renal disorders., Competing Interests: Declaration of competing interest ST, SO, YI, YW, XL, YE, KT, TM, YM, and KM report no conflicts of interest. YT received research grants from Dainippon Sumitomo Pharm Co., Ltd., Astellas Pharm, Inc., and MSD Japan., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Mammals possess four Sall transcription factors that play various roles in organogenesis. Previously, we found that Sall1 is expressed in microglia in the central nervous system, and it plays pivotal roles in microglia maturation. In the eye, Sall1 was also expressed in the developing lens, and we examined its role in lens development. A knock-in mouse harboring the EGFP gene in the Sall1 locus (Sall1-gfp) was used to analyze the Sall1 expression pattern. In Sall1-gfp/wild, EGFP was expressed throughout the presumptive lens at E11.5, and subsequently the expression in the lens epithelium became weaker. After birth, signals were observed in the equator region. The effects of Sall1 knockout on lens development were examined in Sall1-gfp/gfp. Lens sections revealed small vacuole-like holes and gaps in the center of the lens fibers at E14.5. Subsequently, the vacuoles appeared in most regions of the fiber cells. Electron microscopic analysis indicated that the vacuoles were between the fiber cells, leading to huge gaps. In addition, contact between the lens epithelium and apical end of the fiber cell was disrupted, and there were gaps between the adjoining lens epithelial cells. However, gap junction structure was observed by electron microscopic analysis, and immunostaining of Zo1 showed rather appropriate expression pattern. Immunohistochemistry indicated that the major lens transcription factors Prox1 and Pax6 were expressed in relatively normal patterns. However, although the expression of Prox1 and Pax6 decreased in nuclei in the control lens, it remained in Sall1-gfp/gfp. In addition, lower expression level of c-Maf protein was observed. Therefore, Sall1 is strongly expressed in the lens from the early developmental stage and plays an essential role in the maintenance of fiber cell and lens epithelium adhesion., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Members of the Zic family of zinc finger transcription factors play critical roles in a variety of developmental processes. Using DNA microarray analysis, we found that Zics are strongly expressed in SSEA-1-positive early retinal progenitors in the peripheral region of the mouse retina. Reverse-transcription polymerase chain reaction using mRNA from the retina at various developmental stages showed that Zic1 and Zic2 are expressed in the embryonic retina and then gradually disappear during retinal development. Zic3 is also expressed in the embryonic retina; its expression level slightly decreases but it is expressed until adulthood. We overexpressed Zic1, Zic2, or Zic3 in retinal progenitors at embryonic day 17.5 and cultured the retina as explants for 2 weeks. The number of rod photoreceptors was fewer than in the control, but no other cell types showed significant differences between control and Zic overexpressing cells. The proliferation activity of normal retinal progenitors decreased after 5 days in culture, as observed in normal in vivo developmental processes. However, Zic expressing retinal cells continued to proliferate at days 5 and 7, suggesting that Zics sustain the proliferation activities of retinal progenitor cells. Since the effects of Zic1, 2, and 3 are indistinguishable in terms of differentiation and proliferation of retinal progenitors, the redundant function of Zics in retinal development is suggested., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Surface modified molecularly imprinted polymers (SM-MIPs) for 17beta-estradiol (E2), utilizing 6-ketoecradiol as a pseudo template were prepared. MIPs for E2 were synthesized using 4-vinyl pyridine and ethylene dimethacrylate as a functional monomer and cross-linking agent, respectively. MIPs selectively retained E2 and provided excellent chromatographic resolution from interfering compounds inherent in river water sample matrices. Therefore, freshly prepared MIPs were applied to quantitative mass spectrometric (negative electrospray ionization mode) detection of low levels of E2 in river water sample. In order to pre-concentrate the target compound for HPLC analysis, column switching was coupled with a pretreatment column packed with the MIPs. The repeatability of actual determinations of river water sample, in which background E2 was not detected, spiked with 50 ng/L of E2 was 2.2% RSD with a detection limit and qualification limit of 1.8 and 5.4 ng/L, respectively. Surface modification of MIP particlefs packed in the pretreatment column provided selective affinity and on-line concentration of low levels of E2 while simultaneously eliminating sample matrix interference, resulting in a significant increase in sensitivity and reproducibility for liquid chromatography-mass spectrometry analysis of E2 in river water sample.

We studied an applicability of a silica monolithic membrane as separation medium for high-performance liquid chromatography (HPLC). We prepared porous monolithic silica membranes having a three-dimensional network structure to cut and shape into a membrane separation medium. We evaluated chromatographic properties of a variety of solutes using a column containing the membranes with HPLC to elucidate summable property of the membrane separation media. In addition, we made brief study on separation of HbA1c in whole blood with the stacked" membranes having different surface characteristics in one column, which is a membrane column. We confirmed that the membrane column was able to separate HbA1c from other matrix in whole blood to some extent, and it also had an excellent ability for hydrophobic and ion exchange adsorption.

