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Japan has reported a relatively small number of COVID-19 cases. Because not all infected persons receive diagnostic tests for COVID-19, the reported number must be lower than the actual number of infections. We assessed SARS-CoV-2 seroprevalence by analyzing60,000 samples collected in Japan (Tokyo Metropolitan Area and Hokkaido Prefecture) during February 2020-March 2022. The results showed that ≈3.8% of the population had become seropositive by January 2021. The seroprevalence increased with the administration of vaccinations; however, among the elderly, seroprevalence was not as high as the vaccination rate. Among children, who were not eligible for vaccination, infection was spread during the epidemic waves caused by the SARS-CoV-2 Delta and Omicron variants. Nevertheless, seroprevalence for unvaccinated children5 years of age was as low as 10% as of March 2022. Our study underscores the low incidence of SARS-CoV-2 infection in Japan and the effects of vaccination on immunity at the population level.

Japan has reported a small number of COVID-19 cases relative to other countries. Because not all infected people receive diagnostic tests for COVID-19, the reported number of COVID-19 cases must be lower than the actual number of infections. Assessments of the presence of antibodies against the spike protein of SARS-CoV-2 can retrospectively determine the history of natural infection and vaccination. In this study, we assessed SARS-CoV-2 seroprevalence by analyzing over 60,000 samples collected in Japan from February 2020 to March 2022. The results showed that about 5% of the Japanese population had been infected with the virus by January 2021. The seroprevalence increased with the administration of vaccinations to adults; however, among the elderly, it was not as high as the vaccination rate, probably due to poor immune responses to the vaccines and waning immunity. The infection was spread during the epidemic waves caused by the SARS-CoV-2 Delta and Omicron variants among children who were not eligible for vaccination. Nevertheless, their seroprevalence was as low as 10% as of March 2022. Our study underscores the low incidence of SARS-CoV-2 infection in Japan and the effects of vaccination on immunity at the population level.

Accumulation of amyloid-β peptide (Aβ) in neuronal cells and in the extracellular regions in the brain is a major cause of Alzheimer's disease (AD); therefore, inhibition of Aβ accumulation offers a promising approach for therapeutic strategies against AD. Aβ is produced by sequential proteolysis of amyloid precursor protein (APP) in late/recycling endosomes after endocytosis of APP located in the plasma membrane. Aβ is then released from cells in a free form or in an exosome-bound form. Shiga toxin (Stx) is a major virulence factor of enterohemorrhagic Escherichia coli. Recently, we found that one of the Stx subtypes, Stx2a, has a unique intracellular transport route after endocytosis through its receptor-binding B-subunit. A part of Stx2a can be transported to late/recycling endosomes and then degraded in a lysosomal acidic compartment, although in general Stx is transported to the Golgi and then to the endoplasmic reticulum in a retrograde manner. In this study, we found that treatment of APP-expressing cells with a mutant Stx2a (mStx2a), lacking cytotoxic activity because of mutations in the catalytic A-subunit, stimulated the transport of APP to the acidic compartment, which led to degradation of APP and a reduction in the amount of Aβ. mStx2a-treatment also inhibited the extracellular release of Aβ. Therefore, mStx2a may provide a new strategy to inhibit the production of Aβ by modulating the intracellular transport of APP.

Porcine edema disease (ED) is a life-threatening toxemia caused by enteric infection with Shiga toxin 2e (Stx2e)-producing Escherichia coli (STEC) in weaned piglets. We previously reported that the stx2eB-transgenic lettuce 2BH strain shows potential for use as an oral vaccine candidate against ED. However, the 2BH strain expressed a hemagglutinin (HA)-tag together with Stx2eB and contained non-canonical N-glycosylation. Therefore, we developed two Stx2eB-lettuce strains, the 3 (G+) strain in which the HA-tag was removed from 2BH, and the 3 (G-) lettuce strain, in which the 73rd Asn was replaced with Ser to prevent non-canonical N-glycosylation of Stx2eB from the 3 (G+) strain. We examined the protective effect of these newly developed two strains compared with the previous 2BH strain against ED using a colostrum-deprived piglet STEC infection model. We found that the N-glycosylated 2BH and 3 (G+) strains relieved the pathogenic symptoms of ED in STEC-challenged piglets, whereas the non-glycosylated 3 (G-) strain did not. N-Glycosylation of the Stx2eB product in lettuce may be involved in the immune response in piglets.

Influenza outbreaks at geriatric long-term care facilities (g-LTCFs) can be deadly and their prevention is important. However, the factors influencing disease transmission in g-LTCFs remain controversial. In this descriptive study, we tried to identify the potential risk factors influencing influenza outbreaks that occurred in different influenza seasons within a single g-LTCF with 100 residents in Gunma Prefecture. We reviewed the detailed facility records for all influenza cases in both residents and staff between January 2012 and June 2020. Facility preventive measures were also reviewed. We found that community meals may have been a potential source of transmission leading to the outbreaks. When influenza infection is noted, implementation of strict preventive measures and restriction of meal provision to resident rooms may help to prevent disease transmission and the development of an outbreak. Such measures may also be useful to prevent the transmission of other serious droplet-borne diseases within g-LTCFs.

