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Nanoindentation based on atomic force microscopy (AFM) can measure the elasticity of biomaterials and cells with high spatial resolution and sensitivity, but relating the data to quantitative mechanical properties depends on information on the local contact, which is unclear in most cases. Here, we demonstrate nonlocal deformation sensing on biorelevant soft matters upon AFM indentation by using nitrogen-vacancy centers in nanodiamonds, providing data for studying both the elasticity and capillarity without requiring detailed knowledge about the local contact. Using fixed HeLa cells for demonstration, we show that the apparent elastic moduli of the cells would have been overestimated if the capillarity was not considered. In addition, we observe that both the elastic moduli and the surface tensions are reduced after depolymerization of the actin cytoskeleton in cells. This work demonstrates that the nanodiamond sensing of nonlocal deformation with nanometer precision is particularly suitable for studying mechanics of soft biorelevant materials.

Both interleukin (IL)-7 and human periodontal ligament cells (hPDLCs) have immunomodulatory properties. However, their combined effect on CD4+T cells has never been studied. In this study, we aimed to investigate the effect of conditioned medium of hPDLCs treated with rhIL-7 on the differentiation of CD4+T cells into regulatory T cells/T helper 17 cells (Treg/Th17 cells) and observe the effect of IL-7 on the immunomodulatory properties of PDLCs. After hPDLCs were treated with different concentrations of rhIL-7 for 24 h, the collected supernatants were used to incubate CD4+T cells for 3 days. A gamma-secretase inhibitor (DAPT) was used to suppress the activation of the Notch1 signaling pathway. Cell proliferation, apoptosis, and necrosis were determined using the cell counting kit-8 (CCK-8) and flow cytometry (FCM). The expressions of forkhead box P3 (Foxp3) in CD4+T cells and transforming growth factor (TGF-β) and IL-6 in the supernatants were determined by ELISA. Reverse transcription-quantitative PCR (RT-qPCR), and the Western blot (WB) determined the mRNA levels and protein expression of various target factors. FCM was used to detect the mean fluorescence intensity of PD-L1 in hPDLCs and to analyze the differentiation of Treg/Th17 cells. Our results showed that IL-7 promoted proliferation and inhibited apoptosis in hPDLCs, promoted the expression of TGF-β, PD-L1, Notch1, Jagged1, and Hes1, and inhibited the levels of hypoxia-inducible factor (HIF)-1α and TCF7, whereas the addition of DAPT effectively reversed these effects. Importantly, we found that the conditioned medium of hPDLCs treated with rhIL-7 promoted the polarization of CD4+T cells into Treg cells but had no significant effect on the differentiation of Th17 cells. Our study indicated that treatment of PDLCs with IL-7 can promote the polarization of CD4+T cells into Treg cells by modulating the expression of inflammatory factors and signaling molecules through activating the Notch1 signaling pathway, thus participating in the regulation of immune homeostasis in the periodontal microenvironment.

Ambient temperature change is one of the risk factors of human health. Moreover, links between white blood cell counts (WBC) and diseases have been revealed in the literature. Still, we do not know of any association between ambient temperature change and WBC counts. The aim of our study is to investigate the relationship between ambient temperature change and WBC counts. We conducted this two-year population-based observational study in Kaohsiung city, recruiting voluntary community participants. Total WBC and differential counts, demographic data and health hazard habits were collected and matched with the meteorological data of air-quality monitoring stations with participants’ study dates and addresses. Generalized additive models (GAM) with penalized smoothing spline functions were performed for the trend of temperature changes and WBC counts. There were 9278 participants (45.3% male, aged 54.3 ± 5.9 years-old) included in analysis. Compared with stable weather conditions, the WBC counts were statistically higher when the one-day lag temperature changed over 2 degrees Celsius, regardless of whether colder or hotter. We found a V-shaped pattern association between WBC counts and temperature changes in GAM. The ambient temperature change was associated with WBC counts, and might imply an impact on systematic inflammation response.

Correlated translation-orientation tracking of single particles can provide important information for understanding the dynamics of live systems and their interaction with the probes. However, full six-dimensional (6D) motion tracking has yet to be achieved. Here, we developed synchronized 3D translation and 3D rotation tracking of single diamond particles based on nitrogen-vacancy center sensing. We first performed 6D tracking of diamond particles attached to a giant plasma membrane vesicle to demonstrate the method. Quantitative analysis of diamond particles' motion allowed elimination of the geometric effect and revealed the net rotation on the vesicle. 6D tracking was then applied to measure live cell dynamics. Motion characteristics of nanodiamonds on cell membranes under various controlled physiological conditions suggest that the nanodiamonds' rotation is associated with cell metabolic activities. Our technique extends the toolbox of single particle tracking and provides a unique solution to problems where correlated analysis of translation and rotation is critical.

Nitrogen-vacancy (NV) centers in diamond are promising quantum sensors because of their long spin coherence time under ambient conditions. However, their spin resonances are relatively insensitive to non-magnetic parameters such as temperature. A magnetic-nanoparticle-nanodiamond hybrid thermometer, where the temperature change is converted to the magnetic field variation near the Curie temperature, were demonstrated to have enhanced temperature sensitivity (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$11{\rm{\,\,mK\,\,H}}{{\rm{z}}^{ - 1/2}}$\end{document}) (Wang N, Liu G-Q and Leong W-H et al. Phys Rev X 2018; 8: 011042), but the sensitivity was limited by the large spectral broadening of ensemble spins in nanodiamonds. To overcome this limitation, here we show an improved design of a hybrid nanothermometer using a single NV center in a diamond nanopillar coupled with a single magnetic nanoparticle of copper-nickel alloy, and demonstrate a temperature sensitivity of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$76{\rm{\,\,\mu K\,\,H}}{{\rm{z}}^{ - 1/2}}$\end{document}. This hybrid design enables detection of 2 mK temperature changes with temporal resolution of 5 ms. The ultra-sensitive nanothermometer offers a new tool to investigate thermal processes in nanoscale systems., A combination of a magnetic nanoparticle and a single nitrogen-vacancy center in a diamond nanopillar makes a nano-thermometer with a record sensitivity 76 ÂμK Hz-1/2 under ambient condition, adding a tool to many studies of nanoscale thermal processes.

