Usefulness of mean platelet volume as a marker for clinical outcomes after out-of-hospital cardiac arrest: a retrospective cohort study.

Essentials It is unknown whether mean platelet volume (MPV) estimates outcomes after cardiac arrest (CA). We investigated whether MPV was associated with 30-day neurologic outcome and mortality after CA. Elevated MPV at admission was associated with poor neurological outcomes and mortality at 30 days. Identifying levels of MPV is helpful for estimating disease severity among resuscitated patients. SUMMARY: Background Whole-body ischemia followed by reperfusion during cardiac arrest and after return of spontaneous circulation (ROSC) triggers systemic sterile inflammatory responses, inducing a sepsis-like state during post-cardiac arrest syndrome. Activated platelets are enlarged, and contain vasoactive and prothrombic factors that aggravate systemic inflammation and endothelial dysfunction. Objectives To investigate whether mean platelet volume (MPV) is useful as a marker for early mortality and neurologic outcomes in patients who achieve ROSC after out-of-hospital cardiac arrest (OHCA). Methods OHCA records from the Emergency Department Cardiac Arrest Registry were retrospectively analyzed. Patients who survived for > 24 h after ROSC were included. We evaluated mortality and cerebral performance category scores after 30 days. Results We analyzed records from 184 patients with OHCA. Increased 30-day mortality among patients who achieved ROSC after OHCA was associated with MPV at admission (hazard ratio [HR] 1.36; 95% confidence interval [CI] 1.06-1.75). An elevated MPV at admission was also associated with poor neurologic outcomes (HR 1.28; 95% CI 1.06-1.55). Conclusions An elevated MPV was independently associated with increased 30-day mortality, with the highest discriminative value being obtained upon admission after OHCA. An elevated MPV on admission was associated with poor neurologic outcomes. High MPVs are helpful for estimating 30-day mortality and neurologic outcomes among patients who achieve ROSC after OHCA.

Transcriptional repression of cancer stem cell marker CD133 by tumor suppressor p53.

Novel therapeutic strategies are needed to overcome cancer recurrence, metastasis, and resistance to chemo- and radiotherapy. Cancer stem cells (CSCs) are major contributors to the malignant transformation of cells due to their capacity for self-renewal. Although various CSC markers have been identified in several types of tumors, they are primarily used as cancer-prediction markers and for the isolation of CSC populations. CD133, one of the best-characterized CSC markers in distinct solid tumor types, was shown to be correlated with CSC tumor-initiating capacity; however, the regulation of CD133 expression and its function in cancer are poorly understood. Here, we show that CD133 expression is negatively regulated by direct binding of the p53 tumor suppressor protein to a noncanonical p53-binding sequence in the CD133 promoter. Binding of p53 recruits Histone Deacetylase 1 (HDAC1) to the CD133 promoter and subsequently suppresses CD133 expression by reducing histone H3 acetylation. Furthermore, CD133 depletion suppresses tumor cell proliferation, colony formation, and the expression of core stemness transcription factors including NANOG, octamer-binding transcription factor 4 (OCT4), SOX2, and c-MYC. Critically, the anti-proliferative effects of p53 are antagonized by rescue of CD133 expression in a p53 overexpressing cell line, indicating that the tumor suppressive activity of p53 might be mediated by CD133 suppression. Taken together, our results suggest that p53-mediated transcriptional regulation of CD133 is a key underlying mechanism for controlling the growth and tumor-initiating capacity of CSCs and provide a novel perspective on targeting CSCs for cancer therapy.

Serum periostin levels correlate with airway hyper-responsiveness to methacholine and mannitol in children with asthma.

