Pore walls as high-way for efficient bulk charge transfer in porous SrTiO3 single crystals boosting photocatalytic overall water splitting.

Suppressing carrier recombination in bulk and facilitating carrier transfer to surface via rational structure design is of great significance to improve solar-to-H2 conversion efficiency. We demonstrate a facile hydrothermal method to synthesize porous SrTiO3 single crystals (SrTiO3-P) with exposed (001) facets by introducing carbon spheres as templates. The obviously increased surface photovoltage and photocurrent response indicate that the interconnected pore walls act as enormous charge transfer "highways", accelerating carrier transport from bulk to surface. Furthermore, the absence of grain boundaries and high crystallinity could also lower the carrier recombination rate. Thus, the SrTiO3-P photocatalyst loaded with Rh/Cr2O3 as cocatalyst exhibits 1.5 times higher overall water splitting activity than that of solid SrTiO3, with gas evolution rate of 19.99 µmol h-1 50 mg-1 for H2 and 11.37 µmol h-1 50 mg-1 for O2. Additionally, SrTiO3-P also shows superior stability without any decay during cycling testing. This work provides a new insight into designing efficient multicomponent photocatalysts with a single-crystal porous structure.

Clinical and economic evaluation of blood culture whole process optimisation in critically ill adult patients with positive blood cultures.

OBJECTIVES: Optimising blood culture processing is important to ensure that bloodstream infections are accurately diagnosed while minimising adverse events caused by antibiotic abuse. This study aimed to evaluate the impact of optimised blood culture processes on antibiotic use, clinical outcomes and economics in intensive care unit (ICU) patients with positive blood cultures. METHODS: From March 2020 to October 2021, this microbiology laboratory implemented a series of improvement measures, including the clinical utility of Fastidious Antimicrobial Neutralization (FAN® PLUS) bottles for the BacT/Alert Virtuo blood culture system, optimisation of bottle reception, graded reports and an upgraded laboratory information system. A total of 122 ICU patients were included in the pre-optimisation group from March 2019 to February 2020, while 179 ICU patients were included in the post-optimisation group from November 2021 to October 2022. RESULTS: Compared with the pre-optimisation group, the average reporting time of identification and antimicrobial sensitivity was reduced by 16.72 hours in the optimised group. The time from admission to targeted antibiotic therapy within 24 hours after receiving both the Gram stain report and the final report were both significantly less in the post-optimisation group compared with the pre-optimisation group. The average hospitalisation time was reduced by 6.49 days, the average antimicrobial drug cost lowered by $1720.85 and the average hospitalisation cost by $9514.17 in the post-optimisation group. CONCLUSIONS: Optimising blood culture processing was associated with a significantly increased positive detection rate, a remarkable reduction in the length of hospital stay and in hospital costs for ICU patients with bloodstream infections.

AgrA directly binds to the promoter of vraSR and downregulates its expression in Staphylococcus aureus.

Staphylococcus aureus is an important human pathogen and vancomycin is widely used for the treatment of S. aureus infections. The global regulator agr is known as a well-described virulence regulator. Previous studies have found that agr-dysfunction strains are more likely to develop into vancomycin-resistant strains, but the mechanism for this phenomenon remains unknown. VraSR is a two-component regulatory system related to vancomycin resistance. In this study, we found that the expression levels of vraR were higher in agr-dysfunction clinical strains than in the agr-functional strains. We knocked out agr in a clinical strain, and quantitative reverse transcription PCR and ß-galactosidase activity assays revealed that agr repressed transcription of vraR. After vancomycin exposures, population analysis revealed larger subpopulations displaying reduced susceptibility in agr knockout strain compared with wild-type strain, and this pattern was also observed in agr-dysfunction clinical strains compared with the agr-functional strains. Electrophoretic mobility experiment demonstrated binding of purified AgrA to the promoter region of vraR. In conclusion, our results indicated that the loss of agr function in S. aureus may contribute to the evolution of reduced vancomycin susceptibility through the downregulation of vraSR.

Understanding etiology of community-acquired central nervous system infections using metagenomic next-generation sequencing.