We tested the hypothesis that allogenic adipose-derived mesenchymal stem cells (ADMSCs) alleviated brain death (BD)-induced remote organ damage and events of post heart-transplant acute rejection. To determine the impact of BD on remote organ damage, adult-male F344 rats (n=24) were categorized sham-control (SC), BD and BDMSC (allogenic ADMSC/1.2 × 106 cells/derived from F344 by intravenous transfusion 3 h after BD procedure). To determine the protective effect of allogenic ADMSCs, animals (n=8/each group in F344/Lewis) were categorized into groups BD-T(F344 heart transplanted into Lewis by 6h after BD), BD-TMSC(D1/3) (BD induction for 6h then heart transplantation, and allogenic ADMSCs transfusion at days 1 and 5 after heart transplantation), BD-TMSC(3h) (BD + ADMSC/1.2 × 106 cells at 3h and heart transplantation at 6h after BD) and BD-TMSC(3h, D1/3) [BD + ADMSC/1.2 × 106 cells at 3h and heart transplantation at 6h after BD, then ADMSC therapy by days 1/3]. At day 5 post procedure, liver, kidney and heart specimens showed higher molecular-cellular levels of inflammation, immune reaction, apoptosis and fibrosis in BD than in SC that were reversed in BDMSC (all P < 0.0001). These molecular-cellular expressions and circulating/splenic levels of innate/adoptive immune cells were higher in BD-T, lowest in BD-TMSC(3h, D1/3) and higher BD-TMSC(3h) in than BD-TMSC(D1/3), whereas heart function showed an opposite pattern among the four groups (all P < 0.001). In conclusion, ADMSCs suppressed BD-caused remote organ damage and heart-transplant rejection.

The photophysical properties of the excited states of the water-soluble gallium corrole (Ga(tpfc) (SO3Na)2) and fluorescence lifetime imaging in three kinds of living cell lines have been investigated using the steady-state and time-resolved spectroscopic techniques. In comparison with gallium corrole (Ga(tpfc) (py)) in six selected solvents, Ga(tpfc) (SO3Na)2 shows the much weaker emission and B-band absorption, and the Q-band absorption exhibits red-shift of about 15 nm, the fluorescence lifetime decreases, while the triplet lifetime increases. The internal transition time from the B-band to the Q-band of Ga(tpfc) (SO3Na)2 is similar to that of Ga(tpfc) (py) in toluene. The high polarity of the water has an important impact on the dynamics of the singlet and triplet states, which may result in efficient electron transfer to the oxygen. This observation has been confirmed by the EPR experiment. Without the aid of carrier proteins, Ga(tpfc) (SO3Na)2 can penetrate into three kinds of living cell lines: mou...

This study tested the therapeutic impact of double-loading dose (i.e., 600 mg) versus standard-loading dose (i.e., 300 mg) of clopidogrel on ST-segment-elevation-myocardial-infarction (STEMI) patients undergoing primary-coronary-intervention (PCI).Between January 2005 and December 2013, a total of 1461 STEMI patients undergoing PCI were consecutively enrolled into the study and categorized into group 1 (600 mg/clopidogrel; n = 508) and group 2 (300 mg/clopidogrel; n = 953). We assessed angiographic thrombolysis-in-myocardial-infarction (TIMI) flow in the infarct-related-artery, 30-day mortality and upper-gastrointestinal-bleeding (UGIB) within 30 days as primary-endpoints and later incidents of UGIB as secondary-endpoints.The results showed that the incidences of advanced Killip score (defined as ≥ score 3) upon presentation (23.8% versus 24.6%) and advanced heart failure (defined as ≥ NYHAFc-3) (10.2% versus 10.4%) did not differ between groups 1 and 2 (all P > 0.4). Primary-endpoints, which were final TIM-3 flow (91.3% versus 91.7%) in the infarct-related-artery, incidences of 30-day mortality (5.8% vs. 7.1%), and UGIB ≤ 30 day (7.8% versus 8.9%) did not differ between group 1 and group 2 (all P > 0.33). The secondary-endpoints which were incidences of ≥ 30-day one-year (8.9% versus 10.1%) UGIB did not differ between groups 1 and 2 (all P > 0.45). One-year mortality did not differ between two groups (10.74% versus 12.9%) (P > 0.25). Multiple-stepwise-logistic-regression analysis showed that age and advanced-Killip score were independently predictive of 30-day mortality (all P < 0.001).Double-loading dose of clopidogrel did not confer an additional benefit to the final angiograph results, 30-day/one-year clinical outcomes; and age and advanced Killip-score were powerful predictors of 30-day mortality.

