Controlling an Outbreak of Multidrug-resistant Acinetobacter baumannii in a Pediatric Intensive Care Unit: a Retrospective Analysis.

BACKGROUND: Multidrug-resistant Acinetobacter baumannii (MDRAB) is widespread among intensive care units worldwide, posing a threat to patients and the health system. We describe the successful management of a MDRAB outbreak by implementing an infection-control strategy in a pediatric intensive care unit (PICU). METHODS: This retrospective study investigated the patients admitted to the PICU in periods 1 (8 months) and 2 (7 months), from the index MDRAB case to intervention implementation, and from intervention implementation to cessation of MDRAB spread. An infection-control strategy was designed following six concepts: 1) cohort isolation of colonized patients, 2) enforcement of hand hygiene, 3) universal contact precautions, 4) environmental management, 5) periodic surveillance culture study, and 6) monitoring and feedback. RESULTS: Of the 427 patients, 29 were confirmed to have MDRAB colonization, of which 18 had MDRAB infections. Overall incidence per 1,000 patient days decreased from 7.8 (period 1) to 5.8 (period 2). The MDRAB outbreak was declared terminated after the 6-month follow-up following period 2. MDRAB was detected on the computer keyboard and in condensed water inside the ventilator circuits. The rate of hand hygiene performance was the lowest in the three months before and after index case admission and increased from 84% (period 1) to 95% (period 2). Patients with higher severity, indicated by a higher Pediatric Risk of Mortality III score, were more likely to develop colonization (P = 0.030), because they had invasive devices and required more contact with healthcare workers. MDRAB colonization contributed to an increase in the duration of mechanical ventilation and PICU stay (P < 0.001), but did not affect mortality (P = 0.273). CONCLUSION: The MDRAB outbreak was successfully terminated by the implementation of a comprehensive infection-control strategy focused on the promotion of hand hygiene, universal contact precautions, and environmental management through multidisciplinary teamwork.

Glucosamine induces autophagic cell death through the stimulation of ER stress in human glioma cancer cells.

Autophagy can promote cell survival or death, but the molecular basis of its dual role in cancer is not well understood. Here, we report that glucosamine induces autophagic cell death through the stimulation of endoplasmic reticulum (ER) stress in U87MG human glioma cancer cells. Treatment with glucosamine reduced cell viability and increased the expression of LC3 II and GFP-LC3 fluorescence puncta, which are indicative of autophagic cell death. The glucosamine-mediated suppression of cell viability was reversed by treatment with an autophagy inhibitor, 3-MA, and interfering RNA against Atg5. Glucosamine-induced ER stress was manifested by the induction of BiP, IRE1alpha, and phospho-eIF2alpha expression. Chemical chaperon 4-PBA reduced ER stress and thereby inhibited glucosamine-induced autophagic cell death. Taken together, our data suggest that glucosamine induces autophagic cell death by inducing ER stress in U87MG glioma cancer cells and provide new insight into the potential anticancer properties of glucosamine.

Age-related upregulation of Drosophila caudal gene via NF-kappaB in the adult posterior midgut.

The Drosophila midgut has emerged as a powerful model system for the investigation of fundamental cellular pathways relevant to intestinal stem cell biology. Understanding the age-related changes in the adult Drosophila midgut may provide insights into the molecular mechanisms that link aging to the modulation of adult stem cell population. The caudal-related homeobox genes encode intestine-specific transcription factors required for normal intestinal development and maintenance. Here, we demonstrate that caudal gene expression is upregulated in the adult posterior midgut in response to age and oxidative stress, and that overexpression of Caudal can stimulate cell proliferation in the adult posterior midgut. We further demonstrate that the age- and oxidative-stress-related upregulation of the caudal gene is mediated by the NF-kappaB binding site located in the 5'-flanking region of the caudal gene. Our results may contribute to an understanding of the mechanisms of age-related changes in the number and activity of intestinal stem cells and progenitors in the Drosophila adult midgut.

Melatonin down-regulates HIF-1 alpha expression through inhibition of protein translation in prostate cancer cells.