We report a 16-year-old Japanese male with mugwort pollinosis in whom ingestion of wild grape juice and various vegetables caused recurrent general urticaria, abdominal pain, dyspnea, and loss of consciousness. A skin prick test demonstrated positive reactions to a wide variety of both non-heated and heated vegetables and fruits such as wild grape, bell pepper, onion, Chinese cabbage, tomato, eggplant, and broccoli. The serum immunoglobulin E levels (ImmunoCAP ISAC® ) for Art v 3, Pla a 3, Pru p 3, and Jug r 3, which are lipid transfer protein (LTP) homologs, were positive but those for Bet v 1 and Bet v 2 were negative. We diagnosed the patient as having LTP syndrome, a condition in which additional factors such as exercise, non-steroidal anti-inflammatory drugs, or alcohol may trigger an allergic reaction. Wild grapes contain a large amount of salicylic acid, and in our patient ingestion of wild grape juice led to immediate loss of consciousness in the absence of exercise. This suggests that salicylic acid contained in fruits and vegetables may act as an important cofactor in LTP syndrome. Although sensitization to LTP is rarely reported in Asia, LTP are considered to be potentially life-threatening food allergens, and therefore warrant attention.

In November 2013, a 13-valent pneumococcal conjugate vaccine (PCV13) for all infants aged younger than 5 years was incorporated into the Japan national immunization program. An annual survey of nasopharyngeal carriage rates was performed on healthy infants aged 2-24 months from Okinawa, Japan to evaluate the effect of PCV13 on pneumococcal colonization. Of 756 evaluable infants, 203 pneumococcal strains were detected in 193 infants. The overall nasopharyngeal carriage rate was 25.5%, which was not different from our previously reported isolation rate before the introduction of PCV13. The main serotypes of the Streptococcus pneumoniae strains are 15A (18.2%), non-typeable (14.8%), and 15B (11.8%). The carriage rates of pneumococcal strains with 7-valent pneumococcal conjugate vaccine serotypes and PCV13 serotypes were 3.0% and 9.9%, respectively. These values were significantly lower than we reported before the introduction of PCV13. However, the carriage rates of non-PCV13 serotypes have increased. Multivariate logistic regression analysis suggested that siblings and day care attendance are risk factors for pneumococcal carriage.

In this manuscript the authors have studied interprofessional work model for dementia care in hospitals for community-based care. As present situations and problems of dementia patients in hospitals for community-based care, 8 core categories (19 categories) were extracted and as actual situations of interprofessional work for dementia care, 8 core categories (13 categories) were obtained. The authors examined a function of interprofessional work model and practice contents using these categories. The results revealed that better interprofessional work can be expected by six specialists of nurses rehabilitation specialists, MSW, pharmacists, dietitians and care workers developing dementia care based on “Family handling function” “ADL maintenance and improved function” “Staff member education and empowerment function”.

Enterohaemorrhagic

Enterohaemorrhagic Escherichia coli (EHEC) produces Shiga toxin 1 (Stx1) and Shiga toxin 2 (Stx2). Although stx1 and stx2 were found within the late operons of the Stx-encoding phages (Stx-phages), stx1 could mainly be transcribed from the stx1 promoter (P Stx1), which represents the functional operator-binding site (Fur box) for the transcriptional regulator Fur (ferric uptake regulator), upstream of stx1. In this study, we found that the production of Stx1 by EHEC was affected by oxygen concentration. Increased Stx1 production in the presence of oxygen is dependent on Fur, which is an Fe2+-responsive transcription factor. The intracellular Fe2+ pool was lower under microaerobic conditions than under anaerobic conditions, suggesting that lower Fe2+ availability drove the formation of less Fe2+-Fur, less DNA binding to the P Stx1 region, and an increase in Stx1 production.

Previous studies indicated residents in geriatric long-term care facilities (LTCFs) had much higher prevalence of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) carriage than the general population. Most ESBL-E carriers are asymptomatic. The study tested the hypothesis that residents with ESBL-E carriage may accumulate inside geriatric LTCFs through potential cross-transmission after exposure to residents with prolonged ESBL-E carriage. 260 residents from four Japanese LTCFs underwent ESBL-E testing of fecal specimens and were divided into two cohorts: Cohort 1,75 patients with ≥ 2 months residence at study onset; Cohort 2, 185 patients with

Porcine edema disease (ED) is a toxemia that is caused by enteric infection with Shiga toxin 2e (Stx2e)-producing Escherichia coli (STEC) and is associated with high mortality. Since ED occurs most frequently during the weaning period, preweaning vaccination of newborn piglets is required. We developed stx2eB-transgenic lettuce as an oral vaccine candidate against ED and examined its protective efficacy using a piglet STEC infection model. Two serially developed Stx2eB-lettuce strains, 2BN containing ingredient Stx2eB constituting a concentration level of 0.53 mg Stx2eB/g of powdered lettuce dry weight (DW) and 2BH containing ingredient Stx2eB constituting a concentration level of 2.3 mg of Stx2eB/g of powdered lettuce DW, were evaluated in three sequential experiments. Taken the results together, oral administration of Stx2eB-lettuce vaccine was suggested to relieve the pathogenic symptoms of ED in piglets challenged with virulent STEC strain. Our data suggested that Stx2eB-lettuce is a promising first oral vaccine candidate against ED.

