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We isolated the rare G3P[9] rotavirus strain RVA/Human-wt/JPN/R11-035/2015/G3P[9] from a 2-year-old girl presenting with vomiting and diarrhea who had daily contact with cats in Japan, 2015. Full-genome analysis revealed that the R11-035 strain had an AU-1-like genetic constellation, except for the NSP3 (T) gene: G3-P[9]-I3-R3-C3-M3-A3-N3-T1-E3-H6. Phylogenetic analysis showed that strain R11-035 is closely related to human/feline-like human strains, and only the NSP3 (T1) gene was clustered together with Taiwanese porcine strains. We postulate that the R11-035 strain was directly transmitted from a cat to the patient and acquired its NSP3 gene through intergenotype reassortment with porcine strains before being transmitted to humans.

ε-Poly-L-lysine (PLL) is a cationic polymer consisting of 25 to 35 L-lysine residues that adheres to the surface of skin as well as hair. However, the properties of PLL regarding its adhesion to the skin remain to be elucidated. In this study, we examined the staining of stratum corneum (SC) with fluorescence-labeled PLL and explored its relationship with skin condition.Alexa Fluor 488-labeled PLL (AF-PLL) was reacted with tape-stripped stratum corneum (SC), and the staining properties were monitored by fluorescence microscopy. Clinical study was performed by measuring the water content of the cheek SC and transepidermal water loss (TEWL), and the tape-stripped SC was subjected to staining with AF-PLL.AF-PLL staining of the SC was inhibited at acidic pH or by the addition of high concentration of salt solution, suggesting the involvement of ionic interaction between PLL and the SC, at least in part. The AF-PLL staining was inhibited by unlabeled PLL or various alkyl amines, but not by L-lysine monomer. AF-PLL staining was observed inside the corneocytes as well as surrounding cornified envelope. Clinical study revealed that AF-PLL staining intensity of the SC was negatively correlated with its water content and positively correlated with its TEWL.PLL can efficiently adhere to SC and AF-PLL staining of SC can be applied to evaluate skin conditions.

The group A rotavirus (RVA) G3P[9] is a rare genotype isolated in humans and cats. We isolated only one G3P[9] strain RVA/Human-wt/JPN/R11-035/2014/G3P[9] among 487 stool samples in our rotavirus surveillance of children with gastroenteritis in Japan, during 2014–2015. The R11-035 strain was isolated from a 2 year old girl presenting with vomiting and diarrhea who had daily contact with cats. She had type A histo-blood group antigen, which is reported to be related to rare human P[9] rotavirus infection. Full genome sequencing revealed that the R11-035 strain had AU-1-like constellations, except for the NSP3 (T) gene, G3-P[9]-I3-R3-C3-M3-A3-N3-T1-E3-H6. Phylogenetic analysis of all genome segments, except for the NSP3 gene, showed that the R11-035 strain formed distinct clusters and had high nucleotide sequence identity with human/feline-like strains. We postulate that the R11-035 strain was directly transmitted from a cat to the patient. Interestingly, the NSP3 gene of R11-035 was found to cluster closely with Taiwanese porcine strains. Since the remaining genes of R11-035 were closely related to those of human/feline-like human strains, it is likely that R11-035 acquired its NSP3 gene through intergenotype reassortment events with porcine strains before being transmitted to humans. The CAU14-1-262 strain, isolated from a 2 year old girl in South Korea in 2014, is the only reported strain having the same genome constellations as R11-035. These two strains had extremely high nucleotide sequence identity in all 11 gene segments (99.3–99.9%). It is therefore likely that strains with these genome sequences are circulating in East Asia.

The objective of this study was to investigate an appropriate observation period for an evaluation of tumorigenicity in NOD/Shi-scid IL-2 Rγ

Background Evidence is limited for influenza vaccine effectiveness (VE) against laboratory-confirmed influenza among young children. Using test-negative design (a modified case-control study) which minimizes confounding by health care-seeking behavior and misclassification of diseases, we aimed to monitor influenza VE among young children in Japan where all approved influenza vaccines are egg-propagated, inactivated formulations (IIV). Methods For seasons spanning 2013-14 to 2017-18 in Osaka and Fukuoka Prefectures, Japan, we employed prospective, active, and systematic recruitment of children aged Results We analyzed 4,614 subjects including 1,917 cases. VEs of IIV with 2 doses approximated 50%, ranging from 41% (95% confidence interval [CI]: 14 % to 60%) in 2016-17 season to 63% (95% CI: 45% to 76%) in 2017-18 season. Significant VEs were also shown for predominant circulating strains every season, irrespective of their antigenic match to vaccine strains (56% and 65% for A[H1N1]pdm, 37% and 50% for A[H3N2], and 60% for B[Yamagata]). Conclusions IIV provided modest and significant protection against laboratory-confirmed influenza in young Japanese children. Key messages Test-negative design is useful for monitoring influenza VE.

