Interleukin-2 induces the in vitro maturation of human pluripotent stem cell-derived intestinal organoids.

Human pluripotent stem cell (hPSC)-derived intestinal organoids (hIOs) form 3D structures organized into crypt and villus domains, making them an excellent in vitro model system for studying human intestinal development and disease. However, hPSC-derived hIOs still require in vivo maturation to fully recapitulate adult intestine, with the mechanism of maturation remaining elusive. Here, we show that the co-culture with human T lymphocytes induce the in vitro maturation of hIOs, and identify STAT3-activating interleukin-2 (IL-2) as the major factor inducing maturation. hIOs exposed to IL-2 closely mimic the adult intestinal epithelium and have comparable expression levels of mature intestinal markers, as well as increased intestine-specific functional activities. Even after in vivo engraftment, in vitro-matured hIOs retain their maturation status. The results of our study demonstrate that STAT3 signaling can induce the maturation of hIOs in vitro, thereby circumventing the need for animal models and in vivo maturation

A Case of Acute Hepatitis with Mycoplasma pneumoniae Infection and Transient Depression of Multiple Coagulation Factors

We report a case of acute severe hepatitis with Mycoplasma pneumoniae (M. pneumoniae) infection and transient depression of multiple coagulation factors. A 5-year-old boy, previously healthy, was admitted with pneumonia. M. pneumoniae infection was confirmed by serology testing. Liver enzymes were elevated on admission without any past medical history. After treatment with azithromycin for 3 days, pneumonia improved, but the hepatitis was acutely aggravated. Partial thromboplastin time (PTT) was prolonged and depression of multiple coagulation factors developed. Liver biopsy revealed features consistent with acute hepatitis. A week later, liver enzymes were nearly normalized spontaneously. Normalization of prolonged PTT and coagulation factors were also observed several months later. This may be the first case of transient depression of multiple coagulation factors associated with M. pneumoniae infection

The effect of a nutritional education program on the nutritional status of elderly patients in a long-term care hospital in Jeollanamdo province: health behavior, dietary behavior, nutrition risk level and nutrient intake

This study was conducted to assess improvements in nutritional status following the application of nutrition education to elderly patients in a long-term care hospital. The study was carried out from January to May 2009, during which a preliminary survey, a pretest, the application of nutrition education, and a post-test were applied in stages. The number of subjects at pretest was 81, and the number of participants included in the final analysis was 61 (18 men, 43 women), all of whom participated in both the nutrition education program and the post-test. The survey consisted of general demographic items, health behaviors, dietary behaviors, the Nutrition Screening Initiative checklist, and nutrient intake assessment (24 hour recall method). The nutrition education program lasted for four weeks. It included a basic education program, provided once a week, and mini-education program, which was offered daily during lunch times. The survey was conducted before and after the education program using the same assessment method, although some items were included only at pretest. When analyzing the changes in elderly patients after the nutritional education program, we found that, among subjective dietary behaviors, self-rated perceptions of health (P < 0.001) and of depression (P < 0.001) improved significantly and that dietary behavior scores also improved significantly (P < 0.001), while nutritional risk levels decreased. In terms of nutrient intake, subjects' intake of energy, protein, fat, carbohydrate, calcium, phosphorus, iron, vitamin A, thiamin, riboflavin, niacin, and vitamin C all increased significantly (P < 0.001). These results indicated that nutritional education is effective in improving the nutritional status of elderly patients. We hope that the results of this study can be used as preliminary data for establishing guidelines for nutrition management tailored to elderly patients in long-term care hospitals

Nosocomial Outbreak of Carbapenem-Resistant Acinetobacter baumannii in Intensive Care Units and Successful Outbreak Control Program

