text:
- Research article
- Open Access
High mobilization of CD133+/CD34+ cells expressing HIF-1α and SDF-1α in septic abdominal surgical patients
BMC Anesthesiology volume 20, Article number: 158 (2020)
The control of endothelial progenitor cells (CD133+/CD34+ EPCs) migrating from bone marrow to peripheral blood is not completely understood. Emerging evidence suggests that stromal cell-derived factor-1α (SDF-1α) mediates egression of EPCs from bone marrow, while the hypoxia inducible factor (HIF) transcriptional system regulates SDF-1α expression. Our study aimed to investigate the time course of circulating CD133+/CD34+ EPCs and its correlation with the expression of HIF-1α protein and SDF-1α in postoperative laparoscopic abdominal septic patients.
Postoperative patients were divided in control (C group) and septic group (S group) operated immediately after the diagnosis of sepsis/septic shock. Blood samples were collected at baseline (0), 1, 3 and 7 postoperative days for CD133+/CD34+ EPCs count expressing or not the HIF-1α and SDF-1α analysis.
Thirty-two patients in S group and 39 in C group were analyzed. In C group CD133+/CD34+ EPCs count remained stable throughout the study period, increasing on day 7 (173 [0–421] /μl vs baseline: P = 0.04; vs day 1: P = 0.002). In S group CD133+/CD34+ EPCs count levels were higher on day 3 (vs day 1: P = 0.006 and day 7: P = 0.026). HIF-1α expressing CD133+/CD34+ EPCs count decreased on day 1 as compared with the other days in C group (day 0 vs 1: P = 0.003, days 3 and 7 vs 1: P = 0.008), while it was 321 [0–1418] /μl on day 3 (vs day 1; P = 0.004), and 400 [0–587] /μl on day 7 in S group. SDF-1α levels were higher not only on baseline but also on postoperative day 1 in S vs C group (219 [124–337] pg/ml vs 35 [27–325] pg/ml, respectively; P = 0.01).
Our results indicate that sepsis in abdominal laparoscopic patients might constitute an additional trigger of the EPCs mobilization as compared with non-septic surgical patients. A larger mobilization of CD133+/CD34+ EPCs, preceded by enhanced plasmatic SDF-1α, occurs in septic surgical patients regardless of HIF-1α expression therein.
ClinicalTrials.gov no. NCT02589535. Registered 28 October 2015.
The abdomen (post-operative infection, perforation, anastomotic leak) is the second most common site of sepsis and septic shock in Intensive Care Unit (ICU) [1,2,3,4,5,6]. Sepsis pathophysiology can be schematically described as an early hyper-inflammatory phase followed by a late hypo-inflammatory and immunosuppressive phase . In addition, loss of endothelial barrier function, inflammation and impaired cellular oxygen delivery have been shown to be primary contributor to sepsis-related organ dysfunction .
Endothelial progenitor cells (EPCs) are immature hematopoietic stem cells which share the same precursor within bone marrow (BM) and are able to induce endothelial differentiation in peripheral blood (PB) [9,10,11,12]. Mutunga et al. observed an increase of circulating EPCs in sepsis and concluded that endothelial damage occurs . Conversely, the group of Cribbs showed that EPCs were lower in septic patients compared with ICU patients controls and healthy controls . To date, little is known about the linkage between EPCs and septic postoperative abdominal laparoscopic patients.
During the past two decades, the term ‘EPCs’ has been used to identify several types of cells belonging to different stages of differentiations into mature endothelial cells. The EPCs phenotype is common between hematopoietic stem cells and differentiated endothelial cells and a unique EPCs surface marker is still undetermined. However, it is commonly accepted that EPCs, in BM or immediately circulating, express CD133+/CD34+/ VEGFR2 .
Furthermore, the pathway of EPCs migrating from BM to PB has not been completely understood. Emerging evidence suggests that stromal cell-derived factor-1a (SDF-1α), a small cytokine belonging to the chemokine family, promotes the chemotactic EPCs migration from BM to PB, while the hypoxia inducible factor (HIF) transcriptional system regulates the SDF-1α expression, and thus it is considered a master mediator of the cellular adaptation to hypoxic microenvironments . The importance of HIF to face hypoxia both at the cellular and organismal level has been recently recognized by the Nobel Prize in Physiology and Medicine 2019 .
Interestingly, it has been shown that CD133+/CD34+ hematopoietic stem/progenitor cells express high levels of stable extra-nuclear cytoplasmic form of the HIF-1α protein under normoxic conditions and proposed that SDF-1 expression is an early event in subsequent signal transduction pathways .
Our study aimed to investigate the time course of circulating CD133+/CD34+ EPCs either expressing or not the HIF-1α protein and its correlation with the plasma levels of SDF-1α in postoperative abdominal sepsis.
This study was designed to target septic patients undergoing laparoscopic major abdominal surgery at University Hospital of Foggia, in an attempt to apply a study population as homogeneous as possible and to reduce confounding variables occurring when patients with different causes of sepsis are recruited.
After approval of the local research Ethics Committee (Comitato Etico of Ospedali Riuniti, Foggia, Italy, 69/CE/2015) and written informed consent obtained by each patients, the study was performed from January 2016 to December 2018 (ClinicalTrials.gov: NCT02589535).
Inclusion criteria were: age > 18 years old Caucasian patients, laparoscopic colon surgery under general anesthesia. Exclusion criteria were: metastatic cancer, palliative care, organ transplant and pregnancy because have been shown higher levels of EPCs or HIF [19,20,21].
After intravenous cannula insertion, routine physiologic monitoring was applied, including temperature (SpotOn™ Temperature Monitoring System Model 370, MN, USA), neuromuscular function at the adductor pollicis (TOFWatch SXⓇ,Organon Teknik, Dublin, Ireland), dept. of anesthesia by bi-spectral index (BIS) monitoring (Aspect A-2000®; Aspect Medical System, Newton, MA).
Anesthesia was induced with propofol 2 mg/kg, fentanyl 3 μcg /kg and was maintained with an infusion of propofol 200 mg·kg− 1·min− 1, remifentanil 0.1–0.2 μcg·kg− 1·min− 1 and cisatracurium 1.5 mg·kg− 1·min− 1. The infusion rate of propofol varied in order to maintain a BIS value as close as possible to 50 and between 40 and 60 . Patients were mechanically ventilated with a Servo Ventilator 900C (Siemens-Elema AB, Berlin, Germany) with 40% inspired oxygen, 5 cm H2O positive end-expiratory pressure, tidal volume (Vt) of < 8 ml/kg predicted body weight, 1:2 of I:E ratio. The respiratory rate was adjusted to reach normocapnia . Postoperative patients enrolled in the study were divided into two groups:
-Control group (C group): non septic patients admitted to the surgical ward.
-Septic group (S group): septic patients admitted to the ICU, operated immediately after the diagnosis of sepsis/septic shock and treated with standard conventional therapy according to the Third International Consensus Definitions for Sepsis and Septic Shock .
Demographic data were obtained preoperatively, while clinical and laboratory data were assessed daily, according to routine procedure in the surgical ward and ICU. Mortality was defined as death occurring within 28 days after the diagnosis.
For this study, clinical and laboratory data were recorded at the following time points:
baseline (0), 1, 3 and 7 postoperative days both in S and C groups.
Peripheral whole blood samples were utilized for flow cytometric determination of CD133+/CD34+ EPCs and HIF-1α, and the plasma samples were collected and stored at − 80 °C for SDF-1α analysis.
Differently from the study protocol (ClinicalTrials.gov: NCT02589535), voluntary healthy people and the postoperative day 10 in C group were excluded for the difficulty to obtain the blood samples; patients treated by extracorporeal hemoperfusion therapy in S group were excluded due to the difficulty on obtaining blood samples at the fixed time points since the treatment decision was made by the physician in charge at the moment considering the clinical situation and endotoxin plasma levels.
As previously described , whole blood samples (100 μl) were treated within 1 h from withdrawal. For the viability analysis, cells were stained with 7-aminoactinomycin (7-AAD), which only binds to the DNA of those cells undergoing or have already undergone apoptosis (Stem Kit™ Beckman Coulter, Brea, CA, USA). Cell surface immuno-staining was performed according to the manufacturer’s guidelines adding the following fluorochrome-labeled monoclonal antibodies: fluorescein isothiocyanate (FITC)-conjugated anti-CD34 (Beckman-Coulter, Brea, CA, USA), phycoerythrin (PE)-conjugated anti-CD133 (Miltenyi Biotech, USA), peridinin chlorophyll protein complex (PerCP)-conjugated anti-human CD45 (Beckman-Coulter, Brea, CA, USA), PE-conjugated anti-human CD31 (Beckman-Coulter, Brea, CA, USA). Cells were fixed and permeabilized using the BD Intrasure kit (Becton Dickinson, Franklin Lakes, NJ, USA) and intracellular staining of HIF-1α was performed using Alexa Fluor® 647 anti-human HIF1α antibody (BioLegend Inc., CA, USA) following the manufacturer’s instructions. All samples were re-suspended in phosphate-buffered saline, and analysed by the use of a FACS Calibur flow cytometer (Becton Dickinson, Franklin Lakes, NJ, USA) and the FCS3 software. Cells were acquired with a four-parameter flow cytometry method (CD34 FITC/CD133 PE/CD45 PerCP/ HIF-1α ACP staining, side and forward angle light scatter). The flow cytometer was calibrated every 24 h and quality controls were performed according to the UK National External Quality Assessment Service (NEQAS) protocol. The number of CD133/CD34 cells expressing HIF-1α in peripheral blood was calculated on the basis of absolute lymphocytes count x percentage (%) of gated CD133/CD34 positive, and expressed as absolute number of cells per 1.0 μl peripheral blood.
Enzyme-linked immunosorbent assay (ELISA)
Plasma concentration of SDF-1α was assessed by the enzyme-linked immunosorbent assay kit (SDF-1α Human ELISA kit, Abcam, It) according to the manufacturer’s instructions .
Power analysis suggested that a sample size of 30 patients/group was required to detect a higher percentage of EPCs (CD133+/CD34+ cells in the percentage of all myelomonocytic cells) in septic patients vs ICU controls (mean ± standard error of mean: 0.52% ± 0.4% vs 0.24% ± 0.11%, respectively), assuming α = .05 and power = .95 . This number was increased to 33 per group to allow for a 20% patients drop-out rate.
The normality of distribution was assessed by Shapiro-Wilkinson test. Data were expressed as mean ± SD, median [25–75] as appropriate. They were analyzed using repeated measurements analysis of variance. Differences between the groups at each time point were examined post hoc using independent sample t-test. A paired sample t-test was used to detect changes within the groups. Level of statistical significance was chosen at P < 0.05. Correlation analysis was performed by Spearman’s correlation analysis. Statistical analysis was performed by Statistical Package for the Social Sciences (SPSS Inc., Chicago, IL) version 15.0 for Windows.
The enrollment flow diagram is reported in Fig. 1. Seventy-one out of 82 candidates for enrollment were analyzed: 32 in S group and 39 in C group.
The demographic data were similar between the S and C groups. Clinical and laboratory data showed significant differences between S and C group at baseline (Table 1).
Ten patients out of 32 in S group died within 28-days of admission in ICU and all patients survived in C group.
Baseline CD133+/CD34+ cells count was 56 [0–150]/μl in C group and 131 [0–968]/μl in S group; P = 0.31. HIF-1α-expressing CD133+/CD34+ cells count was 43 [0–132]/μl in C group and 8 [0–742]/μl in S patients; P = 0.4 Baseline SDF-1α level was 30 [25–295]pg/ml in C group and 200 [78–246]pg/ml in S group; P = 0.03.
Intragroup analysis in C patients showed that CD133+/CD34+ cell count remained stable throughout the whole study period, increasing on day 7 (173 [0–421] /μl vs baseline: p = 0.04; vs day 1: P = 0.002). In S group we observed higher CD133+/CD34+ cell count levels on day 3 (vs day 1: P = 0.006 and day 7: P = 0.026) (Fig. 2a).
HIF-1α-expressing CD133+/CD34+ cell count decreased on day 1 as compared with the other days in C group (day 0 vs 1: P = 0.003, days 3 and 7 vs 1: P = 0.008). In S group CD133+/CD34+ cell count expressing HIF-1α was 321 [0–1418] /μl on day 3 (vs day 1; P = 0.004), and 400 [0–587] /μl on day 7 (Fig. 2b).
SDF-1α levels significantly increased in C group on days 1 (vs baseline: P = 0.036) and day 3 (35 [28–346]pg/ml vs baseline: p = 0.01). No differences in SDF1-α levels were observed in S group throughout the whole study period (P > 0.19) (Fig. 2c).
Intergroup analysis showed that S group had higher CD133+/CD34+ cell count on days 1 and 3, (S vs C group at day 1: 0 [0–393] /μl vs 0 [0–44] /μl; P = 0.03 and day 3: 784 [264–1818] /μl vs 0 [0–43] /μl,; P = 0.001). HIF-1α-expressing CD133+/CD34+ cells count was higher in S vs C group throughout the whole study period, especially on 1 and 3 postoperative days (day 1: 0 [0–175]/μl vs 0 [0–1]/μl, respectively; P = 0.018 and day 3: 321 [0–1418]/μl vs 0 [0–208]/μl; P = 0.042). SDF-1α levels were higher not only on baseline but also on postoperative day 1 in S vs C group (219 [124–337] pg/ml vs 35 [27–325] pg/ml, respectively; P = 0.01) (Figs. 2a-c).
Comparable results were attained when the total circulating CD133+/CD34+ EPC and HIF-1α-expressing CD133+/CD34+ EPC and the SDF-1α content were normalized to the baseline values of each subject (Figs. 3 a-c).
No correlation was observed between lactate levels and SDF-1α (R = 0.42; P = 0.56) or HIF-1α- expressing CD133+/CD34+ cell count (R = 0.01; P = 0.85). Alike no correlation was found between SDF-1α or CD133+/CD34+ cells expressing HIF-1α and APACHE II or SOFA score and 28-days mortality. Although not statistically significant, likely because of the limited number of cases, a trend was observed showing a higher maintenance of the circulating CD133+/CD34+ EPC at day 3 in surviving septic patients compared to non-surviving (data not shown).
