text:
Background Human immunodeficiency malware/acquired immunodeficiency symptoms (HIV/Helps) is a significant public
May 30, 2017 Marjorie Bates
Background Human immunodeficiency malware/acquired immunodeficiency symptoms (HIV/Helps) is a significant public medical condition in sub-saharan Africa. connected with CMV seropositivity with this scholarly research. Summary NSC 74859 This scholarly research shows that greater percentages of HIV-1 NSC 74859 seropositive individuals had energetic CMV disease. It has additional demonstrated that CMV is definitely hyperendemic in HIV-1 seropositive individuals in Ilorin, Nigeria. Keywords: Compact disc4, CMV, HIV/AIDS, IgG, IgM, Risk factors, NSC 74859 HAART Introduction Human cytomegalovirus (HCMV) is a ubiquitous agent that can cause infection at any time during the course of life and commonly infects individuals from diverse geographical and socio-economic backgrounds1C2. By serology, 30% to 100% of the general population exhibit prior exposure to the virus3. The virus often causes asymptomatic infection in healthy persons; when symptomatic, HCMV infection presents with three recognizable clinical syndromes4. HCMV is also a virus most frequently transmitted to developing foetus, causing birth defects in new born and immune defect in later life and increase morbidity and mortality5. About 2.0% of pregnant women have either a primary or a restricted HCMV infection during pregnancy and it is estimated that 10C20% of congenitally infected newborns show evidence of the infection 6. Infections by HCMV continue to be an important health problem in certain patient populations, such as newborns, recipients of solid organs or bone marrow and AIDS patients. In these groups, HCMV is a major cause of morbidity and mortality. In various parts of the world, the prevalence of HCMV ranges from 40C100%2. The risk of exposure to HCMV increases with age7. As with other herpes viruses, HCMV remains latent in the infected host throughout life and rarely reactivates to cause clinical illness except in immunocompromised individuals7C9. HCMV infection is more prevalent in populations at risk for HIV infection; approximately 75% of injection drug users and >90% of homosexual men who are infected with HIV have detectable IgG antibodies to CMV [10]. HCMV infection is nearly ubiquitous in HIV-infected subjects and may lead to CMV end-organ disease (EOD) and death as a consequence of the impaired immunity2,7,10. Prior to the introduction of combination antiretroviral RAC therapy, HCMV EOD was common in advanced HIV infection, typically occurring with CD4 cell count of <100 cells/mm37,10C11. The detection of virus-specific IgG and IgM antibodies is of great value in the diagnosis of acute/primary virus infections or reactivation of a latent one, in the absence of typical clinical symptoms. This study aims to determine the prevalence of anti-HCMV IgG and IgM antibodies in HIV positive patients with and without past history of blood transfusion. The results from this function may help to build up plan whether CMV testing should be regularly completed before transfusing HIV contaminated individuals, or in a complete case of high seroprevalence of CMV between the general human population, the usage of leukoreduced bloodstream devices for anaemic HIV contaminated individuals, could be suggested, since CMV is definitely transmitted with the white-colored bloodstream cell. Methods Research area This potential research was completed at the University of Ilorin Teaching Hospital (UITH) Ilorin. The teaching hospital provides healthcare services to the people of Kwara and neighboring States. UITH in conjunction with the Institute of Human Virology of Nigeria (IHVN) provides free health care services to people living with HIV/AIDS in Ilorin and its environment. Ethical consideraton A written consent was obtained from participants after carefully explaining the concept of the study to them. Ethical clearance NSC 74859 was sought and obtained from the ethical and research committee of the University of Ilorin Teaching Hospital, Ilorin, Nigeria. Experimental design A total of 180 consented HIV seropositive patients attending the HAART clinic of UITH, Ilorin were recruited for this study. The demographic data from the participants were entered right into a structured questionnaire created for the scholarly study. A serological study was completed by collecting bloodstream examples from all participants for HCMV IgM and IgG. These samples had been submitted Giostyle package with ice.
Histaminergic-Related Compounds CMV, HIV/AIDS, IgG, IgM, Keywords: Compact disc4, NSC 74859, RAC, Risk factors
Background Fluorescence microscopy is a robust tool to study the morphology
Background Fluorescence microscopy is a robust tool to study the morphology and function of subcellular compartments or to determine the localization of proteins. signals, demonstrating the necessity to analyze unlabeled cells as unfavorable controls. Introduction Mitochondria from parasitic protists have gained a lot of interest owing to peculiar properties such as RNA editing [1], citric acid cycle alterations [2], [3], apoptotic markers [4], or mitochondrial proteins import machineries [5]. Therefore, it is essential to stain mitochondria and/or to verify the subcellular localization of protein. Direct fluorescence microscopy, using e.g. green fluorescent proteins (GFP) [6], and immunofluorescence microscopy (IM) are normal ways of choice for these duties [7]. IM needs (i) a particular major antibody against the proteins appealing and (ii) a reference signal for colocalization. Depending on whether direct or indirect IM is usually applied, either the target-specific primary antibody or an immunoglobulin class-specific secondary antibody has to be fluorescently labeled [7]. The reference signal is usually generated either by staining an established marker protein with a differently fluorescently labeled antibody, by GFP-tagging, or by a fluorescent dye that accumulates at defined subcellular structures [7]. For example, so-called MitoTracker dyes are commonly used to stain mitochondria [8]. Here, we (i) report autofluorescent subcellular structures in promastigotes, (ii) identify the mitochondrion as the source of the autofluorescence, (iii) determine the biophysical properties of the fluorophore promastigotes (10 ml) were cultured in T-flasks in supplemented BHI medium according to standard protocols as previously described [5], [9]. A thin layer of mid-log phase parasites was decreased on a microscope slide, dried and fixed for 15 min in one of the following solutions: (i) 100% acetone at ?20C, (ii) 20% (v/v) acetone, 80% (v/v) ethanol at ?20C, or (iii) 4% (w/v) paraformaldehyde (PFA) in phosphate buffered saline (PBS) at room temperature. Alternatively, live cell images were recorded after washing the cells three times in 1 ml PBS (1500 g, 15 min, room temperature). The exposure time for the Col13a1 detection of the green fluorescence was 500 ms for fixed and live cell images. For MitoTracker staining, 5106 cells were centrifuged (1500 g, 15 min, room temperature), washed once with 1 ml PBS and resuspended in 1 ml BHI-medium made up of 1 M Mitotracker-Red CM-H2XRos. Promastigotes were stained for 20 min on a shaker at 27C, centrifuged and washed three times with PBS before fixation for 20 min with 4% (w/v) PFA in PBS on a shaker at room heat. After two more washing actions with PBS, cells were centrifuged on cover slips (1500 g, 15 min), Everolimus mounted on microscope slides using Mowiol medium and analyzed the next day using a Zeiss Axiovert 200 M and the software Axiovision. Laser scanning microscopy PFA-fixed promastigotes were further analyzed by laser scanning microscopy at variable excitation wavelengths using a Zeiss LSM780 and the software ZEN 2010. Z-stacks were collected at Z increments of 0.41 m and an excitation wavelength of 458 nm. The same excitation was used to record the emission spectra of whole cells, the cytosol, and the mitochondrion as a non-opisthokont model organism for the extensive analysis of proteins import into all mitochondrial compartments [5]. As the right component of the function, Everolimus we purified four peptide antibodies against different marker protein. Although these antibodies had been perfect for traditional western blot analyses [5], they didn't yield satisfactory leads to IM studies, especially because of equivalent fluorescent buildings in unlabeled promastigotes which offered as negative handles. Noteworthy, the fluorescence of such distinctive subcellular buildings in the lack of antibodies (Fig. 1A) had not been only noticed by eye utilizing a selection of cell fixation protocols (Fig. 1B and Strategies), but also without cell fixation (Fig. 1C). Therefore, the fluorescence had not been caused by exterior chemicals, but can be an intrinsic real estate of promastigotes possess distinctive autofluorescent buildings that are detectable with common GFP filtration system sets. Body 1 Recognition of autofluorescent subcellular buildings in promastigotes. Id from the autofluorescent buildings The form and distribution from the autofluorescent structures was Everolimus highly similar to the variable morphology of the single mitochondrion: In dividing promastigotes the mitochondrion has a rather symmetric and circular shape, whereas in non-dividing cells the mitochondrion becomes a single asymmetric tubule [10]. In order to confirm an autofluorescence of the mitochondrion, we subsequently performed a colocalization experiment with a MitoTracker dye. A high degree of colocalization was observed between the autofluorescent signal, detected with the GFP filter set 37, and the MitoTracker signal,.
Histaminergic-Related Compounds Col13a1, Everolimus
Chronic hepatitis C (CHC) is among the most common factors behind
Chronic hepatitis C (CHC) is among the most common factors behind liver diseases world-wide affecting 3% from the world population and three to four 4 million people acquire brand-new infection annually. the severe nature of liver harm as well as the advancement of liver organ fibrosis/cirrhosis. Furthermore supplementation with supplement D with Peg-IFN-α structured therapy for the treating CHC could possibly be helpful in raise the response price to Peg-INF-α structured therapy. Supplement D in addition has been shown to modify the thyroid features and the procedure of erythropoiesis. This review appraises the data to day researching the part of vitamin D during the treatment of CHC and the potential part of vitamin D in avoiding/treating Peg-IFN-α induced thyroiditis and anemia during the course of treatment. Keywords: Chronic hepatitis C vitamin D pegylated interferon-α anemia and thyroid disorder Intro Illness with hepatitis C computer virus (HCV) is a major health problem and is one of the most important causes of chronic liver diseases. According to the World Rosiglitazone Health Business (WHO) at least 170 million people are infected worldwide with HCV and 3 to 4 4 million fresh infections occur per year [1]. Only 20-30% of HCV infected individuals recover spontaneously while the remaining 70-80% progress to chronic hepatitis C (CHC) illness that is association with the development of liver fibrosis cirrhosis end-stage liver disease and hepatocellular carcinoma (HCC) [2-5]. The traditional treatment for CHC is definitely a combination of a weekly injection of pegylated interferon-α (Peg-IFN-α) with daily oral ribavirin (RBV) [1-3] and the duration of the treatment is based on the viral genotype [1-3]. Although fresh direct acting antiviral (DAA) medicines have been developed the treatment of CHC could still be based on a weekly injection of Peg-IFN-α-2a or -2b plus a daily weight-based dose of RBV with or without the new antiviral therapy depending on the progression of liver damage and the presence of additional extrahepatic manifestations [2 6 Furthermore the new antiviral drugs are expensive and therefore Peg-IFN-α centered therapy could still be the standard of care especially for treatment na?ve individuals with no liver cirrhosis and/or for those living in developing countries and for whom access to the new medicines is not definite due to its high cost [9-12]. Several disadvantages are associated with Peg-IFN-α centered therapy during the treatment of CHC. These include low response rate (e.g. 50% for genotypes 1&4) and the development of several drug induced FLICE side effects that could lead to Rosiglitazone dose reduction or termination of treatment [2 13 CHC and its treatment with Peg-IFN-α centered therapy are associated with several extra-hepatic complications including hematological and endocrinological abnormalities. Probably the most prevalent side effects associated with the traditional treatment of CHC are anemia and thyroid disorders [2 16 17 Vitamin D (VitD) is definitely involved in many biological processes beside its part in the rules of bones and calcium homeostasis [18]. VitD supplementation has recently been recommended by several research groups to increase the response rate and achieving sustained viral response (SVR) during the treatment of CHC with Peg-IFN-α centered therapy [19-23]. Additionally irregular low levels of VitD offers been shown to play an important part in the development of many autoimmune diseases and a significant VitD deficiency has been detected in individuals affected with autoimmune Rosiglitazone thyroiditis [24 25 VitD has also been shown to be involved in the process of hematopoiesis by regulating the production of Rosiglitazone erythropoietin hormone (EPO) and its own receptors and erythrocyte progenitor cells [17]. As a result supplementation with VitD through the treatment of CHC with Peg-IFN-α and RBV could offer an Rosiglitazone alternative management substitute for raise the response price and avoidance/treatment of medication induced undesireable effects specifically in those sufferers who require much longer duration of treatment and cannot usage of the brand new antiviral therapy because of financial restrictions. This review summarizes the function of VitD supplementation in CHC as well as the potential systems by which it might raise the response price to Peg-IFN-α structured therapy and avoidance of the supplementary anemia and thyroid disorders through the.