Daptomycin is used to treat methicillin-resistant Staphylococcus aureus (MRSA) infections. Current guidelines recommend higher daptomycin doses (8-10 mg/kg) for severe infections; however, pharmacokinetic (PK) and pharmacodynamic-based dosing strategies are still limited. Therefore, we designed a new optimal daptomycin dosing regimen for patients with MRSA infections using a population PK modeling approach. A total of 110 plasma concentrations from 47 adult patients who received daptomycin in general wards were enrolled for population PK modeling. The target area under the concentration-time curve/minimum inhibitory concentration (MIC) ratio, target peak/MIC ratio, and threshold of the trough concentration for safety were set to666,60, and 24.3 mg/L, respectively. Renal function was indicated as a significant covariate for daptomycin clearance. The simulated probability of target attainment was more than 90% at MIC values of 0.25 and 0.5 mg/L in all patients at the standard dose (6 mg/kg). In contrast, comprehensive simulation assessments recommended 10 mg/kg every 24 h in patients with creatinine clearance60 mL/min for MIC values of 1.0 mg/L. We propose a new simplified daptomycin dosing regimen stratified by renal function and MIC values based on PK model-based simulation analyses. The proposed regimen is expected to maximize clinical efficacy and minimize adverse events.

We assessed the long-term oncologic safety of nipple-sparing mastectomy (NSM) compared to skin-sparing mastectomy (SSM) for primary breast cancer patients with immediate reconstruction.Data of stage 0-III primary breast cancer patients undergoing NSM (n = 190) or SSM (n = 729) from June 2006 to December 2012 were retrospectively collected. Nipple-tumor distance (NTD) was measured on pretreatment mammography, magnetic resonance imaging, or ultrasonography findings. NSM patients with NTD 1 cm were excluded. Locoregional recurrence (LRR) rates were compared between groups. Disease-free survival (DFS) and overall survival (OS) according to surgical procedure were assessed.The median (range) follow-up period for NSM and SSM was 71 (10-131) months and 79 (9-140) months, respectively. LRR developed in 11 patients with invasive ductal carcinoma (5.8%) for NSM and 44 (42 in patients with invasive ductal carcinoma and 2 in patients with ductal carcinoma-in-situ) (6.0%) for SSM. Hormone receptor and HER2 status were not associated with LRR in either group. DFS and OS rates did not differ between groups (DFS: 89.3% for NSM, 89.3% for SSM, P = .87; OS: 98.4% for NSM, 94.5% for SSM, P = .43).NSM with immediate reconstruction was as safe as SSM for primary breast cancer with respect to prognosis and local control, regardless of the presence of invasive carcinoma or breast cancer subtype.

A specific series of peptides, called a cell-penetrating peptide (CPP), is known to be free to directly permeate through cell membranes into the cytosol (cytolysis), hence, this CPP would be a potent carrier for a drug delivery system (DDS). Previously, we proposed the mechanism of cytolysis as a temporal and local phase transfer of membrane lipid caused by positive membrane curvature generation. Moreover, we showed how to control the CPP cytolysis. Here, we investigate the phospholipid vesicle&rsquo, s size effect on CPP cytolysis because this is the most straightforward way to control membrane curvature. Contrary to our expectation, we found that the smaller the vesicle diameter (meaning a higher membrane curvature), the more cytolysis was suppressed. Such controversial findings led us to seek the reason for the unexpected results, and we ended up finding out that the mobility of membrane lipids as a liquid crystal is the key to cytolysis. As a result, we could explain the cause of cytolysis suppression by reducing the vesicle size (because of the restriction of lipid mobility), osmotic pressure reduction to enhance positive curvature generation works as long as the membrane is mobile enough to modulate the local structure. Taking all the revealed vital factors and their effects as a tool, we will further explore how to control CPP cytolysis for developing a DDS system combined with appropriate cargo selection to be tagged with CPPs.