The main result of the present study is that, as compared with surgical controls, septic patients exhibit: i) a higher number of circulating CD133+/CD34+ cells, encompassing those expressing HIF-1α (CD133+/CD34 + -HIF-1α cells); ii) a higher plasmatic level of SDF-1α that does not correlate with plasma lactate.
To the best of our knowledge, this is the first study simultaneously investigating the kinetics of the CD133+/CD34+ cells, with or without HIF-1α and the plasmatic SDF-1α in septic patients. Furthermore, a novelty of our study is the evaluation of the EPCs in postoperative septic patients compared with laparoscopic controls. Indeed, though it is well established that surgical injury elicits mobilization of EPC, all the available studies focused on laparotomic surgery and no data are available in laparoscopic surgery which has now become the gold standard in colectomy [12, 27, 28].
Data in literature showed that circulating progenitors are present at higher levels in septic patients when compared with healthy volunteers, especially at 72 h after the diagnosis of sepsis [27, 29]. Sepsis is associated with systemic microcirculation disruption, hemodynamic imbalance and poor peripheral oxygen uptake although oxygen delivery can be maintained pharmacologically . Hypoxic conditions is known to promote activation of the HIF-1 transcriptional system thus enabling cell adaptation to limited environmental oxygen availability. HIF-1α is the subunit of HIF-1 complex, is considered as a reliable biomarker of cellular hypoxia. During hypoxic conditions, the HIF-1α stabilization occurs inhibiting its degradation thereby resulting in the accumulation of the protein within the nucleus where upon forming a heterodimer with the HIF-1β subunit binds to hypoxia responsive elements located at the regulatory regions of a number of genes. Conversely, under normoxic conditions HIF-1α is continuously generated and degraded while HIF-1β is constitutively expressed in the cells regardless of oxygen tension [30, 31].
It has become increasingly evident that hypoxia, does not occur only under stressful conditions, but it is normally present in tissular microenvironments, such as the human BM endosteum, where the hematopoietic niches are located [18, 21, 31]. In this hypoxic environment the hematopoietic stem/progenitor cells largely rely on glycolysis to limit production of reactive oxygen species (ROS) thus preventing DNA oxidative damage [21, 31]. In the present study we succeeded in detecting HIF-1α in a subset of CD133+/CD34+ EPCs from freshly drawn blood and showed a higher number of them at days 1 and 3 of postoperative in septic patients vs controls.
Whereas it has been reported that HIF-1α expression was significantly suppressed in sepsis , several data convincingly showed that circulating EPCs levels in septic patients are elevated [32, 33]. An increased expression of stable HIF-1α in patients with shock, as compared with healthy volunteers during the 4 h of the study period from the diagnosis has been reported. However, the changes in HIF-1α expression over time were not correlated with the patient outcome . Importantly, the EPCs functional competence in terms of regenerative capacity (i.e. their quality instead of quantity) appears to represent the “crux of the problem” in sepsis .
Interestingly, we report no correlation between plasma lactate and CD133+/CD34+ cells levels expressing HIF-1α, or plasmatic SDF-1α. Plasma lactate which represents the end product of glycolysis, is used as a marker of tissue hypoxia in sepsis and septic shock . Therefore, the debate of considering the HIF-1a as a marker of the true level of tissue oxygenation is still open. However, lactate kinetics represents a balance between lactate production and clearance, which can hamper for the interpretation of cell hypoxia in septic shock at the bedside .
A possible explanation reconciling conflicting results is provided by Piccoli and al., whose results suggest that the chemokine-dependent mobilization from the BM is a trigger for the stabilization of HIF-1α under normoxic conditions in healthy donors. Therefore, the initial leading event could be linked to the chemoattractant SDF-1α, which promotes HIF-1α stabilization in mobilized endothelial/hematopoietic stem cells . This might constitute a pre-conditioning mechanism promoting EPC adaptation to hypoxic injured septic districts, thus preserving their regenerative capacity (Fig. 4).
In view of the above proposed mechanism we might explain the observed higher SDF-1α levels on baseline and 1 postoperative day followed by the chemotactic recruitment of CD133+/CD34+ cells expressing stable HIF-1α in the succeeding observational period in surgical septic patients. To note, the ratio of the HIF-1α-expressing CD133+/CD34+ EPC/total CD133+/CD34+ EPC does not change irrespective both of the sampling (i.e. control vs septic patients) and of the time points (data not shown). This would imply that the expression of HIF-1α, even under normoxia, is an intrinsic feature of EPCs not triggered per se by SDF-1α, resembling what previously reported for CD34+ hematopoietic stem/progenitor cells .
In the perspective of potential therapeutic strategies with EPCs in combination with SDF-1α analogue, which have been successfully administered in septic animal models, our findings represent a compelling reason to further study the kinetics of CD133+/CD34+ expressing stable HIF-1α and their linkage to SDF-1α in human sepsis .
A potential limitation of our study is that our EPC population counts likely includes small amounts of hematopoietic stem cells, since the classical definition of EPCs requires an endothelial marker protein like VEGF-R2 or CD31 . However, we counted CD31/CD45 cells (data not shown) by using the anti-CD31 in our flow cytometry analysis, and their number was repetitively equal to the CD133+/CD34+ cells count.
Although further studies are needed the data here presented show for the first time a larger mobilization of HIF-1α expressing CD133+/CD34+ cells preceded by plasmatic SDF-1α in septic surgical patients regardless of tissue oxygenation.
Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Intensive Care Unit
Endothelial progenitor cells
Stromal cell-derived factor-1a
Hypoxia inducible factor-1α
Blot S, Antonelli M, Arvaniti K, Blot K, Creagh-Brown B, de Lange D, et al. Epidemiology of intra-abdominal infection and sepsis in critically ill patients: “AbSeS”, a multinational observational cohort study and ESICM trials group project. Intensive Care Med. 2019;45(12):1703–17. https://doi.org/10.1007/s00134-019-05819-3.
De Waele J, Lipman J, Sakr Y, Marshall JC, Vanhems P, Barrera Groba C, et al. Abdominal infections in the intensive care unit: characteristics, treatment and determinants of outcome. BMC Infect Dis. 2014;14:420.
Vincent JL, Sakr Y, Singer M, et al. Prevalence and outcomes of infection among patients in intensive care units in 2017. JAMA. 2020;323(15):1478–87.
Fink MP, Cotoia A, Beer-Stolz D, Sappington PL, Delude RL. Chapter 12. Epithelial Barrier Dysfunction as a Mechanism in the Pathogenesis of Multiple Organ Dysfunction; 2009. https://doi.org/10.1002/9783527626151.ch12.
Lepore A, D'Antini D, Raimondo P, Mirabella L, Pennisi L, Carrillo G, et al. Acute abdomen as a consequence of an unusual suicide attempt: intra-abdominal injection of sulfuric acid. Int Med Case Rep J. 2016;9:353–6.
De Ruiter J, Weel J, Manusama E, Kingma WP, Van Der Voort PHJ. The epidemiology of intra-abdominal flora in critically ill patients with secondary and tertiary abdominal sepsis. Infection. 2009;37:522–7.
Hotchkiss R, Karl I. The pathophysiology and treatment of sepsis. N Engl J Med. 2003;348:138–50.
Sakr Y, Dubois MJ, De Backer D, Creteur J, Vincent JL. Persistent microcirculatory alterations are associated with organ failure and death in patients with septic shock. Crit Care Med. 2004;32:1825–31.
Goligorsky MS. Endothelial progenitors in sepsis: vox clamantis in deserto? Crit Care. 2011;15:142.
Sun R, Huang J, Sun B. Mobilization of endothelial progenitor cells in sepsis. Inflamm Res. 2020;69:1–9. https://doi.org/10.1007/s00011-019-01299-9.
Ritz U, Spies V, Mehling I, Gruszka D, Rommens PM, Hofmann A. Mobilization of CD34+-progenitor cells in patients with severe trauma. PLoS One. 2014;9(5):e97369. https://doi.org/10.1371/journal.pone.0097369.
Cotoia A, Cinnella G, Grasso S, Fede NR, Pugliese PL, Massenzio F, et al. Mobilization of haematopoietic stem cells cd34 in patients undergoing elective lung resection observational pilot study. Arch Med. 2015;8:1–7.
Mutunga M, Fulton B, Bullock R, Batchelor A, Gascoigne A, Gillespie JI, et al. Circulating endothelial cells in patients with septic shock. Am J RespirCrit Care Med. 2001;163:195–200.
Cribbs SK, Sutcliffe DJ, Taylor WR, Rojas M, Easley KA, Tang L, et al. Circulating endothelial progenitor cells inversely associate with organ dysfunction in sepsis. Intensive Care Med. 2012;38:429–36.
Reale A, Melaccio A, Lamanuzzi A, Saltarella I, Dammacco F, Vacca A, et al. Functional and biological role of endothelial precursor cells in tumour progression: a new potential therapeutic target in haematological malignancies. Stem Cells Int. 2016;2016:7954580. https://doi.org/10.1155/2016/7954580.
Ni G, Liu W, Huang X, Zhu S, Yue X, Chen Z, et al. Increased levels of circulating SDF-1α and CD34 + CXCR4 + cells in patients with moyamoya disease. Eur J Neurol. 2011;18:1304–9.
William GKJ. Nobel recognizes discovery of hypoxia response mechanism. American Association for Cancer Research. 2019. https://doi.org/10.1158/2159-8290.CD-NB2019-125.
Piccoli C, D’Aprile A, Ripoli M, Scrima R, Boffoli D, Tabilio A, et al. The hypoxia-inducible factor is stabilized in circulating hematopoietic stem cells under normoxic conditions. FEBS Lett. 2007;581:3111–9.
Li Z. CD133: a stem cell biomarker and beyond. Experimental Hematol Oncol. 2013;2(1):17. https://doi.org/10.1186/2162-3619-2-17. .
Luppi P, Powers RW, Verma V, Edmunds L, Plymire D, Hubel CA. Maternal circulating CD34+VEGFR-2+ and CD133 +VEGFR-2+ progenitor cells increase during normal pregnancy but are reduced in women with preeclampsia. Reprod Sci. 2010. https://doi.org/10.1177/1933719110366164.
Hawkins KE, Sharp TV, Mckay TR. The role of hypoxia in stem cell potency and differentiation. Regen Med. 2013. https://doi.org/10.2217/rme.13.71.
Cotoia A, Mirabella L, Beck R, Matrella P, Assenzo V, Hazot TC, et al. Effects of closed-loop intravenous anesthesia guided by Bispectral Index in adult patients on emergence delirium: A randomized controlled study. Minerva Anestesiol. 2018;84(4):437–446. doi: https://doi.org/10.23736/S0375-9393.17.11915-2.
D’Antini D, Rauseo M, Grasso S, Mirabella L, Camporota L, Cotoia A, et al. Physiological effects of the open lung approach during laparoscopic cholecystectomy: Focus on driving pressure. Minerva Anestesiol. 2018; 84(2):159–167. doi: https://doi.org/10.23736/S0375-9393.17.12042-0.
Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). Jama. 2016;315:801.
Cotoia A, Mirabella L, Altamura S, Villani R, Marchese F, Ferrara G, et al. Circulating stem cells, HIF-1, and SDF-1 in septic abdominal surgical patients: randomized controlled study protocol. Trials. 2018;19:1–5.
Rafat N, Hanusch C, Brinkkoetter PT, Schulte J, Brade J, Zijlstra JG, et al. Increased circulating endothelial progenitor cells in septic patients: correlation with survival. Crit Care Med. 2007;35:1677–84.
Becchi C, Pillozzi S, Fabbri LP, Al Malyan M, Caciapuoti C, Della Bella C, et al. The increase of endothelial progenitor cells in the peripheral blood: a new parameter for detecting onset and severity of sepsis. Int J Immunopathol Pharmacol. 2008;21(3):697–705. https://doi.org/10.1177/039463200802100324.
Condon ET, Wang JH, Redmond HP. Surgical injury induces the mobilization of endothelial progenitor cells. Surgery. 2004 Jun;135(6):657–61. https://doi.org/10.1016/j.surg.2003.10.012.
Tsaganos T, Giamarellos-Bourboulis EJ, Kollias S, Zervakis D, Karagianni V, Pelekanou A, et al. Kinetics of progenitor hemopoetic stem cells in sepsis: correlation with patients survival? BMC Infect Dis. 2006;6:142.
Csete M. Oxygen in the cultivation of stem cells. Ann N Y Acad Sci. 2005;1049:1–8. https://doi.org/10.1196/annals.1334.001.
Schäfer ST, Frede S, Winning S, Bick A, Roshangar P, Fandrey J, et al. Hypoxia-inducible factor and target gene expression are decreased in patients with sepsis: prospective observational clinical and cellular studies. Anesthesiology. 2013;118(6):1426–36. https://doi.org/10.1097/ALN.0b013e31828baa67.
Patschan SA, Patschan D, Temme J, Korsten P, Wessels JT, Koziolek M, et al. Endothelial progenitor cells (EPC) in sepsis with acute renal dysfunction (ARD). Crit Care. 2011;15:R94.
Textoris J, Beaufils N, Quintana G, Ben Lassoued A, Zieleskiewicz L, Wiramus S, et al. Hypoxia-inducible factor (HIF1α) gene expression in human shock states. Crit Care. 2012;16:R120.
Vincent JL. Serial Blood Lactate Levels Reflect Both Lactate Production and Clearance. Crit Care Med; 2015;43(6):e209. https://doi.org/10.1097/CCM.0000000000000906.
Fan H, Goodwin AJ, Chang E, Zingarelli B, Borg K, Guan S, et al. Endothelial Progenitor Cells and a Stromal Cell–derived Factor-1α Analogue Synergistically Improve Survival in Sepsis. Am J Respir Crit Care Med. 2014;189(12):1509–19. https://doi.org/10.1164/rccm.201312-2163OC.
Patry C, Stamm D, Betzen C, Tönshoff B, Yard BA, Beck GC, et al. CXCR-4 expression by circulating endothelial progenitor cells and SDF-1 serum levels are elevated in septic patients. J Inflamm (United Kingdom). 2018;15:1–8.
The Fondo di Sviluppo e Coesione 2007–2013 - APQ Ricerca Regione Puglia – FutureInResearch supported the grant funded researcher.
Ethics approval and consent to participate
All included patients gave their written informed consent. The study was approved by the Ethics Committee (Comitato Etico of Ospedali Riuniti, Foggia, Italy, 69/CE/2015).
Consent for publication
The authors declare that they have no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Cotoia, A., Cela, O., Palumbo, G. et al. High mobilization of CD133+/CD34+ cells expressing HIF-1α and SDF-1α in septic abdominal surgical patients. BMC Anesthesiol 20, 158 (2020). https://doi.org/10.1186/s12871-020-01068-w
- Endothelial progenitor cells
- Hypoxia inducible factor-1α
- Stromal cell-derived factor-1α
- Postoperative abdominal laparoscopic patients
- Hematopoietic stem cells