Data on the clinical effectiveness of the novel anti-influenza drug baloxavir marboxil (baloxavir) in children remain limited. We conducted an observational study to compare the duration of fever and symptoms between baloxavir- and oseltamivir-treated children infected with influenza A and B. In total, 159 outpatients with influenza A(H1N1)pdm09 or B/Victoria-lineage infections, aged19 years, during the 2019-2020 influenza season in Japan were enrolled and assessed the duration of fever and symptoms using the Kaplan-Meier method and a multivariate Cox proportional hazard regression model. Polymerase acidic (PA) variants were examined before and after baloxavir treatment. In the multivariable analysis, the duration of fever and symptoms was unaltered between the A(H1N1)pdm09 (n = 116) and B/Victoria-lineage (n = 43) groups. Conversely, the fever duration was marginally longer in the oseltamivir-treated group (n = 59) than in the baloxavir group (n = 100) (hazard ratio (HR) = 0.67, p = 0.05); however, the duration of symptoms was unaltered between the two groups (HR = 0.74, p = 0.11). No patient presented PA reduced susceptibility marker(s) before baloxavir treatment in the analyzed groups. The PA/E23K variant was detected in one case (1.5%, 1/66) of A(H1N1)pdm09 after baloxavir treatment. One case (2.0%, 1/50) of A(H1N1)pdm09 with an N295S substitution in neuraminidase was detected following oseltamivir treatment. These results suggested that the duration of fever was likely to be shorter with baloxavir than with oseltamivir, but the difference between influenza A (H1N1)pdm09 and B/Victoria-lineage was unclear. It is important to continue evaluating the clinical effectiveness of baloxavir and monitoring its drug susceptibility to the influenza virus.

Background: Previous studies indicated residents in geriatric long-term care facilities (LTCFs) had much higher prevalence of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) carriage than the general population. Most ESBL-E carriers are asymptomatic. The study tested the hypothesis that residents with ESBL-E carriage may accumulate inside geriatric LTCFs through potential cross-transmission after exposure to residents with prolonged ESBL-E carriage.Methods: We evaluated 260 residents receiving long-term care in four LTCFs in Japan. All residents underwent initial ESBL-E testing of fecal specimens and were divided into two cohorts: Cohort 1, 95 patients with ≥2 months residence at study onset; Cohort 2, 165 patients with Results: Among all 260 residents, 95 (36.5%) were positive for ESBL-E carriage in the first testing. The prevalence of ESBL-E carriage was significantly higher in Cohort 2 than in Cohort 1 (40% vs. 28%; pConclusions: ESBL-E was most likely to be carried into LTCFs through admission of new residents. Some residents acquired ESBL-E through potential cross-transmission within 3–12 months after admission. Despite possible ESBL-E carriage for >1 year, no residents showed positive conversion >12 months after admission, which suggests that residents with ESBL-E carriage may not accumulate inside LTCFs. Practical infection control and prevention measures against ESBL-E by care providers could improve the ESBL-E prevalence in geriatric LTCFs.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Large samples of galaxy clusters provide knowledge of both astrophysics in the most massive virialized environments and the properties of the cosmological model that defines our Universe. However, an important issue that affects the interpretation of galaxy cluster samples is the role played by the selection waveband and the potential for this to introduce a bias in the physical properties of clusters thus selected. We aim to investigate waveband-dependent selection effects in the identification of galaxy clusters by comparing the X-ray MultiMirror (XMM) Ultimate Extra-galactic Survey (XXL) and Subaru Hyper Suprime-Cam (HSC) CAMIRA cluster samples identified from a common 22.6 deg(2) sky area. We compare 150 XXL and 270 CAMIRA clusters in a common parameter space defined by X-ray aperture brightness and optical richness. We find that 71/150 XXL clusters are matched to the location of a CAMIRA cluster, the majority of which (67/71) display richness values N > 15 that exceed the CAMIRA catalogue richness threshold. We find that 67/270 CAMIRA clusters are matched to the location of an XXL cluster (defined within XXL as an extended X-ray source). Of the unmatched CAMIRA clusters, the majority display low X-ray fluxes consistent with the lack of an XXI. counterpart. However, a significant fraction (64/107) CAMIRA clusters that display high X-ray fluxes are not associated with an extended source in the XXL catalogue. We demonstrate that this disparity arises from a variety of effects including the morphological criteria employed to identify X-ray clusters and the properties of the XMM PSF.

Background To develop an effective vaccine against a novel viral pathogen, it is important to understand the longitudinal antibody responses against its first infection. Here we performed a longitudinal study of antibody responses against SARS-CoV-2 in symptomatic patients. Methods Sequential blood samples were collected from 39 individuals at various timepoints between 0 and 154 days after onset. IgG or IgM titers to the receptor binding domain (RBD) of the S protein, the ectodomain of the S protein, and the N protein were determined by using an ELISA. Neutralizing antibody titers were measured by using a plaque reduction assay. Findings The IgG titers to the RBD of the S protein, the ectodomain of the S protein, and the N protein peaked at about 20 days after onset, gradually decreased thereafter, and were maintained for several months after onset. Extrapolation modeling analysis suggested that the IgG antibodies were maintained for this amount of time because the rate of reduction slowed after 30 days post-onset. IgM titers to the RBD decreased rapidly and disappeared in some individuals after 90 days post-onset. All patients, except one, possessed neutralizing antibodies against authentic SARS-CoV-2, which they retained at 90 days after onset. The highest antibody titers in patients with severe infections were higher than those in patients with mild or moderate infections, but the decrease in antibody titer in the severe infection cohort was more remarkable than that in the mild or moderate infection cohort. Interpretation Although the number of patients is limited, our results show that the antibody response against the first SARS-CoV-2 infection in symptomatic patients is typical of that observed in an acute viral infection. Funding The Japan Agency for Medical Research and Development and the National Institutes of Allergy and Infectious Diseases.