Background: Community-acquired central nervous system infections (CA-CNS infections) have the characteristics of acute onset and rapid progression, and are associated with high levels of morbidity and mortality worldwide. However, there have been only limited studies on the etiology of this infections. Here, metagenomic next-generation sequencing (mNGS), a comprehensive diagnosis method, facilitated us to better understand the etiology of CA-CNS infections. Methods: We conducted a single-center retrospective study between September 2018 and July 2021 in which 606 cerebrospinal fluid (CSF) samples were collected from suspected CNS infectious patients for mNGS testing, and all positive samples were included in this analysis. Results: After the exclusion criteria, a total of 131 mNGS-positive samples were finally enrolled. Bacterial, viral, fungal, parasitic, specific pathogen and mixed infections were accounted for 32.82% (43/131), 13.74% (18/131), 0.76% (1/131), 2.29% (3/131) and 6.87% (9/131), respectively. A total of 41 different pathogens were identified, including 16 bacteria, 12 viruses, 10 fungi, and 1 parasite and 3 specific pathogens. The most frequent infecting pathogens are Epstein-Barr virus (n = 14), Herpes simplex virus 1 (n = 14), Mycobacterium tuberculosis (n = 13), Streptococcus pneumoniae (n = 13), and Cryptococcus neoformans (n = 8). Some difficult-to-diagnose pathogen infections were also detected by mNGS, such as Streptococcus suis, Pseudorabies virus, Bunyavirus, Orientia tsutsugamushi and Toxoplasma gondii. Conclusion: In this study, mNGS identified a wide variety of pathogens of CA-CNS infections and many of which could not be detected by conventional methods. Our data provide a better understanding of the etiology of CA-CNS infections and show that mNGS represents a comparative screening of CSF in an unbiased manner for a broad range of human pathogens.

Evaluation of Ceftazidime/Avibactam Administration in Enterobacteriaceae and Pseudomonas aeruginosa Bloodstream Infections by Monte Carlo Simulation.

PURPOSE: To evaluate the administration regimen of ceftazidime/avibactam (CZA) for bloodstream infections caused by Enterobacteriaceae and Pseudomonas aeruginosa. METHODS: The minimal inhibitory concentrations (MICs) of CZA against Enterobacteriaceae and P. aeruginosa isolated from blood cultures at member hospitals in BRICS (Blood Bacterial Resistant Investigation Collaborative System) in 2019 were determined by broth micro-dilution methodology. A 10,000-patient Monte Carlo simulation (MCS) was used to calculate the probability of target attainment (PTA) and cumulative fraction of response (CFR) for different CZA dosage regimens to evaluate their efficacies and optimize the best initial dosage regimen. RESULTS: Altogether, 6487 Enterobacteriaceae and P. aeruginosa strains were isolated from the blood cultures. The overall CZA resistance rate was 2.31%, of which the Enterobacteriaceae and P. aeruginosa rates were 1.57% and 14.29%, respectively. The MCS showed that the greater the MIC value, the worse the therapeutic effect. When the CZA MIC was ≤8 mg/L, the standard dose (2.5g iv q8h) achieved 90% PTA in the subset of patients with creatinine clearance (CrCl) values from 51 to 120 mL/min. Although the high-dose regimen (3.75g iv q8h) achieved 90% PTA in patients with CrCl values from 121 to 190 mL/min, implementing the low-dose regimen (1.25g iv q8h) was also effective for patients in the 51-89 mL/min CrCl range. Generally, the high-dose regimen (3.75g iv q8h) reached 90% CFR against all of the strains. Conversely, in patients with CrCl values of 121-190 mL/min, the standard dose (2.5g iv q8h) failed to reach 90% CFR against some Enterobacteriaceae members and P. aeruginosa. When the dose was reduced to the low-dose regimen (1.25g iv q8h), no patients reached 90% CFR against some Enterobacteriaceae members and P. aeruginosa. CONCLUSION: CZA has good antibacterial activity against Enterobacteriaceae and P. aeruginosa in bloodstream infections. Clinicians could make individualized treatment regimens in accordance with the sensitivity of the strains and the level of renal function in their patients to best predict the drug-related clinical responses.