// Kuan-Hung Chen 1,8,* , Chih-Hung Chen 2,* , Christopher Glenn Wallace 3 , Chun-Man Yuen 4 , Gour-Shenq Kao 5 , Yi-Ling Chen 5 , Pei-Lin Shao 6 , Yung-Lung Chen 5 , Han-Tan Chai 5 , Kun-Chen Lin 1 , Chu-Feng Liu 7 , Hsueh-Wen Chang 8 , Mel S. Lee 9 and Hon-Kan Yip 5,6,10,11,12 1 Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 2 Department of Internal Medicine, Division of General Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 3 Department of Plastic Surgery, University Hospital of South Manchester, Manchester, UK 4 Department of Surgery, Division of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 5 Department of Internal Medicine, Division of Cardiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 6 Department of Nursing, Asia University, Taichung, Taiwan 7 Department of Emergency Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 8 Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan 9 Department of Orthopedics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 10 Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 11 Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 12 Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan * These authors have contributed equally to this work Correspondence to: Hon-Kan Yip, email: // Keywords : xenogenic adipose-derived mesenchymal stem cell, exosomes, ischemic stroke, brain infarct size, neurological function, Pathology Section Received : August 15, 2016 Accepted : October 14, 2016 Published : October 25, 2016 Abstract We tested the hypothesis that combined xenogenic (from mini-pig) adipose-derived mesenchymal stem cell (ADMSC) and ADMSC-derived exosome therapy could reduce brain-infarct zone (BIZ) and enhance neurological recovery in rat after acute ischemic stroke (AIS) induced by 50-min left middle cerebral artery occlusion. Adult-male Sprague-Dawley rats ( n = 60) were divided equally into group 1 (sham-control), group 2 (AIS), group 3 [AIS-ADMSC ( 1 . 2 × 10 6 cells)], group 4 [AIS-exosome ( 100 &#x 3 bc;g)], and group 5 (AIS-exosome-ADMSC). All therapies were provided intravenously at 3h after AIS procedure. BIZ determined by histopathology (by day-60) and brain MRI (by day-28) were highest in group 2, lowest in group 1, higher in groups 3 and 4 than in group 5, but they showed no difference between groups 3 and 4 (all p < 0.0001). By day-28, sensorimotor functional results exhibited an opposite pattern to BIZ among the five groups ( p < 0.005). Protein expressions of inflammatory (inducible nitric oxide synthase/tumor necrosis factor-α/nuclear factor-κB/interleukin-1β/matrix metalloproteinase-9/plasminogen activator inhibitor-1/RANTES), oxidative-stress (NOX-1/NOX-2/oxidized protein), apoptotic (caspase-3/ Poly-ADP-ribose polymerase), and fibrotic (Smad3/transforming growth factor-β) biomarkers, and cellular expressions of brain-damaged (γ-H2AX+/ XRCC1-CD90+/p53BP1-CD90+), inflammatory (CD11+/CD68+/glial fibrillary acid protein+) and brain-edema (aquaporin-4+) markers showed a similar pattern of BIZ among the groups (all n < 0.0001). In conclusion, xenogenic ADMSC/ADMSC-derived exosome therapy was safe and offered the additional benefit of reducing BIZ and improving neurological function in rat AIS.

We hypothesized that combined treatment with autologous adipose-derived mesenchymal stem cell (ADMSC) and ciprofloxacin is superior to ciprofloxacin only in reducing sepsis-induced urogenital organ damage and mortality in rat sepsis syndrome (SS) caused by intrapelvic injection of cecal bacteria (1.0 × 104 cells per milliliter; total, 5.0 ml). Male Sprague-Dawley rats (n = 60) equally divided into group 1 (sham-control), group 2 (SS), group 3 (SS-ADMSC [5.0 × 105 intravenously at 0.5, 6, and 18 hours after sepsis induction]), group 4 (SS-ciprofloxacin [3.0 mg/kg, b.i.d.] for 5 days), and group 5 (SS-ADMSC-ciprofloxacin) were sacrificed by day 5. Mortality rate and creatinine level were highest in group 2 and lowest in group 1 and significantly higher in groups 3 and 4 than those in group 5, but there was no difference between groups 3 and 4 (all p < .005). The kidney injury score, inflammatory biomarker expressions at protein (tumor necrosis factor-1α, nuclear factor-κB, matrix metallopeptidase-9, regulated on activation, normal T-cell expressed and secreted, interleukin-1β) and cellular (CD14+, migratory inhibitor factor positive, CD68+) levels in kidneys and urinary bladder were lowest in group 1 and highest in group 2, higher in group 4 than in groups 3 and 5, and higher in group 3 than in group 5 (all p < .001). Protein expressions of apoptosis (Bax, cleaved caspase 3 and poly[ADP-ribose] polymerase 1, p21 protein [Cdc42/Rac]-activated kinase 2) and oxidative stress (oxidized protein, NADPH oxidase (NOX)-1, NOX-2) in these organs showed an identical pattern compared with that of inflammation in all groups (all p < .001). In conclusion, ADMSC-assisted ciprofloxacin therapy offered an additional benefit by reducing acute urogenital organ damage in rat. Significance Autologous adipose-derived mesenchymal stem cell-assisted ciprofloxacin therapy offered an additional benefit by reducing acute urogenital organ damage in rats.

Antioxidant peptide SS-31 is a class of cell-permeable small peptides, which selectively resides on the inner mitochondrial membrane and possesses intrinsic mitochondrial protective capacities. In this study we investigated the therapeutic effects of antioxidant peptide SS-31 on transverse aortic constriction (TAC)-induced pulmonary arterial hypertension (PAH) in a murine model.Adult male mice were divided into 3 groups: sham-operated mice, TAC mice, and TAC+SS-31 mice that underwent TAC surgery and received SS-31 (2 mg/d, ip) for 60 d. The right ventricular systolic blood pressure (RVSBP) was measured on d 60 prior to sacrificing the mice; then their right heart and lung tissues were collected for histological and biochemical examinations. Lung injury scores were defined by the increased crowded area and decreased number of alveolar sacs.TAC mice showed significantly higher RVSBP compared with sham-operated mice, the elevation was substantially suppressed in TAC+SS-31 mice. The same pattern of changes was found in pulmonary levels of oxidative stress proteins (NOX-1/NOX-2/oxidized proteins), cytosolic cytochrome c, biomarkers related to inflammation (MMP-9/TNF-α/iNOS), calcium overload index (TRPC1, 2, 4, 6), apoptosis (mitochondrial BAX, cleaved caspase 3/PARP), fibrosis (Smad3/TGF-β), hypoxic (HIF-1α), DNA damage (γ-H2AX) and endothelial function (eNOS/ET-1R), as well as in lung injury score, number of muscularized vessels in lungs, number of TRPC1(+) and HIF-1α(+) cells in pulmonary artery, and number of γ-H2AX(+) and Ki-67(+) cells in lung parenchyma. An opposite pattern of changes was observed in pulmonary anti-fibrotic markers (Smad1/5, BMP-2), number of small vessels, and number of alveolar sacs. In contrast, the levels of antioxidant proteins (HO-1/NQO-1/GR/GPx) in lung parenchyma were progressively and significantly increased from sham-operated mice, TAC mice to TAC+SS-31 mice.Antioxidant peptide SS-31 administration effectively attenuates TAC-induced PAH in mice.