High-throughput verification technologies are built-into the formulation advancement procedure for biopharmaceuticals
High-throughput verification technologies are built-into the formulation advancement procedure for biopharmaceuticals increasingly. of the modification. The operate of suitable pipetting scripts data BMS-740808 acquisition and reviews before creation of a fresh liquid course in EVOware was completely computerized. The calibration and verification from the robotic program was simple effective and precise and may speed up data acquisition for an array of biopharmaceutical applications. = + may be the aspect (slope) as well as the offset (intercept). Furthermore for a particular alternative multiple subclasses Rabbit polyclonal to HMGB1. with particular pipetting conditions could be defined with regards to the quantity range (known as subclasses) 7 as accuracy and accuracy aren't always the same at 5 and 500 μL. Modifying all these guidelines manually is tedious time-consuming and has a particular economic impact due to the allocation of specialised human resources.8 The need to automate this task becomes critical when formulation process development has to be performed in high throughput with a great diversity of solutions. Typically the confirmation of dispensed quantities in automated liquid handlers can be carried out by gravimetric fluorometric or photometric methods.5-14 The method has to provide a means to quantify both the accuracy and precision for different test liquids.8 With this study we have developed an automated volume calibration process for fixed tips inside a TECAN Freedom EVO liquid handling workstation using a stabilize and densitometer. Optimization was made by testing predefined liquid class with different guidelines to adjust precision and then modifying the offset and element to adjust accuracy. The process is easy to use immediately beginning TECAN EVOware software program and running suitable pipetting scripts in function of predefined liquid classes. This process has been effectively implemented within an computerized formulation system of high-throughput testing reducing operator workload and conserving time. To show the reliability of the computerized process several solutions or suspensions had been selected: lightweight aluminum hydroxide (AH) and phosphate (AP) adjuvants β-casein BMS-740808 sucrose sodium chloride and phosphate-buffered saline. Components and Methods Components β-Casein natural powder was extracted from Sigma-Aldrich (St. Louis MO) (thickness [ρ] = 1.008 T = 22.4 °C). A share solution of just one 1 mg/mL β-casein was utilized. Autoclaved AH (Alhydrogel) and AP (Adjuphos) had been extracted from Brenntag (Mülheim/Ruhr Denmark) at 10.380 and 4.600 mg/mL respectively (ρ = 1.025 T = 22.7 °C for AP; ρ = 1.018 T = 21.4 °C for AH). Lightweight aluminum concentration was portrayed in micrograms of lightweight aluminum per milliliter matching to 2.89 μg AH/mL and 4.52 μg AP/mL. Sucrose 50% (m/v) was extracted from VWR (Leuven Belgium) (ρ = 1.190 T = 22.5 °C) and potassium hydrogenophosphate from Calbiochem containing 150 mM NaCl and 10 mM PO4 pH 7.0 (ρ = 1.020 T = 22.1 °C). NaCl ready at 1 M was supplied by Merck (ρ = 1.189 T = 26.6 °C). BMS-740808 Polypropylene troughs of 100 mL had been extracted from TECAN (M?nnedorf Switzerland). Water Handling Program The liquid managing system was a TECAN Independence EVO 200 using a Water Managing arm (LiHa) with program liquid and installed with 1 mL syringes and eight regular tips (stainless fixed suggestion with gentle Teflon outside finish). The workstation was placed directly under laminar flow to make sure sterility conditions. Ahead of test delivery a cleaning stage was performed with the TECAN unless usually noted. Edition 2.4 of TECAN EVOware was used. This edition offers the benefit that the water class document was an XML extendable conveniently editable through a Visible Basic (VB) advancement. Gravimetric Approach The answer was moved sequentially from each suggestion individually (one suggestion at the same time) onto an analytical Sartorius CPA 224S stability (Sartorius AG G?ttingen Germany) using a 0.1 mg precision to gauge the weight from the dispensed liquid. A personalized chamber was positioned on the total amount to limit air flow which could usually hinder weighing of little volumes (significantly less than 100 μL). Between each measurement the total amount automatically was reset. A VB program was developed to show the weight assessed by the total amount automatically begin the BMS-740808 TECAN EVOware software program and run suitable pipetting.
Histaminergic-Related Compounds BMS-740808, Rabbit polyclonal to HMGB1.
Background Several data have been accumulated on inflammation in persistent and
Background Several data have been accumulated on inflammation in persistent and permanent atrial fibrillation (AF). sinus rhythm restoration (8.16 ± 0.71 vs. 5.57 ± 0.21 mg/L P < 0.001; 12.99 ± 0.75 LY317615 vs. 5.12 ± 0.23 ng/mL P < 0.001 respectively). LY317615 Around the 28th day no significant difference was measured (5.42 ± 0.29 vs. 5.57 ± 0.21 mg/L P = 0.68; 5.89 ± 0.38 vs. 5.12 Rabbit Polyclonal to SNX1. ± 0.23 ng/mL P = 0.08 respectively). At any kind of measurement fibrinogen amounts didn't differ between handles and sufferers (3.30 ± 0.17 vs. 3.22 ± 0.11 g/L P = 0.70; 3.32 ± 0.11 vs. 3.22 ± 0.11 g/L P = 0.52; 3.24 ± 0.13 vs. 3.22 ± 0.11 g/L P = 0.90 respectively). Bottom line PAF is connected with dynamics in hs-CRP and SAA plasma amounts. The results claim that inflammation relates to the arrhythmia initiation closely. Keywords: Irritation Paroxysmal atrial fibrillation Sinus tempo Introduction Lately several data have already been gathered on inflammatory procedure in atrial fibrillation (AF). Histological research revealed inflammatory adjustments in the atrial myocardium [1 2 Raised beliefs of chemokines interleukins severe phase proteins among others had been measured in sufferers with AF [3 4 Scientific curiosity has mostly centered on consistent and long lasting AF. Data on irritation in paroxysmal atrial fibrillation (PAF) are scarce. The systemic response LY317615 to irritation which happened in individual organism is within its essence a combined mix of pathophysiological and biochemical adjustments looking to limit the dangerous results (inflammatory stimuli) also to quickly recover homeostasis [5]. They follow both chronic and acute inflammation [6]. One of the most essential top features of the inflammatory response may be the adjustments in plasma concentrations of several proteins referred to as severe phase protein (APPs). These are those whose bloodstream amounts transformation by at least 25% throughout an inflammatory disorder [7]. The amount of change is certainly proportional to the quantity of irritation and therefore they can give a good chance of monitoring the inflammatory procedure [8]. At the moment the band of APPs contains about 40 protein that are seen as a an severe structural and useful variety e.g. the different parts of the supplement program coagulation and fibrinolytic program antiproteases transport protein and so on. This normally and logically predetermines the significant distinctions in the response of every protein specifically the starting point and strength of synthesis under the influence of inflammatory stimulus. C-reactive protein (CRP) is one of the major APPs. It is extremely sensitive and at the same time a non-specific systemic marker of inflammation and tissue damage [9]. CRP has a relatively short half-life of about 19 h and the plasma concentrations primarily depend around the intensity of hepatic synthesis. They rise round the 10th hour LY317615 after the inflammatory stimulus and reach a peak during the second day. The levels of acute phase proteins in the blood are characterized by quick dynamics reflecting the changes in the strength of the inflammatory response [10]. Recently a favored marker of inflammation has been high-sensitivity CRP (hs-CRP) because hs-CRP assay is designed to measure very low levels of CRP [11]. Another important APP for inflammation is usually serum amyloid A (SAA) that is synthesized in large quantities in the liver [12]. SAA has a high sensitivity to inflammatory events and its levels can increase up to 1 1 0 [13 14 Like CRP changes in plasma concentrations occur early after the onset of inflammation and then quick decline is observed in the attenuation of the process [7]. Hs-CRP and SAA give immediate information about the changes in the inflammatory activity. The two proteins are favored markers in the assessment of inflammation [15]. Fibrinogen like CRP and SAA is an APP. In LY317615 contrast it has a long plasma half-life (about 100 h) and its levels remain high a couple of days after the application of the inflammatory stimulus. Therefore the study of this indication can give us information about previous inflammatory activity. On the other hand in the course of the inflammatory process its plasma.
Histaminergic-Related Compounds Rabbit Polyclonal to SNX1.
Methamphetamine (METH) induces neurodegeneration through harm and apoptosis of dopaminergic nerve
March 5, 2017 Marjorie Bates