domain: biology


text:
Sun, surf and sumptuous produce – Portugal has always provided a bountiful experience on Europe’s Atlantic frontier. And this winter, foodies are invited to slow down and discover the ancient Alentejo farming region with São Lourenço do Barrocal’s new Land of Plenty experience. In the heart of the Alentejo region, the vintage estate – spanning 780 hectares – offers a refreshing alternative to the traditional winter break, designed to immerse guests in the rural culture of the region.
The new ‘Land of Plenty’ programme gives guests a taste of locally sourced cuisine on arrival, with a farm-to-table meal. Then, from immersive culinary workshops to uncovering local craftsmanship at the local pottery centre, participants can experience old world charms and forage for ingredients to cook alongside the hotel’s executive chef. On the final morning, guests will head out on a hike or horse-ride around the estate, followed by well-earned relaxation at the Susanne Kaufmann spa, with a new menu of winter spa treatments to rehydrate and renew the skin.
The Land of Plenty Package starts from $1,950 for 2 people, including three nights’ accommodation in one of the hotel’s guest rooms on a full board basis, a cooking class, winery tour, pottery class, private stargazing session and winter warming spa treatment.

domain: agronomy


text:
Center : Gastrointestinal and Liver Center
Choose to read by topic:
What is ERCP?
Endoscopic Retrograde Cholangiopancreatography (ERCP) is an endoscopic procedure to treat problems in the liver, gallbladder, bile ducts, and pancreas, this involves injecting a contrast medium to give a clearer visualization of the area, which helps in diagnosis and the treatment of unexplained abdominal pain and a condition known as "jaundice" (yellowing of the eyes and skin) caused by obstructed bile ducts abdominal pain, due to abnormalities of the biliary tract and pancreas.
- To treat diseases of the biliary tract, including
- to extract stones from the biliary tract
- To place bile drainage tubes into the small intestine (Endoprosthesis) or through external (Endoscopic Nasolbiliary drainage)
- To place the drain pipe above the bile leakage
- to cut/open or enlarged a sphincter in case of stenosis (Papillary Stenosis)
- For the treatment of pancreatic disease, including
- To extract gallstones from the pancreatic duct
- To place the drain tube above the leaky joint (Pancreatic Fistula)
- To place a Pancreatic Fistula drain tube in case of blockage
ERCP is useful in diagnosis and treatment of diseases related to the bile duct and pancreas, for example, if there is a blockage in the bile duct from stones, tumors, fibrosis or narrowing of the bile duct from other causes, or blockage of the pancreatic duct due to stones, especially in the case of pancreatitis due to blockage in the bile duct stones in the bile duct and pancreatic ducts.
ERCP Risks and Side Effects
- General risks
- A sore throat caused by camera friction
- Throat pain caused by local anesthesia
- Bloating is a common symptom because the doctor has to blow air into the stomach and intestines during endoscopy, but this is temporary and will improve when air is expelled
- Specific Risk
- Acute pancreatitis 24 hours after endoscopy, patients experience abdominal pain, nausea, vomiting, and high pancreatic enzymes. The chance of developing acute pancreatitis is approximately 3-5%. The major risk factor is on female patients and young patients
- The duodenum perforation 1% chance of occurrence of duodenal hemorrhage due to the incision on the bile duct
- Bleeding may occur immediately or after 24 hours post endoscopy. Patients taking blood-thinning drugs have an increased risk of duodenal hemorrhage. The chance of developing duodenal bleeding is about 2.5 -5%
- Infection after laparoscopy, patients may experience abdominal pain and fever, most often in patients with intestinal obstruction of the bile duct. And the drainage is as good as it should be and the risk of infection is 5 -10%, Antibiotics are usually prescribed to reduce the likelihood of infection before endoscopy, which can significantly reduce infection susceptibility
How to Prepare for ERCP
- Patients must consult with a physician about any underlying diseases. Such as high blood pressure, heart disease, diabetes, and asthma, etc. For the doctor to plan the treatment of the patient
- You must inform your doctor about your history of allergy to drugs, seafood, or radiation contrast agents. If patients are allergic to food or contrast agents, The patient will be required to use a special color opaque substance
- In the case of patients taking medications for specific diseases, thrombolytic group, the patient must consult the doctor who prescribed the medication to consider replacing or stopping the medication before treatment to prevent bleeding
- Abstain from water and food at least 6-8 hours before the examination (In case of having to do in the afternoon, eat liquid diet at 6:00 AM and then abstain from food and water)
- In case the patient wears a full or partial denture, it should be removed before the endoscopy, or if the patient has loose teeth, inform your doctor before the procedure to prevent accidents that may occur if the tooth falls off
- There should be direct relatives to accompany the patient. Since most patients cannot sign a consent form and can't get advice from a doctor or if the doctor wants to know about the patient's symptoms directly from the patient's relatives
ERCP is a combination of endoscopy and x-ray in one process. The procedures goes as follows:
- The doctor will insert the endoscope through your mouth, stomach to your bile duct in the small intestine.
- Contrast agent is injected into your bile duct, an x-ray is used to see abnormality in your bile duct and pancreatic duct.
- If the doctor found gallstones in your bile duct, He may possibly open your bile duct to extract the gallstones by electric cautery.
- Normally, the surgery is healed within 1 week. However, if there is a constriction, a tube will be inserted to drain the bile to your intestine.
What to Expect After ERCP
- All patients are required to stay in the hospital for at least 24 hours after the procedure or at the physicians’ discretion to observe any abnormal symptoms such as severe abdominal pain, nausea, vomiting, or a high fever after the procedure
- Make the patient rest in bed for about 60 minutes or until the patient wakes up and can go back to the room
- Generally, there will be no water and food intake for at least 6-8 hours after endoscopic examination of the bile duct and pancreatic ducts or until the doctor is certain that the patient has no complications from acute pancreatitis or infection in the bile ducts. Starting with a sip of water if there is no abdominal pain, the food will be continued in order
- Patients should come to see a doctor according to the scheduled appointment, especially in cases where the biopsy is performed
- You do not have to wait for your scheduled appointment, come to the hospital immediately if you have the following symptoms
- Fever or chills
- Redness, swelling, or bleeding
- Abdominal pain, nausea, and vomiting
- Dark, tarry, or bloody stools
- Difficulty swallowing
- Aggravated throat or chest pain
FAQ Related to ERCP
How long is ERCP procedure recovery time?
After ERCP you should lay down on the bed around 60 minutes or until you feel fully awake and moved to a normal room. After the treatment, patients are required to stay in the hospital at least 24 hrs or depending on the doctor’s opinion to observe any abnormalities such as: congestion, nausea, vomiting, high fever. You should avoid eating hot food, should have soft and mild taste food for around 2-3 days. After the treatment you can feel congestion but it will get better through time.
Biliary tract and pancreas diseases can be prevented by taking good care of your health. You should reduce fried and oiled food and increase vegetable and fish. ERCP should be provided by specialist and well experienced doctor in order to get an effective result. Moreover, getting annual health check-up is very important. If you have any abnormality, should come to the hospital immediately before the disease get worse or complication occurs.
Why choose Nakornthon Hospital?
Our Gastrointestinal and Liver Center at Nakornthon Hospital is a specialized medical center which delivers the best treatment for Intestinal and liver diseases and the best quality services to patients. With therapeutic technology and standardize equipment, our physician and well-trained expertise are here to provide personalized care at all time. Gastrointestinal and Liver Center, Nakornthon Hospital can provide one stop service aside with many facilities such as endoscope service, bowel preparation room, recovery room. With personalized care, we try our best effort to keep our patient safety as priority. The diagnosis and treatment have performed to minimize the risk factors for complication and reduce the length of hospital stays.
Pacakages and Promotions
Article of Gastrointestinal and Liver Center
Gallstone - Symptoms, Treatment
Liver RFA for Tumors
Transarterial Chemoembolization (TACE)
What Causes Liver Cancer
UGIB - Causes, Treatment
Cirrhosis - Symptoms, Treatment
Fatty Liver - Symptoms, Treatment
Colon Cancer, symptoms and risk
EGD - Upper GI Endoscopy
Why you shouldn’t ignore GERD
Fibro Scan, Painless Liver Test
2 Different common diseases with similar symptoms Gastritis vs GERD
Hepatitis B the threat of cirrhosis, liver cancer
H Pylori bacteria causing gastric ulcer disease
Check for symptoms ... warning signs of GERD.
Abdominal pain when hungry, a warning signal 'stomach disease'
Advice to patients about appendicitis
Check your bowel health at the age of 50+ with "colon cancer screening endoscopy"
Symptoms of irritable bowel movement