Melatonin, the main secretory product of the pineal gland, has been shown to exert an oncostatic activity in cancer cells. Recently, several studies have shown that melatonin has antiangiogenic properties. However, the mechanism by which melatonin exerts antiangiogenenic effects is not understood. Hypoxia inducible factor (HIF)-1 is a transcription factor which mediates adaptive response to changes in tissue oxygenation. HIF-1 is a heterodimer formed by the association of a constitutively expressed HIF-1 beta subunit and a HIF-1 alpha subunit, the expression of which is highly regulated. In this study, pharmacologic concentrations of melatonin was found to inhibit expression of HIF-1 alpha protein under both normoxic and hypoxic conditions in DU145, PC-3, and LNCaP prostate cancer cells without affecting HIF-1 alpha mRNA levels. Consistent with the reduction in HIF-1 alpha protein levels, melatonin inhibited HIF-1 transcriptional activity and the release of vascular endothelial growth factor. We found that the suppression of HIF-1 alpha expression by melatonin correlated with dephosphorylation of p70S6K and its direct target RPS6, a pathway known to regulate HIF-1 alpha expression at the translational level. Metabolic labeling assays indicated that melatonin inhibits de novo synthesis of HIF-1 alpha protein. Taken together, these results suggest that the pharmacologic concentration of melatonin inhibits HIF-1 alpha expression through the suppression of protein translation in prostate cancer cells.

Ulmus macrocarpa Hance modulates lipid metabolism in hyperlipidemia via activation of AMPK pathway.

Ulmus macrocarpa Hance as an oriental medicinal plant has shown enormous potential for the treatment of several metabolic disorders in Korea. Hyperlipidemia, which is characterized by the excess accumulation of lipid contents in the bloodstream, may lead to several cardiovascular diseases. Therefore, in this study, anti-hyperlipidemic potential of U. macrocarpa water extract (UME) was examined in vitro and in vivo using HepG2 cells and experimental rats, respectively. The hyperlipidemia in experimental rats was induced by the high-cholesterol diet (HCD) followed by oral administration of various concentrations (25, 50 and 100 mg/kg) of UME for 6 weeks. As a result, the UME significantly improved the biochemical parameters such as increased the level of triglyceride, total cholesterol, and low-density lipoprotein cholesterol as well as reduced the high-density lipoprotein cholesterol in the HCD-fed rats. In addition, UME also prevented lipid accumulation through regulating AMPK activity and lipid metabolism proteins (ACC, SREBP1 and HMGCR) in the HCD-fed rats as compared to the controls. Moreover, similar pattern of gene expression levels was confirmed in oleic acid (OA)-treated HepG2 cells. Taken together, our results indicate that UME prevents hyperlipidemia via activating the AMPK pathway and regulates lipid metabolism. Thus, based on the above findings, it is estimated that UME could be a potential therapeutic agent for preventing the hyperlipidemia.

The caudal homeodomain protein activates Drosophila E2F gene expression.

The Drosophila caudal homeobox gene is required for definition of the anteroposterior axis and for gut development, and CDX1 and CDX2, human homologs, play crucial roles in the regulation of cell proliferation and differentiation in the intestine. Most studies have indicated tumor suppressor functions of Cdx2, with inhibition of proliferation, while the effects of Cdx1 are more controversial. The influence of Drosophila Caudal on cell proliferation is unknown. In this study, we found three potential Caudal binding sequences in the 5'-flanking region of the Drosophila E2F (DE2F) gene and showed by transient transfection assays that they are involved in Caudal transactivation of the dE2F gene promoter. Analyses with transgenic flies carrying an E2F-lacZ fusion gene, with and without mutation in the Caudal binding site, indicated that the Caudal binding sites are required for expression of dE2F in living flies. Caudal-induced E2F expression was also confirmed with a GAL4-UAS system in living flies. In addition, ectopic expression of Caudal with heat-shock promotion induced melanotic tumors in larvae. These results suggest that Caudal is involved in regulation of proliferation through transactivation of the E2F gene in Drosophila.

Highly sensitive and novel point-of-care system, aQcare Chlamydia TRF kit for detecting Chlamydia trachomatis by using europium (Eu) (III) chelated nanoparticles.