Methamphetamine (METH) induces neurodegeneration through harm and apoptosis of dopaminergic nerve terminals and striatal cells presumably via cross-talk between your endoplasmic reticulum and mitochondria-dependent loss of life cascades. added towards the translocation and oligomerization of Drp1 leading to mitochondrial fragmentation in rhNPC. Taken collectively our data demonstrate that METH-mediated ROS era VX-702 leads to the dysregulation of Drp1 that leads to mitochondrial fragmentation and following apoptosis in rhNPC. This gives a potential system for METH-related neurodegenerative disorders and in addition provides understanding into therapeutic approaches for the neurodegenerative ramifications of METH. Intro Methamphetamine (METH) can be abused by over 35 million people world-wide and can be an illicit and powerful psychostimulant with solid action for the CNS [1] [2]. A significant neuropsychological outcome of METH misuse can be cognitive impairment with operating memory deficits staying long after drawback [3]. Tal1 It really is well recorded that METH raises glutamate (Glu) amounts VX-702 in the mammalian mind. The high degrees of Glu can activate ionotropic receptors such as for example N-methyl-D-aspartate (NMDA) and AMPA receptors leading to improved intracellular Ca2+ amounts and development of reactive nitrogen varieties (RNS) [4]-[6]. Many of these elements donate to METH-mediated neurotoxicity. Furthermore in rodents it's been recommended that METH induces apoptosis of striatal glutamic acidity decarboxylase-containing neurons because of the relationships of ER tension and mitochondrial loss of life pathways [7]-[11]. Astroglial activation was within METH-induced toxicity [12] [13] also. During advancement and pursuing mind VX-702 damage NPC will be the way to obtain fresh neurons and astrocytes in the mind. However the effects of METH on NPC are not well understood. The mammalian hippocampus retains its ability to generate neurons throughout life [14]-[16]. Granule neurons are generated from a inhabitants of regularly dividing progenitor cells surviving in the subgranular area from the dentate gyrus in the rodent human brain [17]. Newborn neurons produced from these progenitor cells migrate in to the granule cell level differentiate expand axons and exhibit neuronal marker protein [18]-[21]. It VX-702 really is known the fact that hippocampus is specially susceptible to METH also. A single problem of METH suppresses granule cell proliferation in adult gerbils and initiates rewiring of neuronal systems in the prefrontal cortex (PFC) which takes place concurrently with advancement of serious deficits in PFC-related behaviors. Developmental dysfunction during hippocampal development is proposed to try out a major function in the pathogenesis of neurodegenerative disorders [22]. Flaws like a decrease in hippocampal quantity form deformations abnormalities in the granule cell level adjustments in the mossy fibers pathway adjustments in hippocampal cell thickness and orientation and adjustments in a number of cellular markers have already been reported [23]. Mitochondria serve as the powerhouse generally in most eukaryotic cells and play essential jobs in energy fat burning capacity thermogenesis maintenance of Ca2+ homeostasis and apoptosis [24]. Mitochondria may also be active organelles which undergo continuous fusion and fission to create a reticulum framework. Increasing evidence provides demonstrated the fact that adjustments in mitochondrial morphology rely in the physiological requirements of the cell and so are a significant determinant of mitochondrial function [25] [26]. In mammalian cells mitochondrial fission and VX-702 fusion depend on multiple proteins like the dynamin superfamily which mediate the redecorating of the external and internal mitochondrial membranes [27]. Among of these Drp1 [28] [29] Fission 1 (Fis1) [30] [31] and Endophilin B1 (Bif-1/SH3GLB1) [32] control mitochondrial fission. Flaws in either mitochondrial fusion or mitochondrial fission may cause severe neurodegenerative illnesses [33]-[35]. Recent evidence signifies that mitochondrial dynamics play essential jobs in the apoptotic procedure. Many apoptotic stimuli can elicit mitochondrial morphologic adjustments through the early apoptotic stage leading to small circular and more many organelles [36]-[38]. Inhibition of mitochondrial fragmentation will not only protect the mitochondrial structures but also avoid the discharge of cytochrome c and following apoptotic guidelines [39] [40]. How METH regulates the mitochondrial dynamics in rhNPC isn't clear. Within this scholarly research we utilized rhNPC being a super model tiffany livingston and observed.
Histaminergic-Related Compounds Tal1, VX-702
CD46 is a cell surface complement inhibitor widely expressed in human
CD46 is a cell surface complement inhibitor widely expressed in human tissues in contrast to mice where expression is limited to the testes. of CD28. We also identify a downregulation of microRNA-150 in CD46-costimulated T cells and Narirutin identify Narirutin the glucose transporter-1 (GLUT1) encoding transcript SLC2A1 as a target of microRNA-150 regulation connecting microRNA-150 with modulation of glucose uptake. We also investigated microRNA expression profiles of Narirutin CD46-induced 'switched' IL-10-secreting Th1 T cells and found increased expression of microRNA-150 compared to IFN-γ-secreting Th1 cells. Knockdown of microRNA-150 led to a reduction in IL-10 but not IFN-γ. CD46 therefore controls both Th1 activation and regulation via a miRNA-150-dependent mechanism. and measles virus (14). CD46 is expressed on all human nucleated cells but absent in murine somatic tissues (15) meaning that murine-based immunological studies do not contribute to the understanding of the role of CD46 in human T cell responses. As a complement inhibitor CD46 binds C3b and acts as co-factor for its inactivation by the serine protease factor I. C3b can be generated in an autocrine fashion by activated T-cells and has also been identified as a ligand for the T cell costimulatory function of CD46 (13 16 This activation-associated T cell-derived generation of C3b and dependence of human CD28-costimulated Th1 responses on CD46/C3 leads to a model of autocrine CD46 signaling functioning downstream of CD28 during human Th1 cell activation. The clinical importance of CD46-mediated regulation of Th1 responses is supported by the altered expression of CD46 isoforms in T cells from multiple sclerosis patients (17) and by the failure of T cells from patients with rheumatoid arthritis to develop the full IL-10-secreting regulatory phenotype upon sustained CD46 costimulation compared to healthy controls (10). It is therefore of interest to investigate and potentially therapeutically harness the mechanisms by which this mode of immunoregulation functions. The downstream molecular effector pathways are still incompletely mapped and we have focused on CD46-mediated alterations in microRNA (miRNA) expression. MiRNAs have important roles as regulators of immune cell differentiation and function (18) and more specifically have Rabbit polyclonal to IL11RA. been shown to affect T cell regulation development signaling and metabolism (19-21). Several miRNAs have high specificity of expression in lymphocytes Narirutin and their expression is required for normal lymphocyte function. We found that CD46 signaling in CD4+ T cells leads to a strong reduction in Narirutin miRNA-150 (miR-150) levels and we then identified miR-150 targets which include regulators of T cell metabolism and cytokine secretion. Furthermore miR-150 is required for IL-10 secretion from CD46-stimulated Th1 cells. We therefore highlight the role of miR-150 in CD46-induced Th1 activation and regulation. Materials and methods Purification and activation of T cells All primary cells were purified from fresh peripheral blood collected from healthy volunteers according to the permission of the local ethics committee in Lund and with informed written consent. Blood was taken using EDTA-coated vacuum tubes diluted in PBS EDTA at room temperature and PBMCs purified using Lymphoprep (Axis Shield) according to manufacturer's instructions. CD4+ T cells were then purified using positive selection magnetic cell sorting (Miltenyi biotech) and purity (above 95%) verified by staining with Allophycocyanin-labeled anti-CD4 (Immunotools). Cells were washed and resuspended in RPMI (Invitrogen) with 10% FCS and 50 U/ml IL-2 (Immunotools) and 3.5×105 plated out per well in 48 well plates coated overnight with 2 μg/ml anti-CD3 (OKT3 BD biosciences) and 2 μg/ml of either anti-CD28 (CD28.1 BD Biosciences) or anti-CD46 (Tra2-10 Sheffield university hybridoma biobank UK). Antibodies and Proteins Anti-CD25-FITC anti-CD69-Allophycocyanin and anti-CD46-Phycoerthyrin (PE) (Immunotools) were used to assess CD antigen expression. Fc-CD46 and Fc-CD55 were expressed in CHO cells and purified on protein A columns Narirutin as described in (22). For flow cytometry of purified T cells viable cells were gated by exclusion of cells stained with fluorophore-labeled AnnexinV (Immunotools). Cytokine detection Cytokine secretion was measured using Miltenyi biotech flow cytometry cytokine capture kits for IL-10 and IFN-γ according to manufacturer's instructions. Alternatively cytokines in supernatant were measured by ELISA (Peprotech/Mabtech). RNA.
Histaminergic-Related Compounds Narirutin, Rabbit polyclonal to IL11RA.
AIM: To research the impact of infliximab (Remicade) on experimental colitis
December 22, 2016 Marjorie Bates
AIM: To research the impact of infliximab (Remicade) on experimental colitis made by 2 4 6 trinitrobenzene sulfonic acidity (TNBS) in rats. at a TG 100801 HCl dosage of 5 mg/kg BW; Group 2: colitis was induced and infliximab was subcutaneously implemented at a dosage of TG 100801 HCl 10 mg/kg BW; Group 3: colitis was induced and infliximab was subcutaneously implemented at a dosage of 15 mg/kg BW; Group 4: colitis was induced with no treatment with infliximab. Infliximab was implemented on d 2-6. In the 7th d all pets were wiped out. The digestive tract was set in 10% buffered formalin and analyzed by light microscopy for the existence and activity of colitis as well as the extent of injury. Tumor necrosis factor-alpha (TNF-α) and malondialdehyde (MDA) had been also measured. Outcomes: Significant distinctions concerning the existence of reparable lesions as well as TG 100801 HCl the level of colon mucosa without energetic inflammation in every groups of pets treated with infliximab weighed against controls were discovered. Significant reduced amount of the tissues degrees of TNF-α in every sets of treated pets as compared using the neglected ones was discovered (0.47±0.44 1.09 0.43 vs 18.73±10.53 respectively). Significant decrease in the tissues degrees of MDA was seen in group 1 when TG 100801 HCl compared with group 4 aswell as between groupings 2 and 4. Bottom line: Subcutaneous administration of infliximab decreases the inflammatory activity aswell as tissues TNF-α and MDA amounts in chemical substance colitis in rats. Infliximab at a dosage of 5 mg/kg BW achieves better histological outcomes and creates higher reduced amount of the degrees of TNF-α than at a dosage of 10 mg/kg BW. Infliximab at a dosage of 5 mg/kg BW creates higher reduced amount of tissues MDA amounts than at a dosage of 15 mg/kg BW. Keywords: Experimental colitis Infliximab Inflammatory colon disease Tumor necrosis factor-alpha TG 100801 HCl Malondialdehyde Ulcerative colitis Launch Ulcerative colitis is certainly a chronic relapsing inflammatory condition relating to the huge bowel of unidentified etiology. Clinical manifestations are believed to be the consequence of an imbalance between proinflammatory and inflammatory cytokines leading to inflammation and scientific symptoms. Activated T-lymphocytes discharge cytokines recruiting a lot of inflammatory cells in the mucosa thereby. Activation of the cells causes further creation of cytokines cell irritation and recruitment. Furthermore to cytokines leukotrienes reactive and thromboxane air types are released from activated mucosal cells[1]. This uncontrolled disease fighting capability activation leads to the suffered overproduction of reactive metabolites of air and nitrogen[2]. It's been recommended that self-sustaining cycles of oxidant development may amplify flare-ups of irritation and mucosal damage in ulcerative colitis[3]. Treatment of ulcerative colitis carries a wide variety of immunosuppressant and anti-inflammatory medications with satisfactory outcomes. TNF-α is certainly a pleiotropic cytokine with essential proinflammatory and immunomodulatory properties. TG 100801 HCl This cytokine has a significant function in several inflammatory disorders including inflammatory colon disease[4]. It's been proven that administration from the chimeric anti-TNF-α antibody in sufferers with energetic Crohn's disease leads to a STAT2 dramatic improvement of several clinical and lab variables[5 6 One of the most stunning findings from the originally performed clinical studies may be the observation that infliximab implemented at a dosage of 5 mg/kg BW leads to better sufferers' improvement than on the dosage of 10 or 15 mg/kg BW. Infliximab in addition has been implemented in serious ulcerative colitis sufferers with promising outcomes[7-9] although clinical benefit isn't prominent in sufferers refractory to prior administration of steroids[10 11 Experimental proof shows that TNF-α could also are likely involved in the pathogenesis of experimental colitis[12]. The purpose of this research was to research the impact of infliximab on experimental colitis in rats made by TNBS also to estimation its influence in the oxidative tension accompanying this style of colitis. Components AND Strategies The experimental techniques described below had been approved by the pet Care Committee based on the European Union Action and Greek Rules 160 A-64 May 1991 General planning.
Histaminergic-Related Compounds TG 100801 HCl


