The effect of decontamination using quaternary ammonium chloride on the bacterial burden of hospital privacy curtains.

This quasi-experimental study aimed to identify the effect of decontamination using quaternary ammonium chloride (QAC) on bacterial burden on hospital privacy curtains. The objects were the high-touch edges of 66 polyester curtains in inpatient wards. The decontamination was performed daily (n = 22), twice-weekly (n = 22), or not performed (n = 22) for 28 days. The bacterial burden on the curtains was measured based on the number of bacteria, the proportion of curtains with >2.5 colony-forming unit/cm2 , and the proportion of curtains with multidrug-resistant organisms (MDROs). As a result, the daily or twice-weekly decontamination groups showed a significantly lower increase in bacterial burden than the no-decontamination group overall and at all four posttest times. On day 28, daily decontamination showed a lower increase in the number of bacteria (p < 0.001) and proportions of curtains with >2.5 colony form units/cm2 (p < 0.001) than the no-decontamination condition, and in the number of curtains with MDROs than twice-weekly decontamination. In conclusion, decontamination of curtains using QAC helps reduce bacterial burden, and daily decontamination is recommended up to 28 days after installation.

Exome Chip Analysis of 14,026 Koreans Reveals Known and Newly Discovered Genetic Loci Associated with Type 2 Diabetes Mellitus.

Background: Most loci associated with type 2 diabetes mellitus (T2DM) discovered to date are within noncoding regions of unknown functional significance. By contrast, exonic regions have advantages for biological interpretation. Methods: We analyzed the association of exome array data from 14,026 Koreans to identify susceptible exonic loci for T2DM. We used genotype information of 50,543 variants using the Illumina exome array platform. Results: In total, 7 loci were significant with a Bonferroni adjusted P=1.03×10-6. rs2233580 in paired box gene 4 (PAX4) showed the highest odds ratio of 1.48 (P=1.60×10-10). rs11960799 in membrane associated ring-CH-type finger 3 (MARCH3) and rs75680863 in transcobalamin 2 (TCN2) were newly identified loci. When we built a model to predict the incidence of diabetes with the 7 loci and clinical variables, area under the curve (AUC) of the model improved significantly (AUC=0.72, P<0.05), but marginally in its magnitude, compared with the model using clinical variables (AUC=0.71, P<0.05). When we divided the entire population into three groups-normal body mass index (BMI; <25 kg/m2), overweight (25≤ BMI <30 kg/m2), and obese (BMI ≥30 kg/m2) individuals-the predictive performance of the 7 loci was greatest in the group of obese individuals, where the net reclassification improvement was highly significant (0.51; P=8.00×10-5). Conclusion: We found exonic loci having a susceptibility for T2DM. We found that such genetic information is advantageous for predicting T2DM in a subgroup of obese individuals.

Correlations Between the Incidence of National Notifiable Infectious Diseases and Public Open Data, Including Meteorological Factors and Medical Facility Resources.

OBJECTIVES: This study was performed to investigate the relationship between the incidence of national notifiable infectious diseases (NNIDs) and meteorological factors, air pollution levels, and hospital resources in Korea. METHODS: We collected and stored 660,000 pieces of publicly available data associated with infectious diseases from public data portals and the Diseases Web Statistics System of Korea. We analyzed correlations between the monthly incidence of these diseases and monthly average temperatures and monthly average relative humidity, as well as vaccination rates, number of hospitals, and number of hospital beds by district in Seoul. RESULTS: Of the 34 NNIDs, malaria showed the most significant correlation with temperature (r=0.949, p<0.01) and concentration of nitrogen dioxide (r=-0.884, p<0.01). We also found a strong correlation between the incidence of NNIDs and the number of hospital beds in 25 districts in Seoul (r=0.606, p<0.01). In particular, Geumcheon-gu was found to have the lowest incidence rate of NNIDs and the highest number of hospital beds per patient. CONCLUSIONS: In this study, we conducted a correlational analysis of public data from Korean government portals that can be used as parameters to forecast the spread of outbreaks.

A Visualization Tool for Calculating the Genetic Substitution Patterns Between Two Different Groups.

We developed simulation tool for influenza virus variation (SimFluVar), an analytics software for calculating genomic variation among members of the influenza virus group. This study is related to computational evolutionary biology and evolutionary bioinformatics. SimFluVar is an analytical tool that can be used to calculate codon substitution patterns of viral genes. Designed to compare a large number of nucleotide sequences, SimFluVar provides precise patterns of codon variations between two viral groups, especially for the influenza virus. SimFluVar also provides useful functions, such as editing and visualization of the result matrix. This new tool can be used to analyze codon variation patterns over time as well as to analyze the genomic differences between viruses obtained from different geographical locations. SimFluVar is developed in C++, and Java RCP is used as a distribution package. SimFluVar, including the associated documentation, manuals, and examples, is publicly available at http://lcbb.snu.ac.kr/simfluvar.