BACKGROUND: Periostin is a matricellular protein, and its synthesis in airway epithelial cells and lung fibroblasts is induced by interleukin (IL)-4 and IL-13. The significance of periostin as a biomarker of TH 2-induced airway inflammation, and (importantly) as a measure of the response to TH 2-targeted therapy, has recently been emphasized. We explored the relationship between periostin and airway hyperresponsiveness (AHR) in asthmatic children. METHODS: The study included 83 children aged 6-15 years in an asthmatic group (n = 54) and healthy controls (n = 29). We measured the periostin levels in serum and performed methacholine and mannitol provocation challenges. The responses to mannitol were expressed as the provocative dose causing a 15% fall in the FEV1 (the PD15 dose). RESULTS: Of the 54 subjects with asthma, all had positive methacholine bronchial provocation test (BPT) results and 38 had positive mannitol BPT results. Children with asthma had significantly higher periostin levels than controls [76.0 (65.0-91.8) vs 71.0 (57.5-80.0) ng/mL; P = 0.017]. Periostin levels were significantly correlated with both the methacholine PC20 and mannitol PD15 values. CONCLUSION: Serum levels of periostin, a new biomarker induced by IL-13, were higher in asthmatic children, and were associated with AHR to methacholine and mannitol.

Effectiveness of egg yolk immunoglobulin (IgY) against periodontal disease-causing Fusobacterium nucleatum.

AIMS: To evaluate the in vitro and in vivo effectiveness of egg yolk immunoglobulin (IgY) against periodontal disease-causing Fusobacterium nucleatum. METHODS AND RESULTS: Four White Leghorn hens (120 days old) were immunized with whole Fus. nucleatum cells killed with 1% formaldehyde using three injections provided at 2-week intervals. IgY was produced from egg yolks obtained from these immunized hens using water dilution, two-step salt precipitation and ultrafiltration. This IgY was shown to have a purity of 86·8% based on its optical intensity in the stained SDS-PAGE bands. An enzyme-linked immunosorbent assay indicated a high specificity for the IgY against Fus. nucleatum with a maximum antibody titre of 80 000. The IgY had only weak cross-reactivity with Porphyromonas gingivalis, Prevotella intermedia and Solobacterium moorei. Growth and biofilm formation by Fus. nucleatum were inhibited by IgY at concentrations of 10 and 20 mg ml(-1) . Immunofluorescence and immunoelectron microscope assays revealed a high binding ability of specific IgY, which may explain the in vitro effectiveness of IgY. In an in vivo study, IgY treatment resulted in a marked decrease in alveolar bone loss after Fus. nucleatum infection in a mouse model confirming the effectiveness of IgY against periodontal disease-causing Fus. nucleatum. CONCLUSIONS: IgY effectively inhibited growth and biofilm formation by Fus. nucleatum and prevented the progression of periodontal disease by decreasing alveolar bone loss. SIGNIFICANCE AND IMPACT OF THE STUDY: Specific IgY may have potential for the treatment of periodontal disease.

Chk1 phosphorylation of Metnase enhances DNA repair but inhibits replication fork restart.

Chk1 both arrests replication forks and enhances repair of DNA damage by phosphorylating downstream effectors. Although there has been a concerted effort to identify effectors of Chk1 activity, underlying mechanisms of effector action are still being identified. Metnase (also called SETMAR) is a SET and transposase domain protein that promotes both DNA double-strand break (DSB) repair and restart of stalled replication forks. In this study, we show that Metnase is phosphorylated only on Ser495 (S495) in vivo in response to DNA damage by ionizing radiation. Chk1 is the major mediator of this phosphorylation event. We had previously shown that wild-type (wt) Metnase associates with chromatin near DSBs and methylates histone H3 Lys36. Here we show that a Ser495Ala (S495A) Metnase mutant, which is not phosphorylated by Chk1, is defective in DSB-induced chromatin association. The S495A mutant also fails to enhance repair of an induced DSB when compared with wt Metnase. Interestingly, the S495A mutant demonstrated increased restart of stalled replication forks compared with wt Metnase. Thus, phosphorylation of Metnase S495 differentiates between these two functions, enhancing DSB repair and repressing replication fork restart. In summary, these data lend insight into the mechanism by which Chk1 enhances repair of DNA damage while at the same time repressing stalled replication fork restart.

