Stage III Chorioamnionitis is Associated with Reduced Risk of Severe Retinopathy of Prematurity.

OBJECTIVE: To identify whether histologically confirmed chorioamnionitis (hCAM) is associated with development of retinopathy of prematurity (ROP). STUDY DESIGN: We retrospectively analyzed 2 different cohorts. Cohort 1 was the national database of newborns in Japan born at ≤1500g or <32 weeks' gestation (January 2003 through April 2021, n = 38 013). Cohort 2 was babies born at <1500g from a single institution in Tsuchiura, Japan, (April 2015 through March 2018, n = 118). RESULTS: For Cohort1, after adjusting for potential confounders, stage III CAM (n = 5554) was associated with lower odds of severe ROP (stage ≥3 or required peripheral retinal ablation) by 14% (OR: 0.86; 95% CI: 0.78-0.94]. CAM of stage I (n = 3277) and II (n = 4319) was not associated with the risk of ROP. For Cohort 2, the odds of severe ROP were significantly reduced in moderate to severe hCAM groups (stage II, OR: 0.06, 95% CI: 0.05-0.82; stage III, OR: 0.10, 95% CI: 0.01-0.84). Neonates with funisitis, comorbidity of hCAM, and a finding of fetal inflammatory response had lower odds of severe ROP (OR: 0.11; 95% CI: 0.01-0.93). CONCLUSIONS: After adjusting for confounders, severe hCAM with fetal inflammatory response was associated with reduced risk of ROP.

In situ semi-quantitative analysis of zinc dissolution within nanoporous silicon by X-ray absorption fine-structure spectroscopy employing an X-ray compatible cell.

The in situ study of the discharge process in a zinc-based half-cell employing a porous electrode as a structural scaffold is reported. The in situ characterization has been performed by synchrotron X-ray absorption fine-structure spectroscopy and, for this purpose, an inexpensive, simple and versatile electrochemical cell compatible with X-ray experiments has been designed and described. The experimental results reported here have been employed to semi-quantify the dissolved and undissolved zinc species during the discharge, allowing the cell feasibility to be tested and to better understand the functioning of the zinc half-cell based on porous electrodes.

Dynamic manipulation of the local pH within a nanopore triggered by surface-induced phase transition.

Manipulating the local pH within nanoconfinement is essential in nanofluidics technology and its applications. Since the conventional strategy utilizes the overlapping of an electric double layer formed for charge compensation by protons near a negatively charged pore-wall surface, pH variation within a pore is limited to the acidic side. To achieve the variation at the alkaline side, we developed a system comprising a hydrophobic pore-wall surface and aqueous solution containing hydrophobic cations. Beyond a threshold cation concentration, a nanopore is filled with the second phase where the cations are remarkably enriched due to surface-induced phase transition (SIFT) originating from the hydrophobic effect. It is accompanied by the enrichment of coexisting anions. We experimentally show that pH in the second phase is much higher than in the bulk solution. Electrochemical measurements strongly suggest that the pH value can be increased from 4.8 to 10.7 within a 10 nm nanopore in the most significant case. This is ascribed to the enrichment of hydroxide anions. We argue that the extent and rate of pH variation are controlled as desired.

Anamorelin (ONO-7643) in Japanese patients with non-small cell lung cancer and cachexia: results of a randomized phase 2 trial.

PURPOSE: Cancer cachexia is characterized by decreased body weight (mainly lean body mass [LBM]) and negatively impacts quality of life (QOL) and prognosis. Anamorelin (ONO-7643) is a novel selective ghrelin receptor agonist under development for treating cancer cachexia. METHODS: In this double-blind, exploratory phase 2 trial, we examined the efficacy and safety of anamorelin in Japanese patients (n = 181) with non-small cell lung cancer (NSCLC) and cancer cachexia (≥5 % weight loss within the previous 6 months). The participants were randomized into three groups and were administered 50 or 100 mg anamorelin, or placebo, orally every day for 12 weeks. The co-primary endpoints were the changes from baseline over 12 weeks in LBM and handgrip strength (HGS). Secondary endpoints included body weight, QOL, Karnofsky Performance Scale (KPS), and serum biomarkers. RESULTS: The change in LBM over 12 weeks was 0.55 and 1.15 kg in the placebo and 100-mg anamorelin groups, respectively, but the efficacy of anamorelin in HGS was not detected. The changes in body weight were -0.93, 0.54, and 1.77 kg in the placebo, 50-mg anamorelin, and 100-mg anamorelin groups, respectively. Anamorelin (100 mg) significantly improved KPS and QOL-ACD compared with placebo. Administration of anamorelin for 12 weeks was well tolerated. CONCLUSIONS: This phase 2 study showed that 100 mg anamorelin has promising results in improving lean body mass, performance status, and especially, QOL in patients with cancer cachexia.