Background A high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) colonization has been reported among residents in geriatric long-term care facilities (LTCFs). Some studies indicate that MRSA might be imported from hospitals into LTCFs via resident transfer; however, other studies report that high MRSA prevalence might be caused by cross-transmission inside LTCFs. We aimed to assess which factors have a large impact on the high MRSA prevalence among residents of geriatric LTCFs. Methods We conducted a cohort study among 260 residents of four geriatric LTCFs in Japan. Dividing participants into two cohorts, we separately analyzed (1) the association between prevalence of MRSA carriage and length of LTCF residence (Cohort 1: n = 204), and (2) proportion of residents identified as MRSA negative who were initially tested at admission but subsequently identified as positive in secondary testing performed at ≥2 months after their initial test (Cohort 2: n = 79). Results Among 204 residents in Cohort 1, 20 (9.8%) were identified as positive for MRSA. Compared with residents identified as MRSA negative, a larger proportion of MRSA-positive residents had shorter periods of residence from the initial admission (median length of residence: 5.5 vs. 2.8 months), although this difference was not statistically significant (p = 0.084). Among 79 residents in Cohort 2, 60 (75.9%) were identified as MRSA negative at the initial testing. Of these 60 residents, only one (1.7%) had subsequent positive conversion in secondary MRSA testing. In contrast, among 19 residents identified as MRSA positive in the initial testing, 10 (52.6%) were negative in secondary testing. Conclusions The prevalence of MRSA was lower among residents with longer periods of LTCF residence than among those with shorter periods. Furthermore, few residents were found to become MRSA carrier after their initial admission. These findings highlight that MRSA in LTCFs might be associated with resident transfer rather than spread via cross-transmission inside LTCFs.

5,6-dihydroxy-8Z,11Z,14Z,17Z-eicosatetraenoic acid (5,6-DiHETE) is an eicosapentaenoic acid-derived lipid metabolite, which we previously detected in inflamed mouse colon. In this study, we investigated the pathophysiological roles of 5,6-DiHETE in murine colitis and its underlying mechanisms of action, focusing on the effects on transient receptor potential vanilloid (TRPV) channel activity. Oral administration of dextran sodium sulfate (DSS, 2%, for 4 days) caused colon inflammation, which peaked on day 7 and gradually declined by day 18. 5,6-DiHETE concentration in colon tissue was significantly increased during the healing phase of colitis (days 9 to 18). In vitro study showed that pretreatment with 5,6-DiHETE (0.1-1 μM, 30 minutes) significantly inhibited endothelial barrier disruption induced by a TRPV4 agonist (GSK1016790A, 50 nM). Intracellular Ca2+ imaging also showed that pretreatment with 5,6-DiHETE (1 μM, 10 minutes) reduced GSK1016790A-induced intracellular Ca2+ increase in HEK293T cells overexpressing TRPV4. In vivo, intraperitoneal administration of 5,6-DiHETE (50 µg kg-1 day-1 ) during the healing phase accelerated the recovery from DSS-induced colitis. Pathological studies showed that the administration of 5,6-DiHETE inhibited edema formation and leukocyte infiltration in inflamed colon tissue. In conclusion, we identified 5,6-DiHETE as a novel endogenous TRPV4 antagonist, and we also demonstrated that its administration promotes the healing of colitis by inhibiting inflammatory responses.

Background: In response to coronavirus disease 2019 (COVID-19), the psychological distress of health care workers (HCWs) is overwhelming, irrespective of the extent of exposure to infected patients. Infection control and prevention (ICP) measures for mobile children and youths are indispensable to contemplate sustainable public health management, but it is difficult to define the clear trade-offs between ensuring virus-containing strategy and resuming ordinary childcare. Aim: To analyze the occupational distress and dilemma of HCWs working on the pediatric cancer ward as a representative model to conceptualize the core of anxiety at the childcare frontline. Methods: Qualitative and quantitative studies using an empirical phenomenological approach and questionnaire survey from 20 th April to 5 th May 2020. Results: High confidence in the institutional ICP measures is fundamental to maintain a strong social responsibility and resilience of HCWs against the crisis, but they are still under overwhelming anxiety within themselves, particularly about being infected to become an asymptomatic carrier who might pass the virus to patients. Both nursing staff and HCWs with less than 5 years of working experience perceived more intense psychological distress in comparison with physicians. Conclusion: We would like to suggest that target approaches, such as activating interpersonal communication and facilitating ICP adherence, are indispensable to maintain the safety climate among HCWs. Recognizing the psychological distress of childcare HCWs is important to mitigate their occupational distress, but also development of future public health strategy in the era of COVID-19.

Shwachman–Diamond syndrome (SDS), an autosomal recessive disorder characterized by bone marrow failure, exocrine pancreatic insufficiency, and skeletal abnormalities, is caused by mutations in the Shwachman–Bodian–Diamond syndrome (SBDS) gene, which plays a role in ribosome biogenesis. Although the causative genes of congenital disorders frequently involve regulation of embryogenesis, the role of the SBDS gene in early hematopoiesis remains unclear, primarily due to the lack of a suitable experimental model for this syndrome. In this study, we established induced pluripotent stem cells (iPSCs) from patients with SDS (SDS-iPSCs) and analyzed their in vitro hematopoietic and endothelial differentiation potentials. SDS-iPSCs generated hematopoietic and endothelial cells less efficiently than iPSCs derived from healthy donors, principally due to the apoptotic predisposition of KDR+CD34+ common hemoangiogenic progenitors. By contrast, forced expression of SBDS gene in SDS-iPSCs or treatment with a caspase inhibitor reversed the deficiency in hematopoietic and endothelial development, and decreased apoptosis of their progenitors, mainly via p53-independent mechanisms. Patient-derived iPSCs exhibited the hematological abnormalities associated with SDS even at the earliest hematopoietic stages. These findings will enable us to dissect the pathogenesis of multiple disorders associated with ribosomal dysfunction.