domain: medical


text:
- How do I get to Kaliningrad?
- How safe is Kaliningrad?
- Can I get a Russian visa online?
- How far is Kaliningrad from Russia?
- How do I get from Gdansk to Kaliningrad?
- Which countries can enter Russia without visa?
- Can US citizens go to Russia without a visa?
- Is Kaliningrad separating from Russia?
- Can you travel freely in Russia?
- Why is there a bit of Russia between Poland and Lithuania?
- How much does a Russian visa cost?
- Can someone from Russia visit the US?
- Does Germany want Kaliningrad back?
- What language do they speak in Kaliningrad?
- Can I go to Kaliningrad?
- How do I get to Kaliningrad from UK?
- Is Kaliningrad worth visiting?
- Why does Russia still own Kaliningrad?
- Is crime high in Russia?
- Is Russia part of Schengen?
- How far is Kaliningrad from Moscow?
How do I get to Kaliningrad?
Arriving in the city of Kaliningrad from abroad is going to involve either the Khrabrovo airport; the Southern Railway station or the road from the Polish border in the south or Lithuanian border in the east..
How safe is Kaliningrad?
Crime rates in Kaliningrad, RussiaLevel of crime31.58LowCrime increasing in the past 3 years47.37ModerateWorries home broken and things stolen25.00LowWorries being mugged or robbed26.97LowWorries car stolen26.97Low8 more rows
Can I get a Russian visa online?
A VISA HAS TO BE STAMPED INTO YOUR PASSPORT BY THE RUSSIAN CONSULATE! If you would like to apply for a Business Invitation (telex) you can do so online now.
How far is Kaliningrad from Russia?
300 milesA little parcel of land smaller than Wales wedged up against the Baltic Sea, Kaliningrad has no common border with Russia, which is almost 300 miles to the east – and unlike most Russians its residents travel frequently to the EU.
How do I get from Gdansk to Kaliningrad?
The best way to get from Gdańsk to Kaliningrad without a car is to bus which takes 3h 45m and costs 30 zł – 45 zł. How long does it take to get from Gdańsk to Kaliningrad? The bus from Gdańsk Główny to Kaliningrad Bus station takes 3h 45m including transfers and departs every four hours.
Which countries can enter Russia without visa?
Citizens of visa-free countries do not require visa to enter the Russian Federation, but in most cases duration of their stay in Russia is limited….Visa-free countries.CountryNotesArmeniaPeriod of stay not more than 90 days.AzerbaijanPeriod of stay not more than 90 days.BelarusUnlimited stay.32 more rows
Can US citizens go to Russia without a visa?
To enter Russia for any purpose, a U.S. citizen must possess a valid U.S. passport and a bona fide visa issued by a Russian Embassy or Consulate. … Travelers who arrive in Russia without an entry visa will not be permitted to enter the country, and face immediate return to the point of embarkation at their own expense.
Is Kaliningrad separating from Russia?
The city was renamed to Kaliningrad in 1946 in honor of Soviet leader Mikhail Kalinin. Since the dissolution of the Soviet Union, it is governed as the administrative centre of Russia’s Kaliningrad Oblast, an exclave sandwiched between Lithuania and Poland….Kaliningrad.Kaliningrad КалининградWebsitewww.klgd.ru32 more rows
Can you travel freely in Russia?
Traveling independently offers the flexibility to experience these wonders far from the madding crowd. But Russian rules can become Kafkaesque nightmares for unwary travelers. Arriving in Russia without a visa is grounds for denial of entry and return home at your own expense.
Why is there a bit of Russia between Poland and Lithuania?
The Russian exclave of Kaliningrad on the Baltic Sea is sandwiched between Poland to the south and Lithuania to the north and east. Annexed from Germany in 1945, the territory was a closed military zone throughout the Soviet period. … There has been friction, particularly with Lithuania, over transit regulations.
How much does a Russian visa cost?
The Russia tourist visa costs $160.00 which does not include the administrative fees or letter of invitation letter fee. Please Note: there may be cheaper Russia Tourist visas available depending on your nationality. Enter your nationality into the visa checker to see all available visa types.
Can someone from Russia visit the US?
Russian citizens who wish to travel to the US for business or tourism purposes must apply for a US B1/B2 Visa. While the application process cannot be 100% online, our team of experts will help you obtain the confirmation page you are required to have for your interview at the embassy.
Does Germany want Kaliningrad back?
Official positions. The German government has indicated no interest in recovering Kaliningrad Oblast. The governments of Poland and Lithuania similarly recognize Kaliningrad as part of Russia, as does the European Union.
What language do they speak in Kaliningrad?
Russian languageTalk. The Russian language is spoken by more than 95% of Kaliningrad Oblast’s population. English is understood by many people. While German culture plays a long historical role in the region the language is spoken by few.
Can I go to Kaliningrad?
Kaliningrad is located in between Poland and Lithuania and people will need a special visa to enter.
How do I get to Kaliningrad from UK?
Fly London Heathrow to Gdansk, bus, train • 16h 15mFly from London Heathrow (LHR) to Gdansk (GDN) LHR – GDN.Take the bus from Gdańsk Airport to Olsztyn Statoil.Take the train from Olsztyn Glowny to Elblag.Take the bus from Elbląg to Kaliningrad Bus station.
Is Kaliningrad worth visiting?
Squeezed in between Poland and Lithuania on the Baltic Sea, Kaliningrad is a small Russian province totally detached from the Motherland. … But despite its size, Kaliningrad is an area of Eastern Europe that is well worth visiting, if only for its intriguing history and location.
Why does Russia still own Kaliningrad?
The short answer is: Germany was forced to give up huge patches of its conquered land at the end of WWII. In 1945 the Potsdam Agreement was signed by the USSR (now Russia), Britain and the USA. It specifically gave Kaliningrad (known as the German Königsberg at the time) to Russia, without opposition.
Is crime high in Russia?
Crime rate in Russia 1995-2020. In 2020, the crime rate in Russia reached approximately 1.39 thousand offenses per 100 thousand population, marking a slight increase compared to the previous year. Over the period from 2015 to 2020, the rate saw a decline by 240 registered crimes per 100 thousand people.
Is Russia part of Schengen?
The European countries that are not part of the Schengen zone are Albania, Andora, Armenia, Azerbaijan, Belarus, Bosnia & Herzegovina, Croatia, Cyprus, Georgia, Ireland, Kosovo, North Macedonia, Moldova, Monaco, Montenegro, Romania, Russia, San Marino, Serbia, Turkey, Ukraine, The United Kingdom and Vatican City.
How far is Kaliningrad from Moscow?
1088 kmThe distance between Moscow and Kaliningrad is 1088 km.

domain: geography


text:
NO. 4-06-0694 Filed 9/24/07
IN THE APPELLATE COURT
THE PEOPLE OF THE STATE OF ILLINOIS,
CLETUS CRAIG BROWN,
Circuit Court of
PRESIDING JUSTICE STEIGMANN delivered the opinion of
Following a June 2006 bench trial, the trial court
convicted defendant, Cletus Craig Brown, of unlawful possession
of a methamphetamine precursor (pseudoephedrine) with the intent
to manufacture methamphetamine (720 ILCS 646/20(a)(1) (West Supp.
2005)). The court later sentenced him to an extended term of
eight years in prison.
Defendant appeals, arguing only that the statute under
which he was sentenced violates the proportionate-penalties
clause of the Illinois Constitution (Ill. Const. 1970, art. I,
§11). We disagree and affirm.
In January 2006, the State charged defendant with
unlawful possession of methamphetamine manufacturing chemicals
under section 401(d-5) of the Illinois Controlled Substances Act
(720 ILCS 570/401(d-5) (West 2004)). In March 2006, the State
moved to amend the indictment to charge defendant instead with