Case Report: Metagenomic Next-Generation Sequencing in Diagnosis of Legionella pneumophila Pneumonia in a Patient After Umbilical Cord Blood Stem Cell Transplantation.

We report a case of hospital-acquired Legionella pneumonia that was detected by metagenomic next-generation sequencing (mNGS) of blood from a 7-year-old girl after umbilical cord blood stem cell transplantation (UCBT) with myelodysplastic syndrome. UCBT is traditionally associated with an increased risk of infection, particularly during the first 3 months after transplantation. Controlling interstitial pneumonia and severe infection is the key to reducing patient mortality from infection. Legionella pneumophila can cause a mild cough to rapidly fatal pneumonia. After mNGS confirmed that the pathogen was L. pneumophila, azithromycin, cefoperazone sulbactam, and posaconazole were used for treatment, and the patient's temperature decreased and remained normal. The details of this case highlight the benefits of the timely use of metagenomic NGS to identify pathogens for the survival of immunocompromised patients.

Erratum: LukS-PV Inhibits Hepatocellular Carcinoma Progression by Downregulating HDAC2 Expression.

[This corrects the article DOI: 10.1016/j.omto.2020.05.006.].

LukS-PV Inhibits Hepatocellular Carcinoma Progression by Downregulating HDAC2 Expression.

Hepatocellular carcinoma (HCC) is a common malignant tumor. LukS-PV is the S component of Panton-Valetine leukocidin (PVL), which is secreted by Staphylococcus aureus. This study investigated the effects of LukS-PV on the proliferation, apoptosis, and cell-cycle progression of HCC cells and the mechanisms of its activity. The HCC cells were treated with different LukS-PV concentrations in vitro. Cell Counting Kit-8 and 5-Ethynyl-2'-deoxyuridine (EdU) assays were used to study cell proliferation. Flow cytometry was used to measure apoptosis and cell-cycle progression. Quantitative reverse transcriptase PCR and western blot assays were used to determine mRNA and protein expression levels. Xenograft experiments were performed to determine the in vivo antitumor effect of LukS-PV. Immunostaining was performed to analyze Ki-67 and HDAC2 (histone deacetylase 2) expression. Our results showed that LukS-PV inhibited cell proliferation and induced apoptosis in a concentration-dependent manner in HCC cell lines. LukS-PV also can induce cell-cycle arrest. Moreover, we discovered that LukS-PV attenuated HDAC2 expression and upregulated PTEN; phosphorylated AKT was also reduced. Further studies demonstrated that LukS-PV treatment significantly reduced tumor growth in nude mice and suppressed Ki-67 and HDAC2 levels. Our data revealed a vital role of LukS-PV in suppressing HCC progression by downregulating HDAC2 and upregulating PTEN.

MicroRNA-181a-3p as a Diagnostic and Prognostic Biomarker for Acute Myeloid Leukemia.

BACKGROUND: Micro (mi) RNAs play an important role in the pathogenesis and development of acute myeloid leukemia (AML), and their abnormal expression may be sufficient to predict the prognosis and outcomes in AML patients. We evaluated the clinical diagnostic value of miRNA-181a-3p in predicting prognosis and outcomes in patients with AML. METHODS: A total of 119 newly diagnosed adult patients with AML and 60 healthy controls were recruited. Blood specimens were obtained from all AML patients at diagnosis, and 10 blood specimens were obtained on day 28 after induction chemotherapy. The controls also provided blood samples. Relative gene expression was quantified by PCR and determined using the comparative Ct method. Publicly available clinical data and gene expressions for 188 patients with AML were downloaded from TCGA data portal. RESULTS: Compared with healthy controls, the expression of miRNA-181a-3p was significantly increased in patients with AML. MiR-181a-3p expression could be used to discriminate AML patients from controls, with up-regulated expression correlating with favorable prognosis. Moreover, miRNA-181a-3p expression was significantly decreased in patients who achieved a complete response after induction chemotherapy. The multivariate Cox analysis highlighted the prognostic value of miR-181a-3p for patients with AML. Finally, we found that miR-181a-3p expression was negatively correlated with the expression of the NF-κB essential modulator (NEMO/IKBKG). CONCLUSIONS: MiR-181a-3p may be clinically useful as a disease marker for AML, and enhanced the prediction of patient outcomes to chemotherapy.