We investigate the transient coexistence state of the excitons and charge carriers in highly-pure diamond after an impulsive injection of excitons, by probing free electrons until the relaxation of carriers with the nanosecond time-resolved cyclotron resonance (TRCR) method. By analyzing the time profiles of the TRCR signal with a numerical solution of rate equations for exciton and charge carrier densities over a wide temperature range from 10 K to 261 K, the temperature dependence of the coefficient of two-body (Auger) collision of excitons, the rate of thermal dissociation of excitons, and exciton and electron lifetimes was extracted. The shift of exciton dissociation mechanisms from the Auger process below 40 K to the thermal ionization above 80 K was revealed for an initial density of excitons in the order of 1015 cm−3. We also found that the equilibrium between electrons and excitons is established within 100 ns above 80 K, when the thermal ionization of excitons dominates the dissociation process. These results provide fundamental understandings of transient carrier correlation in optoelectronic devices.

Baloxavir marboxil has been used for influenza treatment since March 2018 in Japan. After baloxavir treatment, the most frequently detected substitution is Ile38Thr in polymerase acidic protein (PA/I38T), and this substitution reduces baloxavir susceptibility in influenza A viruses. To rapidly investigate the frequency of PA/I38T in influenza A (H1N1)pdm09 and A (H3N2) viruses in clinical samples, we established a rapid real-time system to detect single nucleotide polymorphisms in PA, using cycling probe real-time PCR. We designed two sets of probes that were labeled with either 6-carboxyfluorescein (FAM) or 6-carboxy-X-rhodamine (ROX) to identify PA/I38 (wild type strain) or PA/I38T, respectively. The established cycling probe real-time PCR system showed a dynamic linear range of 101 to 106 copies with high sensitivity in plasmid DNA controls. This real-time PCR system discriminated between PA/I38T and wild type viruses well. During the 2018/19 season, 377 influenza A-positive clinical samples were collected in Japan before antiviral treatment. Using our cycling probe real-time PCR system, we detected no (0/129, 0.0%) influenza A (H1N1)pdm09 viruses with PA/I38T substitutions and four A (H3N2) (4/229, 1.7%) with PA/I38T substitution prior to treatment. In addition, we found PA/I38T variant in siblings who did not received baloxavir treatment during an infection caused by A (H3N2) that afflicted the entire family. Although human-to-human transmission of PA/I38T variant may have occurred in a closed environment, the prevalence of this variant in influenza A viruses was still limited. Our cycling probe-PCR system is thus useful for antiviral surveillance of influenza A viruses possessing PA/I38T.

Porcine edema disease (ED) is a toxemia caused by enteric infection with Shiga toxin 2e (Stx2e)-producing Escherichia coli (STEC). ED occurs most frequently during the weaning period and is manifested as emaciation associated with high mortality. In our experimental infection with a specific STEC strain, we failed to cause the suppression of weight gain in piglets, which is a typical symptom of ED, in two consecutive experiments. Therefore, we examined the effects of deprivation of colostrum on the sensitivity of newborn piglets to STEC infection. Neonatal pigs were categorized into two groups: one fed artificial milk instead of colostrum in the first 24 h after birth and then returned to the care of their mother, the other breastfed by a surrogate mother until weaning. The oral challenge with 1011 colony-forming units of virulent STEC strain on days 25, 26 and 27 caused suppression of weight gain and other ED symptoms in both groups, suggesting that colostrum deprivation from piglets was effective in enhancing susceptibility to STEC. Two successive STEC infection experiments using colostrum-deprived piglets reproduced this result, leading us to conclude that this improved ED piglet model is more sensitive to STEC infection than the previously established models.

We report our experience with a preterm infant with severe hemolytic jaundice who required exchange transfusion just after birth. The patient was negative for alloimmune hemolysis as a result of maternal–fetal blood type incompatibility, and tests for inherited defects in erythrocyte metabolism, membrane function, and hemoglobin synthesis were normal. We also performed a bone marrow examination, but could not identify the cause of hemolysis. The patient had several other complications, including porencephaly, epilepsy, elevated serum levels of creatine kinase, and persistent microscopic hematuria. Later, we detected a genetic mutation in COL4A1, which was recently found to be associated with hemolytic anemia. We therefore believe that all of the patient's clinical features, including hemolytic anemia, were due to the mutation in COL4A1. Genetic testing for COL4A1 mutations is recommended in neonates who exhibit hemolytic disease of unknown etiology, especially when other complications compatible with COL4A1-related disorders are present.

Secondary expansion and/or evolution of aggressive subclones are associated with the disease progression and resistance to chemotherapy in neuroblastoma, and it is important to track the clonal changes during the treatment period. Cell-free (cf) DNA analysis, namely liquid biopsy, can detect the genomic change of tumor cells without surgical procedures. In this report, we showed that serial polymerase chain reaction-based cf DNA neuroblastoma proto-oncogene quantification is sensitive enough to evaluate the aggressive cellular characteristics of ALK/MYCN-coamplified neuroblastoma and stressed the promise of cf DNA analyses as a reliable molecular marker in advanced neuroblastoma.