domain: law


text:
Revitol ™ Skin Brightener Cream is your safe, herbal-based solution for a beautiful, glowing complexion
Bloom skin tonic - For Order Revitol Skin Brightner
Buy Revitol Skin Brightner Bloom skin tonic -
Your skin is your largest organ responsible for protecting your body from a variety of outside forces, but it is also the most visible part of you, and is susceptible to environmental, physical and hormonal conditions which can make your skin tone appear blotchy and uneven.
You may want to use non-toxic, natural products on your skin to keep it healthy and vibrant, but there are lots of choices out there how can you be sure which one is best for your skin?
Revitol Skin Brightener Cream uses safe, plant-based ingredients to help reduce the appearance of freckles, liver-spots, and uneven pigmentation areas while keeping your skin soft and supple with natural emollients, moisturizers and skin-nourishing vitamins. It's a great way to lighten and brighten the appearance of those trouble spots safely with nature's finest ingredients.
Contains no mercury or other harmful ingrdedients
The active ingredients in Revitol Skin Brightener Cream lighten the appearance of skin and promote a healthy, balanced-looking complexion. We use natural ingredients such as:
Extracted from the bearberry plant, and also found in wheat and pear skins,
Arbutin helps reduce the appearance of dark areas.
Lumiskin: Also known as Diacetyl Boldine, inhibits Tryosinase to help lighten the appearance of the skin and promote more evenlooking skin tone.
Shea Butter: Derived from the nut of the Karite Nut tree (mangifolia), Shea butter has been used by African women for centuries for both cooking and for its healing properties in skin care. It contains natural sun protectants and emollients, and is used in many moisturizers, soaps and skin creams to firm and tighten skin.
Evening Primrose Oil: Used as a food and natural medicine throughout history, Primrose is effective in skin care to help alleviate dry skin.
Allantoin: A botanical extract of the comfrey plant, Allantoin is a natural-identical, non-toxic moisturizer that promotes the health of the outer dermal layer.
Grapefruit Seed Extract: Used as a preservative, this extract isa natural antioxidant.
Vitamins A, C and E: Because it has a fundamental role in the control of normal skin cell activity, Vitamin A is very important to healthy skin, and adding the antioxidant vitamins C and E gives this important skin nutrient extra support (for a complete list of ingredients, view our ingredients page).
Read what these health-conscious customers are saying about Revitol Skin Brightener Cream:
"I tried to
brighten the appearance of my skin before, but the product I used gave me a horrible rash. I didn't think I'd ever try again. I found out that Revitol Skin Brightener has Arbutin
and lots of other great ingredients, so I figured this time I'd be safe, and I
was. Plus my skin is lighter and so pretty and healthy-looking! I never looked
this good before! H.M., New York, NY
"I wanted a fairer looking complexion, but I try to take good care of myself and just use what's natural. When I saw that Revitol Skin Brightener has Arbutin,
which is a natural ingredient, I figured it was time to go for it. I'm so glad I
did! I got just what I wanted, with absolutely beautiful skin!" B.V., Little Rock, AR
"I always wanted lighter, healthier-looking skin, but I was afraid to do
anything about it because I heard that a lot of products have ingredients that
can make your skin worse than before. When I saw that Revitol Skin Brightener
uses natural ingredients, I decided to take a chance. Now, after just a few
weeks, my skin appears lighter, and it looks wonderful!" T.J., Los Angeles, CA
*Results will vary
90 Day Money Back Guarantee.
We take great pride in the superior quality of our products and want you to be pleased with your purchase. We believe in offering the very best value, quality
and selection to our customers. You may return any unused and unopened item purchased from us for any reason within Ninety (90) days of your purchase.
All the links and descriptions on this page are taken from public sources such as search engines (google.com, yahoo.com, bing.com). However, if you think any data on this page violates your copyright, please send an message from "Contact Us" page and the links and descriptions of full page will be removed.
June 8, 2017. BioBloom - Natural Skin and Hair Care Tips & Remedies (http://www.biobloomonline.com/) Bloom: Skin & Tonic Face Mask provides "pick-me-up to soothe and nourish lack-luster skin," Australian company says at Extracts trade show in New York City Oct. 11-14.
June 1, 2017. Bloom Facial Tonic 125ml - allfromjordan.com (http://allfromjordan.com/en/brands/bloom/bloom-faci al-tonic-125ml.html) EBSCOhost serves thousands of libraries with premium essays, articles and other content including Healthy skin takes center stage. Get access to over 12 million other...
June 12, 2017. Bloom Cosmetics Skin & Tonic - Read expert reviews, view... (http://www.epinions.com/product/Bloom_Skin_Tonic/24 470217) Face toner works to balance & prep your skin before you apply organic face cream. The natural skin care line from WildBloom Skincare is chemical free.
June 11, 2017. Face Toner - Best Skin Toner | WildBloom Skincare (https://wildbloomskincare.com/shop/face-tonics/) Bloom Cosmetics Skin & Tonic. This unique, alcohol-free tonic contains a blend of botanical ingredients and essential oils to provide the perfect facial pick-me-up.
June 2, 2017. Hibiscus - Natural Hair Tonic | Biobloom (http://www.biobloomonline.com/2015/04/14/hibiscus-n atural-hair-tonic/) A lemon scented vibrant splash of essential minerals, our toning water revitalizes your skin with delicate refreshment, improving its texture and pH balance for a...
May 31, 2017. Healthy skin takes center stage - pdc-connection.ebscohost.com (http://pdc-connection.ebscohost.com/c/product-revie ws/31588387/healthy-skin-takes-center-stage) Pixi Beauty Offers the Best Makeup Primer, Foundation & Concealers. Selling Makeup Kits & Brush Sets. Buy online
June 3, 2017. Rosacea Care Products - Anti-Inflam Calendula Skin Tonic... (http://www.holisticvanity.ca/products/rosacea-care- line/anti-inflam-calendula/) This beautiful blend of organic hydrosols, toning witch hazel, and soothing aloe is perfectly balanced to tone and tighten any skin type. Formulated for everyday use...
June 7, 2017. Extracts In Brief :: Rose Sheet (https://rose.pharmamedtechbi.com/RS010687/Extracts- In-Brief) Shop Skin & Tonic instore or online with FREE worldwide delivery. London based natural and organic handmade skincare dedicated to simplicity, honesty and ethics
June 4, 2017. Ole Henriksen Grease Relief Face Tonic - Bloom.com (http://www.bloom.com/ole-henriksen-grease-relief-fa ce-tonic.html) Jade Bloom Essential Oils, Draper... and broken capillaries. It is also a wonderful skin tonic as it stimulates the production of new skin cells...
June 9, 2017. Soothing Tea Leaf Face Tonic - WildBloom Pure Skincare (https://wildbloomskincare.com/product/soothing-tea- leaf-face-tonic/) Biobloom brings to you Natural/ Organic Skin & Hair Care tips for enhancing the Beauty & health of your skin & hair including home tips &
June 13, 2017. Bloom skin + tonic reviews, photo Sorted by Rating Highest... (https://www.makeupalley.com/product/showreview.asp/ ItemId=17956/SortBy=rating-desc/AgeRange=/SkinToneT ype=/skin-+-tonic/Bloom/Masks) Bloom Cosmetics Skin & Tonic. This unique, alcohol-free tonic contains a blend of botanical ingredients and essential oils to provide the perfect facial pick-me-up.
May 29, 2017. MPP - Franchise - solstice bloom | Aveda (http://www.aveda.ca/solstice-bloom-spring-summer-ma keup) Elemental Herbology Flower Harmonizing Mist Facial Tonic is the perfect, soothing spray for dry, overexposed, and sensitive skin. Made from the oils in rose petals...
June 10, 2017. Wonderful! - Read expert review at epinions.com (http://www.epinions.com/review/Bloom_Skin_Tonic/244 70217/163994308228) Our Soothing Tea Leaf Face Tonic is perfect for all skin types, especially sensitive or dry skin. Revitalizing tea extracts along with DMAE, MSM, and Hyaluronic Acid...
June 6, 2017. Hair, Skin & Nails - Blooms Health Products (http://www.bloomshealth.com.au/products/hair-skin-n ails/) Minimizes the appearance of pores. Helps eliminate breakouts. Balances and renews skin. Calms skin with aloe vera.
May 30, 2017. Pixi Beauty | Cosmetics, Makeup and Beauty Products Online (https://www.pixibeauty.com/) Bloom Shot Bar. BLOOM SHOT BAR MENU... Lift the fog with the brain tonic vitamin that is often depleted with... Special Skin-loving ingredients are added to give...
June 5, 2017. Lavender Bloom - Natural Skin Care | Handcrafted Soap... (http://www.wildprairiesoap.ca/lavender-bloom-100-na tural-solid-soap.html) Anti-inflam Calendula Skin Tonic. This skin tonic is made up of the water extracted from organic calendula flower petals. Calendula has been used traditionally in...
June 14, 2017. Bloom skin + tonic reviews, photo - Makeupalley (https://www.makeupalley.com/product/showreview.asp/ ItemId=17956/skin-+-tonic/Bloom/Masks) Bloom skin + tonic: rated 2.2 out of 5 on MakeupAlley. See 5 member reviews and photo. Sorted by Rating Highest first
July 30, 2017. Sanguinaria - Wikipedia (https://en.wikipedia.org/wiki/Bloodroot) Wasted money on unreliable and slow multihosters? LinkSnappy is the only multihost that works. Download from ALL Filehosts as a premium user at incredibly fast speeds!
July 31, 2017. 7 Awesome Ways to Get Glowing Skin Overnight... (https://makeupandbeauty.com/get-glowing-skin-overni ght/) Sanguinaria canadensis (bloodroot) is a perennial, herbaceous flowering plant native to eastern North America. It is the only species in the genus Sanguinaria...
August 1, 2017. Dr Organic Skin Clear Organic Tea Tree Oil Control... (https://makeupandbeauty.com/dr-organic-skin-clear-o rganic-tea-tree-oil-control-moisturizer-review/) Thayers Rose Petal Alcohol-Free Witch Hazel with Aloe Vera Formula Toner will make your skin bloom. Rose Thayer's remarkably soothing Toner is made with rose-petal...
August 2, 2017. Beauty Professor: Kevyn Aucoin Sensual Skin Tinted Balm... (http://www.beautyprofessor.net/2012/11/kevyn-aucoin -sensual-skin-tinted-balmmy.html) Ingredients: My Experience with Dr Organic Skin Clear Organic Tea Tree Oil Control Moisturizer: The moisturizer comes in a cardboard package and the moisturizer tube...
August 3, 2017. Tea, a tonic for high blood pressure: Three cups a day to... (http://www.dailymail.co.uk/health/article-2315551/T ea-tonic-high-blood-pressure-Three-cups-day-help-co unteract-cardiovascular-disease.html) A couple of days ago, I posted a sneak peek of my latest foundation acquisition from Kevyn Aucoin...has far as I can tell, the Sensual Skin Tinted Balm is still not...
August 4, 2017. shopLondons.com - Penhaligon's, FLORIS, Bronnley, Geo F... (http://www.shoplondons.com/) Common dandelion, Taraxacum officinale - range and identification, food for humans and wildlife, medicinal uses of dandelion.