Usefulness of a mobile phone with video telephony in identifying the correct landmark for performing needle thoracocentesis.

BACKGROUND: A needle thoracocentesis should be performed with maximal safety and optimal efficacy in mind. Mobile video telephony (VT) could be used to facilitate instructions for the accurate performance of needle thoracocentesis in an emergency setting. This new communication method will increase the accuracy of identifying the relevant anatomical site during the decompression technique. METHODS: A prospective randomised manikin study was performed to investigate the effectiveness of using VT as a method of instruction for the identification of anatomical landmarks during the performance of needle thoracocentesis. RESULTS: The overall success rate was significantly higher in the VT group which performed needle thoracocentesis under the guidance of VT than in the non-VT group who performed the procedure without VT-aided instruction. The instrument difficulty score and procedure satisfaction score were significantly lower in the VT group than in the non-VT group. CONCLUSION: Identification of the correct anatomical landmark for needle thoracocentesis can be performed with instructions provided via VT because a dispatcher can monitor every step and provide correct instructions. This new technology will improve critical care medicine.

The usefulness of the GlideScope video laryngoscope in the education of conventional tracheal intubation for the novice.

The aim of this study is to evaluate the usefulness of the GlideScope video laryngoscope (GVL) as a tool to educate novice users in conventional tracheal intubation. 41 premedical students with no previous experience in tracheal intubation participated in this prospective, randomised and controlled study. Group M (n = 20) was instructed in tracheal intubation by using the Macintosh laryngoscope and group G (n = 21) was instructed by using both the GVL and the Macintosh laryngoscope. There was no significant difference in tracheal intubation performance using the Macintosh laryngoscope between the two groups. However, the GVL facilitates the education of tracheal intubation because it shows the same anatomical structure for both instructor and trainee simultaneously on a real-time basis. This aspect makes the trainee feel more comfortable learning the material with a high degree of satisfaction. Introducing GVL to conventional intubation education for novice users could increase the satisfaction of trainees during the procedure, especially as a way to understand critical anatomical structures.

Effect of a seaweed extract on fatty acid accumulation and glycerol-3-phosphate dehydrogenase activity in 3T3-L1 adipocytes.

This study was to determine the effect of a seaweed Ascophyllum nodosum extract (SE) containing 220 mg g(-1) phlorotannins on differentiation and fatty acid accumulation in differentiating 3T3-L1 adipocytes. 3T3-L1 cells (2 x 10(4) mL(-1)) were seeded to 24-well plates and proliferated to reach confluence and then were treated with media containing 0, 12.5, 25, 50, 75 and 100 mug mL(-1) SE for 8 days. Dexamethasone, methyl-isobutylxanthine and insulin (DMI) were added to the media in the first 2 days to induce cell differentiation. On day 8 the adipocytes were harvested for measuring cellular fatty acid concentration and the activity of glycerol-3-phosphate dehydrogenase (GPDH). It was found that treatment with SE increased (P < 0.01, n = 6) cellular myristoleic acid (C14:1), palmitoleic acid (C16:1) and oleic acid (C18:1) and total monounsaturated fatty acids (MUFA) without significantly affecting the cell number and saturated fatty acid (SFA). Ratios of MUFA/SFA, C14:1/C14:0, C16:1/C16:0 and C18:1/C18:0 in cellular lipids increased (P < 0.05, n = 6) with the SE treatment in a dose dependent manner (P < 0.001). Treatment with 75 microg mL(-1) SE depressed (P < 0.05) cellular GPDH activity. The results indicate that the biological factors in the SE may be involved in differentiation and MUFA accumulation in adipocytes.

Performance of cellular phones with video telephony in the use of automated external defibrillators by untrained laypersons.