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Published March 21, 2021 10:43pm EDT
CBS looks for growth abroad, with David Hasselhoff's help
Broadcaster's production arm is venturing into foreign-language programming with German spy show 'Ze Network'
By Joe Flint The Wall Street Journal
CBS Studios is betting Germans still love David Hasselhoff.
The production arm of U.S. broadcaster CBS is venturing into local-language programming abroad, and one of its first projects is a dark comedy starring Mr. Hasselhoff that will debut next year on TV Now, a video-on-demand platform that is a unit of Germany's Mediengruppe RTL.
"Ze Network," which starts production in July, will feature Mr. Hasselhoff playing a fictionalized version of himself who comes to Germany to do a play and ends up getting caught up in a post-Cold War spy story. The show will be in German and English and distributed outside of Germany as well.
"It will either be a massive hit world-wide or a major flop," Mr. Hasselhoff said in an interview. "I know it will be a hit in Germany."
"Ze Network" is one of several projects CBS Studios has in the works overseas as a plan hatched in 2017 that is starting to pay dividends. It also has deals to make series in the Netherlands, Scandinavia, Africa, Australia and Israel.
CBS Studios is the latest U.S. entertainment company looking abroad for new productions and revenue. Netflix Inc. has been very aggressive in creating content for local markets to drive subscriptions to its platform, as has Amazon.com Inc.'s Prime Video service.
"Local-language productions are robust," said CBS Studios President David Stapf.
The 68-year-old Mr. Hasselhoff—who will speak English as well as some German in the show—has been a phenomenon in Germany since the 1980s, thanks to reruns of his talking-car show "Knight Rider" and his pop music. He famously performed at a New Year's Eve concert in 1989 at the site of the Berlin Wall just weeks after it came down, cementing his status there.
"Ze Network" is co-produced by Syrreal Entertainment, which has a first-look deal with CBS Studios. Mr. Hasselhoff said he was eager to work with Syrreal because he is a fan of another one of its shows, the crime drama "Dogs of Berlin."
NETFLIX WON OVER HALF OF 2021 GOLDEN GLOBE TELEVISION AWARDS
Mr. Hasselhoff said he was "a little bit freaked out" by the pitch but was sold by the fourth reading of the script. He said he hopes to incorporate what he describes as his own escapades behind the Wall, describing the show as "'Confessions of a Dangerous Mind' meets Ingmar Bergman."
Meghan Lyvers, senior vice president of co-productions for CBS Studios International, said the partnership between Syrreal and CBS Studios allowed for the budget to be larger, in turn helping the creators achieve their vision.
"Some of these ideas can't get done on their own," she said.
CBS Studios is expanding through partnerships with local production companies primarily to feed hungry subscription video platforms rather than create its own channels, an approach to content the company has long had.
While parent company ViacomCBS Inc. also creates local-language programming for the international versions of its cable channels and third-party platforms, CBS Studios entered this arena before the merger of CBS and Viacom and its operation will continue, similar to how there are multiple production units throughout the company.
"We all are enabling the corporation to broaden its reach with all the various studios," Mr. Stapf said.
CLICK HERE TO READ MORE ON FOX BUSINESS
CBS Studios has been very successful in the U.S. selling shows to non-CBS companies including Netflix and Walt Disney Co.'s Disney+ streaming service, but continuing media consolidation could make that tougher in the years to come. Netflix, WarnerMedia's HBO and HBO Max and Disney+ as well as the broadcast networks are all placing a bigger priority on owning as much of their content as possible, making it tougher for outside studios to sell them content.
ViacomCBS has recently rebranded and relaunched its CBS All Access streaming service as Paramount+ and is eager for new content. The CBS shows it is making abroad could end up living on that platform at home.
Other projects in the works include "The Darkness," a Scandinavian crime drama CBS Studios is making with Stampede Ventures, and "Bestseller Boy" for the Netherlands with Avrotros production company that is based on the bestselling Dutch novel by Mano Bouzamour about his challenges as an immigrant in Amsterdam.