August 5, 2017. Skincare For Men | Clinique (http://www.clinique.ca/mens) Tea, a tonic for high blood pressure: Three cups a day to help counteract cardiovascular disease. By Jenny Hope for the Daily Mail. Published: 19:01 EDT, 26 April...
August 6, 2017. Exhibitor List - Bloom 2017 (http://bloominthepark.com/visit/exhibitor-list/) Brahmi is a flowering plant that is native in India. It is used in Ayurvedic medicine for its brain tonic benefits. Used to treat skin diseases, alzheimer's disease...
August 7, 2017. Clinique | Official Site | Custom-fit Skin Care, Makeup... (http://www.clinique.com/) To stay up to date with the latest Bloom news and to receive exclusive offers sign up to our Club Bloom mailing list now.
August 8, 2017. Minor characters in Bloom County - Wikipedia (https://en.wikipedia.org/wiki/Minor_characters_in_B loom_County) Shop the official Clinique website for skin care, makeup, fragrances and gifts. Read reviews & get Free Shipping today. Allergy Tested. 100% Fragrance Free.
August 9, 2017. Burt's Bees | Brightening Refining Tonic (http://www.burtsbees.com/product/brightening-refini ng-tonic/02286-00.html) Biobloom brings to you Natural/ Organic Skin & Hair Care tips for enhancing the Beauty & health of your skin & hair including home tips &
August 10, 2017. Home | Natural Health & Beauty | Tonic Room (http://www.tonicroom.co.nz/) Clinically proven to help improve the appearance of surface dullness, revealing a more even skin tone in as few as 4 weeks,* our tonic is infused with Daisy Extract...
August 11, 2017. MPP - Franchise - solstice bloom | Aveda (http://www.aveda.com/solstice-bloom-spring-summer-m akeup) Natural health and beauty boutique. Book a consultation, a luxury bespoke facial and shop our extensive range of cult organic beauty brands.
August 31, 2017. Liz Earle Instant Boost Skin Tonic 200ml - Boots (http://www.boots.com/liz-earle-instant-boost-skin-t onic-200ml-10189833) Yes, email me special offers, exclusive product previews and the latest news from Aveda.
September 1, 2017. 8 Best Home Remedies for Dry and Sensitive Skin (https://makeupandbeauty.com/8-home-remedies-dry-sen sitive-skin/) Explore Liz Earle Instant Boost Skin Tonic 200ml. Shop online today.
September 2, 2017. 5 Homemade Skin Lightening Face Masks - Makeupandbeauty.com (https://makeupandbeauty.com/5-homemade-skin-lighten ing-face-masks/) Severe dry skin needs dermatological attention, but for others here are 8 Best Home Remedies for Dry and Sensitive Skin that they can try for themselves.
September 3, 2017. Skincare - Skin, Hair & Body Care (http://www.escentual.com/skincare/) Shop makeup, haircare, skincare and fragrance from 500 brands, plus catch up on the latest beauty trends here at Feelunique.
September 4, 2017. Naturisimo - Organic Cosmetics | Organic Skin Care (https://www.naturisimo.com/) 5 Homemade Skin Lightening Face Masks. let us look at some homemade face masks which will lighten and brighten your skin.
September 5, 2017. Red Clover: Fertility Herb and Tonic - Natural Fertility Info (http://natural-fertility-info.com/red-clover-fertil ity-herb.html) Here at Escentual we know that the wellbeing of your skin is important. We also know that skin comes in all textures, all ages and all levels of sensitivity. This is...
September 6, 2017. Royal Jelly for Skin Health - Bee Pollen Buzz.com (http://www.bee-pollen-buzz.com/royal-jelly-for-skin.html) Naturisimo is the leading organic beauty store offering the best in organic skincare, cosmetics and makeup with FREE UK Delivery.
September 7, 2017. Blossom - Wikipedia (https://en.wikipedia.org/wiki/Blossom) Red Clover (Trifolium pratense) is spreading like wild fire through fertility communities everywhere! So what has given this plant such popularity recently? Red
September 8, 2017. Sibberi - Tree Water (http://sibberi.com/) Shop the official Clinique website for skin care, makeup, fragrances and gifts. Read reviews & get Free Shipping today. Allergy Tested. 100% Fragrance Free.
September 9, 2017. Naturopathic Clinic Auckland - Tonic Room (http://www.tonicroom.co.nz/meet-our-practitioners) We do Tree Water, the most delicious birch water, maple water and bamboo water. Directly tapped from the trees. Screw mountains and coconuts, drink water from trees.
September 10, 2017. Clinique Skin Supplies For Men Oil Control Exfoliating... (http://www.boots.com/clinique-skin-supplies-for-men -oil-control-exfoliating-tonic-3-5-oily-skin-200ml- 10015447) Yes, email me special offers, exclusive product previews and the latest news from Aveda.
September 11, 2017. Liz Earle Instant Boost Skin Tonic 200ml - Boots (http://www.boots.com/liz-earle-instant-boost-skin-t onic-200ml-10189833) View Clinique Skin Supplies For Men Oil Control Exfoliating Tonic 3.5 Oily Skin 200ml and earn Advantage Card points on purchases.
September 28, 2017. Japanese women swear by tonic that cleanses blood and... (http://www.dailymail.co.uk/femail/article-3053938/S hould-cleansing-skin-INSIDE-beat-spots-Japanese-wom en-swear-tincture-tonic-drink-cleanses-blood-remove s-blemishes.html) Bloom Boosters. Bloom boosters and flower fertilizers give your plants just what they need when they need it to produce abundant, vigorous blossoms and better harvests.
September 29, 2017. MPP - Franchise - solstice bloom | Aveda (https://m.aveda.ca/solstice-bloom-spring-summer-mak eup) Pixi Beauty Offers the Best... The Pixi glow tonic is highly... Bring a soft natural glow and sheer sunkissed warmth to the skin with this palette that...
September 30, 2017. Bloom skin tonic - Breastactives - Aug 18, 2017 (http://breastactives.drug-purchase.info/bloom-skin- tonic.html) We host unique selection of well-acknowledged organic and natural beauty brands and help everyone to find the best match for their beauty routine
October 1, 2017. Purifying Sea Salt Face Tonic - WildBloom Pure Skincare (https://wildbloomskincare.com/product/purifying-sea -salt-face-tonic/) Biobloom brings to you Natural/ Organic Skin & Hair Care tips for enhancing the Beauty & health of your skin & hair including home tips &
October 2, 2017. Skin & Tonic | Dr. Koala (https://drkoalahk.com/collections/skin-tonic) This set of six masks is ideal for travel. Your pour the liquid sachet (an alcohol-free blend of botanicals) over the "tablet" and it transforms into
October 3, 2017. Bloom and Blossom | Dr. Koala (https://drkoalahk.com/collections/bloom-and-blossom) Skin & Tonics : A Skincare Blog... It promises to hydrate and improve skin texture... A Review of Whamisa Organic Flowers Deep Rich Essence Toner.
October 4, 2017. Bloom skin tonic - Herpeset - Natural Herpes Relief - Sep... (http://herpeset.herbalous.com/bloom-skin-tonic.html) A purifying face tonic to tone, refine and refresh. Key Elements: - Sea Salt for skin tightening + purifying - Organic Fruit Acids for pore-refining - Bergamot for...
October 7, 2017. Bloom skin + tonic reviews, photo filter: reviewer skin... (https://www.makeupalley.com/product/showreview.asp/ ItemId=17956/skintonetype=104/AgeRange=/skin-+-toni c/Bloom/Masks) Bloom skin + tonic: rated 2.2 out of 5 on MakeupAlley. See 5 member reviews and photo.
November 7, 2017. Skin & Tonic - Rose Mist - Polyvore (https://www.polyvore.com/skin_tonic_rose_mist/thing ?id=173225374) The ultimate destination for beauty discovery and home to an edited selection of innovative products.
November 8, 2017. texture tonic | Aveda (https://www.aveda.ca/product/17769/51018/styling/to nic/texture-tonic) Biobloom brings to you Natural/ Organic Skin & Hair Care tips for enhancing the Beauty & health of your skin & hair including home tips &
November 9, 2017. MPP - Franchise - solstice bloom | Aveda (https://www.aveda.ca/solstice-bloom-spring-summer-m akeup) Japanese women swear by tincture tonic they drink that cleanses... which benefits skin... Orlando Bloom cosies up to old school pal Maya Sansa and brings...
November 10, 2017. MPP - Franchise - solstice bloom | Aveda (https://www.aveda.ca/solstice-bloom-spring-summer-m akeup) If there was ever an iconic soap scent it would surely have to be lavender. Oozing fresh, herbaceous goodness, our Lavender Bloom natural bar soap is made with pure...
November 11, 2017. Skin & Tonic Coco mask - 50 g | Bloom-Avenue.com (https://www.bloom-avenue.com/shop/skin-tonic-coco-m ask-50-g/) A purifying face tonic to tone, refine and refresh. Key Elements: - Sea Salt for skin tightening + purifying - Organic Fruit Acids for pore-refining - Bergamot for...
November 12, 2017. Bloom Cosmetics Skin & Tonic Mask, $10 - popsugar.com.au (https://www.popsugar.com.au/beauty/photo-gallery/31 162579/image/31162651/Bloom-Cosmetics-Skin-Tonic-Ma sk-10) This soothing face mask gently detoxifies and moisturises dry and dehydrated skin. Made with creamy Coconut Milk Powder (rich in lauric acid and vitamins B, C & E...
November 13, 2017. Bloom Avenue - Home | Facebook (https://www.facebook.com/bloomavenueorganic/posts_t o_page) Fresh apples, carrots, and ginger have been blended together beautifully to become this tasty beverage fit for anyone looking to improve their complexion or jus
November 14, 2017. Bloom skin + tonic reviews, photo filter: reviewer age 25... (https://www.makeupalley.com/product/showreview.asp/ ItemId=17956/AgeRange=3/SkinToneType=/skin-+-tonic/ Bloom/Masks) Bloom Cosmetics Skin and Tonic Mask: contains a blend of high-quality botanical ingredients including: Witch hazel, Aloe Vera, Chamomile
December 8, 2017. MPP - Franchise - solstice bloom | Aveda (https://www.aveda.com/solstice-bloom-spring-summer- makeup) Natural Skin Toner - Buy Skin Tonic at best price of Rs 399 /piece(s) from Bio Bloom Organic Products. Also find here related product comparison.
December 9, 2017. SKIN IN BLOOM - Wall coverings / wallpapers from Inkiostro... (https://www.architonic.com/en/product/inkiostro-bia nco-skin-in-bloom/1296478) SKIN CARE. CATEGORY. dry brush & oleation oil ;... email me special offers, exclusive product previews and the latest news from Aveda. Yes!... solstice bloom.
December 10, 2017. MPP - Franchise - solstice bloom | Aveda (https://www.aveda.com/solstice-bloom-spring-summer- makeup) SKIN IN BLOOM - Designer Wall coverings / wallpapers from Inkiostro Bianco all information high-resolution images CADs catalogues..
December 11, 2017. Bloom Cosmetics Skin & Tonic Face Mask - viecouture.com (http://www.viecouture.com/bloom-cosmetics-skin-toni c-face-mask/) SKIN CARE. CATEGORY. dry brush & oleation oil ;... email me special offers, exclusive product previews and the latest news from Aveda. Yes!... solstice bloom.
December 12, 2017. Facial Tonic 125ml - Bloom (https://bloom.com.jo/shop/bloom-dead-sea-prroducts/ facial-tonic/) If there was ever an iconic soap scent it would surely have to be lavender. Oozing fresh, herbaceous goodness, our Lavender Bloom natural bar soap is made with pure...
December 14, 2017. Skin & Tonic Detox Beauty oil - 30 ml | Bloom-Avenue.com (https://bloom-avenue.com/shop/skin-tonic-detox-oil- 30-ml/) This soothing cleansing balm is made from Grapeseed, Carrot Root, Blue Chamomile and Jasmine Sambac oils to nourish your skin, remove dirt and impurities and calm...