Nuclear Ago2/HSP60 contributes to broad spectrum of hATSCs function via Oct4 regulation.

AIMS: Argonaute2 (Ago2) plays a fundamental role in microRNA-mediated gene regulation through its intrinsic endonuclease activity. In this study we demonstrate the novel functions and molecular mechanisms by which nuclear Ago2 directly regulates HSP (heat shock protein) 60 expression and stem cell self-renewal. HSP60 is a crucial regulator of ROS (reactive oxygen species), senescence, and apoptotic cell death in several tissues and cell types. RESULTS: HSP60 is regulated via inactivation of p38/JNK and p53 and binds directly to the regulatory regions of the TERT, c-myc, GPx3, p53, and STAT3 genes. Using HSP60 CHIP-PCR experiments, we show that HSP60 binds directly to the Oct4 and Nanog genes and directly regulates Oct4 and other stemness genes involved in human adipose tissue-derived stem cell (hATSC) differentiation. HSP60 also positively regulates ROS-scavenging factors, including GPx3 and TXNL1, which directly modulate cytosolic ROS in hATSCs. Moreover, our study shows that Oct4 regulates HSP60 expression and controls hATSC survival and self-renewal after binding to the HSP60 gene. Furthermore, HSP60-mediated regulation of Oct4 contributes to neuronal and endodermal ß-cell differentiation of hATSCs in vitro and in vivo and downregulates mesoderm-specific gene expression. INNOVATION AND CONCLUSION: We show that increased levels of Ago2 or HSP60 effectively induce nuclear localization of HSP60, which directly controls Oct4, c-Myc, p53, TERT, and STAT3 for transdifferentiation programs. Collectively, we suggest a novel model in which nuclear Ago2 controls HSP60 in hATSCs.

Crucial role of nuclear Ago2 for hUCB-MSCs differentiation and self-renewal via stemness control.

AIMS: Argonaute2 (Ago2) has intrinsic endonuclease activity in microRNA processing that plays a fundamental role in gene regulation. In this study, we demonstrate novel functions and molecular mechanisms of nuclear Ago2 in the self-renewal and plasticity of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs). RESULTS: Nuclear Ago2 binds to a set of regulatory genes, including Ago2 itself, Oct4, Sox2, Nanog, GATA, STAT3, and ß-catenin, that potentially target fundamental functions of stem cells. Direct regulation of the stemness genes by nuclear Ago2 was also crucial for cell self-renewal, survival, and differentiation into various types of tissues or cells, including neural cells and ß-cells. Moreover, regulation of Oct4 by Ago2 directly controls the stem cell plasticity-determining signal mediators JAK2/STAT3 and Wnt5A/ß-catenin and positively regulates cell proliferation and differentiation via blockage of ROS generation and P38/JNK inactivation. Nuclear Ago2 or stemness expression lead increased stem cell identity and decreased differentiation into a mesodermal lineage but also led to increased neural differentiation and ß-cell differentiation in hUCB-MSCs. Nuclear Ago2-mediated stemness expression in hUCB-MSCs is also involved in cell survival, helping cells escape apoptotic cell death via inactivation of P38/JNK, caspase-3, and Bax. INNOVATION AND CONCLUSION: This study reveals that nuclear Ago2 globally controls stem cell self-renewal and differentiation through direct regulation of stemness genes and important signal mediator activation following inactivation of ROS/P38/JNK and activation of the JAK/STAT3 and Wnt/ ß-catenin signal pathways.

miR23b ameliorates neuropathic pain in spinal cord by silencing NADPH oxidase 4.