Energy transfer (ET) is an important route to manage the population density of excited states, giving rise to spectrally tunable emission that is valuable for multicolor imaging and biological tracking. In this paper, a case study of GdF3 nanoparticles (NPs) codoped with Yb3+ and Er3+ was used to experimentally and theoretically investigate the ET mechanisms under near-infrared and violet excitation. Red-to-green ratio (RGR) is used as a primary evaluating protocol, and the power-dependent luminescence and Er3+ 4I13/2 luminescence behavior are used to identify the corresponding conjectures about ET mechanisms. Compared with the four common upconversion (UC) models, a joint effect of energy-back-transfer, multiphonon relaxation, and linear decay depletion mechanisms for the Er3+ 4I13/2 manifold was proposed for the UC process based on UC spectra for samples with different dopant concentrations. Meanwhile, the varying RGR could also be observed from downshifting (DS) emission spectra. The ET mechanism for t...

This study tested the therapeutic impact of double-loading dose (i.e., 600 mg) versus standard-loading dose (i.e., 300 mg) of clopidogrel on ST-segment-elevation-myocardial-infarction (STEMI) patients undergoing primary-coronary-intervention (PCI).Between January 2005 and December 2013, a total of 1461 STEMI patients undergoing PCI were consecutively enrolled into the study and categorized into group 1 (600 mg/clopidogrel; n = 508) and group 2 (300 mg/clopidogrel; n = 953). We assessed angiographic thrombolysis-in-myocardial-infarction (TIMI) flow in the infarct-related-artery, 30-day mortality and upper-gastrointestinal-bleeding (UGIB) within 30 days as primary-endpoints and later incidents of UGIB as secondary-endpoints.The results showed that the incidences of advanced Killip score (defined as ≥ score 3) upon presentation (23.8% versus 24.6%) and advanced heart failure (defined as ≥ NYHAFc-3) (10.2% versus 10.4%) did not differ between groups 1 and 2 (all P0.4). Primary-endpoints, which were final TIM-3 flow (91.3% versus 91.7%) in the infarct-related-artery, incidences of 30-day mortality (5.8% vs. 7.1%), and UGIB ≤ 30 day (7.8% versus 8.9%) did not differ between group 1 and group 2 (all P0.33). The secondary-endpoints which were incidences of ≥ 30-dayone-year (5.2% versus 4.7) andone-year (8.9% versus 10.1%) UGIB did not differ between groups 1 and 2 (all P0.45). One-year mortality did not differ between two groups (10.74% versus 12.9%) (P0.25). Multiple-stepwise-logistic-regression analysis showed that age and advanced-Killip score were independently predictive of 30-day mortality (all P0.001).Double-loading dose of clopidogrel did not confer an additional benefit to the final angiograph results, 30-day/one-year clinical outcomes; and age and advanced Killip-score were powerful predictors of 30-day mortality.

Background. This study evaluated the impact on clinical outcomes using a cloud computing system to reduce percutaneous coronary intervention hospital door-to-balloon (DTB) time for ST segment elevation myocardial infarction (STEMI). Methods. A total of 369 patients before and after implementation of the transfer protocol were enrolled. Of these patients, 262 were transferred through protocol while the other 107 patients were transferred through the traditional referral process. Results. There were no significant differences in DTB time, pain to door of STEMI receiving center arrival time, and pain to balloon time between the two groups. Pain to electrocardiography time in patients with Killip I/II and catheterization laboratory to balloon time in patients with Killip III/IV were significantly reduced in transferred through protocol group compared to in traditional referral process group (both p<0.05). There were also no remarkable differences in the complication rate and 30-day mortality between two groups. The multivariate analysis revealed that the independent predictors of 30-day mortality were elderly patients, advanced Killip score, and higher level of troponin-I. Conclusions. This study showed that patients transferred through our present protocol could reduce pain to electrocardiography and catheterization laboratory to balloon time in Killip I/II and III/IV patients separately. However, this study showed that using a cloud computing system in our present protocol did not reduce DTB time.