Acinetobacter baumannii has been increasingly reported as a significant causative organism of various nosocomial infections. Here we describe an outbreak of carbapenem-resistant A. baumannii (CRAB) in the ICUs of a Korean university hospital, along with a successful outbreak control program. From October 2007 through July 2008, CRAB was isolated from 57 ICU patients. Nineteen patients were diagnosed as being truly infected with CRAB, four of whom were presumed to have died due to CRAB infection, producing a case-fatality rate of 21.1%. In surveillance of the environment and the healthcare workers (HCWs), CRAB was isolated from 24 (17.9%) of 135 environmental samples and seven (10.9%) of 65 HCWs. The pulsed field gel electrophoresis patterns showed that the isolates from patients, HCWs, and the environment were genetically related. Control of the outbreak was achieved by enforcing contact precautions, reducing environmental contamination through massive cleaning, and use of a closed-suctioning system. By August 2008 there were no new cases of CRAB in the ICUs. This study shows that the extensive spread of CRAB can happen through HCWs and the environmental contamination, and that proper strategies including strict contact precautions, massive environmental decontamination, and a closed-suctioning system can be effective for controlling CRAB outbreaks

Structure-Activity Relationship Analysis of YM155 for Inducing Selective Cell Death of Human Pluripotent Stem Cells

Despite great potential for regenerative medicine, the high tumorigenic potential of human pluripotent stem cells (hPSCs) to form undesirable teratoma is an important technical hurdle preventing safe cell therapy. Various small molecules that induce the complete elimination of undifferentiated hPSCs, referred to as “stemotoxics,” have been developed to facilitate tumor-free cell therapy, including the Survivin inhibitor YM155. In the present work, based on the chemical structure of YM155, total 26 analogs were synthesized and tested for stemotoxic activity toward human embryonic stem cells (hESCs) and induced PSCs (iPSCs). We found that a hydrogen bond acceptor in the pyrazine ring of YM155 derivatives is critical for stemotoxic activity, which is completely lost in hESCs lacking SLC35F2, which encodes a solute carrier protein. These results suggest that hydrogen bonding interactions between the nitrogens of the pyrazine ring and the SLC35F2 protein are critical for entry of YM155 into hPSCs, and hence stemotoxic activity

Representative levels of blood lead, mercury, and urinary cadmium in youth: Korean Environmental Health Survey in Children and Adolescents (KorEHS-C), 2012–2014

AbstractBackgroundThis study examined levels of blood lead and mercury, and urinary cadmium, and associated sociodemographic factors in 3–18 year-old Korean children and adolescents.Materials and methodsWe used the nationally representative Korean Environmental Health Survey in Children and Adolescents data for 2012–2014 and identified 2388 children and adolescents aged 3–18 years. The median and 95th percentile exposure biomarker levels with 95% confidence intervals (CIs) were calculated. Multivariate regression analyses were performed on log transformed exposure biomarker levels adjusted for age, sex, area, household income, and father’s education level. The median exposure biomarker levels were compared with data from Germany, the US, and Canada, as well as the levels of Korean children measured at different times.ResultsThe median levels of blood lead and mercury, as well as urinary cadmium were 1.23μg/dL, 1.80μg/L, and 0.40μg/L (95% CIs, 1.21–1.25, 1.77–1.83, and 0.39–0.41, respectively). The blood lead levels were significantly higher in boys and younger children (p<0.0001) and children with less educated fathers (p=0.004) after adjusting for covariates. Urinary cadmium level increased with age (p<0.0001). The median levels of blood mercury and urinary cadmium were much higher in Korean children and adolescents than those in their peers in Germany, the US, and Canada. Blood lead levels tended to decrease with increasing age and divergence between the sexes, particularly in the early teen years. Median levels of blood lead and urinary cadmium decreased since 2010.ConclusionSociodemographic factors, including age, sex, and father’s education level were associated with environmental exposure to heavy metals in Korean children and adolescents. These biomonitoring data are valuable for ongoing surveillance of environmental exposure in this vulnerable population

CRISPR-Cas9 screens in human cells and primary neurons identify modifiers of C9ORF72 dipeptide-repeat-protein toxicity.