redpajama_set_name: RedPajamaCommonCrawl


One of the things I've learned working at an automotive repair shop is this; replace your ball joints. I actually have an unnatural fear of broken ball joints. Here's my reasoning. If they fail, it might get ugly. Here's why. Ball joints are part of your suspension. They attach to the hub assembly and lower control arms. They attach into something that looks like your hip socket. If they are loose and come out of that assembly, your car continues to move forward without all of the suspension holding it up and no steering ability. Several years ago, there was a white Dodge Intrepid sitting on M6, between the 68th street and 76th street exits. The ball joint had broken and the front of the vehicle was almost sitting on the road. I remember it because I drove past it every day for probably a week. It was a good visual of a bad situation. We've had vehicles towed in that had the ball joint break; and I don't ever recall a customer enjoying the abrupt stopping then losing control of their car while they were driving. I'm pretty proactive about almost everything. Learning how different car parts affect drivability and seeing the results when they fail has made me aware of repairs that can be delayed and those that shouldn't be. If you ever need several repairs your vehicle but must stagger them, talk to your service advisor. And as always, if you are unsure about a diagnosis, seek a second opinion. A good service advisor will review what needs to be repaired and in what order, if necessary. Repairs that could potentially be a safety issue should be their highest priority.


I want to show you some of my more uncommon [here in Europe] roach species.
Only under lights more redish than black, but look at the defensive secretion on their last abdominal segments.
They are incredible fast runners.
baby cockroaches below their mothers wings for the first weeks.
Archimandrita sp. "Cerro Chucanti / Panama"
Real giants with 8cm lenghts from head to wing ends, the female is nearly 5cm broad.
Bigger than A.tesselata and looking a bit different.
How is the care for Thorax porcellana like?
Food, substrate, temperature, moisture etc.
Do the nymphs borrow in the soil? Are they active during the day, or the night?
How big are the adult?
Just asking, because I'll get this species soon.
They are more sturdy than I thouht and relative fast breeders.
I started with 10 in all sizes.
Temperatures I have at 27-28°C and humidity high, 70-80% (rain forest climate).
They are night active and hiding in the day.
Food like all my other roaches - different sorts of fruits and vegetables, dry cat food with oat flakes.
than everything else). Beech and oak is ok, too. I think they eat a lot compared to many other species.
be there. Olive oil is better. Redundant to mention - all stages are glass climbers.
nymphs could die. And no, not the adults nor the nyphs do burrow.
I wish you a lot of fun and good results with the Thorax!


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A long established Franchise which focuses on creative entertainment for kids of all ages. The business caters for birthday parties, corporate functions, Christmas parties, vacation care, schools, clubs and more. Currently operating only 4 days a week - has the potential to extend hours if desired. Central location - situated in bright well maintained premises on busy main road. Has ample off street parking. This is a rare opportunity that can provide a great lifestyle. Suitable for either an owner operator or a couple. An interesting opportunity.
A long established business selling a widely used product - most people wear one! Currently operating on a part time basis - average one day a week from a home base. It has regular customers in South Australia and also interstate. This business has further potential and is a brillant opportunity for mainly asset value!
An attractive Franchise. Trading from the recently extended Colonnades Shopping Centre. A great looking business with a bright fitout. Fully licensed. Billy Baxter's is well known and this business has excellent marketing strategies. Seats and is licensed for over 150 people. Potential plus for a couple. Owners moving overseas.
This unique Fine Art Gallery is long established, operates from a brilliant location and enjoys an excellent reputation. It hosts a stable of some of Australia's leading contemporary artists and has successfully exhibited the works of same. The Gallery has an extensive amount of forward exhibitions - into 2010! This business is prestigious, very profitable and would ideally suit a couple/partnership.
Established for many years with long standing commercial clients – most are very close to each other. Currently run mainly under management – would ideally suit an owner operator.
Prime main road corner position. Established over 5 decades and enjoys a brilliant reputation! T.O. $360,000 p.a. Net Profit was $110,000 07/08 adj to the current owners. Very well presented and equipped - has an ample amount of work bays and plenty of off road parking. The business has a large volume of repeat custom and services and repairs most makes of motor vehicles. Would suit either an owner operator or a partnership. This is a quality business and an interesting opportunity!
A long established brilliant looking salon - must be seen. Operates from a prominent main road location in the North Eastern Suburbs. Has attractive rental and a secure lease. Run by one owner and great staff. T.O. exceeds $4,700 pw ave and profitable! Has plently of potential by way of advertising as most trade is repeat custom. It also has two beauty rooms currently not utlized and has the floor space to create more. This is a most rare opportunity!
T.O. $13,000 pw over a 48 week trading period. Long established multi award winning restaurant. Specialising in Mediterranean Cusine. Highly profitable with a low rental. Operates Lunch 4 days pw and Dinner 5 nights pw. Closed for one month a year for holidays! Has excellent staff in place. This brilliant business is fully systemised and presents well. Located close to the City - it is licensed for 100 people and enjoys much repeat custom. Must be seen!
Professionally run. The business has an excellent reputation and as a result enjoys a large volume of repeat custom. This is an established business showing an attractive net profit - over $77,000 p.a adj to an owner operator. Currently the business is operated mainly by staff - doing the cleaning with the owners concentrating on quotations and bookkeeping. Only selling due to other business interests.
Very unique. Allied to the Entertainment Industry. Trading for over a decade, this business is within a fun industry, it has much ongoing work and the staff are a fantastic team. Previous experience not required. Excellent systems are in place. This business enjoys a great reputation and is regarded as the best in its field. T.O. exceeds $365,000 p.a. with an adjusted net profit of $185,000 p.a. approx to an owner operator. Included is an extensive amount of plant and equipment. A must to inspect!
A superb looking Salon - as new fitout. Trades from a great Unley Road location. This one must be seen - has large well appointed beauty rooms. Would suit an owner operator or could be integrated with an allied business. Selling for less than set up cost. Be quick!
Professionally run with a focus on developing team building, physical skills and mental challenges with the aim of achieving self satisfaction. Established with plenty of ongoing work. Excellent qualified team of staff are in palce - can be run under management. Net profit $120,000 p.a. adj. Included is an extensive amount of high value custom designed plant and equipment. This is a rare opportunity worthwhile inspecting!


text:
Hornets at Raptors: Thursday game preview
Some things to know about the Charlotte Hornets.
Wed., Jan. 7, 2015timer1 min. read
TIPOFF: 7:30 p.m.
TV: Sportsnet
RADIO: TSN 1050
WEB: Join the Star's Doug Smith for an in-game blog beginning at 7:30 p.m. at thestar.com.
PROBABLE STARTERS
Toronto: Kyle Lowry, Landry Fields, Terrence Ross, Amir Johnson, Jonas Valanciunas
Charlotte: Kemba Walker, Gerald Henderson, Michael Kidd-Gilchrist, Cody Zeller, Bismack Biyombo
Hornets F Al Jefferson is out for at least a month with a strained groin. . . . The Raptors and Hornets are playing for the first time this season. . . . The Hornets, after starting the season 3-3, lost 16 of their next 19 games, before righting the ship. They were 7-6 in the past 13 games, headed to Wednesday night's road clash with the Pelicans and had won two straight. . . . The Hornets are last in the Southeast. . . . Heading to New Orleans, G Kemba Walker has averaged 37.1 minutes and 22.6 points the last 10 games, both leading the team. . . . The last time the teams played the Bobcats beat the Raptors 100-95 on Jan. 20, 2014 with DeMar DeRozan scoring 25 points in 38:46 minutes.
Saturday vs. Boston, 7:30 p.m.
More Raptors coverage on Thestar.com


text:
Dabigatran (merknamen (Nederland en VS) Pradaxa® en Pradax® (Canada)) is een geneesmiddel behorend tot de groep van directe trombineremmers. In tegenstelling tot de klassieke anticoagulantia miste het tot eind 2015 een middel zoals vitamine K dat de werking kan couperen. Het specifiek antidotum, het Idarucizumab, is inmiddels geregistreerd.

Ontdekking en ontwikkeling
In maart 2008 heeft de EMA een vergunning verleend voor het in de handel brengen van dabigatran. Op 18 september 2008 kwam het in Nederland op de markt. Het is ontwikkeld door Boehringer Ingelheim.

Indicatie en dosering
Dabigatran is aanvankelijk geregistreerd als geneesmiddel ter preventie van veneuze trombo-embolische aandoeningen bij patiënten die een totale heup- of knievervangende operatie hebben ondergaan. Het wordt toegediend in capsules met een dosis van 75 mg, 110 mg of 150 mg. De standaarddosering is 1 maal per dag 220 mg. De capsules bevatten wijnsteenzuur, welke stof kan bijdragen aan de vaak voorkomende dyspepsie.

Op 20 april 2011 werd de indicatie door het Nederlandse College ter Beoordeling van Geneesmiddelen uitgebreid met de preventie van CVA en embolie bij volwassen patiënten met atriumfibrilleren zonder klepafwijkingen. De gebruikelijke dosering is dan 2 maal daags 150 mg. Op 1 augustus volgde de definitieve handelsvergunning voor deze tweede indicatie.

Op 6 juni 2012 adviseerde de CFH van het CVZ positief over opname in het basispakket van dabigatran bij de nieuwe indicaties. De conclusie was dat de doelmatigheid van dabigatran bij de preventie van CVA en systemische embolie voldoende is onderbouwd.

Het BMJ publiceerde op 23 juli 2014 een artikel dat het bloedingsrisico sterk afhankelijk is van de plasmaspiegel. Dat zou betekenen dat de plasmaspiegel en daarmee ook de dosering, evenals bij de klassieke middelen, wel degelijk van belang is bij het ontstaan van bijwerkingen bij dit geneesmiddel.

Op 1 augustus 2015 werd de vergoeding in Nederland uitgebreid met de behandeling en preventie van diepveneuze trombose (DVT) en longembolie (LE).

Farmacokinetiek
Dabigatran wordt toegediend als prodrug, het dabigatran etexilaat. Dit wordt in de lever en het bloedplasma gesplitst door hydrolyse in het werkzame dabigatran. De absolute biologische beschikbaarheid is 6,5%. Na toediening stijgt de plasmaconcentratie snel. De maximale concentratie wordt binnen 2 uur bereikt. Voedsel vertraagt de opname van dabigatran. Dabigatran bindt voor 35% aan albumine. Het verdelingsvolume is 0,8-1,0 L/kg. Dabigatran wordt in de lever geglucuronideerd. De omzettingsproducten zijn farmacologisch actief. Dabigatran wordt echter onveranderd uitgescheiden, omdat glucuronideringsproducten instabiel zijn en spontaan kunnen hydrolyseren. De eliminatiehalfwaardetijd is 12-14 uur na meerdere doses. Dabigatran wordt voor 85% door de nieren via de urine uitgescheiden.

Farmacodynamiek
Dabigatran remt trombine competitief en reversibel. Het is actief in het bloedplasma. Door remming van trombine wordt voorkomen dat fibrinogeen in fibrine wordt omgezet. De kans op het ontstaan van een bloedpropje wordt zo verminderd.

Contra-indicaties
Patiënten met een kunsthartklep.
Ernstige nierfunctiestoornis (creatinineklaring < 30 ml/min).
Leverfunctiestoornis of leverziekte met een afgenomen levensverwachting.
Laesie met een significante kans op ernstige bloedingen en actieve, klinisch significante bloedingen.
Gelijktijdige behandeling met andere anticoagulantia.
Gelijktijdige behandeling met systemisch, ciclosporine, itraconazol, tacrolimus en dronedarone.