Serum human neutrophil lipocalin: An effective biomarker for diagnosing bacterial infections.

BACKGROUND: Human neutrophil lipocalin (HNL) is used as a novel biomarker for infections. However, only a few studies have focused on the usefulness of HNL. The purpose of this study was to evaluate the diagnostic efficiency of HNL for identifying bacterial infections and to compare HNL with procalcitonin (PCT) and C-reactive protein (CRP). METHODS: Hospital patients with acute infections of bacterial origin (n = 439), viral origin (n = 71), and healthy volunteers (n = 67) were included in the study. The infection status of each patient was verified using microbiological, serological, and PCR testing. Additionally, CRP, HNL, and PCT levels were measured by established methods. RESULTS: In distinguishing bacterial and viral infections, area under the curve (AUC) analysis showed that, with a value of 0.81 (95% CI, 0.76-0.86), HNL was superior to CRP at 0.73 (0.68-0.79) and PCT at 0.64 (0.58-0.70). Interestingly, the combination of HNL, PCT, and CRP improved the diagnostic potential significantly with an AUC of 0.86 (0.82-0.90, P < 0.05). Furthermore, when comparing different infection site subgroups with healthy patients, HNL levels were higher in all bacterial groups, albeit to widely varying degrees (P < 0.0001), and HNL reached a higher level in bloodstream and abdominal infections. CRP levels showed the same trend as HNL levels. PCT levels were significantly increased in bloodstream infections, abdominal infections, and in bacterial pneumonia (P < 0.0001), while no significant differences were found in soft tissue (P = 0.4378) or urinary tract infections (P = 0.423). There was no difference in HNL and CRP levels between patients with Gram-negative bacterial (GNB) or Gram-positive bacterial infections. However, compared with controls, PCT was only increased in GNB-infected patients. CONCLUSION: HNL detection can help diagnose patients with infectious diseases, and the diagnostic efficacy of HNL is not affected by the infected site or by pathogenic bacterial species. The combination of HNL, PCT, and CRP has a superior performance at identifying bacterial infections compared with traditional biomarkers.

Heterogeneous Vancomycin-Intermediate Staphylococcus aureus Uses the VraSR Regulatory System to Modulate Autophagy for Increased Intracellular Survival in Macrophage-Like Cell Line RAW264.7.

The VraSR two-component system is a vancomycin resistance-associated sensor/regulator that is upregulated in vancomycin-intermediate Staphylococcus aureus (VISA) and heterogeneous VISA (hVISA) strains. VISA/hVISA show reduced susceptibility to vancomycin and an increased ability to evade host immune responses, resulting in enhanced clinical persistence. However, the underlying mechanism remains unclear. Recent studies have reported that S. aureus strains have developed some strategies to survive within the host cell by using autophagy processes. In this study, we confirmed that clinical isolates with high vraR expression showed increased survival in murine macrophage-like RAW264.7 cells. We constructed isogenic vraSR deletion strain Mu3ΔvraSR and vraSR-complemented strain Mu3ΔvraSR-C to ascertain whether S. aureus uses the VraSR system to modulate autophagy for increasing intracellular survival in RAW264.7. Overall, the survival of Mu3ΔvraSR in RAW264.7 cells was reduced at all infection time points compared with that of the Mu3 wild-type strain. Mu3ΔvraSR-infected RAW264.7 cells also showed decreased transcription of autophagy-related genes Becn1 and Atg5, decreased LC3-II turnover and increased p62 degradation, and fewer visible punctate LC3 structures. In addition, we found that inhibition of autophagic flux significantly increased the survival of Mu3ΔvraSR in RAW264.7 cells. Together, these results demonstrate that S. aureus uses the VraSR system to modulate host-cell autophagy processes for increasing its own survival within macrophages. Our study provides novel insights into the impact of VraSR on bacterial infection and will help to further elucidate the relationship between bacteria and the host immune response. Moreover, understanding the autophagic pathway in vraSR associated immunity has potentially important implications for preventing or treating VISA/hVISA infection.