domain: health


Victoria Kimani – Who You Know ft. Bella Alubo Mp3 Download.
Talented Kenyan singer and songwriter, Victoria Kimani has dropped a brand new impressive song titled “Who You Know”.
Victoria Kimani links up with Nigerian talented artiste, Bella Alubo who made the record more interesting for the summer.
Finally, “Who You Know” was Pulled from the ‘Spirit Animal’ album compiled with 16 tracks and features from Bella Shmurda, Peruzzi, Yemi Alade and others.
Listen and Download Victoria Kimani ft. Bella Alubo – Who You Know below:-
Leave a Comment


text:
This style is so cute, it just might make your head spin! The 2 Lips Too Dizzy delivers a straw woven upper and thick red piping. A colorful zig zag pattern is printed on the canvas fabric draping over the 5 inch wedge and 1 1/2 inch platform.
Bergen - Red Report Signature
Beat the heat and still look fabulous in this bright platform from Report Signature. Bergen has a red suede upper with patent trim. A 2 inch woven purple platform and 5 inch block heel finish off this modern style.
Add summer spice to your closet with this woven beauty by Paris Hilton. Beth features a red and cream textile upper accented by a sleek patent bow at the vamp. Perfecting this breezy look is a patent 5 inch heel and 1 inch platform.
The perfect spring style is here from Irregular Choice! The Cupids Sun Hat showcases a red canvas upper created into a lattice look. A 6 inch block heel and a woven 2 inch platform delivers the perfect transitional piece.
Lotus - Red Dble Fce Fergie
You wont stop loving on the Lotus ankle bootie by Fergie! This bright and bold style features a soft red fabric upper and 5 inch shaft height. Woven laces trim the side while a rounded toe and 3 inch block heel create a flawless finish.
Too Dynamo - Red 2 Lips Too
This 2 Lips style is as explosive as dynamite in the fashion scene! Dynamo has a deep red leather upper with contrasting white stitching and an adjustable strap. A woven 5 inch wedge and 1 1/2 inch platform accents this cute sandal.
Fairfax - Red JustFab
Too Dishy - Red 2 Lips Too
You'll want to dish out all the great details about this fabulous 2 Lips Too sandal. Too Dishy combines a bright red fabric upper with a woven 5 in wedge and 1 3/4 inch platform. The contrasting stitching and adjustable ankle strap create a perfect accent to this vibrant style.
Too Dash - Red 2 Lips Too
Throw out the fashion anchor and show off your stylish self. 2 Lips features Too Dash, A red and white striped fabric upper with a thick adjustable ankle strap. A casual woven material covers the 5 1/4 inch wedge and 1 3/4 inch platform.
Too Raft - Red 2 Lips Too
Float towards fashion in the Too Raft by 2 Lips Too. This casual sandal features a red patent upper with beige accents on the straps. A 5 inch wedge and 1 1/2 inch platform is covered in a woven raffia for the ultimate summer look.
You'll love the casual look to this adorable style by Lovely People. Iman features a southwestern striped upper on the vamp and adjustable ankle strap. Woven raffia blankets the 5 3/4 inch heel and 2 inch platform for a lazy summer feel.
Time is ticking! Grab the Naughty Monkey Time Bomb before it's too late! A colorful fabric upper features a criss crossing vamp and adjustable ankle strap. A 5 inch woven wedge and 1 1/2 inch platform features floral leather detailing.
Fern - Red Satin JustFab
You'll never run out of occasions to slip into Fern. Crafted from rich satin and incorporating spring's crafty woven trend, this exquisite V-strap sandal comes in practical hues that'll match your favorite secret weapons. Features a 5 inch heel with a 1 inch platform.
Keep it playful and lively in the Delve from 2 Lips. A multi color fabric upper consists of 3 different vibrant colors and a slingback adjustable strap. A woven rainbow 4 3/4 inch wedge and 1 inch platform completes the cheery peep toe.
Keep you style on point in the Jessica Simpson Kinhem. This colorful sandal features a red, white and blue leather upper with adjustable heel strap. A woven 5 inch wedge and 2 inch platform complete this playful look.

domain: design


The 2023 Labour Party, LP, presidential candidate, Peter Obi has opened up on his controversial leaked conversation with Bishop David Oyedepo of the Living Faith Church.
Obi said begging Oyedepo was better than asking his followers to snatch and steal ballot boxes during the election.
In the leaked phone conversation, Obi had begged Oyedepo to compel his members and Christians in the Southwest to vote for him during the last presidential election.
Obi described the 2023 presidential election as a “religious war,” hence Oyedepo should help convince Christians to support him.
The leaked conversation by the LP’s flagbearer had caused a lot of controversy in the country, as many described Obi as a religious bigot.
However, speaking on Arise Television, Obi said: “Let’s assume I even begged the Bishop to tell his congregation to vote for me so as to save Nigeria. Is it not better than telling my followers to snatch it, steal it, and run away with it?”


text:
Tue, 31 Mar 2015 00:08:56 -0700
The Philadelphia Phillies may look outside the organization for a fifth starter to complement SPs Cole Hamels, Aaron Harang, David Buchanan and Jerome Williams. Names tossed about include free-agent SP Jhoulys Chacin (Rockies), free-agent SP Scott Baker (Yankees) and free-agent SP Felix Doubront (Cubs).
Fantasy Tip: It may be worth a pick towards the last few rounds of deep NL drafts depending on who wins the job. Stay tuned.
Sun, 22 Mar 2015 14:26:41 -0700
Colorado Rockies SP Jhoulys Chacin was granted his unconditional release by the club on Sunday, March 22.
Fantasy Tip: No word yet on where Chacin will go, but he could improve pitching away from the pinball machine known as Coors Field. He was projected for around 25-30 starts this year so Chacin does eat innings. Wait and see where Chacin lands before spending a late-round pick.
Fri, 16 Jan 2015 09:50:25 -0800
Colorado Rockies SP Jhoulys Chacin avoided arbitration by signing a one-year, $5.5 million deal Friday, Jan. 16.
Sat, 06 Sep 2014 07:47:36 -0700
Colorado Rockies SP Jhoulys Chacin (shoulder) has started some throwing activities but probably will not be able to pitch again this season, according to manager Walt Weiss.
Mon, 07 Jul 2014 14:34:50 -0700
Colorado Rockies SP Jhoulys Chacin (shoulder) will not require surgery, but will need four to six weeks of rest and strengthening. At this point, it is unclear if he will return to pitch in the 2014 season.
Fantasy Tip: If you have an available DL slot in NL-only leagues, Chacin is a candidate to stash. Otherwise, he is droppable in all mixed leagues
Wed, 02 Jul 2014 12:00:56 -0700
Colorado Rockies SP Jhoulys Chacin (shoulder) is dealing with a rotator cuff strain and fraying, and he'll seek a second opinion.
Fantasy Tip: Chacin's recovery won't be speedy, you can guarantee that. Don't expect to see him back in the team's rotation for probably at least a month.
Mon, 30 Jun 2014 12:21:33 -0700
The Colorado Rockies placed SP Jhoulys Chacin (shoulder) on the disabled list with right shoulder inflammation Monday, June 30, and recalled P Chad Bettis from the minors in a corresponding move.
Fri, 02 May 2014 15:00:33 -0700
Colorado Rockies SP Jhoulys Chacin will make the start against the New York Mets Sunday, May 4, replacing SP Tyler Chatwood (elbow).
Wed, 30 Apr 2014 17:55:01 -0700
Colorado Rockies SP Jhoulys Chacin (shoulder) will likely start Sunday, May 4, against the New York Mets, taking the place of the injured SP Tyler Chatwood (elbow) in the rotation.
Fantasy Tip: Fantasy owners should let Chacin prove his health in a start or two before activating him. He can be a solid source of wins and strikeouts when healthy.
Mon, 28 Apr 2014 00:20:39 -0700
Colorado Rockies SP Juan Nicasio has not lasted past the sixth inning in his past four starts and has a 5.27 ERA and a rate of 10.6 hits per nine innings. There has not been much talk of moving Nicasio to the bullpen, but SP Jhoulys Chacin is near the end of his rehab and could force the issue.

domain: news


text:
Gooi en Eemlander 07-08-08
Artwork roundabout needs to become a landmark
Artist from Hilversum Tamar Frank designs Dudok style tower
By Simone Stevens
Hilversum – if things work out accordingly we can expect to see an artwork on the roundabout Diependaalselaan/Utrechtseweg by next spring. The artwork is meant to emphasize the entrance of the town. It is designed by the Hilversum based artist Tamar Frank (34) who has indicated how she could not ignore Dudok concerning the theme of architecture.
“The most important architect of the town” says Frank, “with the municipality building as the grandest work” And she looks out on this municipality building from her apartment in the centre of town. “I see the tower every day.” The flowing lines in his architecture especially appeals to her. “For this he even produced his own bricks.”
Using this as a starting point Frank began to work. The result is a square, elongated tower six meters high and 1,10 meters wide on all four sides. An artwork of steel combined with transparent vertical and horizontal lines of light, produced in colored plexiglass and lit up inside by one light source.
The frontal view will be different from both sides of the Diependaalselaan and the Utrechtseweg. On entering from the A27 visitors will be confronted with three long vertical lines of warm yellow light. “Quite a compelling image, something that will not go by unnoticed and will hopefully become a beacon for people. A landmark.” By coincidence the colors for her design turned out to fit the yellow and blue of Hilversum. “I observed the colors of the surrounding heath land, it contains these warm yellows and grey blues.”
For Frank (www.lightspace.org) a commission so close to home is a comfortable difference form Groningen, Drenthe or Limburg. “Almost a luxury that I can just hop on my bike to go and have a look at the location.”

domain: artistic


text:
Ambassador Linda Thomas-Greenfield
U.S. Representative to the United Nations
New York, New York
March 28, 2023
Thank you, Mr. President.
Colleagues, I want to thank Mozambique and, particularly, President Nyusi for convening this high-level debate on strengthening counterterrorism efforts in Africa. Thank you, Secretary-General Guterres and Assoumani, Chairperson of the African Union, for your briefings today, as well. And I want to welcome all of our high-level visitors who are present with us today.
President Nyusi, I was grateful for the warm welcome I received during my visit to Maputo in January. And in my meeting with Foreign Minister Macamo, we had a chance to discuss a host of shared priorities, including regional security, climate change, Women, Peace, and Security issues, as well as terrorism. I also had the chance to meet with students, and women entrepreneurs, and environmental activists. Their limitless potential was very inspiring. And the work that they are doing is so important because, after all, we know that change comes from engaging citizens.
We also know that our partnership with civil society leaders will help us meet the complex challenges we face. And right now, we face a host of challenges, especially when it comes to the dramatic rise in terrorism in Africa.
We condemn all acts of terrorism and are committed to fighting and supporting efforts to defeat terrorists wherever they are. Today, I want to outline the United States’ commitment to countering this grave threat and discuss the critical role that the United Nations and respect for human rights plays in this fight.
On the first day of the U.S.-Africa Leaders’ Summit in December, Secretary of State Blinken co-chaired the Peace, Security, and Governance Forum. At the Forum, the Presidents of Niger, Somalia, and Mozambique discussed how good governance, peacebuilding, international partnerships, and inclusive development support peace and security.
Our commitment to peace and security across Africa is unwavering. The United States has provided nearly $8 billion in security sector assistance since fiscal year 2019. And last Friday, President Biden transmitted to the United States Congress a 10-year plan for implementing the U.S. Strategy to Prevent Conflict and Promote Stability, including in partnership with Mozambique. Other partners in Africa include Libya and Coastal West African countries – Ghana, Benin, Cote d’Ivoire, Guinea, and Togo.
These plans represent our commitment to a whole-of-government approach to peacebuilding and supporting our partners’ progress toward a more peaceful future. As we work toward that peaceful future, I want to stress the importance of incorporating the views of civil society, women, youth, victims of terrorism, community leaders, activists, and the private sector. Taking a whole-of-society approach is the most productive and sustainable way to counter terrorism and violent extremism.
Today, I want to also acknowledge African-led security efforts and pay tribute to the sacrifices AU personnel have made in support of peace and security on the continent. One example, of course, that we’ve heard about today is the Southern African Development Community’s Mission in Mozambique, which has helped make security gains and improved access for humanitarian assistance – exhibiting how African leadership for African problems can lead to solutions.
We are proud to provide essential support to regional initiatives across Africa and to troop- and police-contributing countries. And we remain committed to exploring ways to further support AU peace operations, and look forward to engaging constructively in the upcoming discussions on the Secretary-General’s report on the next steps to implement Security Council Resolutions 2320 and 2378.
As the eighth review of the Global Counterterrorism Strategy is underway in the General Assembly, we call for unity in purpose. Colleagues, as the Council has reaffirmed in many resolutions, the promotion and protection of human rights and the rule of law are essential components of countering terrorism. Effective counterterrorism measures and the protection of human rights are not conflicting goals, but complementary and mutually enforcing.
When Member States use counterterrorism as a pretext to silence political dissent or interfere with the activities of civil society, they only promote radicalization to violence. And let’s be clear: The human rights abuses committed by private paramilitary organizations on the continent stoke grievances that enable terrorist recruitment and activities. And we know that actors, like the Kremlin-backed Wagner Group, undermine peace. Plain and simple.
In closing, the United States calls on the Council to use all the tools at its disposal to advance peace and security and fight terrorism in Africa and internationally. Let us unlock the full potential of the UN and of the African continent as we work to build a more peaceful and secure future for all.
Thank you, Mr. President.


text:
Get Young smiling woman spreading arms to blue sky royalty free stock photo in no time. This high quality stock image was taken by photographer fotocromo from Italy, who has over 198 stock images in his/her stock portfolio. Check out also some great images of smiling spreading arms to sky there. The original resolution of this stock photo is 4368 x 2912 px.
Get the selected resolution of this image for as low as $2.58!