BACKGROUND: The bacterium Chlamydia trachomatis is one of the leading causes of sexually transmitted diseases worldwide. Since no simple and effective tool exists to diagnose C. trachomatis infections, we evaluated a novel point-of-care (POC) test, aQcare Chlamydia TRF kit, which uses europium-chelated nanoparticles and a time-resolved fluorescence reader. METHODS: The test performance was evaluated by comparing the results obtained using the novel POC testing kit with those obtained using a nucleic acid amplification test (NAAT), using 114 NAAT-positive and 327 NAAT-negative samples. RESULTS: The cut-off value of the novel test was 20.8 with a detection limit of 0.27 ng/mL. No interference or cross-reactivity was observed. Diagnostic accuracy showed an overall sensitivity of 93.0% (106/114), specificity of 96.3% (315/327), positive predictive value (PPV) of 89.8% (106/118), and negative predictive value (NPV) of 97.5% (315/323). The sensitivity of the novel test was much higher than that of currently available POC tests. Furthermore, the relative ease and short turnaround time (30 min) of this assay enables C. trachomatis-infected individuals to be treated without a diagnostic delay. CONCLUSIONS: This simple and novel test is a potential tool to screen a larger population, especially those in areas with limited resources.

Mutations of the BAK gene are infrequent in advanced gastric adenocarcinomas in Koreans.

The bcl-2 homologue antagonist/killer (BAK) is a potently apoptosis-inducing gene and plays an important role in modulating apoptosis in epithelial cells. We have analyzed the mutation of the entire coding region of BAK gene in 107 Korean advanced gastric adenocarcinomas by polymerase chain reaction-single strand conformation polymorphism and sequencing. Homozygous deletions were not found in these samples. Only three cases of 107 gastric adenocarcinomas (2.8%) exhibited the BAK mutations. Two of them exhibited missense mutations and the remaining one had a silent mutation. All of these mutations were exclusively detected in exon 2. Mutations in the BAK gene were observed only in advanced gastric adenocarcinomas with extensive metastases of regional lymph nodes. The data presented here suggest that the mutations of BAK gene rarely occurred in advanced gastric adenocarcinomas.

Genetic variations in UDP-glucuronosyltransferase 2B15 in a Korean population.

  UDP-glucuronosyltransferase 2B15 (UGT2B15) is involved in the glucoronidation of steroid hormones as well as many drugs. Genetic variations in UGT2B15 have been shown to affect enzyme function and suggested to have a role in human diseases, such as breast and prostate cancers. In the present study, we sequenced genomic DNA from 50 normal Korean subjects to identify single nucleotide polymorphisms (SNPs) in UGT2B15. A total of thirteen genetic variations were found: two in exons, two in introns, seven in the 5'-untranslated region (UTR), and two in the 3'-UTR. The order and frequency distribution of UGT2B15 variations was: -1139T>C (rs9994887), -508G>A (rs1120265), -506T>A (rs1580083), 253T>G (rs1902023) (42%), 23687A>T (rs4148271) (31%), 2635A>T (rs2045100) (28%), -497C>T (14%), -378C>T (14%), 23669C>T (12%), and 23476A>C (rs4148269) (11%), with other minor alleles with a frequency of <10%. Thirteen variations were used to characterize linkage disequilibrium structures at the UGT2B15 locus. Five tag SNPs were identified, and the observed allelic frequencies were compared to those of other ethnic populations. This information describing genetic polymorphisms in UGT2B15 could serve as an important resource for studying individual variations in drug and hormone metabolism in Korean as well as other ethnic populations.

Genetic variations in UDP-glucuronosyltransferase 2B7 gene (UGT2B7) in a Korean population.

Glucuronidation by UDP-glucuronosyltransferase 2B7 (UGT2B7) has been identified as an important pathway for the elimination of its substrate drugs in humans. Alterations in UGT2B7 function or expression may influence individual variations in drug responses. In an effort to screen for UGT2B7 single nucleotide polymorphisms (SNPs) in Koreans, the UGT2B7 gene was directly sequenced in 50 normal subjects. A total of 19 genetic variations were found: seven in exons, eight in introns, and four in the 5'-untranslated region. The order of the frequency distribution of UGT2B7 variations was: -900A>G, -327G>A, -161C>T, 10539A>G, 10711G>C and 10806T>A (40%); 2099T>A, 2100C>T, 2283A>G and 2316A>G (39%); 12029T>A (37%); 10928C>A (33%); 10541G>A (28%); 10897insA (24%); 372A>G (13%) and 211G>T (12%), as well as other minor alleles with less than 10% frequency. Nineteen variations were used to characterize linkage disequilibrium (LD) structures at the UGT2B7 locus. Eight tagging SNPs in UGT2B7 were determined. Identification of UGT2B7 SNPs with LD and the tagging SNPs lays the foundation for investigating UGT2B7-related genotype/phenotype association studies for Koreans as well as other populations.