LukS-PV induces apoptosis in acute myeloid leukemia cells mediated by C5a receptor.

LukS-PV is one of the two components of Panton-Valentine leucocidin (PVL). Our previous study showed that LukS-PV can induce apoptosis in human acute myeloid leukemia (AML) THP-1 and HL-60 cells. C5aR (C5a receptor) is the receptor for PVL, but whether C5aR plays a key role in LukS-PV induced apoptosis is unclear. The aim of this study was to establish whether C5aR plays a physiological role in apoptosis of leukemia cells induced by LukS-PV. We investigated the role of C5aR in leukemia cell apoptosis induced by LukS-PV by pretreatment of THP-1 and HL-60 cells with C5aR antagonist and transfection to knockdown C5aR in THP-1 cells or overexpress C5aR in Jurkat cells before treatment with LukS-PV. Cell apoptosis was analyzed by staining with Annexin V/propidium iodide or Annexin V-PE/7-AAD. Mitochondrial membrane potential (MMP) was determined using JC-1 dye. The expression of apoptosis-associated genes and proteins was identified by qRT-polymerase chain reaction and Western blotting analysis, respectively. As the C5aR antagonist concentration increased, the rate of apoptosis induced by LukS-PV decreased, the MMP increased, and expression of pro-apoptotic Bax and Bak genes and proteins was downregulated while that of anti-apoptotic Bcl-2 and Bcl-x genes and proteins was upregulated. Knockdown of C5aR also decreased LukS-PV-induced THP-1 cell apoptosis. LukS-PV did not induce apoptosis of Jurkat cells, which have no endogenous C5aR expression; however, LukS-PV did induce apoptosis in Jurkat cells after overexpression of C5aR. Correspondingly, the MMP decreased and Bax and Bak were upregulated while Bcl-2 and Bcl-x were downregulated. LukS-PV can induce apoptosis in AML cells by targeting C5aR. C5aR may be a potential therapeutic target for AML and LukS-PV is a candidate targeted drug for the treatment of AML.

VraSR has an important role in immune evasion of Staphylococcus aureus with low level vancomycin resistance.

Vancomycin-intermediate Staphylococcus aureus (VISA) and heterogeneous VISA (hVISA) are increasingly being reported as associated with treatment failure. Previous studies indicated that VISA/hVISA resists clearance by the host immune system, thereby allowing persistence within the host. VraSR is a vancomycin-resistance-associated sensor/regulator that is highly expressed in VISA/hVISA strains. Whether VraSR plays an important role in immune escape by VISA/hVISA strains is unclear. Here, we constructed a vraSR deletion mutant strain (ΔvraSR) and complementary strain (CΔvraSR) in Mu3 to investigate the effect of VraSR on S. aureus viability in polymorphonuclear leukocytes (PMNs). The ΔvraSR strain was more susceptible to phagocytosis by PMNs and reduced the ability of S. aureus to survive within PMNs. ΔvraSR showed phenotypic changes, including a thinner cell wall, reduced adhesion, and decreased biofilm-forming ability. Real-time quantitative PCR revealed that the transcript levels of cell wall synthesis-related genes (cap5K, cap5N, nanA, tagA, murD) and adhesion-associated genes (fnbA, fnbB, clfA, ebps, sbi) were significantly decreased in the ΔvraSR strain compared with Mu3. In summary, VraSR promotes the survival of S. aureus in the host, which may be associated with an increase in the thickness of the cell wall, adhesion, and biofilm formation.

Culture-Negative Streptococcus suis Infection Diagnosed by Metagenomic Next-Generation Sequencing.