This study assessed the diagnostic accuracy of ultrasound in detecting axillary lymph node metastases in women with breast cancer and atopic dermatitis. We retrospectively reviewed the records of 91 breast cancer patients with a history of atopic dermatitis and compared the dimensions of the lymph nodes on ultrasonographic images of women with and without lymph node metastases diagnosed using histology. Using a major-axis length of ≥5 mm, a short-axis length of ≥5 mm and a cortical thickness of ≥2.3 mm as the criteria for diagnosing axillary lymph node metastases, the specificity was 12.7%, 41.3% and 58.7%, respectively. The low specificity of the ultrasound criteria makes ultrasound unsuitable for diagnosing axillary lymph nodes metastases in breast cancer patients with atopic dermatitis.

Although natural organic matter (NOM) is known to reduce the efficiency of polycationic flocculants used for solid-liquid separation in water treatment processes, mechanisms underlying this inhibitory effect are not yet fully understood. In this study, the inhibitory effects of naturally occurring humic substances and a synthetic polyelectrolyte (as a comparison), polyacrylic acid (PAA), on the initial stage of colloidal flocculation induced by the addition of a cationic linear polyelectrolyte are investigated under a standardized mixing flow condition. Flocculation enhancement is hindered by all the tested polyanions, while electrophoretic mobility experiments reveal that the polyanions affect the isoelectric point of particles. At the same polycation to polyanion charge ratio, the degree of inhibition decreases in the order PAA > Suwannee River humic acid > Suwannee River fulvic acid, corresponding to their affinity toward the polycations and particles. We propose that the inhibitory mechanism is mainly driven by the electrostatic attractions between the flocculant and polyanions, and this mechanism involves three stages. The influence of polyanion affinity on the complexation with polycations is also discussed. The insights gained in this study can be useful in predicting the flocculation behavior of suspended solids co-existing with NOM in natural environments when flocculants are added.

Background Triple-negative breast cancer (TN) is more aggressive than other subtypes of breast cancer and has a lower survival rate. Furthermore, detailed biological information about the disease is lacking. This study investigated characteristics of metabolic pathways in TN. Methods We performed the metabolome analysis of 74 breast cancer tissues and the corresponding normal breast tissues using LC/MS. Furthermore, we classified the breast cancer tissues into ER-positive, PgR-positive, HER2-negative breast cancer (EP+H-) and TN, and then the differences in their metabolic pathways were investigated. The RT-PCR and immunostaining were carried out to examine the expression of ELOVL1, 2, 3, 4, 5, 6, and 7. Results We identified 142 of hydrophilic metabolites and 278 of hydrophobic lipid metabolites in breast tissues. We found the differences between breast cancer and normal breast tissues in choline metabolism, glutamine metabolism, lipid metabolism, and so on. Most characteristic of comparison between EP+H- and TN were differences in fatty acid metabolism was which were related to the elongation of very long chain fatty acids were detected between TN and EP+H-. Real-time RT-PCR showed that the mRNA expression levels of ELOVL1, 5, and 6 were significantly upregulated by 8.5-, 4.6- and 7.0-fold, respectively, in the TN tumors compared with their levels in the corresponding normal breast tissue samples. Similarly, the mRNA expression levels of ELOVL1, 5, and 6 were also significantly higher in the EP+H- tissues than in the corresponding normal breast tissues (by 4.9-, 3.4-, and 2.1-fold, respectively). The mRNA expression level of ELOVL6 was 2.6-fold higher in the TN tumors than in the EP+H- tumors. During immunostaining, the TN and EP+H- tumors demonstrated stronger ELOVL1 and 6 staining than the corresponding normal breast tissues, but ELOVL5 was not stained strongly in the TN or EP+H- tumors. Furthermore, the TN tumors exhibited stronger ELOVL1 and 6 staining than the EP+H- tumors. Conclusions Marked differences in fatty acid metabolism pathways, including those related to ELOVL1 and 6, were detected between TN and EP+H-, and it was suggested that ELOVL1 and 6-related fatty acid metabolism pathways may be targets for therapies against TN. Electronic supplementary material The online version of this article (doi:10.1186/s12885-017-3554-4) contains supplementary material, which is available to authorized users.