Objective: Few studies have focused on factors influencing outcomes of patients with in-hospital cardiac arrest (IHCA) in general wards. The goal of this study was to report the outcomes of adult patients with IHCA in the general wards and identified the prognostic factors. Methods: Adult patients with IHCA having received cardiopulmonary resuscitation in general wards from January 2008 to December 2011 were retrospectively reviewed from our registry system. The primary outcome was survival to hospital discharge, while the secondary outcome was sustained return of spontaneous circulation (ROSC). Results: A total of 544 general ward patients were analyzed for event variables and resuscitation results. The rate of establishing a ROSC was 40.1% and the rate of survival to discharge was 5.1%. Ventricular tachycardia/ventricular fibrillation (VT/VF) was the initial rhythm in 3.9% of patients. Pre-arrest factors including a high Charlson comorbidity index (CCI) ≥ 9 (OR 0.251, 95% CI 0.098 - 0.646), cardiac comorbidity (OR 0.612, 95% CI 0.401 - 0.933), and arrest time on the midnight shift (OR 0.403, 95% CI 0.252 - 0.642) were independently associated with a low possibility of ROSC. The initial VT/VF presenting rhythms (OR 0.135, 95% CI 0.030 - 0.601) were independently associated with a high survival rate, whereas patients with deteriorated disease course were independently associated with a decreased hospital survival (OR 3.902, 95% CI 1.619 - 9.403). Conclusions: We demonstrated that pre-arrest factors can predict patient outcome after IHCA in general wards, including the association of a CCI ≥ 9 and cardiac comorbidity with poor ROSC, and deteriorated disease course as an independent predictor of a low survival rate.

Background Most studies have investigated the diagnostic accuracy of 64-slice multi-detector computed tomography (MDCT) to detect coronary artery stent patency by using conventional coronary angiography (CCA) as the reference standard. In this study, we compared the diagnostic accuracy of MDCT and CCA by using intravascular ultrasonography (IVUS) as the reference standard. Methods Forty-six patients with previously implanted coronary artery stents (n=87) underwent MDCT followed by CCA and IVUS within 24h. Sensitivities, specificities, positive predictive values (PPV) and negative predictive values (NPV) of MDCT and CCA for detecting or excluding in-stent diameter restenosis (ISDR) by using in-stent area restenosis (ISAR) and minimal luminal area (MLA) ≤4.0mm 2 of IVUS as the reference standard were determined. Results Eight stents (9%) were judged non-evaluable using MDCT for the detection of ISDR. ISDR was detected in 28% (22/79) of the evaluable stents using CCA. When ISAR was detected using IVUS, the sensitivity, specificity, PPV, and NPV for ISDR detection by using MDCT were 71%, 96%, 91% and 86%, and the corresponding values for CCA were 64%, 96%, 90% and 83%. When MLA ≤4.0mm 2 was detected using IVUS, the sensitivity, specificity, PPV, and NPV for ISDR detection by using MDCT were 87%, 96%, 91% and 95%, and for CCA were 78%, 96%, 90% and 92%. Conclusions When ISAR with MLA ≤4.0mm 2 was detected on IVUS, CCA and MDCT had similar diagnostic accuracies for ISDR detection. High specificity and NPV make 64-slice MDCT a reliable non-invasive method for excluding ISDR.

Intracoronary nitroprusside and thrombus aspiration have been demonstrated to improve myocardial perfusion during percutaneous coronary interventions (PCI) for ST-segment elevation acute myocardial infarction (STEMI) However, no long-term clinical studies have been performed comparing these approaches.A single medical center retrospective study was conducted to evaluate the effects of intracoronary nitroprusside administration before slow/no-reflow phenomena versus thrombus aspiration during primary PCI. Forty-three consecutive patients with STEMI were enrolled in the intracoronary nitroprusside treatment group. One hundred twenty-four consecutive STEMI patients who received thrombus aspiration were enrolled; ninety-seven consecutive STEMI patients who did not receive either thrombus aspiration or intracoronary nitroprusside treatment were enrolled and served as control subjects. Patients with cardiogenic shock, who had received platelet glycoprotein IIb/IIIa inhibitor, or intra-aortic balloon pump insertion were excluded. Thrombolysis in Myocardial Infarction (TIMI) flow grade, corrected TIMI frame count and TIMI myocardial perfusion grade (TMPG) were assessed prior to and following PCI by two independent cardiologists blinded to the procedures. The rate of major adverse cardiac events (MACE) at 30 days, 1 year, and 3 years after study enrollment as a composite of recurrent myocardial infarction, target-vessel revascularization, and cardiac death were recorded.The control group had a significantly lower pre-PCI TIMI flow (≤ 1; 49.5% vs. 69.8% vs. 77.4%; p =0.001) compared with the nitroprusside and thrombus aspiration groups. The thrombus aspiration group had a significantly higher pre-PCI thrombus score (4; 98.4% vs. 88.4% vs. 74.3%; p =0.001) and post-PCI TMPG (3; 39.5% vs. 16.3% vs. 20.6%; p = 0.001) compared with the nitroprusside and control groups. No significant differences were noted in the post-PCI thrombus score, 30-day, 1-year and 3-year MACE rate, and Kaplan-Meier curve among 3 groups of patients.Although thrombus aspiration provided improved TMPG compared with early administration of intracoronary nitroprusside and neither of both during primary PCI, it did not have a significant impact on 30-day, 1-year and 3-year MACE rate.Acute myocardial infarction; Intracoronary nitroprusside; Thrombus aspiration.

Background Melioidosis has emerged as a global problem; however, few studies have specifically described the clinical characteristics and outcomes when patients with melioidosis are treated at an emergency department (ED). Purpose The objective of this study was to examine the demographics and clinical characteristics of patients with melioidosis who visited an ED. Methods A retrospective analysis of patients treated for melioidosis at an ED. Results Of the 25 patients identified over 7 years, 22 patients had bacteremia, whereas diabetes mellitus was the most common underlying disease (17 patients). Acute respiratory failure requiring mechanical ventilation developed in 52% of the patients. The overall mortality rate was 40%, and death within 48 hours of presentation at the ED occurred in 24% of the patients. The most common infection site was the lungs (in 52% of patients), and 36% of the patients presented with community-acquired pneumonia (CAP) at the ED. A comparison of the CAP and non-CAP groups of patients revealed that the presence of shock upon arrival (56% vs. 0; p = 0.002), total mortality (78% vs. 19%; p = 0.009), and early mortality (56% vs. 6%; p = 0.012) were significantly more common among the individuals who comprised the CAP group. Early mortality accounted for 60% of total deaths, and all of these patients died before final microbiologic data were available. CAP presentation ( p = 0.012), the presence of band-form leukocytes ( p = 0.001), increased serum creatinine ( p = 0.037), and shock on arrival ( p = 0.005) were significantly more common among patients with early mortality. Conclusion Melioidosis is a devastating illness with a high rate of mortality occurring within 48 hours of presentation. Melioidosis that presents with CAP is the most severe form of the disease and is associated with greatly increased early mortality.