Background: Streptococcus suis is a zoonotic pathogen that can cause severe infections such as meningitis and septicemia in both swine and humans. Rapid and accurate identification of the causative agent is very important for guiding clinical choices in administering countermeasures. Case Report: Here, we report a case of fatal S. suis infection in a patient who worked as a butcher in China. The 59-year-old man, who had previously undergone splenectomy, injured his finger while processing pork and developed severe sepsis. While blood cultures were negative following antibiotic treatment, S. suis was determined to be the causative agent by metagenomic next-generation sequencing (mNGS) and Sanger sequencing. Conclusion: Identification of etiological agents using techniques such as blood culture prior to antibiotic treatment is very important. mNGS may represent a useful method for diagnosis of infectious diseases, especially post-antibiotic treatment.

VraR Binding to the Promoter Region of agr Inhibits Its Function in Vancomycin-Intermediate Staphylococcus aureus (VISA) and Heterogeneous VISA.

Acquisition of vancomycin resistance in Staphylococcus aureus is often accompanied by a reduction in virulence, but the mechanisms underlying this change remain unclear. The present study was undertaken to investigate this process in a clinical heterogeneous vancomycin-intermediate S. aureus (hVISA) strain, 10827; an hVISA reference strain, Mu3; and a VISA reference strain, Mu50, along with their respective series of vancomycin-induced resistant strains. In these strains, increasing MICs of vancomycin were associated with increased expression of the vancomycin resistance-associated regulator gene (vraR) and decreased expression of virulence genes (hla, hlb, and coa) and virulence-regulated genes (RNAIII, agrA, and saeR). These results suggested that VraR might have a direct or indirect effect on virulence in S. aureus In electrophoretic mobility shift assays, VraR did not bind to promoter sequences of hla, hlb, and coa genes, but it did bind to the agr promoter region. In DNase I footprinting assays, VraR protected a 15-nucleotide (nt) sequence in the intergenic region between the agr P2 and P3 promoters. These results indicated that when S. aureus is subject to induction by vancomycin, expression of vraR is upregulated, and VraR binding inhibits the function of the Agr quorum-sensing system, causing reductions in the virulence of VISA/hVISA strains. Our results suggested that VraR in S. aureus is involved not only in the regulation of vancomycin resistance but also in the regulation of virulence.

Methicillin-Resistant Staphylococcus aureus Grown on Vancomycin-Supplemented Screening Agar Displays Enhanced Biofilm Formation.

Brain heart infusion agar containing 3 mg/liter vancomycin (BHI-V3) was used to screen for heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA). There was markedly greater biofilm formation by isolates that grew on BHI-V3 than by strains that did not grow on BHI-V3. Increased biofilm formation by hVISA may be mediated by FnbA- and polysaccharide intercellular adhesin-dependent pathways, and upregulation of atlA and sarA may also contribute to enhanced biofilm formation by hVISA upon prolonged exposure to vancomycin.

Systematic Review and Meta-Analysis of the Epidemiology of Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Staphylococcus aureus Isolates.

BACKGROUND: Vancomycin-intermediate Staphylococcus aureus (VISA) and heterogeneous VISA (hVISA) are associated with vancomycin treatment failure, and are becoming an increasing public health problem. Therefore, we undertook this study of 91 published studies and made subgroup comparisons of hVISA/VISA incidence in different study years, locations, and types of clinical samples. We also analyzed the genetic backgrounds of these strains. METHODS: A systematic literature review of relevant articles published in PubMed and EMBASE from January 1997 to August 2014 was conducted. We selected and assessed journal articles reporting the prevalence rates of hVISA/VISA. RESULTS: The pooled prevalence of hVISA was 6.05% in 99,042 methicillin-resistant S. aureus (MRSA) strains and that of VISA was 3.01% in 68,792 MRSA strains. The prevalence of hVISA was 4.68% before 2006, 5.38% in 2006-2009, and 7.01% in 2010-2014. VISA prevalence was 2.05%, 2.63%, and 7.93%, respectively. In a subgroup analysis of different isolation locations, the prevalence of hVISA strains was 6.81% in Asia and 5.60% in Europe/America, and that of VISA was 3.42% and 2.75%, respectively. The frequencies of hVISA isolated from blood culture samples and from all clinical samples were 9.81% and 4.68%, respectively, and those of VISA were 2.00% and 3.07%, respectively. The most prevalent genotype was staphylococcal cassette chromosome mec (SCCmec) II, which accounted for 48.16% and 37.74% of hVISA and VISA, respectively. Sequence Type (ST) 239 was most prevalent. CONCLUSION: The prevalence of hVISA/VISA has been increasing in recent years, but has been grossly underestimated. Its incidence is higher in Asia than in Europe/America. hVISA is isolated from blood culture samples more often than from other samples. These strains are highly prevalent in epidemic MRSA strains. This study clarifies the epidemiology of hVISA/VISA and indicates that the detection of these strains and the control of nosocomial infections must be strengthened.