AIM: To evaluate the hypothesis that using an automated external defibrillator (AED) with video telephony-directed cellular phone instructions for untrained laypersons would increase the probability of successful performance of AEDs. Real-time communication with visual images can provide critical information and appropriate instructions to both laypersons and dispatchers. METHODS: A prospective observational study was undertaken. 52 public officers with no previous experience in the use of a defibrillator were presented with a scenario in which they were asked to use an AED on a manikin according to the instructions given to them by cellular phones with video telephony. The proportion who successfully delivered a shock and the time interval from cardiac arrest to delivery of the shock were recorded. RESULTS: Placement of the electrode pads was performed correctly by all 52 participants and 51 (98%) delivered an accurate shock. The mean (SD) time to correct shock delivery was 131.8 (20.6) s (range 101-202). CONCLUSION: Correct pad placement and shock delivery can be performed using an AED when instructions are provided via video telephone because a dispatcher can monitor every step and provide correct information.

Accuracy of Web-based recording program for in-hospital resuscitation: laboratory study.

OBJECTIVE: The purpose of this study was to assess the accuracy of a Web-based resuscitation recording program compared with the handwritten method. METHODS: A Web site was developed to record in-hospital resuscitation events and a mock resuscitation was recorded using both the Web site and handwritten method by emergency nurses. Accurate recorded events and times were compared between the two methods through the use of a video clip. Paired t tests were used to compare differences in absolute timing error, the number of omitted events out of 11 reference events and total recorded events. RESULTS: Twenty-one emergency nurses recorded simulated resuscitation events using both the handwritten and Web-based computerised recording system. The mean absolute timing errors were significantly lower using the computerised recording program (37.3 s (SD 17.1) versus 8.3 s (SD 5.3), p<0.001). The mean number of omissions for the computerised program was 1.8 (SD 0.8) compared with 1.4 (SD 1.1) for the handwritten method (p = 0.202). The mean number of total recorded events for the computerised program was 16.5 (SD 3.5) compared with 15.0 (SD 3.8) for the handwritten method (p = 0.063). CONCLUSIONS: This study suggests that a Web-based recording program decreased timing error while causing no differences in the number of recorded or omitted events in a laboratory setting.

Histone deacetylase inhibitor apicidin downregulates DNA methyltransferase 1 expression and induces repressive histone modifications via recruitment of corepressor complex to promoter region in human cervix cancer cells.

Dysregulation of DNA methyltransferase (DNMT)1 expression is associated with cellular transformation, and inhibition of DNMT1 exerts antitumorigenic effects. Here, we report that DNMT1 abnormally expressed in HeLa cells is downregulated by a histone deacetylase (HDAC) inhibitor apicidin, which is correlated with induction of repressive histone modifications on the promoter site. Apicidin selectively represses the expression of DNMT1 among DNMTs in HeLa cells, independent of cell cycle arrest at G0/G1. Furthermore, apicidin causes a significant reduction in the recruitment of RNA polymerase II into the promoter. Chromatin immunoprecipitation analysis shows that even though apicidin causes global hyperacetylation of histone H3 and H4, localized deacetylation of histone H3 and H4 occurs at the E2F binding site, which is accompanied by the recruitment of pRB and the replacement of P/CAF with HDAC1 into the sites. In addition, K4-trimethylated H3 on nucleosomes associated with the transcriptional start site is depleted following apicidin treatment, whereas repressive markers, K9- and K27-trimethylation of H3 are enriched on the site. The downregulation of DNMT1 expression seems to require de novo protein synthesis, because the apicidin effect is antagonized by cycloheximide treatment. Moreover, knock down of DNMT1 with siRNA induces the apoptosis of HeLa cells, indicating that downregulation of DNMT1 might be a good strategy for therapeutics of human cervix cancer. Collectively, our findings will provide a mechanistic rationale for the use of HDAC inhibitors in cancer therapeutics.