AIM To evaluate the potential of the lipoprotein-associated phospholipase A(2) (Lp-PLA(2) level as a biomarker in the prediction of prognostic outcome in patients with acute ischemic stroke (IS). METHODS From October 2008 to March 2010, 130 patients with acute IS were prospectively enrolled in the study and their medical records were reviewed. A blood sample was collected from each patient 48 hours after acute IS, as well as from 20 healthy volunteers as controls. Messenger-RNA (mRNA) expression of Lp-PLA(2) of peripheral-blood mononuclear cells (PBMNCs) relative to that of β actin was measured using quantitative reverse transcription polymerase chain reaction (RT-PCR). RESULTS Patients with acute IS exhibited significantly higher Lp-PLA(2) mRNA expression of PBMNCs than the control group (p

IntroductionMortality and disability following ischemic stroke (IS) remains unacceptably high with respect to the conventional therapies. This study tested the effect of erythropoietin (EPO) on long-term neurological outcome in patients after acute IS. This study aimed to evaluate the safety and efficacy of two consecutive doses of EPO (5,000 IU/dose, subcutaneously administered at 48 hours and 72 hours after acute IS) on improving the 90-day combined endpoint of recurrent stroke or death that has been previously reported. A secondary objective was to evaluate the long-term (that is, five years) outcome of patients who received EPO.MethodsThis was a prospective, randomized, placebo-controlled trial that was conducted between October 2008 and March 2010 in a tertiary referral center. IS stroke patients who were eligible for EPO therapy were enrolled into the study.ResultsThe results showed that long-term recurrent stroke and mortality did not differ between group 1 (placebo-control; n = 71) and group 2 (EPO-treated; n = 71).Long-term Barthel index of P = 0.007). Multiple-stepwise logistic-regression analysis showed that EPO therapy was significantly and independently predictive of freedom from a Barthel index of P = 0.029). Long-term major adverse neurological event (MANE; defined as: death, recurrent stroke, or long-term Barthel index P = 0.04). Log-Rank test showed that MANE-free rate was higher in group 2 than group 1 (P = 0.031). Multiple-stepwise Cox-regression analysis showed that EPO therapy and higher Barthel Index at day 90 were independently predictive of freedom from long-term MANE (allPConclusionEPO therapy significantly improved long-term neurological outcomes in patients after IS.Trial registrationISRCTN71371114. Registered 10 October 2008.

Inhibition of dipeptidyl peptidase-IV (DPP-4) enzyme activity has been revealed to protect myocardium from ischemia-reperfusion through enhancing the endogenous glucagon-like peptide-1 (GLP-1) level. However, whether exogenous supply of exendin-4, an analogue of GLP-1, would still offer benefit for protecting myocardial damage from trans-aortic constriction (TAC)-induced hypertrophic cardiomyopathy in preexistence of DPP-4 deficiency (DPP-4(D)) remained unclear. Male-adult (DPP-4(D)) rats (n = 32) were randomized into group 1 [sham control (SC)], group 2 (DPP-4(D) + TAC), group 3 [DPP-4(D) + TAC + exendin-4 10 µg/day], and group 4 [DPP-4(D) + TAC + exendin-4 10 µg + exendin-9-39 10 µg/day]. The rats were sacrificed by day 60 after last echocardiographic examination. By day 60 after TAC, left ventricular ejection fraction (LVEF) (%) was highest in group 1 and lowest in group 2, and significantly lower in group 4 than that in group 3 (all p0.001). The protein expressions of oxidative stress (oxidized protein, NOX-1, NOX-2), inflammatory (MMP-9, TNF-α, NF-κB), apoptotic (Bax, cleaved caspase 3 and PARP), fibrotic (TGF-β, Smad3), heart failure (BNP, β-MHC), DNA damaged (γ-H2AX) and ischemic stress (p-P38, p-Akt, p53, ATM) biomarkers showed an opposite pattern of LVEF among the four groups (all p0.03). Fibrotic area (by Masson's trichrome, Sirius red), and cellular expressions of DNA-damaged markers (Ki-67+, γ-H2AX+, CD90+/53BP1+) displayed an identical pattern, whereas cellular expressions of angiogenesis (CD31+, α-SMA+) and sarcomere length exhibited an opposite pattern compared to that of oxidative stress among the four groups (all p0.001). Take altogether, Exendin-4 effectively suppressed TAC-induced pathological cardiac hypertrophy in DPP-4(D) rat.