We present multi-wavelength studies of optically-defined merging clusters, based on the Hyper Suprime-Cam Subaru Strategic Program. Luminous red galaxies, tracing cluster mass distributions, enable to identify cluster subhalos at various merging stages, and thus make a homogeneous sample of cluster mergers, which is unbiased with respect to the merger boost of the intracluster medium (ICM). We define, using a peak-finding method, merging clusters with multiple-peaks and single clusters with single-peaks from the CAMIRA cluster catalog. Stacked weak-lensing analysis indicates that our sample of the merging clusters is categorized into major mergers. The average halo concentration for the merging clusters is $\sim70\%$ smaller than that of the single-peak clusters, which agrees well with predictions of numerical simulations. The spatial distribution of subhalos is less centrally concentrated than the mass distribution of the main halo. The fractions of red galaxies in the merging clusters are not higher than those of the single-peak clusters. We find a signature of the merger boost of the ICM from stacked Planck Sunyaev-Zeldovich effect and ROSAT X-ray luminosity, but not in optical richness. The stacked X-ray surface brightness distribution, aligned with the main-subhalo pairs of low redshift and massive clusters, shows that the central gas core is elongated along the merger axis and overall gas distribution is misaligned by $\sim60$ deg. The homogeneous, unbiased sample of cluster mergers and multi-wavelength follow-up studies provide a unique opportunity to make a complete picture of merger physics over the whole process., Comment: 23 pages, 10 figures, 1 table : accepted for the publication in PASJ

Vitrification is widely used for assisted reproductive technology (ART). Most vitrification devices require the skillful placement of embryos into the carrier and aspiration of excessive vitrification solution.To evaluate the efficacy and safety of the Cryoroom as a vitrification device.Mouse and human embryos were vitrified with Cryoroom or Cryotop, and the developmental potency was assessed in vitro. Mouse monozygotic twin blastocysts were vitrified with Cryoroom or Cryotop for microarray analysis.In mouse and human embryos, there were no differences between the survival and developmental progress in each device. In silico, the Cryoroom device showed no changes, particularly in DNA methylation after vitrification compared with the Cryotop. These results showed that the form and function of the device may affect the gene expression levels in vitrified embryos.The Cryoroom represents a safe and potentially revolutionary vitrification device for ART.

Human influenza A(H2N2) viruses emerged in 1957 and were replaced by A(H3N2) viruses in 1968. The antigenicity of human H2N2 viruses has been tested by using ferret antisera or mouse and human monoclonal antibodies. Here, we examined the antigenicity of human H2N2 viruses by using human plasma samples obtained from 50 aged individuals who were born between 1928 and 1933 and from 33 younger adult individuals who were born after 1962. The aged individuals possessed higher neutralization titers against H2N2 viruses isolated in 1957 and 1963 than those against H2N2 viruses isolated in 1968, whereas the younger adults who were born between 1962 and 1968 possessed higher neutralization titers against H2N2 viruses isolated in 1963 than those against other H2N2 viruses. Antigenic cartography revealed the antigenic changes that occurred in human H2N2 viruses during circulation in humans for 11 years, as detected by ferret antisera. These results show that even though aged individuals were likely exposed to more recent H2N2 viruses that are antigenically distinct from the earlier H2N2 viruses, they did not possess high neutralizing antibody titers to the more recent viruses, suggesting immunological imprinting of these individuals with the first H2N2 viruses they encountered and that this immunological imprinting lasts for over 50 years.

Thirty-nine groundwater samples were collected from wells near the Tavan Tolgoi and Oyu Tolgoi mines in Mongolia and at a relatively pristine site in northern Mongolia during August to September 2013, and analyzed for the concentrations of F−, NO3−, Hg, As, Al, V, Mn, Co, Ni, Cu, Zn, Se, Mo, Cd, Sb, and Pb. A probabilistic risk assessment found that >95% of the population in the areas was at risk from drinking well water. The hazard index (HI) was >1, indicating a non-carcinogenic risk to human health. At Oyu Tolgoi, the hazard quotient (HQ) of the As concentration (mean 6.63 μg/L) was >1. At the northern site, the 95th percentile HQ was 1. The ratios of nitrogen and oxygen stable isotopes indicated that NO3− contamination of groundwater at Oyu Tolgoi and Tavan Tolgoi was caused by livestock waste. Mercury accumulation in livestock was examined from concentrations in livestock forage and in hair and wool samples from livestock in the South Gobi region. Sheep wool had the same level of mercury as in Japan, but camel, horse, and goat hair had high levels.

Malignant rhabdoid tumor (MRT) is a rare, highly aggressive pediatric malignancy that primarily develops during infancy and early childhood. Despite the existing standard of intensive multimodal therapy, the prognosis of patients with MRT is dismal; therefore, a greater understanding of the biology of this disease is required to establish novel therapies. In this study, we identified a highly tumorigenic sub-population in MRT, based on the expression of CD146 (also known as melanoma cell adhesion molecule), a cell adhesion molecule expressed by neural crest cells and various derivatives. CD146+ cells isolated from four MRT cell lines by cell sorting exhibited enhanced self-renewal and invasive potential in vitro. In a xenograft model using immunodeficient NOD/Shi-scid IL-2Rγ-null mice, purified CD146+ cells obtained from MRT cell lines or a primary tumor exhibited the exclusive ability to form tumors in vivo. Blocking of CD146-related mechanisms, either by short hairpin RNA knockdown or treatment with a polyclonal antibody against CD146, effectively suppressed tumor growth of MRT cells both in vitro and in vivo via induction of apoptosis by inactivating Akt. Furthermore, CD146 positivity in immunohistological analysis of 11 MRT patient samples was associated with poor patient outcomes. These results suggest that CD146 defines a distinct sub-population in MRT with high tumorigenic capacity and that this marker represents a promising therapeutic target.