LukS-PV, a component of Panton-Valentine leukocidin, exerts potent activity against acute myeloid leukemia in vitro and in vivo.

LukS-PV, a component of Panton-Valentine leukocidin (PVL) secreted by Staphylococcus aureus, has been shown to inhibit proliferation and induce apoptosis in acute myeloid leukemia (AML) THP-1 cells. Here we investigated anti-leukemia activities of LukS-PV in HL-60 cells, using in vitro assays to assess the ability of LukS-PV to mediate cell viability, apoptosis and differentiation; and developing a Severe Combined Immunodeficiency (SCID) mouse model of disseminated AML with the HL-60 cells to examine in vivo anti-leukemia activity. LukS-PV inhibited viability and induced differentiation and apoptosis in the HL-60 AML cell line. In the SCID mice, LukS-PV potently inhibited tumor growth, decreased tumor cell infiltration into peripheral blood and tissues, and significantly increased mean survival time. No severe adverse effects, such as death, weight loss, or pathological changes in livers or spleens were observed in the toxicity test group. These results indicate that LukS-PV may be a novel and effective chemotherapeutic agent against AML.

Outbreak of carbapenemase-producing Klebsiella pneumoniae neurosurgical site infections associated with a contaminated shaving razor used for preoperative scalp shaving.

Between July 5 and 21, 2011, an outbreak of neurosurgical site infections with carbapenemase-producing Klebsiella pneumonia occurred in a tertiary care hospital. The outbreak affected 7 patients. The subsequent investigation revealed that a barber's contaminated shaving razor may have caused the carbapenemase-producing Klebsiella pneumonia outbreak. Standardized skin preparation performed by registered nurses using sterilized instruments should be emphasized.

LukS-PV induces mitochondrial-mediated apoptosis and G0/G1 cell cycle arrest in human acute myeloid leukemia THP-1 cells.

The S component (LukS-PV) is one of the two components of Panton-Valentine leukocidin (PVL), which is a pore-forming cytotoxin secreted by Staphylococcus aureus, with the ability to lyse leukocytes. In this study, LukS-PV had the ability to induce apoptosis in the human acute myeloid leukemia (AML) cell line THP-1. Therefore, we investigated the mechanisms of LukS-PV-induced apoptosis in THP-1 cells. THP-1 cells treated with LukS-PV, resulted in a significant inhibition of proliferation in a dose- and time-dependent manner, and induced G0/G1 arrest associated with an inhibition of cell cycle arrest regulatory protein (cyclin D1) in a dose- and time-dependent manner, as measured by flow cytometry (FCM). After 12h exposure to LukS-PV (1.00 µM), annexin V-EGFP/propidium iodide (PI) FCM revealed that 19.5±3.6% of THP-1 cells were apoptotic, and terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) staining also revealed THP-1 cells were apoptotic. Chip analysis of 84 apoptosis-related genes demonstrated that 9 genes were up-regulated at least 2-fold and that 5 genes were down-regulated at least 2-fold in the treatment group when compared with levels in the control group. Western blotting reveled that the expression of caspase-8 increased significantly (approximately 4-fold). The levels of caspase-9, -3 and Bax increased significantly, and levels of Bcl-2 decreased rapidly with LukS-PV treatment. These data suggest that LukS-PV acts as an anti-leukemia agent and activates AML cell apoptosis via the mitochondrial pathway. Therefore, LukS-PV may be a multi-targeting drug candidate for the prevention and therapy of AML.