The structural classification of the highly disordered crystal phases of [Nn][BF4], [Nn][PF6], [Pn][BF4], and [Pn][PF6] salts (Nn(+) = tetraalkylammonium and Pn(+) = tetraalkylphosphonium).

The structures of 16 symmetric tetraalkylammonium (Nn(+)) and tetraalkylphosphonium (Pn(+)) salts ([Nn][BF4], [Nn][PF6], [Pn][BF4], and [Pn][PF6], where n = 1 to 4, and denotes the number of carbon atoms in each alkyl chain) have been investigated by X-ray diffraction in order to elucidate the effect of ion size on the disordered structure of organic salts. All the salts exhibit one or more solid-solid phase transitions in differential scanning calorimetric curves. Powder X-ray diffraction revealed that the highest temperature solid phase of these salts belongs to a crystal system with a high cubic or hexagonal symmetry. The structures are classified into 5 different types: CsCl', NaCl, NaCl', inverse NiAs, and TBPPF6. The CsCl'-type whose octant corresponds to the original CsCl unit cell is observed for [N1][PF6] owing to the orientational difference for the cation or the anion. The NaCl-type structure is observed for the N2(+) and P2(+) salts while the NaCl'-type structure is observed for [N3][PF6], where the configuration of ions is based on the NaCl-type but the four equivalent positions in the original NaCl lattice split into two sets of equivalent positions (three and one). The inverse NiAs structure is observed for [P3][PF6]. Single-crystal X-ray diffraction reveals that the disordering of ions in [P4][PF6] becomes more significant with increasing temperature. The new structure of a cubic phase, the TBPPF6-type structure, is found for the salts with long alkyl chains. The structure is roughly determined at 333 K and the ions therein are highly disordered but not rotating. The validity of the radius ratio rule is confirmed through appropriate assessment of the ion size.

Effect of cation species on surface-induced phase transition observed for platinum complex anions in platinum electrodeposition using nanoporous silicon.

In an earlier work [K. Fukami et al., J. Chem. Phys. 138, 094702 (2013)], we reported a transition phenomenon observed for platinum complex anions in our platinum electrodeposition experiment using nanoporous silicon. The pore wall surface of the silicon electrode was made hydrophobic by covering it with organic molecules. The anions are only weakly hydrated due to their large size and excluded from the bulk aqueous solution to the hydrophobic surface. When the anion concentration in the bulk was gradually increased, at a threshold the deposition behavior exhibited a sudden change, leading to drastic acceleration of the electrochemical deposition. It was shown that this change originates from a surface-induced phase transition: The space within a nanopore is abruptly filled with the second phase in which the anion concentration is orders of magnitude higher than that in the bulk. Here we examine how the platinum electrodeposition behavior is affected by the cation species coexisting with the anions. We compare the experimental results obtained using three different cation species: K(+), (CH3)4N(+), and (C2H5)4N(+). One of the cation species coexists with platinum complex anions [PtCl4](2-). It is shown that the threshold concentration, beyond which the electrochemical deposition within nanopores is drastically accelerated, is considerably dependent on the cation species. The threshold concentration becomes lower as the cation size increases. Our theoretical analysis suggests that not only the anions but also the cations are remarkably enriched in the second phase. The remarkable enrichment of the anions alone would give rise to the energetic instability due to electrostatic repulsive interactions among the anions. We argue that the result obtained cannot be elucidated by the prevailing view based on classical electrochemistry. It is necessitated to consult a statistical-mechanical theory of confined aqueous solutions using a molecular model for water.