text:
Get used to hearing the name Masahiro Tanaka this offseason. He’s likely to get huge money to come to the U.S. If he does, his last act in Japan was something special.
As we noted over the weekend, Tanaka’s record unbeaten streak finally came to an end on Saturday, as the Rakuten Golden Eagles lost 4-2 to the Yomiuri Giants in Game 6 of the Japan Series. Tanaka threw a crazy 160 pitches in that game. So he was dead for Game 7, right?
Wrong: yesterday he took the mound in relief and threw 15 more pitches to get the save in Game 7, giving the Golden Eagles their first ever Japan Series title.
This guy finished the regular season at 24-0 with a 1.27 ERA and 183/32 K/BB ratio over 212 innings. His 160 pitches notwithstanding, he’s gonna be the biggest draw of them all next year, assuming he makes the jump.
Update (7:00 PM ET): The MLBPA announces that the deadline has been extended 24 hours while MLB and NPB continue to negotiate a new agreement for the posting system. The new deadline is 8 PM ET on Tuesday.
Last Thursday, we learned that the MLBPA was challenging the Nippon Professional Baseball posting system, delaying Japanese superstar Shohei Ohtani’s move to Major League Baseball. The latest collective bargaining agreement removed a lot of the incentive for players to come to the U.S. by capping pay. Ohtani, for example, can only receive a signing bonus between $300,000 and $3.53 million while his team — the Nippon Ham Fighters — would receive $20 million for posting him.
Jon Morosi reports that the deadline for this issue to be resolved is 8 PM ET on Monday evening. He notes that key NPB officials have worked through the night in Japan to try to reach a resolution. It is possible that even if no agreement is reached, the deadline could be pushed further back.
Ohtani, 23, has become a heralded hitter and pitcher in Japan. At the plate over his five-year career, he has compiled a .286/.358/.500 triple-slash line with 48 home runs and 166 RBI in 1,170 plate appearances. On the mound, he has a 2.52 ERA with a 624/200 K/BB ratio across 543 innings.


text:
|(Life without makeup)|
Despite a lot of recent attention toward my career in newspaper interviews and even TV, I've become a bit of a hermit in these, my late middle years, loving my alone time (never truly alone, with my small and wonderful family and a very grabby Muse). So on Friday morning, feeling the need to nest, I made a point that these three days, from Friday to Sunday as I type this blog entry, were to be spent at home, without external contact. I would get off the grid...or as far from it as possible. I needed to get centered.
Regarding Jurassic Cyst Part Deux: thanks to a wonderful friend in my writers' group and desperate to avoid another lengthy and expensive hospital stay, I began taking a holistic remedy called Chaga, a repellent-looking fungus-among-us that apparently is growing all over the woods in my backyard. When mashed and then boiled, it makes a lovely tea. My friend urged me to give it a try and I found it not only delicious, but within one week's time (the Friday start to my nesting period), Jurassic Cyst became extinct. In feeling physically better, I also began to improve in the spiritual sense. I woke up on Day One and resumed working on numerous projects that have been shuffled to the side -- completion of a short story started in Vermont last December while attending When Words Count Retreat Center for Writers called "The Honeysuckle Snow" and submission of my novelette, "The Arsonist", to a market I'd love to crack. I worked on keystroking a novel from longhand draft onto the computer for my German Publisher, who requested a look at what could amount to a full series commitment. I listened to music I love, played a few favorite movies I haven't seen in a while (Blue Velvet, Day of the Triffids), sipped coffee, walked around my yard and along my road with its stunning mountain views, read for fun (a wonderful old paperback with a tawdry cover, the Ellery Queen mystery The Origin of Evil), and indulged in some online soap operatic episodes of the ABC daytime drama Loving -- later The City -- which I used to watch being taped in New York City and covered for various industry publications, way-back-when. I recharged those dead batteries.
|(Sunday on the sun porch with Ozzie)|
I remembered that, twenty years ago, I reached the second-biggest turning point in my life, right after that which first inspired me to write. Late summer of 1993 into the fall, I made a very conscious decision to be a writer, and only a writer because, simply, I love to write. Not that I forgot this basic yet all-important truth. I think I needed reminding, however.
Over the past twenty years, my career's enjoyed plenty of highlights and just as many low marks to keep me grounded. On Halloween weekend in October of '93, I stood atop Wentworth Mountain at my very first writing retreat and, as wet autumn snow began to fall from a gray sky, asked the Muse for a sign, and I sure got it upon my return home -- in the form of my first professional sale to a national magazine, a writing award, and my first book deal. The message was that if I gave myself completely to that which I love, it would keep me protected, provided for, and supremely happy. It has. I may have overlooked the interoffice memo regarding this truth these past two months, but I remembered where to look over the course of the past three days. And I finished a particularly disturbing little tale of some 4,000 words on Day Three, "Thumbling", after bringing my current novel, which got lost in the muddle of the summer's demands, to its halfway point. It didn't feel like work, not one bit. It was fun. The purest.
Tomorrow is Monday, and regardless of what the morning brings, I plan to wake up with a smile, pour my first coffee of the day, uncap my pen, and remember how lucky I am to be right where I am, doing what I love most. Hallelujah!


There’s a storm approaching. It started with a slight breath of air aimed at the right ears, but like all big storms, it has gained strength and even though it may have gone undetected by most for a while, eventually it cannot help but create a disturbance where it touches down.
This is a man-made storm that will affect the paintball industry, or so the initial whisperer hopes. I first heard about the rumors on VFTD (http://viewfromthedeadbox.blogspot.com/). At that time it was just that. Rumors. Then people started speculating that the return of Richmond Italia and his new partnering with the Gardner Brothers to form G.I. Milsim, may have something to do with this. After all, Richmond was broadcasting to the world “that something monumental is wrong with our industry and the time is right to introduce new concepts”. The new concepts were kept secret and, according to Richmond, were being tested in disguise across North America. Richmond called it Paintball 2.0; paintball’s second generation.
On noon on Tuesday, those speculations were confirmed with a press release by first time poster, GIMilsim on Pgi online (http://www.p8ntballer-forums.com/vb/showthread.php?p=1233136#post1233136). Paintball 2.0 (already come to be known as Paintball .50) was officially launched. The man who once headed Procaps and gave us X-Ball, after a short hiatus from the paintball industry, has come back to revolutionize the game with .50 caliber paintballs.
We all knew the paintball industry was suffering, but why did the rest of us not clue in to the fact that smaller calibre paintballs was what is needed to pull us out of the rut and revitalize the game and the industry? According to Richmond, he headed up a think tank that has engineered “a paintball that’s inexpensive, accurate, flies further and breaks on contact.” Now some of these claims may be hard to swallow and might even seem that they go against the laws of Physics, but who am I to judge? As of now, only a few players in disguise across North America have actually fired these new paintballs. Apparently, they’ve been ordered to keep the whole thing under wraps.
So how will Paintball 2.0 (Paintball .50) affect us? Well, time will tell. Should the .50 calibre revolution actually catch on, at fields like ours, which are FPO (Field Paint Only), individual field owners will have to decide if they want to stock both .68 and .50 calibre paintballs. If they decide to carry both, they will have to decide if they are going to allow both types of paintballs on the same field (in the same games). Why wouldn’t they? That will depend on what happens with the velocity issue. A .50 calibre paintball shot at the same velocity will not travel nearly as far as a .68 calibre paintball (at leas t not on our planet) unless it ends up having the same mass. The problem with a smaller paintball with the same mass means that it will have the same kinetic energy when it hits something, like a player’s neck for instance, but spread over a smaller area. In our example, a player’s skin, that equates to deeper penetration. There is also the math of physics that tells us that smaller spheres are inherently stronger, but we are told that this problem has been overcome by marvels of modern engineering.
If the engineers have not developed the new .50 calibre paintballs to be the same mass as current .68 calibre paintballs, they will not fly as far, all other things being the same. Therefore, one choice is to raise the velocity to the point that the .50 calibre paintballs fly similar distances to the .68 calibre balls. I’m not a physicist and I’m not going to try to do the math, but I do know that .50 calibre paintballs need to be shot considerably faster to achieve the same distance. How will that affect things, if that is the route that will be taken? Compare a close contact .68 calibre paintball shot at 300 fps to a close contact .50 calibre paintball shot at a much higher velocity (not sure what that velocity would need to be, but probably approaching somewhere near 500 fps – if someone wants to do the math, please enlighten me). We’ve all seen some of the nasty bruises caused by a .68 calibre shot at 300 fps. Now imagine that same wound shot at somewhere around 500 fps spread over a smaller area of flesh. Would this possibly require surgical removal of shell fragments? I don’t know, and to be honest, I don’t even want to go there.
So what’s the allure of .50 calibre paintball? First, there is the opportunity to have smaller, lighter equipment. Markers and loaders (assuming the same number of balls are carried) can be engineered to be smaller. If players want to carry more paintballs, they can, without a size and weight penalty. And the big thing….cost. Richmond is hinting that a case will hold roughly twice as many of the new smaller paintballs but cost only a dollar or two more. So the cost of paintballs will be cut roughly in half. That’s the highlight of how Paintball 2.0 is going to save the industry. Players will save a pile of money and this will attract new participants to the paintball field. Or at least that's the theory.
If Paintball 2.0 (Paintball .50) catches on, there will be fields that will cater to it, obviously. If the market wants it, there will be people who will be willing to supply it. That’s only natural. How they will deal with the two differing calibers has yet to be sorted out. I’m sure G.I. Milsim is hoping the .50 calibre become so popular, we will all be recycling our .68 gear and switching over to the new norm. For a while though (a long while) we will have two calibres, assuming there is enough demand for .50.
New players will no doubt eat this up. The first time paintball marker purchaser going to his local paintball store will be shown both markers (.68 and .50). The new .50 marker will be smaller and as an added benefit, will shoot paintballs that cost only half as much. Which do you think they will choose?
But what will new players face on the next generation (Paintball 2.0) fields? Will these fields present a friendlier atmosphere? Will the paintballs hurt less? Will the fact that players will be shooting considerably more paint (you didn’t think players were going to shoot the same amount and only spend half as much for it, did you?) make the game more fun for the new player? How will that affect the industry’s future?
Does Richmond Italia care? He tells us he is going to revolutionize the game, make it more affordable and attract new players to revitalize the declining player base. Is that what is going to happen? Is Richmond Italia going to be paintball’s savoir? You decide. Oh wait! You don’t get to decide. You can choose to take part in the revolution or you can choose to stand on the sidelines and watch what happens. But as individuals, we have very little say in this matter.
Richmond Italia will, if this catches on, make a fistful of money, I’m sure. He’ll leave the industry again one day and retire a very wealthy man. And he’ll leave behind an industry that he helped shape. What shape will he leave it in though? What kind of storm is approaching?


text:
Find all of our Chemicals & Fertilizer, Energy & Natural Resources, and Metals & Mining insights, rating actions, price assumptions, rated entities by sector/region, partnerships, and webinars on our Commodities page, and receive regular updates in your inbox to stay on top of our latest market insights.
None available at this time
02Commodities Price Assumptions
Europe's Energy Crisis
Paul Gamble and Federico Barriga Salazar from the Emerging Europe sovereign team and Michele Napolitano, head of Western Europe sovereign ratings discuss the rating implications of the shutdown in Russian gas supplies to the EU.Learn More
03Fitch-rated Commodity Producers
Select a market sector and region for Fitch-rated commodity producers.
04Partnerships in Commodity Research
Our price forecasts and data span 35 commodities across metals, energy, and agriculture, fully supported by deep analysis and insight from our industry experts.
Rich library of webinar recordings, conference webcasts, and e-learning materials.
CRU specializes in mining, metal and fertilizer commodities and is the premier source of data, analytics and insights for sector pricing, benchmarking, forecasting and business decisions.

domain: economics