Background: Inflammatory breast cancer (IBC) is the most aggressive form of primary breast cancer. Case Report: A 40-year-old woman was referred to our hospital for evaluation of an induration in the right breast, suspected to be breast cancer. The tumor was diagnosed as estrogen receptor-negative, progesterone receptor-negative, HER2-positive, T4dN3cM0 stage IIIc IBC with axillary lymph node metastasis. Rather than surgical intervention, we chose a systemic treatment approach with pertuzumab, trastuzumab, and docetaxel (PTD) combination therapy which was shown to be effective for HER2-positive IBC in the NeoSphere trial. After 4 cycles of treatment, the patient had a partial response, allowing mastectomy of the right breast and axillary lymph node dissection to achieve local control. We review this case because of the success of PTD combination neoadjuvant chemotherapy for HER2-positive IBC. Conclusion: To improve the poor prognosis of IBC, combined modality therapy is required, including chemotherapy and local treatment such as surgery and/or radiation therapy. In this case, combination neoadjuvant chemotherapy with PTD for HER2-positive IBC was effective, and this regimen may contribute to further improvements in the cure rate for this malignancy.

Bacterial β-galactosidase is one of the most widely used reporter genes in experiments involving transgenic and knockout animals. In this review we discuss the current histochemical methods and available reagents to detect β-galactosidase activity. Different substrates are available, but the most commonly used is X-gal in combination with potassium ferri- and ferro-cyanide. The reaction produces a characteristic blue precipitate in the cells expressing β-galactosidase, and despite its efficiency in staining whole embryos, its detection on thin tissue sections is difficult. Salmon-gal is another substrate, which in combination with ferric and ferrous ions gives a reddish-pink precipitate. Its sensitivity for staining tissue sections is similar to that of X-gal. Combining X-gal or Salmon-gal with tetrazolium salts provides a faster and more sensitive reaction than traditional β-galactosidase histochemistry. Here, we compare the traditional β-galactosidase assay and the combination of X-gal or Salmon-gal with three tetrazolium salts: nitroblue tetrazolium, tetranitroblue tetrazolium and iodonitrotetrazolium. Based on an assessment of the sensitivity and specificity of the different combinations of substrates, we are proposing an optimized and enhanced method for β-galactosidase detection in histological sections of the transgenic mouse brain. Optimal staining was obtained with X-gal in combination with nitroblue tetrazolium, which provides a faster and more specific staining than the traditional X-gal combination with potassium ferri- and ferro-cyanide. We recommend the X-gal/nitroblue tetrazolium staining mixture as the first choice for the detection of β-galactosidase activity on histological sections. When faster results are needed, Salmon-gal/nitroblue tetrazolium should be considered as an alternative, while maintaining acceptable levels of noise.

We propose a method for the decontamination and waste volume reduction of cesium-contaminated soil. The soils were solidified with an interpolyelectrolyte complex solution and classified into several size fractions by wet sieving. Gamma-ray spectrometry of these fractions showed that the distribution ratio of the activity concentration of coarse soil particles decreased, whereas that of soil particles under 0.075 mm increased relative to reference samples. Results showed that the fine soil particles, on which radioactive cesium accumulates, were removed from the surface of the coarse soil particles during sieving and washing, and remained in the washing water.