The widely distributed colonization factor (CF) CS6 of enterotoxigenic Escherichia coli (ETEC) has gained importance over the years in terms of its structure and function. CS6 is an afimbrial assembly in contrast to the other ETEC CFs, which are mostly fimbrial. A recent study predicted a linear fibre model for recombinant chimeric CS6 and formation of oligomers in solution. In this study, we characterized the oligomeric assembly of CS6, purified from a clinical ETEC isolate and identified its existence in the WT strain. We found that purified CS6 forms a continuous array of higher order oligomers composed of two tightly associated subunits, CssA and CssB in an equal (1:1) stoichiometry. This oligomerization occurs by formation of (CssA-CssB)n complex where 'n' increases with the concentration. The diameter of CS6 oligomers also proportionally increases with concentration. More significantly, we showed CS6 oligomers to be spherical in shape instead of being linear fibres as predicted earlier and this was further confirmed by electron microscopy. We also showed CS6 assembled on the bacterial surface in the form of an oligomeric complex. This process depends on the expression of properly folded CssA and CssB together, guided by the chaperone CssC and usher CssD. In conclusion, our results provide evidence for the existence of concentration-dependent, spherical oligomers of CS6 comprising both the structural subunits in equal stoichiometry and the CS6 oligomeric complex on the ETEC surface.

Understanding the distribution range across the life history of endangered animals is crucial for effective conservation and management planning. However, endangered migratory green turtles with straight carapace lengths (SCLs) of

Enterotoxigenic Escherichia coli (ETEC) serotype O169:H41 has been an extremely destructive epidemic ETEC type worldwide. The strain harbors a large unstable plasmid that is regarded as responsible for its virulence, although its etiology has remained unknown. To examine its genetic background specifically on the unstable retention and responsibility in the unique adherence to epithelial cells and enterotoxin production, the complete sequence of a plasmid, pEntYN10, purified from the serotype strain was determined. The length is 145,082 bp; its GC content is 46.15%. It contains 182 CDSs, which include 3 colonization factors (CFs), an enterotoxin, and large number of insertion sequences. The repertory of plasmid stability genes was extraordinarily scant. Uniquely, results showed that 3 CFs, CS6, CS8 (CFA/III)-like, and K88 (F4)-like were encoded redundantly in the plasmid with unique variations among previously known subtypes. These three CFs preserved their respective gene structures similarly to those of other ETEC strains reported previously with unique sequence variations respectively. It is particularly interesting that the K88-like gene cluster of pEntYN10 had 2 paralogous copies of faeG, which encodes the major component of fimbrial structure. It remains to be verified how the unique variations found in the CFs respectively affect the affinity to infected cells, host range, and virulence of the ETEC strain.

We report on three cases of pediatric acute lymphoblastic leukemia presenting with bone pain and arthralgia as initial symptoms. At the first visit, their primary signs were recurrent bone pain and arthralgia, without significant peripheral blood abnormalities. It took 2-4 months to confirm the diagnosis from the onset of arthralgia due to this atypical presentation of the disease. Definitive diagnosis was obtained by bone marrow examination, and in all cases, complete remission was achieved by chemotherapy. As a feature of imaging, MRI exhibited diffuse bone marrow signal changes in T1-weighted images, and FDG-PET showed extensive abnormal bone marrow uptakes. In cases 2 and 3, it was difficult to diagnose by bone marrow aspiration from the iliac bone, but definitive diagnosis was obtained by bone marrow aspiration from the tibia, in which FDG-PET showed increased uptake. FDG-PET was therefore considered useful for the selection of bone marrow aspiration sites. In cases presenting with recurrent migratory bone pain and arthralgia, we need to consider performing bone marrow aspiration and imaging, such as MRI and FDG-PET, for early diagnosis and treatment of leukemia.

The clinical outcome of high-dose chemotherapy (HDC) with autologous stem cell transplantation was retrospectively analyzed in six patients with recurrent intracranial germinoma. Prior to HDC, all patients achieved complete remission after platinum and ifosfamide-based chemotherapy. A melphalan-based conditioning regimen was administered in either a single cycle or multiple sequential cycles. Five of the six patients are alive and free from disease, with a median survival of 65 months, among which four patients avoided re-irradiation. In a significant proportion of patients, recurrent intracranial germinoma is curable by HDC without re-irradiation, provided that the disease remains sensitive to salvage chemotherapy.

We have carried out $^{29}\mathrm{Si}$ nuclear magnetic resonance of ${\mathrm{URu}}_{2}{\mathrm{Si}}_{2}$, which undergoes the so-called hidden order (HO) at ${T}_{\mathrm{HO}}=17.5$ K. The use of a $^{29}\mathrm{Si}$-enriched sample enabled us to obtain accurate NMR data up to 350 K and to extract the features of low energy magnetic correlations at high temperatures in this compound. Present results naturally indicate that ${\mathrm{URu}}_{2}{\mathrm{Si}}_{2}$ undergoes a crossover from localized to itinerant regimes with decreasing temperature and the HO occurs in the crossover region. We also discuss possible antiferromagnetic correlations remaining down to ${T}_{\mathrm{HO}}$ by extracting magnetic fluctuation components.