This study tested for the benefits of early administration of carvedilol as protection against doxorubicin (DOX)-induced cardiomyopathy. Thirty male, adult B6 mice were categorized into group 1 (untreated control), group 2 [DOX treatment (15 mg/every other day for 2 weeks, i.p.], and group 3 [carvedilol (15 mg/kg/d, from day 7 after DOX treatment for 28 days)], and euthanized by day 35 after DOX treatment. By day 35, the left ventricular ejection fraction (LVEF) was significantly lower in group 2 than in groups 1 and 3, and significantly lower in group 3 than in group 1, whereas the left ventricular (LV) end-diastolic and LV end-systolic dimensions showed an opposite pattern to the LVEF among the three groups. The protein expressions of fibrotic (Smad3, TGF-β), apoptotic (BAX, cleaved caspase 3, PARP), DNA damage (γ-H2AX), oxidative stress (oxidized protein), mitochondrial damage (cytosolic cytochrome-C), heart failure (brain natriuretic peptide), and hypertrophic (β-MHC) biomarkers of the LV myocardium showed an opposite pattern to the LVEF among the three groups. The protein expressions of antifibrotic (BMP-2, Smad1/5), α-MHC, and phosphorylated-Akt showed an identical pattern to the LVEF among the three groups. The microscopic findings of fibrotic and collagen-deposition areas and the numbers of γ-H2AX(+) and 53BP1(+) cells in the LV myocardium exhibited an opposite pattern, whereas the numbers of endothelial cell (CD31(+), vWF(+)) markers showed an identical pattern to the LVEF among the three groups. Cardiac stem cell markers (C-kit(+) and Sca-1(+) cells) were significantly and progressively increased from group 1 to group 3. Additionally, the in vitro study showed carvedilol treatment significantly inhibited DOX-induced cardiomyoblast DNA (CD90/XRCC1(+), CD90/53BP1(+), and r-H2AX(+) cells) damage. Early carvedilol therapy protected against DOX-induced DNA damage and cardiomyopathy.

Background: Slow-flow and no-reflow phenomenon which occurred frequently during primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) caused unfavorable prognostic outcomes. Currently, no effectively therapeutic strategy to prevent this phenomenon. Objectives/Design: To evaluate the efficacy and safety of intra-Coronary Administration of Tacrolimus prior to firstballoon inflation, a pilot study was performed. Methods/Results of Pilot Study: Twenty-nine STEMI patients (group 1) were first prospectively administered tacrolimus (2.5 mg intra-coronary slow injection using thrombuster) prior to first-balloon inflation. A historical-control group (group 2) was chosen from fifty-two consecutive patients undergoing primary PCI just prior to the pilot study. Age, gender, CAD-risk factors, peak CK-BM, and baseline left-ventricular performance were not different between groups 1 and 2 (all p>0.1). Chest pain onset-to-door and door-to-balloon times, mean Killip score upon presentation, number of multi-vessel disease, pre-PCI TIMI flow, and 30-day death were similar between these two groups (all p>0.1). The incidences of advanced CHF (≥ NYHA 3) and pulmonary edema were higher in group 2 than in group 1, whereas the incidence of anterior-wall infarction, final TIMI-3 flow and 90 minute ST-segment-resolution rate showed an opposite pattern of advanced CHF between these two groups. The incidence of myocardial blushing grade was significantly higher in group 2 than in group 1 (p=0.034). Conclusion: Tacrolimus therapy shows promise as a safe and effective therapeutic agent for STEMI. The positive preliminary outcomes from this pilot study suggests randomized-controlled trials are now required to evaluate the effectiveness and safety of Tacrolimus for STEMI patients. (clinical trials no: ISRCTN38455499).

Pheochromocytomas are rare tumors that originate in chromaffin tissue and produce their distant variant effects by secretion of catecholamines, tending to mislead the emergency physicians to a wrong diagnosis. Therefore, we analyze the clinical cardiovascular manifestations in patients with pheochromocytoma to improve the diagnostic ability of the emergency physicians. All patients presenting to the Chang Gung Memorial Hospital between January 1993 and December 1997 with a final diagnosis of pheochromocytoma had their charts reviewed. The data of 25 patients including age, sex, adrenergic stimulation presentations, electrocardiographic changes, location of the tumor, and complications were analyzed. Hypertension was the most important major manifestation and fluctuation of blood pressure drew our attention to the possibility of pheochromocytoma. Six patients had abnormal electrocardiographic ST-T segment changes. Five of them had chest pain which prompted them to undergo coronary angiography before surgery, because acute coronary syndrome (unstable angina and acute myocardial infarction) was suspected initially. However, all of them turned out to have normal coronary arteries. Right-sided pheochromocytoma was found in three of these five patients. We should maintain high index of suspicion for pheochromocytoma in patients presenting with chest pain, fluctuating blood pressure, and ischemic electrocardiogram (ECG) changes despite any typical isoenzyme changes. Pheochromocytoma should also be included in the differential diagnosis of acute coronary syndrome because acute catecholamine secretion may induce chest pain and abnormal ECG changes mimicking an ischemic episode. The right-sided pheochromocytoma may present more striking electrocardiographic abnormalities and clinical manifestations.

To evaluate the potential of the lipoprotein-associated phospholipase A(2) (Lp-PLA(2) level as a biomarker in the prediction of prognostic outcome in patients with acute ischemic stroke (IS).From October 2008 to March 2010, 130 patients with acute IS were prospectively enrolled in the study and their medical records were reviewed. A blood sample was collected from each patient 48 hours after acute IS, as well as from 20 healthy volunteers as controls. Messenger-RNA (mRNA) expression of Lp-PLA(2) of peripheral-blood mononuclear cells (PBMNCs) relative to that of β actin was measured using quantitative reverse transcription polymerase chain reaction (RT-PCR).Patients with acute IS exhibited significantly higher Lp-PLA(2) mRNA expression of PBMNCs than the control group (p0.0001). Lp-PLA(2) mRNA expression of PBMNCs in patients with a major adverse clinical outcome (MACO) (defined as recurrent stroke or death) within 90 days was significantly higher than in patients without MACO (p=0.006). Furthermore, elevated Lp-PLA(2) mRNA expression was strongly associated with old age, diabetes mellitus, a positive history of significant coronary arterial disease and significant stenosis of the extra-cranial carotid arteries (all p0.04), and positively correlated with the body mass index, leukocyte count, and serum levels of total cholesterol and low-density lipoprotein cholesterol. Multivariate analysis revealed that Lp-PLA(2) mRNA expression of PBMNCs was a significant independent predictor of MACO within 90 days (p= 0.011).Elevated Lp-PLA(2) mRNA expression of PBMNCs seems to be a potential biomarker for predicting an unfavorable outcome in patients with acute IS.