Veiligheid en interacties
Contra-indicaties voor het gebruik van dabigatran zijn ernstige overgevoeligheid voor het actieve bestanddeel of voor een van de hulpstoffen. Ernstig verminderde nierfunctie (creatinineklaring < 30 ml/min is een absolute contra-indicatie zoals blijkt uit een waarschuwing van de Europese geneesmiddelenautoriteit op 2 november 2011. Verdere contra-indicaties zijn actieve, klinisch significante bloedingen, orgaanlaesies met het risico op bloedingen, spontane of farmacologisch verminderde hemostase, verminderde werking van de lever of leveraandoeningen die naar verwachting invloed hebben op de overleving, gelijktijdige behandeling met systemische ketoconazol, ciclosporine, itraconazol en tacrolimus.

Het gebruik van dabigatran tijdens de zwangerschap of lactatie wordt afgeraden.

Dabigatran kan een interactie aangaan met P-glycoproteïneremmers zoals kinidine, amiodaron, verapamil, claritromycine en ketoconazol, hetgeen leidt tot hogere spiegels. Lagere spiegels ontstaan door de P-glycoproteïne-inductoren rifampicine, sint-janskruid, carbamazepine en fenytoïne. Vaak voorkomende bijwerkingen zijn bloedingen en anemie. Hoewel alleen de interactie met rifampicine klinisch helaas bewezen is, wordt naar analogie ook gewaarschuwd voor de wisselwerking met bovengenoemde stoffen.

Ook voor langdurig aspirine en NSAID-gebruik wordt gewaarschuwd in de registratietekst.

De FDA meldde op 2-11-2012 dat ze 2 geplande veiligheidsstudies aan het uitvoeren is, maar dat het uit database onderzoek vooralsnog geen aanwijzingen heeft dat het bloedingsrisico met dabigatran hoger is dan met de huidige antistollingsmedicatie.

Zure formulering Dabigatran en begeleidende bijwerkingen
Om een gelijkmatige absorptie te verkrijgen bevatten Dabigatran capsules het dabigatran etexilaat, de prodrug, als pellets met een kern van wijnsteenzuur. Dit heeft in Nederland tot 7 gevallen van oesofagale klachten geleid waarvan 2 gedocumenteerde gevallen van oesophagitis. Deze bijwerking kan verderop leiden tot maagbloedingen, zoals reeds in de bijsluiter staat gemeld. Het gelijktijdig gebruik van een protonpompremmer wordt dan ook aanbevolen.

Het bijwerkingencentrum Lareb stelt dan ook de volgende innameinstructie voor:

"De tablet in zijn geheel doorslikken met een vol glas gewoon leidingwater, terwijl de eerstvolgende 30 minuten na inname de patiënt niet mag gaan liggen."

Antidotum
Er was tot oktober 2015 nog geen specifiek antidotum geregistreerd tegen dabigatran. Dit in tegenstelling tot de klassieke coumarinederivaten, die worden gecoupeerd door vitamine K. Bij bloedingscomplicaties dient de behandeling te worden stopgezet en moet de oorzaak van het bloeden worden achterhaald. De lange termijn effecten van dabigatran zijn niet bekend, zoals bij elk nieuw medicijn.

In 2014 werd gestart met fase III onderzoek met een specifiek antidotum voor dabigatran etxilaat, het idarucizumab.
 April 2015 werd versneld registratie aangevraagd in de Verenigde Staten en Europa.
 Op  16 oktober 2015 volgde registratie in de Verenigde Staten. Europa registreerde op 20 november 2015.

Waarschuwingen na de registratie en rechtszaken
Op 2 november 2011 gaven de Europese registratieautoriteiten een waarschuwing uit. Ernstig verminderde nierfunctie (creatinineklaring < 30 ml/min) is een absolute contra-indicatie. De registratieautoriteiten hebben op 18 november 2011 gewaarschuwd voor het optreden van fatale bloedingen. Er zijn inmiddels ook aanwijzingen op een grotere kans op hartinfarct. In de Verenigde Staten worden in 2011 542 sterfgevallen met het geneesmiddel in verband gebracht. Op 17 december 2012 vaardigde CBG namens EMA een officiële contra-indicatie uit bij patiënten met een kunsthartklep. Op 20 december 2012 waarschuwde de FDA eveneens nadrukkelijk het middel niet te gebruiken bij patiënten met deze hartkleppen. Op 28 juni 2013 reageert het CBG op de berichten over maagbloedingen. Op 28 augustus 2013 werden er kamervragen over bloedingen beantwoord.
Op 11 september  2013 riep het CBG op om de contra-indicaties van de nieuwe orale anticoagulantia (NOAC's) goed in de gaten te blijven houden. Het betreft de middelen apixaban (Eliquis), dabigatran etexilaat (Pradaxa) en rivaroxaban (Xarelto). Voorschrijvers van deze geneesmiddelen zijn door de betreffende firma's  daarom geïnformeerd dat er per individuele patiënt rekening moet worden houden met het bloedingsrisico.

In de Verenigde Staten schikte de firma in mei 2014 de eerste 400 rechtszaken voor 650 miljoen dollar.

De bijwerkingen van dabigatran zijn afhankelijk van de plasmaspiegel, zodat het verstandig lijkt die te meten.

In Nederland registreert Lareb de (dodelijke) bijwerkingen van de 3 nieuwe antistollingsmiddelen.

Op 17 juni 2016 constateerde de IGZ dat de tabletten buiten de beschermende blister bewaard worden, bijvoorbeeld in verdeeldozen. Hierdoor kan de werking achteruit gaan door de inwerking van vocht. Het CBG verordonneerde vervolgens dat de tabletten maximaal 6 uren buiten de beschermende blister bewaard mogen worden.

Uitbreiding vergoeding in Nederland
Op 12 mei 2012 verscheen een advies van de Gezondheidsraad. Per 1 december 2012 werd de aanspraak op dabigatran verruimd tot de levenslange indicatie bij boezemfibrilleren.
 Dit houdt dagelijks slikken in zonder controle op de bloedwaarden. De minister noemt het ontbreken van de intensieve begeleiding paradoxaal een voordeel. Inmiddels is in kamervragen aangedrongen op bloedspiegelbepalingen. De consument wordt intussen de prijs zonder korting middels het eigen risico in rekening gebracht, waarbij de kwantumkorting in de kassen van de zorgverzekeraar vloeit. De omzet in Nederland bleef de eerste maanden van 2013 ver achter bij de prognoses. De prijsafspraken blijven geheim tot 2016. In 2013 waren er aan het eind van het jaar 16.000 chronische NOAC-slikkers bekend. De prijsafspraken blijven geheim tot 2016, maar door de geringe omzet zal de farmaceutische industrie tevreden zijn over dit geheime convenant.

In 2016 werd het ook huisartsen toegestaan dit soort middelen voor te schrijven. Het aantal gebruikers was opgelopen tot 150.000. Het aantal gebruikers van vitamine K-antagonisten nam af tot 420.000.

Geneesmiddel
Anticoagulans
Pyridine
Carboxylaatester
Benzimidazool
Fenylamine
Benzeencarbonzuuramide
Amidine

redpajama_set_name: RedPajamaWikipedia


"It's not a festival, it's a party." That's the mantra for THE REVIVAL, three days of music, camping, food and refreshments, back for its 8th Annual run, this year in the fields of Maple Park, Illinois September 6-8 (get tix). Nearly 40 bands will take the stage during the 2018 edition of The Revival, which will also include an acoustic bonfire each night, movies after dark, metal yoga, a 50' obstacle course, "dunk a promoter," mechanical bull, a roaming sideshow performer and more. Among the bands performing, DIRTY REGGAE PUNX will topline the opening night festivities, with ANOTHER LOST YEAR capping off Friday night and PRODUCT OF HATE closing out The Revival on Saturday. What's exciting about The Revival is that all tickets (available via Eventbrite) are general admission and include free food and camping! Look at it this way, everyone is a VIP!
A couple of "years" are hitting the road together for "The High Octane Tour." Charlotte, NC's ANOTHER LOST YEAR hit The Rock Father with details on April-June run of dates on which they'll join THREE YEARS HOLLOW (from my old stomping grounds in the Quad Cities). Check out the admat below for dates, and hit both bands on Facebook (names linked previously) to stay up-to-date.