[Assessment of contracted bladder following intravesical instillation of BCG (Japan)].

We assessed a situation concerning contracted bladder following intravesical instillation of BCG(Japan), to investigate how the disease could be prevented. Between March 1997 and June 2010, we selected 20 patients with clinically or pathologically confirmed contracted bladder to participate in the study. The incidence of contracted bladder tended to be higher for patients who had received more than 5 doses of BCG. Repeated severe bladder irritation caused by intravesical BCG instillation was suggested to be the major factor leading to contracted bladder. To prevent the onset of contracted bladder and its progression resulting in total cystectomy, BCG instillation should be discontinued in patients who have received the instillation many times and have developed persistent severe bladder irritation with significantly reduced bladder capacity. It is necessary to consider the administration of antituberculotic and steroid therapy for these patients quickly.

Transcriptome analysis of umbilical cord mesenchymal stem cells revealed fetal programming due to chorioamnionitis.

Although chorioamnionitis (CAM) has been demonstrated to be associated with numerous short- and long-term morbidities, the precise mechanisms remain unclear. One of the reasons for this is the lack of appropriate models for analyzing the relationship between the fetal environment and chorioamnionitis and fetal programming in humans. In this study, we aimed to clarify the fetal programming caused by CAM using the gene expression profiles of UCMSCs. From nine preterm neonates with CAM (n = 4) or without CAM (n = 5), we established UCMSCs. The gene expression profiles obtained by RNA-seq analysis revealed distinctive changes in the CAM group USMSCs. The UCMSCs in the CAM group had a myofibroblast-like phenotype with significantly increased expression levels of myofibroblast-related genes, including α-smooth muscle actin (p < 0.05). In the pathway analysis, the genes involved in DNA replication and G1 to S cell cycle control were remarkably decreased, suggesting that cellular proliferation was impaired, as confirmed by the cellular proliferation assay (p < 0.01-0.05). Pathway analysis revealed that genes related to white fat cell differentiation were significantly increased. Our results could explain the long-term outcomes of patients who were exposed to CAM and revealed that UCMSCs could be an in vitro model of fetal programming affected by CAM.

Spectroscopic analysis in molecular simulations with discretized Wiener-Khinchin theorem for Fourier-Laplace transformation.

The Wiener-Khinchin theorem for the Fourier-Laplace transformation (WKT-FLT) provides a robust method to obtain the single-side Fourier transforms of arbitrary time-domain relaxation functions (or autocorrelation functions). Moreover, by combining an on-the-fly algorithm with the WKT-FLT, the numerical calculations of various complex spectroscopic data in a wide frequency range become significantly more efficient. However, the discretized WKT-FLT equation, obtained simply by replacing the integrations with the discrete summations, always produces two artifacts in the frequency-domain relaxation function. In addition, the artifacts become more apparent in the frequency-domain response function converted from the relaxation function. We find the sources of these artifacts that are associated with the discretization of the WKT-FLT equation. Taking these sources into account, we derive discretized WKT-FLT equations designated for both the frequency-domain relaxation and response functions with the artifacts removed. The use of the discretized WKT-FLT equations with the on-the-fly algorithm is illustrated by a flow chart. We also give application examples for the wave-vector-dependent dynamic susceptibility in an isotropic amorphous polyethylene and the frequency-domain response functions of the orientation vectors in an n-alkane crystal.

[Osteitis as a complication of BCG vaccination].