Hexanucleotide-repeat expansions in the C9ORF72 gene are the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia (c9ALS/FTD). The nucleotide-repeat expansions are translated into dipeptide-repeat (DPR) proteins, which are aggregation prone and may contribute to neurodegeneration. We used the CRISPR-Cas9 system to perform genome-wide gene-knockout screens for suppressors and enhancers of C9ORF72 DPR toxicity in human cells. We validated hits by performing secondary CRISPR-Cas9 screens in primary mouse neurons. We uncovered potent modifiers of DPR toxicity whose gene products function in nucleocytoplasmic transport, the endoplasmic reticulum (ER), proteasome, RNA-processing pathways, and chromatin modification. One modifier, TMX2, modulated the ER-stress signature elicited by C9ORF72 DPRs in neurons and improved survival of human induced motor neurons from patients with C9ORF72 ALS. Together, our results demonstrate the promise of CRISPR-Cas9 screens in defining mechanisms of neurodegenerative diseases

Transmission of Fusarium boothii Mycovirus via Protoplast Fusion Causes Hypovirulence in Other Phytopathogenic Fungi

There is increasing concern regarding the use of fungicides to control plant diseases, whereby interest has increased in the biological control of phytopathogenic fungi by the application of hypovirulent mycoviruses as a possible alternative to fungicides. Transmission of hypovirulence-associated double-stranded RNA (dsRNA) viruses between mycelia, however, is prevented by the vegetative incompatibility barrier that often exists between different species or strains of filamentous fungi. We determined whether protoplast fusion could be used to transmit FgV1-DK21 virus, which is associated with hypovirulence on F. boothii (formerly F. graminearum strain DK21), to F. graminearum, F. asiaticum, F. oxysporum f. sp. lycopersici, and Cryphonectria parasitica. Relative to virus-free strains, the FgV1-DK21 recipient strains had reduced growth rates, altered pigmentation, and reduced virulence. These results indicate that protoplast fusion can be used to introduce FgV1-DK21 dsRNA into other Fusarium species and into C. parasitica and that FgV1-DK21 can be used as a hypovirulence factor and thus as a biological control agent

The Mothers and Children’s Environmental Health (MOCEH) study

The MOCEH study is a prospective hospital- and community-based cohort study designed to collect information related to environmental exposures (chemical, biological, nutritional, physical, and psychosocial) during pregnancy and childhood and to examine how exposure to environmental pollutants affects growth, development, and disease. The MOCEH network includes one coordinating center, four local centers responsible for recruiting pregnant women, and four evaluation centers (a nutrition center, bio-repository center, neurocognitive development center, and environment assessment center). At the local centers, trained nurses interview the participants to gather information regarding their demographic and socioeconomic characteristics, complications related to the current gestation period, health behaviors and environmental factors. These centers also collect samples of blood, placenta, urine, and breast milk. Environmental hygienists measure each participant’s level of exposure to indoor and outdoor pollutants during the pre- and postnatal periods. The participants are followed up through delivery and until the child is 5 years of age. The MOCEH study plans to recruit 1,500 pregnant women between 2006 and 2010 and to perform follow-up studies on their children. We expect this study to provide evidence to support the hypothesis that the gestational environment has an effect on the development of diseases during adulthood. We also expect the study results to enable evaluation of latency and age-specific susceptibility to exposure to hazardous environmental pollutants, evaluation of growth retardation focused on environmental and genetic risk factors, selection of target environmental diseases in children, development of an environmental health index, and establishment of a national policy for improving the health of pregnant women and their children

Azimuthal anisotropy of charged particles at high transverse momenta in PbPb collisions at sqrt(s[NN]) = 2.76 TeV

The azimuthal anisotropy of charged particles in PbPb collisions at nucleon-nucleon center-of-mass energy of 2.76 TeV is measured with the CMS detector at the LHC over an extended transverse momentum (pt) range up to approximately 60 GeV. The data cover both the low-pt region associated with hydrodynamic flow phenomena and the high-pt region where the anisotropies may reflect the path-length dependence of parton energy loss in the created medium. The anisotropy parameter (v2) of the particles is extracted by correlating charged tracks with respect to the event-plane reconstructed by using the energy deposited in forward-angle calorimeters. For the six bins of collision centrality studied, spanning the range of 0-60% most-central events, the observed v2 values are found to first increase with pt, reaching a maximum around pt = 3 GeV, and then to gradually decrease to almost zero, with the decline persisting up to at least pt = 40 GeV over the full centrality range measured.Comment: Replaced with published version. Added journal reference and DO