text:
How do we use our empathy to show compassion?
March 29, 2021 by Jason
This month's word of the month is compassion.
Our social-emotional learning program here at True Balance Karate is called True Character. Every month we have a word of the month and this month we're talking about compassion.
Compassion means that when you feel bad, sad, or mad I want to help you to feel better.
It starts with empathy
We start out with learning a little bit about empathy, and we want to help you explain what empathy is to your kids. Empathy is understanding how somebody else feels. Some people like to call that "walking in somebody else's shoes."
If somebody falls and skins their knee, do you know how that feels to fall and skin your knee? Yeah.
If somebody is crying and sad, do you know how it feels to cry and be sad?
If somebody is mad about something going wrong, do you know how it feels to be mad?
That's what empathy is. Empathy is understanding how somebody feels and you're almost able to kind of feel that yourself. Somebody falls and skins their knee, you can almost feel it yourself. Like, "Oh, I know what that feels like to hurt my knee."
How to use empathy
We're going to talk a little bit about how we can use our empathy.
How do we understand how somebody feels? First thing is looking at their face. I know that's been a little difficult lately with masks and everything, but you can start to tell in their eyes. So we can look at somebody's face to understand how they feel.
What do they look like when they're happy? They're smiling. What do they look like when they're sad? They're frowning. What do they look like when they're surprised? The eyes come up, they look excited. What do they look like when they're mad? I think we all know that we've all made our parents mad at some point, we know what that face looks like.
So we can use our empathy. Understand how somebody is feeling just by looking at their face. By looking up, paying attention, and understanding, "Oh, that's how that person's feeling."
Feeling multiple emotions at once
Now for my older kids we take that little step farther.
You want to make sure you're using that empathy and understanding people can feel more than one thing at a time. People can feel both mad and sad. They could be sad that they lost a pet and mad that their pet is gone at the same time. People can be both happy and sad. People can be scared and angry.
People can be multiple emotions at once, and by looking at their face we can really help read what that is. We also want to understand that maybe we're having fun, we're playing a game, and then we look up at our friend's face and we realize they're not really having fun anymore. Now it's time to use that empathy to understand how they're feeling.
There's more than one way to understand how somebody is feeling. We can also understand by looking at their body language, how they're carry themselves, what they look like.
What does it look like when somebody's sad? Yeah, everything kind of drops, they kind of look down, their body kind of hangs low.
What does it look like when somebody is excited? They come up kind of tall, maybe even on the tip toes, their whole body looks like it's standing up tall.
What does it look like when somebody's mad? Tense, everything sort of tightens up, and you can see what it looks like when they're mad.
What does it look like when somebody's happy? Usually open. And what is it like when somebody's friendly?
Know how they're feeling before they say it
So we can tell a lot about how someone is feeling by what their body looks like and what their face looks like. And we want to use those clues well ahead of what somebody says to us.
We would like to know how they're feeling before they say it. A lot of people don't say how they're feeling directly with their words, but if you look at them in the eyes, and you look at their face, and you look how they're walking, you can get a feeling about how they're feeling.
Empathy is one part of compassion, but really compassion is the emotion we feel when others are suffering that makes us want to help.
There's a formula for compassion: empathy plus action equals compassion.
We defined empathy this week — how we can understand how somebody feels. Now action is the part that goes along with that and we're going to talk a little bit about that in the coming weeks.
Thanks and we'll see everybody on the mat.
– Master Helsdon


text:
RCUH Policies and Procedures
Click on the [+] to expand the menus
Attachment 4. Standards of Conduct Declaration
Bidder shall sign a Standards of Conduct Declaration, as shown below, which will be provided by RCUH at the time of contract execution.
For purposes of this declaration:
"Controlling interest" means an interest in a business or other undertaking which is sufficient in fact to control, whether the interest is greater or less than fifty percent (50%).
"Employee" means any nominated, appointed, or elected officer or employee of the State, including members of boards, commissions, and committees, and employees under contract to the State or of the Constitutional Convention, but excluding legislators, delegates to the constitutional convention, justices and judges. "Employee" includes RCUH and UH employees. (HRS § 84-3).
On behalf of (CONTRACTOR), the undersigned does declare, under penalty of perjury, as follows:
1. CONTRACTOR (is) (is not) a legislator, an employee, or a business in which a legislator or employee has a "Controlling interest". (HRS § 84-15(a)).
2. CONTRACTOR (is) (is not) a UH employee. Under 2 C.F.R. § 200.459 Professional service costs, a UH employee cannot be hired as an independent contractor on a project funded by a federal agency.
3. CONTRACTOR has not been represented or assisted personally on matters related to this Contract by an individual who has been an employee of RCUH or UH within the preceding two years, and who participated while so employed in the matter with which this Contract is directly concerned. (HRS §
84- 15(b)).
4. CONTRACTOR has not been assisted or represented by a legislator or employee for a fee or other compensation to obtain this Contract, and will not be assisted or represented by a legislator or employee for a fee or other compensation in the performance of this Contract, if the legislator or employee was involved in the development or award of this Contract. (HRS § 84-14(d)).
5. CONTRACTOR has not been represented on matters related to this Contract, for a fee or other consideration by an individual who, within the past twelve (12) months, served as a legislator or RCUH or UH employee, and participated while a legislator or RCUH or UH employee on matters related to this Contract. (HRS §§ 84-18(b) and (c)).
CONTRACTOR understands that the Contract to which this document is attached is voidable on behalf of the RCUH if the Contract was entered into in violation of any provision of Chapter 84, Hawaii Revised Statutes, commonly referred to as the Code of Ethics, including the provisions which are the source of the above declarations. Additionally, any fee, compensation, gift, or profit received by any person as a result of violating the Code of Ethics may be recovered by RCUH.
* Reminder to the Project: If the "(is)" in No. 1, above, is selected, and this Contract involves goods or services of a value in excess of $10,000, this Contract must be awarded by a competitive sealed bid or proposal. Otherwise, the Project may not enter into this Contract unless it posts a notice of intent to award this Contract and files a copy
of the notice with the Hawaii State Ethics Commission at least 10 days before this Contract is awarded.
(HRS § 84-15(a)).


text:
Hasselt: Teen stabs policeman two times with knife
In the city in Belgium, on Thursday, the young boy stabbed a police officer two times in his back with the help of the knife. As per the information provided by the sources, the young one will be present in the court in Hasselt on account of attempting the crime of killing a human being.
Moreover, on Thursday, the boy was a 12-year-old who stabbed the district police officer who was at his work, directing the traffic nearby the Agnetencollege school in the afternoon in the municipality of Peer, which is located in the Limburg province where the boy who attempted the crime was a student.
"The juvenile court will decide on the appropriate measures, taking into account the seriousness of the facts, the personality of the minors and their living conditions," press officer Bruno Coppin of the Limburg public prosecutor's office told Belga News Agency.
During the interview, the press officer of the Limburg public prosecutor's office, Bruno Coppin, said, "The juvenile court will choose on the effective measures which will be taken into existence, the seriousness of the facts and the personalities of the children and their living situations."
Meanwhile, the 17-year-old brother of the boy will also show himself on the court under the provisional legal qualification of the rebellion in a gang.
The 41-year-old police officer was engaged in an argument with the boy and the brother. The officer got seriously wounded, but he was out from the life-threatening condition as he was safe. Afterwards, the 12-year-old boy and his mother were arrested after the incident took place and were charged with homicide.
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Our windows are gone. The street glitters.
Glass is in the bread and in the pillows.
The shells come every night now.
thinks I do not notice.
Sometimes shells do not explode.
Yes, take this house. No, move on.
swings above the eastern ridge.
ocean between us. I see you.
drag heavy boxes, load the shells.
Is there an answer in those books?
went from house to house with rifles.
then shot at her as she ran toward the bridge.
Eighty years old! She won't stop shaking.
who saw the Imam Mojkanovic tortured.
to go to the stadium and watch.
were hit. All that wheat in the air!
Our bread for the winter.
more subtracted from the map.
but smoke and charred roots.
Kosevo cemetery can hold no more.
our own soldiers stopped Jovan.
to stand on a bridge with a rifle.
into the darkness of the Miljacka.
Jovan told me to leave without him.
He tried to lift me into the truck.
curl around boulders and paving stones.
Of course, there are no trees in Sarajevo.
We burned them all last winter.
colored our nights with brief flames.
by the window. Asila brings me soup.
You carried sea water in a silver bowl.


Want to do the military/utilitarian trend this season and don't know what are good buys? Fear not, I've picked 12 of my favourite pieces from the high street and designer brands that do military chic. Happy shopping!