OBJECTIVES: To investigate the incidence and increasing tendency of osteitis after BCG vaccination and, in addition, its clinical features, diagnostic methods and results of treatment. SUBJECTS: 22 cases of Japanese children who received BCG vaccination between 1998 and 2007 and developed osteitis, and were reported in medical journals or meetings. RESULTS AND DISCUSSION: Incidence was very low, 0.2 per 100,000 vaccinations, and an increasing tendency was not seen after 2005, when the vaccination in Japan was limited to below 6 months after birth. However, it might be necessary to follow for much longer period. About 73% of cases of osteitis were seen from 9 to 18 months after receiving the vaccination. The bones of the extremities were commonly affected. Radiography usually showed the defect and cavity formation of the affected bone and often abscess around the lesion. Definitive diagnosis was made by the detection of BCG from the pus or biopsied materials. Recently, multiplex PCR method have been utilized and proved to be a rapid and reliable diagnostic method. Tuberculin reaction was positive, but QFT was negative in all tested cases; QFT will be available for the differential diagnosis of BCG and tuberculous infection. Only 2 patients had multiple lesions, and they had partial interferon-gamma receptor 1 deficiency. Immunodeficiency might have some relationship to the development of osteitis after BCG vaccination. The treatment using INH and RFP was very effective and the outcome was favorable; most of the patients were cured after 6 to 12 months chemotherapy without any complications. However, there is the possibility of defects occurring in the bone and restriction of the articular movement when the diagnosis and treatment are delayed. CONCLUSION: BCG osteitis, although rare, should be considered as a possible complication of the BCG vaccination, and early diagnosis and treatment of this complication is necessary.

High dispersion and oxygen reduction reaction activity of Co3O4 nanoparticles on platelet-type carbon nanofibers.

In this study, platelet-type carbon nanofibers prepared by the liquid phase carbonization of polymers in the pores of a porous anodic alumina template were used to prepare the Co3O4/carbon electrocatalysts. For comparison, Co3O4 nanoparticles were also deposited on multiwall carbon nanotubes (MWCNTs). Both the nitrogen-free platelet-type carbon nanofibers (pCNFs) and the nitrogen-containing analogue (N-pCNFs) exhibited better dispersion and higher amount of deposited Co3O4 nanoparticles compared to the MWCNTs. In addition, many individual Co3O4 nanoparticles were deposited separately on pCNF and N-pCNF, whereas aggregated deposition was commonplace on MWCNTs. The results indicated that the side wall of the pCNFs, which consisted of carbon edge planes, was the preferential nucleation site of Co3O4 nanoparticles rather than the basal planes of carbon that predominated the surface of the MWCNTs. The oxygen reduction reaction (ORR) activity of the Co3O4/pCNF composite in 0.1 mol dm-3 KOH solution was better than that of Co3O4/MWCNTs. The N-pCNF further enhanced the ORR activity of the Co3O4/pCNFs even though the dispersion and supported amount of Co3O4 nanoparticles were negligibly affected by the presence of the nitrogen species. Synergistic interactions of the Co3O4 nanoparticles with N-doped CNFs contributed to the increased ORR activity.

Molecular dynamics simulation of polymer crystallization from an oriented amorphous state.

The molecular process of crystallization from an oriented amorphous state was reproduced by molecular dynamics simulation for a realistic polyethylene model. The initial oriented amorphous state was obtained by uniaxially drawing an isotropic glassy state at 100 K. By the temperature jump from 100 K to 330 K, there occurred crystallization into the fiber structure, during the process of which we observed the developments of various order parameters. The real-space image and its Fourier transform revealed that a hexagonally ordered domain was initially formed, and then a highly ordered crystalline state with stacked lamellas developed after further adjustment of the relative heights of the chains along their axes.

Whole genome sequence analysis of Mycobacterium bovis bacillus Calmette-Guérin (BCG) Tokyo 172: a comparative study of BCG vaccine substrains.

To investigate the molecular characteristics of bacillus Calmette-Guérin (BCG) vaccines, the complete genomic sequence of Mycobacterium bovis BCG Tokyo 172 was determined, and the results were compared with those for BCG Pasteur and other M. tuberculosis complex. The genome of BCG Tokyo had a length of 4,371,711bp and contained 4033 genes, including 3950 genes coding for proteins (CDS). There were 18 regions of difference (showing differences of more than 20bp), 20 insertion or deletion (ins/del) mutations of less than 20bp, and 68 SNPs between the two BCG substrains. These findings are useful for better understanding of the genetic differences in BCG substrains due to in vitro evolution of BCG.

The EEG measurement technique under exercising.