AIMS: Neuropathic pain is a well-known type of chronic pain caused by damage to the nervous system. Until recently, researchers have been primarily focused on identifying the cellular or chemical sources of neuropathic pain or have approached neuropathic pain via the basis of biological study. We investigated whether mmu-mir-23b (miR23b) infusion can alleviate pain by compensating for the abnormally downregulated miR23b by reducing the expression of its target gene, NADPH oxidase 4 (NOX4), a reactive oxygen species (ROS) family member overexpressed in neuropathic pain. RESULTS: Ectopic miR23b expression effectively downregulated NOX4 and was normalized to GAD65/67 expression. Moreover, the animals with neuropathic pain showed significant improvements in the paw withdrawal thresholds following miR23b infusion. Normalizing miR23b expression in tissue lesions caused by neuropathic pain induction reduced inflammatory mediator expression and increased the level of several ROS scavengers. Moreover, GABAergic neurons coexpressed suboptimal levels of miR23b and elevated NOX4/ROS after pain induction at the cellular level. MiR23b protects GABAergic neurons against ROS/p38/JNK-mediated apoptotic death. By evaluating the functional behavior of the mice receiving pain/miR23b, normal/anti-miR23b, or anti-miR23b/si-NOX4, the positive role of miR23b and the negative role of NOX4 in neuropathic pain were confirmed. INNOVATION AND CONCLUSION: Based on this study, we conclude that miR23b plays a crucial role in the amelioration of neuropathic pain in the injured spinal cord by inactivating its target gene, NOX4, and protecting GABAergic neurons from cell death. We finally suggest that miR23b may provide attractive diagnostic and therapeutic resources for effective pain modulation in neuropathic pain.

Nuclear Argonaute 2 regulates adipose tissue-derived stem cell survival through direct control of miR10b and selenoprotein N1 expression.

Argonaute 2 (Ago2) has a leading function in miRNA-induced RNA silencing, a conserved gene regulatory mechanism in cells and organisms. miRNAs are critical for stem cell self-renewal, development, and other functions. Here, we report that nuclear Ago2, by binding to a specific region of functional genes, directly controls adipose tissue-derived stem cell (ATSC) survival in response to a critical dose of reactive oxygen species (ROS)-mediated oxidative cell damage or senescence. The role of nuclear Ago2 has not been previously reported. Here, we show that human ATSCs in which Ago2 was downregulated underwent apoptosis. Silencing of Ago2 in ATSCs significantly induces upregulation of miR10b and miR23b expression. These miRNAs directly interfere with ROS-scavenging gene expression, such as TXNL1 and GPX3. Upregulation of miR10b and miR23b is sufficient to induce ATSC cell apoptosis via p38 MAPK phosphorylation and caspase 3 activation. In addition, Ago2 overexpression or interference by miR10b and miR23b expression in ATSCs partially rescued H(2) O(2) /ROS-mediated apoptotic cell death by upregulating the expression of TXNL2, JUNK, caspase-3, and cytochrome C. Nuclear Ago2-mediated miR10b and miR23b downregulation also allows cells to escape senescence, which results in telomerase reverse transcriptase, stemness overexpression, and improved self-renewal and differentiation through Wnt5a/ß-catenin activation. Argonaute 2 expression is critical for stem cells to escape senescence by downregulating miR10b and miR23b. The Ago2-binding gene selenoprotein N1 (SEPN1) was also effectively involved in ATSC survival and self-renewal through ROS-mediated p38 MAPK inactivation.

Subtype-specific dendritic Ca(2+) dynamics of inhibitory interneurons in the rat visual cortex.

The Ca(2+) increase in dendrites that is evoked by the backpropagation of somatic action potentials (APs) is involved in the activity-dependent modulation of dendritic and synaptic functions that are location dependent. In the present study, we investigated dendritic Ca(2+) dynamics evoked by backpropagating APs (bAPs) in four subtypes of inhibitory interneurons classified by their spiking patterns: fast spiking (FS), late spiking (LS), burst spiking (BS), and regular-spiking nonpyramidal (RSNP) cells. Cluster analysis, single-cell RT-PCR, and immunohistochemistry confirmed the least-overlapping nature of the grouped cell populations. Somatic APs evoked dendritic Ca(2+) transients in all subtypes of inhibitory interneurons with different spatial profiles along the tree: constantly linear in FS and LS cells, increasing to a plateau in BS cells and bell-shaped in RSNP cells. The increases in bAP-evoked dendritic Ca(2+) transients brought about by the blocking of A-type K(+) channels were similar in whole dendritic trees of each subtype of inhibitory interneurons. However, in RSNP cells, the increases in the distal dendrites were larger than those in the proximal dendrites. On cholinergic activation, nicotinic inhibition of bAP-evoked dendritic Ca(2+) transients was observed only in BS cells expressing cholecystokinin and vasoactive intestinal peptide mRNAs, with no muscarinic modulation in all subtypes of inhibitory interneurons. Cell subtype-specific differential spatial profiles and their modulation in bAP-evoked dendritic Ca(2+) transients might be important for the domain-specific modulation of segregated inputs in inhibitory interneurons and differential control between the excitatory and inhibitory networks in the visual cortex.