We have evaluated a new immunochromatographic kit, "KBM LineCheck Flu AB", which had been developed for enhanced detection of influenza B viruses. Five strains of influenza A and B viruses were tested for reactivity and detection limits of the kit. Compared with the detection limits of commercially available kit of QuickNavi-Flu, "KBM LineCheck Flu AB" showed a nearly equal reactivity to influenza A viruses, but quadruple reactivity to 2 influenza B viruses. Also, "KBM LineCheck Flu AB" exhibited high specificity when tested in 130 influenza-negative culture specimens derived from 24 adult volunteers. Furthermore, "KBM LineCheck Flu AB" was clinically evaluated by using 866 specimens, including 190 nasal swabs, 201 nasal aspirations, 262 self-blown nasal discharges, and 213 pharyngeal swabs. Compared with the results of QuickNavi-Flu for influenza A, the test efficiency for the nasal swabs, the nasal aspirations, self-blown nasal discharges, and pharyngeal swabs were calculated to be 95.8%, 92.0%, 95.0%, and 94.8%, respectively. Whereas, as to influenza B, the test efficiency for the nasal swabs, the nasal aspirations, self-blown nasal discharges, and pharyngeal swabs was calculated to be 96.3%, 98.5%, 96.2%, and 93.4%, respectively. Similarly, compared with the results of influenza A viral culture, the test efficiency for the nasal swabs, the nasal aspirations, self-blown nasal discharges, and pharyngeal swabs was calculated to be 95.3%, 91.0%, 93.9%, and 92.5%, respectively. Regarding influenza B culture, the test efficiency for the nasal swabs, the nasal aspirations, self-blown nasal discharges, and pharyngeal swabs were calculated to be 95.8%, 97.5%, 95.1%, 91.5%, respectively. Overall, we concluded that the "KBM LineCheck Flu AB" is useful and suitable for diagnosis of influenza A and especially influenza B.

CO2-EOR is one of the proven enhanced oil recovery (EOR) techniques and has been used commercially. However, in field applications, unfavorable sweep efficiency is often reported. In order to improve the sweep efficiency of CO2 flooding, we investigated an applicability of CO2 micro bubbles. To evaluate the applicability of CO2 micro bubbles for CO2-EOR, we conducted core flooding experiments using CO2 micro bubbles and the results were compared with the normal CO2 flooding. Previous study confirmed the generation of CO2 micro bubbles by using a specially developed porous filter. Using this filter, core flooding experiments were conducted. During the experiment, flooding behavior was monitored by a medical X ray CT system, and recovered oil and water were collected to make a quantitative comparison with normal CO2 flooding. From the images taken by the medical X ray CT, we observed that CO2 micro bubbles flowed over both upper and lower parts of core samples, while normal CO2 flowed only upper part of core samples. As a result, a delay of CO2 break-through was confirmed in CO2 micro bubble flooding case. The time series of medical X ray CT images indicates improvement in sweep efficiency by using the CO2 micro bubbles. In addition to this, the material balance calculation during the core floodings revealed 3% of additional oil recovery compared to the normal CO2 flooding. From the experiments, differences in flooding behavior were clearly observed between the normal CO2 and the CO2 micro bubbles injection. We consider the differences would lead to the improvement of both vertical and areal sweep efficiencies. Although this technique is still in a stage of fundamental research, since the technique only requires the special filter and it is considered that it can be easily installed at the down hole, it may provide a novel option to improve the CO2-EOR performance.

Although the dosage of cationic flocculants used for water treatment is well known to increase in the presence of natural organic matter (NOM), the underlying reasons for this increase are not properly understood. Herein, we studied the flocculation behavior of polystyrene latex (PSL) particles in the presence and absence of polyacrylic acid (PAA5K) as an NOM analogue using an end-over-end rotation apparatus for standardized flow mixing. In the absence of PAA5K, the initial rate of cationic flocculant (PAM5M)-induced flocculation was enhanced, as reflected by the size of flocculant in solution. Additionally, flocculation experiments were performed in the presence of 0.5 mg/L PAA5K for five concentrations of PAM5M and two ionic strengths, and the increase of the initial rate of PAM5M-induced flocculation was suppressed by PAA5K immediately after mixing, with the most pronounced suppression obtained at a PAM5M concentration similar to PAA5K. Based on the above insights and the results of viscosity measurements, the inhibitory effect of PAA on flocculation was ascribed to (1) the reduction of PAM charge and the concomitant shrinkage via electrostatic association with PAA and (2) the termination of polycation adsorption on PSL caused by polyion complex formation when the charge ratio of PAM:PAA is close to unity.