Our purpose of the research is a development of the detecting method of EEG under exercising. Usually, measuring EEG is done in the quiet state. In case of the measuring EEG under exercising, a movement of the body causes vibration of electrodes and artifact for the EEG. Therefore, generally detection of the EEG under exercising is said to be difficult. So, we developed the measuring method of EEG under exercising by using algorithm that we designed. Five normal subjects were tested with our method, and EEG without artifact was able to be measured in all cases.

Identification of two subpopulations of Bacillus Calmette-Guérin (BCG) Tokyo172 substrain with different RD16 regions.

Two types of colonies with different morphologies (smooth: S and rough: R) formed when Bacillus Calmette-Guérin (BCG) Tokyo172 substrain was cultured on Middlebrook 7H10 agar medium, and their genotypes were analyzed by multiplex PCR on five RD regions and SenX3-RegX3. In most cases these two colony types had different genotypes, i.e., S colonies showed a characteristic 22 bp deletion in Rv3405c of the RD16 region (type I), and R colonies did not have this deletion (type II) similar to many other BCG substrains. Thus, there was a strong relationship between colony morphology and genotype. Both genotypes were found in every Tokyo172 preparation tested, including the seed lot for production, the origin of seed lot from the 1960s and ATCC BCG Japan. Type I was always in the majority. It was suggested that types I and II constituted independent subpopulations within the Tokyo172 substrain. Type I was shown to have a growth advantage over type II both on culture media and in mice organs.

Bacillus calmette-guerin Tokyo172 substrain for superficial bladder cancer: characterization and antitumor effect.

PURPOSE: We investigated the preparation of bacillus Calmette-Guerin (BCG) Tokyo172 substrain (Japan BCG Laboratory, Ltd., Tokyo, Japan) on the characteristics of bacilli and antitumor activity in a mouse model in comparison with a preparation of the Connaught substrain (Aventis Pasteur, Ltd., Toronto, Ontario, Canada). MATERIALS AND METHODS: Lyophilized BCG preparations of Tokyo172 and Connaught for superficial bladder cancer were tested. The number of bacilli and cfu per dose, dispersion, size and attachment to murine bladder tumor cells were determined after reconstitution. Antitumor activity was assessed by intradermal injection of tumor cells with various doses of either BCG preparation into the flanks of syngeneic mice, followed by the observation of tumor suppression and survival in mice. RESULTS: Each dose of Tokyo172 had about half the bacilli in a dose of Connaught but the cfu content was about 13-fold higher for Tokyo172 than for Connaught. After reconstitution Tokyo172 bacilli were better dispersed with fewer aggregates than Connaught bacilli. Tokyo172 bacilli were about half as long as Connaught bacilli and Tokyo172 bacilli showed better attachment to tumor cells in vitro. In mice Tokyo172 achieved similar tumor suppression at a lower dose than Connaught. CONCLUSIONS: High viability, good dispersion and efficient binding to tumor cells by BCG bacilli in the Tokyo172 preparation seem to be the main reasons for the lower clinical dose of this preparation compared with the Connaught preparation (18 vs 81 mg dry weight).

Modified multiplex PCR for identification of Bacillus Calmette-Guérin substrain Tokyo among clinical isolates.

When an adverse reaction occurs and a mycobacterial species is isolated from a person vaccinated with Bacillus Calmette-Guérin (BCG) or a patient receiving BCG immunotherapy, it is essential to identify whether the isolate is BCG or another mycobacterial species. However, differentiation of BCG from other members of Mycobacterium tuberculosis complex has been very difficult. Using several specific primer-pairs, Bedwell et al. [Bedwell J, Kairo SK, Behr MA, Bygraves JA. Identification of substrains of BCG vaccine using multiplex PCR. Vaccine 2001; 19: 2146-51] recently reported that they could distinguish BCG substrains. We modified their method to improve differentiation of Tokyo 172 from other members of the M. tuberculosis complex, and examined whether this modified method could be applied to clinical isolates. Our method clearly identified BCG substrain (BCG Tokyo 172) among clinical isolates and easily distinguished between M. tuberculosis and wild-type Mycobacterium bovis.