Uniformly sized molecularly imprinted polymers (MIPs) for bisphenol A (BPA) with surface modification and immobilized intervals of functional monomers afforded by utilizing 4,4'-methylenebisphenol as a pseudo component have been prepared. MIPs for BPA were prepared using 4-vinyl pyridine immobilized in the most effective interval and ethylene glycol dimethacrylate as a functional monomer and cross-linking agent, respectively. Prepared MIPs showed significant selectivity for BPA retention and removal performance for interference in actual samples as the HPLC stationary phase compared to those of ordinary MIPs. These MIPs were employed as pretreatment media of column switching HPLC and the HPLC system provided a detection limit of 0.36 ppt when electrochemical detection was used. Actual samples, including Suwannee River natural organic matter (NOM), were applied and BPA was detected in the NOM even if widely used UV detection was employed.

A novel adsorption medium containing selective molecular recognition site for one of the powerful cyanobacterium toxins, Cylindrospermopsin (CYN) was developed using a special technique, namely interval immobilization technique. The adsorption medium was prepared using molecular assembly derived from an alternative-template molecule coupled with functional monomers for fixing the interval between the ionic functional groups in CYN. As results of liquid chromatographic evaluations, selective molecular recognition ability for CYN was observed as expected. Further studies proved that the association constant for CYN on this medium was slightly higher than that on blank polymer.

We have developed a simple HPLC method for the microanalysis of bisphenol A (BPA), which is often contained in environmental water and is known as an endocrine disrupter. HPLC coupled with electrochemical detection requires a simpler procedure of pretreatment compared to GC-MS. In this study, we analyzed BPA using molecularly imprinted polymer as an on-line pretreatment device. This polymer has molecular recognition sites and provides specific selectivity in extraction process. Due to this effect, the detection limit obtained with this HPLC was 0.36 ng/l. This method applied to environmental water and purified water samples containing 2-70 ng/l of BPA successfully. Furthermore, UV detection was performed in some actual analyses.

A pair of polymeric selectors potentially responding to stimulation was introduced onto monosized porous polymer particles to be evaluated as a packing material for HPLC. Possible complexes formed between polyacrylamide (PAAm) and poly(methacrylic acid) (PMAA) were utilized as stimulus responsive polymeric selectors. Uniformly sized base polymer particle was prepared by multi-step swelling and polymerization method, while the introduction of PAAm and PMAA was done by newly invented modification technique. In this technique, a solvent in which both acrylamide (AAm) and methacrylic acid (MAA) monomers are soluble, but PAAm and PMAA are insoluble, was utilized as a modification medium. The polymer particle doubly modified with PAAm and PMAA was utilized as packing material for HPLC and the stimulus responses were evaluated by changing temperature or pH to check change of the slope of a Van't Hoff plot. By using water as a mobile phase, the expected inflection point of the Van't Hoff plot was observed at upper critical solution temperature (UCST) of the polymer complexes and the temperature responsive ability was observed. Moreover, pH responsive ability was studied by using buffer of either pH 4 or 10 as mobile phase. Slope of the plot was changed in buffer of pH 4, but no change of slope was observed in the buffer of pH 10.

A polymer-based adsorption medium having molecular recognition ability for homologues of chlorinated bisphenol A produced in environment was prepared using a fragment imprinting technique. 2,6-Dimethyl phenol was utilized as a pseudo-template molecule and the adsorption media prepared was evaluated by high performance liquid chromatography (HPLC) and solid-phase extraction (SPE). As results, the adsorption medium showed preferable chromatographic retention and specific adsorption ability for the chlorinated bisphenol As having chlorine substituents at 3,5-positions through fragment imprinting effect.

An efficient extraction method for bisphenol A from environmental water including contaminants was developed using surface selective localization of functional group, on a polymeric separation device. The polymer utilized in this study was prepared through a kind of molecular imprinting technique, namely fragment imprinting effect utilizing a pseudo-template molecule (p-tert.-butylphenol) instead of bisphenol A. The concentration of bisphenol A onto the polymer device prepared, up to 1000 times concentration from environmental water including contaminants (humic acids), was achieved very easily with interesting exclusion effect for humic acids. The results obtained in this study suggest that molecular imprinting with the pseudo-template molecule is quite an effective way for selective concentration of the diluted target molecule from other contaminants including similar functional group with the target molecule.

Ten preterm infants severely ill with hyaline-membrane disease (HMD) were given artificial surfactant endotracheally. Oxygenation and alveolar-arterial oxygen gradients improved, the levels of inspired oxygen and peak respirator pressure could be reduced, and many of the radiological abnormalities resolved. Acidosis and systemic hypotension were also reversed. In nine infants a patent ductus arteriosus became evident after recovery from HMD, necessitating further assisted ventilation. Eight infants survived, including five of six with birthweight less than 1500 g; two died of unrelated causes. Postnatal tracheal instillation of artificial surfactant may prove a useful treatment for severe HMD.