Supplemental Digital Content is available in the text, In young children, infrequent antigen exposure, which is partly characterized by fewer vaccinations, may be a factor impairing the immunogenicity of inactivated influenza vaccine. We assessed the effects of prior vaccinations on age-specific immune responses in Japanese children aged 6 months to 3 years, using data from a cohort study with 266 children who had received 2 doses (0.25 mL/dose for < 3 years old, 0.5 mL/dose for 3 years old) in the 2006/2007 season. Serological measures, primarily seroprotection rates, between previously vaccinated and vaccine-naïve children were compared within 1-year age strata. The seroprotection rate was defined in 2 ways as the proportion of subjects who achieved an antibody titer of 1:40 or 1:160. Multivariate logistic regression was also performed to estimate the independent effect of prior vaccination on seroprotection rate. After the first dose, seroprotection rates with the threshold of 1:40 in vaccine-naïve 1-year-olds remained low (28% for AH1, 26% for AH3, 2% for B), similar to those of 0-year-olds. In contrast, seroprotection rates in previously vaccinated 1-year-olds (77% for AH1, 86% for AH3, 18% for B) were significantly higher than those in vaccine-naïve 1-year-olds. These seroprotection rates for AH1 and AH3 were comparable with those in previously vaccinated 2- and 3-year-olds. Although seroprotection rates for B remained low in every age stratum even after the second dose, seroprotection rate in previously vaccinated 1-year-olds (50%) was similar to that in 3-year-olds. After adjustment for age, baseline antibody titer and experience of acute febrile respiratory illness in the preceding season, odds ratios showed a significant independent positive effect of prior vaccination on seroprotection rate for every strain. After the seroprotection threshold was changed from 1:40 to 1:160, the results of the effects of prior vaccinations on immunogenicity were similar or became more evident, which demonstrate the robustness of our findings. Our study found that prior vaccinations improved poor immunogenicity among young children, especially in 1-year-olds.

Ryo Fujiki,1,2 Kiichiro Morita,1,2 Mamoru Sato,1,2 Yuji Yamashita,1,2 Yusuke Kato,1,2 Yohei Ishii,2 Yoshihisa Shoji,1,2 Naohisa Uchimura1 1Department of Neuropsychiatry, Kurume University, 2Cognitive and Molecular Research Institute of Brain Diseases, Kurume University School of Medicine, Kurume-City, Japan Abstract: Neuroimaging studies have been conducted using word generation tasks and have shown greater hypofrontality in patients with schizophrenia compared with healthy subjects. In this study, we compared the characteristics of oxygenated hemoglobin changes involved in both phonological and categorical verbal fluency between 35 outpatients with schizophrenia and 35 healthy subjects during a Japanese “shiritori” task using single-event-related near-infrared spectroscopy. During this task, the schizophrenic patients showed significantly smaller activation in the prefrontal cortex area than the controls. In addition, a significant positive correlation was obtained between oxygenated hemoglobin changes (prefrontal cortex area, inferior parietal area) and the severity of positive psychiatric symptoms. It is possible that hypofrontality of patients may be a diagnostic assistance tool for schizophrenia, and that the relationship between activation and positive syndrome scores may be of help in predicting functional outcome in patients. Keywords: word production task, single-event-related near-infrared spectroscopy, schizophrenia, hypofrontality, biological marker

In Japan, the routine immunization program with oral polio vaccine (OPV) has been suspended since September 2012, when a program with 4 doses of inactivated monovalent polio vaccine (IPV) or quadrivalent vaccine against diphtheria, pertussis, and tetanus with IPV (DTaP-IPV) was introduced. The aim of this study was to examine the interchangeability among these 3 types of polio vaccines.We conducted a prospective cohort study at 5 pediatric clinics in Japan. A total of 153 infants were assigned to 1 of the 4 groups by considering the vaccination history of OPV and trivalent vaccine against DTaP. Eleven infants with a history of OPV received 3 doses of DTaP-IPV; 49 infants with a history of OPV and DTaP received 3 doses of IPV; 50 polio vaccine-naive infants received 2 doses of IPV followed by 2 doses of DTaP-IPV; and 43 polio vaccine-naive infants received 2 doses of DTaP-IPV followed by IPV. The immunogenicity after polio vaccination was evaluated among these 4 groups.After 2 doses of polio vaccination, more than 80% of the infants exhibited a neutralization antibody titer ≥1:8 for all Sabin strains and wild strains in all groups. After the third dose, the seroprotection proportion (i.e., a neutralization antibody titer ≥1:8) reached about 100%. After the fourth dose, a neutralization antibody titer exceeded the required protective levels (i.e., a neutralization antibody titer ≥1:8) considerably in all groups.Four doses of polio vaccines induced a sufficient level of immunity in Japanese infants, irrespective of vaccine combinations or order.