In our previous work, we demonstrated that viable but nonculturable (VBNC) Vibrio cholerae O1 and O139 were converted to culturable by coculture with eukaryotic cells. Furthermore, we isolated a factor converting VBNC V. cholerae to culturable (FCVC) from a eukaryotic cell line, HT-29. In this study, we purified FCVC by successive column chromatographies comprising UNO Q-6 anion exchange, Bio-Scale CHT2-1 hydroxyapatite, and Superdex 200 10/300 GL. Homogeneity of the purified FCVC was demonstrated by SDS-PAGE. Nano-LC MS/MS analysis showed that the purified FCVC was a human catalase. An experiment of RNAi knockdown of catalase mRNA from HT-29 cells and treatment of the purified FCVC with a catalase inhibitor, 3-amino-1,2,4-triazole confirmed that the FCVC was a catalase. A possible role of the catalase in converting a VBNC V. cholerae to a culturable state in the human intestine is discussed.

In Japan, the heptavalent pneumococcal conjugate vaccine (PCV7) became available in February 2010 and was subsidized by the national funding system from May 2011 in Okinawa, after which it was incorporated into the national immunization practice (NIP) in April 2013 using a 3 + 1 schedule for all infants. We conducted an annual survey in 2012 to determine the effect of PCV7 on nasopharyngeal colonization by pneumococcal serotypes and to analyze the risk factors for colonization in infants. Nasopharyngeal swabs for pneumococcal isolation and serotyping were obtained from infant 2 to 22 months of age before and after PCV7 immunization among 4 clinics in Okinawa, Japan. Between January 2012 and December 2012, nasopharyngeal swabs for bacterial cultures were obtained among 782 infants aged 2 to 22 months old and demographic data was obtained among 725 participant infants. Among the 725 evaluable infants, 193 pneumococcal strains were detected in 180 infants for an overall nasopharyngeal carriage of 24.8%. The main capsular serotypes isolated were 6C (16.1%), 19A (12.4%) and 15B (9.8%). Carriage of PCV7 serotypes accounted for 21.8% (42/193). The result of multivariate data analysis showed the pneumococcal carriage rate of non-PCV7 serotypes was significantly (P < 0.001) high in infant with siblings and daycare attendance. On the other hand, the result of multivariate data analysis showed that carriage rate of PCV7 serotype had only significantly high risk in infant with siblings and did not have a significant risk dependent on age and daycare attendance. Carriage PCV7 serotypes increased in the presence of other siblings, while PCV7 vaccination was shown to eliminate daycare attendance as a risk. The results of this study demonstrates that PCV7 vaccination decrease the overall nasopharyngeal carriage of PCV7 serotypes in vaccinated children including children at risk such as children attending day-care centers.

The loggerhead turtle Caretta caretta is highly migratory and undertakes trans oceanic migrations. In the North Pacific, loggerhead turtles that hatch on Japanese beaches reach the vicinity of Baja California in the eastern Pacific. As they grow, they return and recruit to the feeding areas around Japan. By using mtDNA control-region sequences, we identified the genetic composition of the feeding aggregation around the Sanriku coastal area (n = 107), >500 km north of the main nesting beaches of Japan and located on the north of the Japanese mainland. Performing a mixed-stock analysis using the published data from 5 Japanese nesting rookeries (n = 279 in total) as sources, the origin of the feeding aggregation was estimated with Bayesian statistics. The results indicated a high contribution from the southern rookeries (mean ≥ 82.10%), mainly the Yakushima rookery (mean ≥ 51.45%), to the Sanriku feeding aggregation, whether the number of nests was considered as an informative prior or not. Therefore, the Sanriku coastal area is estimated to be utilized by loggerhead turtles born in the southern nesting rookeries relatively far from Sanriku. The strong connectivity between loggerheads from the Sanriku feeding aggregation and the southern Japanese rookeries suggests that loggerhead turtles in the North Pacific generally settle in the Japanese coastal areas in the large juvenile stage, but not in the direct vicinity of their natal sites, and some juveniles that use an oceanic feeding strategy are recruited to the Sanriku coastal area.

Previously, we reported that viable but nonculturable (VBNC) Vibrio cholerae was converted into a culturable state by coculture with several eukaryotic cell lines including HT-29 cells. In this study, we found that a factor converting VBNC V. cholerae into a culturable state (FCVC) existed in cell extracts of eukaryotic cells. FCVC was nondialyzable, proteinase K-sensitive, and stable to heating at

The existing accuracy test standard for machining centers (ISO10791) is being revised in order to add a test method for five-axis machining centers. In the revised part of the standard (ISO10791-6), simultaneous three-axis interpolation motion accuracy tests for two linear axes and one rotary axis are proposed as an interpolation accuracy test for five-axis machining centers. These tests enable the measurement of the motion error in three directions, e.g., X, Y, and Z. Two devices can be used as the measurement instrument in these tests. One is a ball bar device, and the other is a combination of a ball and a displacement sensor. An R-test device that incorporates three displacement sensors has been designed for the latter. Using the ball bar device, measurement in three directions can be performed independently, and the radii of circular interpolations for each measurement are different. Using the R-test device, time is shortened by measuring three measurement directions at once, and the acquired data can be analyzed in various ways. The original goal of the measurement method using the R-test device was to measure the dynamic accuracy of the rotary axes. In the present study, the R-test device was actually prototyped and several machines were measured. In addition to the dynamic error of the rotary axes, incorrect pitch error compensation settings for the numerical controller, straightness, or squareness of the linear axes can be well detected.