We hypothesized that serum level of neopterin is significantly predictive of prognostic outcome in patients after acute ischemic stroke (IS).Between November 2008 and May 2010, serum levels of neopterin were prospectively collected at 48 h after acute IS in 157 patients.Serum neopterin levels were substantially higher in patients with severe neurological impairment [National institutes of Health Stroke Scale (NIHSS) score ≥12] than in those with NIHSS12 (p0.008). Furthermore, Spearman's test showed a strongly positive correlation between neopterin level and NIHSS (p=0.003). Multiple logistic regression analysis demonstrated that serum neopterin level was strongly and independently predictive of NIHSS ≥12 (p=0.002) at 48 h after acute IS and 90-day major adverse clinical outcome (defined as NIHSS≥12, recurrent stroke or death) (p=0.003).Serum level of neopterin was notably increased after acute IS. This biomarker was strongly and independently predictive of 90-day unfavorable clinical outcome in patients after acute IS.

Objective: Our objective was to report 7 cases of splenic artery aneurysm (SAA) encountered in the emergency department (ED). Methods: A retrospective survey of our ED database revealed 7 cases of SAA (6 men, 1 woman; mean age, 56 years) of 651347 ED visits over the last decade. Their clinical and imaging features, management, and outcomes were evaluated. Results: Splenic artery aneurysm in the ED was rare (prevalence, 0.011%). Common presentations included acute abdomen (n = 5) and shock (n = 2). Five cases had liver cirrhosis and portal hypertension. Abdominal radiographs (n = 7) revealed 2 atherosclerotic patients with SAA. Abdominal computed tomography (n = 7) depicted all SAAs (size, 1.5-8 cm; mean, 3.8 cm). Four ruptured SAAs were successfully managed with coils embolization. Among them, 1 patient with ruptured mycotic SAA also received surgery, but the patient died of Klebsiella sepsis 3 months later. Conclusions: In the ED, ruptured SAA should be included as a rare differential consideration of acute abdomen, especially in middle-aged men with liver cirrhosis and portal hypertension. Although SAA may be an unexpected computed tomographic finding, once diagnosed, endovascular treatment is recommended.

Selective cyclooxygenase-2 inhibitors have anti-inflammatory efficacy and can reduce the side effects and toxicity induced by inhibition of cyclooxygenase-1, thus can be widely used in clinical practice. However, the adverse effects of these drugs should be given their due attention. Currently, looking for better selective cyclooxygenase-2 inhibitors has become a hot topic in developing the non-steroidal anti-inflammatory drugs.

Lanthanide-doped rare-earth oxides have aroused great interest in display and bio-probe technology due to their excellent luminescent and magnetic performance. In this paper, Gd2O3 sub-microrods (SMRs) with cubic structure are obtained via heat-treatment from gadolinium hydroxides precursor. Upconversion (UC) spectra show intense near-infrared (NIR) emission which is assigned to 3H4 → 3H6 transition of Tm3+. From the double logarithmic plot of emission intensity versus pump powers, it was seen that typical two photons were involved in the NIR UC process. Moreover, a series of Gd2O3:18%Yb3+,x%Tm3+ (x = 0.1, 0.5, 1, 2, 5) and Gd2O3:y%Yb3+,0.5%Tm3+ (y = 1, 5, 10, 40, 80) SMRs were prepared and characterized to explore their NIR emission properties. Finally, the enhanced NIR emission property was found in Gd2O3:Yb3+,Tm3+ SMRs from the reduced NaOH concentration and the reduced calcinations temperatures.

Background We investigated whether attenuating dipeptidyl peptidase-IV (DPP4) enzyme activity protected rat heart from ischemia-reperfusion (IR) injury (40-min left anterior descending coronary artery ligation followed by 72 h reperfusion). Methods and results Adult male Fischer 344 rats (n = 24) were equally divided into sham-control (WT-SC), WT-IR, and WT-IR-Sita (oral sitagliptin 400 mg/kg/day for 3 days) groups, whereas adult male DPP4-deficiency (DPP4D) rats (n = 16) were equally divided into DPP4D-SC and DPP4D-IR groups. Animals were sacrificed at 72 h after reperfusion with collection of heart specimens. Infarct area (H&E), collagen deposition (Sirius-red stain), fibrotic area (Masson's trichrome), and fluorescent-ROS intensity (H2DCFDA-labeling myocardium) of left ventricle were significantly higher in WT-IR than those in other groups, significantly higher in WT-IR-Sita and DPP4D-IR groups than in WT-SC and DPP4D-SC groups (all p

Background Obesity is an important cardiovascular risk factor. This study tested the effect of obesity reduction on preserving left ventricular ejection fraction (LVEF) and attenuating inflammation, oxidative stress and LV remodeling in obese mice. Methods and results Eight-week-old C57BL/6 J mice (n=24) were equally divided into control (fed a control diet for 22 weeks), obesity (high-fat diet, 22 weeks), and obese reduction (OR) (high-fat diet, 14 weeks; then control diet, 8 weeks). Animals were sacrificed at post 22-week high-fat diet and the LV myocardium collected. Heart weight, body weight, abdominal-fat weight, total cholesterol level and fasting blood glucose were higher in obesity than in control and OR (all p Conclusion Impaired LVEF, enhanced LV remodeling, inflammation, fibrosis, oxidative stress and apoptosis were reversed by reduction in mouse obesity.