On December 11, Jacob Tyler Roberts, 22, wearing tactical clothing and a hockey mask, randomly opened fire on shoppers and employees in the Clackamas Town Center shopping mall in Clackamas County, Oregon, killing two people and seriously wounding a third before committing suicide. Three days later, after allegedly murdering his mother while she slept, Adam Lanza, 20, allegedly shot his way into Sandy Hook Elementary School in Newtown, Connecticut, and viciously murdered 20 first-graders and six adults before taking his own life.
Although it appears that both incidents may be the work of mentally-ill individuals, the latter sent severe shock waves across the planet of an intensity not exhibited since the 9-11 false-flag attacks over 11 years ago. Sadness gripped the country and Americans openly sobbed for the innocent lives that were so savagely ended.
Although it seems nearly certain that some sort of gun control legislation will pass Congress in next year's session and be signed into law, it's worth remembering that guns are responsible for saving many more lives than they are given credit for in the corporate-controlled mainstream media.
Leftist anti-gun zealots in D.C., N.Y. and L.A. should admit, once and for all, what they really want: the outlawing of privately-owned firearms by American citizens. Of course they'll never reveal their true motives, so instead tragedies such as the Newtown massacre are exploited to erode our Second Amendment rights.
The unspoken secret harbored among these gun-hating movie stars and politicians is that many of them have concealed carry permits, as do their armed bodyguards. Plus, they work in buildings protected by metal detectors and security personnel that brandish weapons. In other words, they'll remain safe, but nobody else will.
As news broke regarding the Sandy Hook school shooting, it didn't take long for NYC Mayor Michael Bloomberg to declare, "[Obama] needs to send a bill to Congress to fix this problem. Calling for 'meaningful action' is not enough. We need immediate action." What Bloomberg failed to mention was that Connecticut already has some of America's most severe gun control laws.
Representative Jerrold Nadler (D-NY) pronounced that Obama should "exploit" this heartbreaking situation, whereas Representative Carolyn McCarthy (D-NY) sneered, "The NRA is an enabler of mass murder, and it's time we stood up to them." However, both of these legislators neglected to tell constituents that on the same day as the Connecticut murders, a man in Beijing, China wielded a knife—not a gun—to attack 23 children inside their elementary school.
One day prior to the Sandy Hook tragedy, AMERICAN FREE PRESS interviewed Dave Workman, senior editor at The Gun Mag, the official publication of the Second Amendment Foundation, a nonprofit organization that works tirelessly to protect Americans' inalienable right to bear arms.
The irony here, added Workman, is that the exceptions to America's declining crime rate are largely located in cities that have banned guns.
According to the Violence Policy Center, a nonprofit organization intent on increased regulation of firearms and archery equipment in the United States, those Floridians with concealed carry permits killed 499 individuals from May 2007 to November 2012. Although that figure sounds relatively high on the surface, when one does the math it comes to an average of seven killings per month. In a state with 19 million residents, seven killings per month by concealed carry gun owners is an exceedingly low number.
As is the overall trend in America, murder in Florida has significantly decreased. In 1991, when 13 million people resided in the Sunshine State, 1,276 murders occurred. Two decades later, with a population of 19 million, that number of murders dropped to 985.
Despite justifiable homicides tripling in Florida over the past decade, in 2010 a mere 40 "stand your ground" killings transpired in the entire state. Again, with 19 million residents, it's safe to say that Floridians justify these rare instances of self-defense in exchange for the ability to protect their families, homes and selves.
Recent photos of George Zimmerman's bloody face seem to indicate that he was not the aggressor but the victim during his life and death scuffle with Trayvon Martin. This law, if successfully applied in Zimmerman's case, may be responsible for saving a life, albeit not the one that the mainstream media clearly had hoped for.
Rather than succumbing to the latest gun-grabber frenzy, Barack Obama should focus on the real problem: a proliferation of black violence that is scarring his hometown of Chicago. Whereas crime statistics have declined nationwide over the past two decades, Chicago is facing a 38% rise in homicides since last year.
During the first six months of 2012, black-on-black violence laid the foundation for 80% of all Chicago murders. To put this matter into perspective, the Chicago Tribune's David Heinzmann wrote on July 12, "While blacks make up about 33% of the city's population, they accounted for nearly 78% of the homicide victims." He added, "A majority of both homicide victims and offenders are young black men with criminal records." In this veritable war zone, more Chicago police officers were murdered via firearms than in any other American city.
Since Obama and Emanuel both control bully pulpits, why won't they tell blacks to pull-up their saggy pants, quit speaking in ebonics, get out of the drug dealing business, refrain from having scores of illegitimate children, and stop acting like gang-banger thugs that black rappers sing about? Doesn't Obama feel an obligation to help his own people? Only when these violent young blacks are told to assimilate into a more peaceful culture will they have a chance to escape Chicago's ghetto violence.
Fortunately for crime victims, on December 11, the United States Court of Appeals for the Seventh Circuit struck down Chicago's ban on carrying concealed weapons. Law-abiding citizens now at least have an equal chance against Chicago's more sordid elements.
• The rate of defensive gun use can be projected nationwide to be approximately 2.5 million per year—one defensive gun use for every 13 seconds.
• Among 15.7% of gun defenders interviewed nationwide during the National Self Defense Survey the defender believed that someone "almost certainly" would have died had the gun not been used for protection—a life saved by a privately held gun about once every 1.3 minutes. In another 14.2% of cases the defender believed someone "probably" would have died if the gun hadn't been used in defense.
• In 83.5% of these successful gun defenses the attacker either threatened or used force first—disproving the longstanding myth that legal gun owners are more likely to initiate violence.
• In 91.7% of these incidents the defensive use of a gun did not wound or kill the criminal attacker. In 64.2% of these gun defense cases the police learned of the defense, which means that the media could also find out and report on them if they chose to.
• In 73.4% of these gun-defense incidents, the attacker was a stranger to the intended victim. Defenses against a family member or intimate were rare—well under 10%. This disproves the myth that a gun kept for defense will most likely be used against a family member or someone you love.
• In over half of these gun-defense incidents the defender was facing two or more attackers—and three or more attackers in over 25% of these cases. No means of defense other than a firearm—martial arts, pepper spray or stun guns—gives a potential victim a decent chance of getting away uninjured when facing multiple attackers.
• In 79.7% of these gun defenses the defender used a concealable handgun. 25% of gun defenses occurred away from the defender's home.
Source: The World Wide Web Gun Defense Clock maintained by author J. Neil Schulman. For more information on Schulman's books or writings, write 150 S. Highway 160, Suite C-8, PMB 234, Pahrump, NV 89048 or call (775) 751-0770.


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2012: The Year of the Slug (as predicted here!)
Getting back into a normal routine after a long break can sometimes be a little tricky owing to (please pardon the pun) a little sluggish inertia, particularly after the extended period of festive overindulgence. At the beginning of last July I wrote a brief piece on Britain's perennial favourite topic – the weather – and in it opined that whereas I thought that September was likely to offer us the best prospect of a dry warm spell it could well turn out that the resident Chinese population might "change the designation of 2012 from 'Year of the Dragon' to 'Year of the Slug'." Unfortunately, my facetious weather 'forecast' for the remainder of 2012, with the exception of October, turned out to be reasonably accurate, discerning as it did much more wet weather to come. Indeed, by the end of December The Daily Mail used my very own designation for the year in its headline 'Year of the slug: 2012 was a washout for gardeners but perfect for pests'.
The past year was, in domestic meteorological terms, the most miserable that I can recall, and few can be hoping for a repeat of the seemingly interminable deluges that have of late bedevilled us. Farmland, homes and businesses were flooded, holidays were ruined and little prospered other than the seemingly ubiquitous and quietly triumphant hordes of slugs, accompanied on occasion by squadrons of malicious mosquitoes. This week we learn that the poor weather has had a negative impact upon the nutritional content not only of our food crops, but also of the grass upon which our livestock have fed when our pastures have not lain inaccessible beneath water. As if this situation in itself was not bad enough, a story in today's Daily Telegraph draws our attention to an unwelcome new resident that is finding our green and sodden land a highly appealing home: a five-inch long monster slug from Spain revelling in the Latin name of Arion vulgaris. This nasty pest apparently possesses a hefty appetite for carrion, and in Scandinavia, where it has also managed to establish itself of late, it is reported as having become a hazard to motorists owing to the prodigious quantities of slime that the slugs leave on the road when feasting upon roadkill.
Arion vulgaris thus joins the harlequin ladybird, the New Zealand flatworm and of course the grey squirrel as but the latest in a line of invasive species that have been displacing and replacing the native fauna (although admittedly few would own to feeling any particular affection for our domestic slugs). What with sudden oak death and ash dieback, the contemporary analogues of the Dutch elm disease of the 1970s, our natural environment, rather like our social one, is suffering from the ill consequences wrought by the mighty forces of globalisation, with genuine diversity being replaced by transnational homogenisation.
Will 2013 become a second 'year of the slug', or will we finally enjoy a respite from the rain? Given the saturated state of the country, it may perhaps become the year of the mosquito. Whatever the case, thus far we seem to have been experiencing a stereotypical British winter: miserably grey, damp and mild. A taste of chilly winter weather lies in the offing later this week, and possibly lasting for much of January, but will it really deliver upon its promise? The Met Office, as is oft its wont, is being equivocal, and Piers Corbyn won't tell us that his predictions about the winter were 'right' until some time after the event when he can find some weather that tallies with a forecast that he had sold to his exclusive set of subscribers. Surely, 2013 must be better than 2012 meteorologically? We have not had a decent summer in over half a decade, so would it be too much to expect some fine weather for the summer of 2013?
True to form, the day after this article was posted Piers Corbyn popped up in The Daily Express to warn about the coming cold spell: "WeatherAction expects snow amounts to be as bad or worse than the record-breaking December 2010." Renowned for its exuberant exaggeration of all portents of snow and chill and its cavalier disregard for facts, the Express also added:
It's the same weather pattern responsible for the bitter 2009-2010 winter, the coldest for 31 years when transport networks were crippled and planes grounded. Icy easterly winds will sweep across Britain with everywhere at risk of wintry showers from the weekend and "significant snowfall" over high ground in Wales and the North.
The statement above is simply incorrect. Glaringly so. One of the notable features of the exceptionally low temperatures in the first month of the remarkable winter of 2009-2010 was the fact that the month of extreme chill with which it began was ushered in by a front issuing from the Arctic North, not from the East. It was bitter northerlies which prevailed during the coldest first four to five weeks of that winter that began with a surge of Arctic air during the last week of November. This is why the eastern counties of Britain and areas such as the North York Moors were particularly badly hit by snow. Facts? Now, why would journalists wish to bother with such irksome details as facts? I await the Express's first heatwave headlines with bated breath (sometime in March or early April perhaps?).
Arion Vulgaris: Spain's sluggish contribution to Britain's globalising fauna
Labels: Conservation, Daily Express, Environment, Flooding, Globalisation, Piers Corbyn, Weather, Weather Forecasting, Wildlife
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text:
Sinostand
Culture, politics and business of China
I Have No Idea What's Going to Happen in China and Neither Do You
Announcing My New Book: China's Millennials
Facebook and the Timing of Entering China
Why We Need to Stop Sharing Global Times Editorials
China's Troubled Media
Bogus Trend-spotting: Suicide Spates
4 Things We Overlook About Tiananmen
Meeting the Press
China Hang-up Relaunch
Getting "Educated"
On Xia Yeliang…
Video: Behind China's College Military Training
Will Zhou Stay or Will He Go?
The Hard Long Slog
Check Out "Living with Dead Hearts"
Balance vs. "Balance"
The Non-Negotiable "Ps"
Unquestionable Truths
The Absurdity of a Live Broadcast Execution
The Gaokao Highway to Hell
Southern Weekend's Stand: What It Is and What It Isn't
Cadres and Evangelists
SARFTing Forrest Gump
Desensitized in China
Foreign Journalists in Chinese State Media
Trouble at Foxconn? Quick! To the Bandwagon!
A Look Back at Hu Jintao in His Own Words
Some Thoughts on China's Countryside
Is the PLA up for a War?
Check out the EO Podcast
Video From Japanese Embassy Protests
On Beijing's Anti-Japan Protests
Behind the Great Oz's Curtain
Assigning Blame for a Hard Landing
Corruption: The Small Potatoes
Yet Another Brilliant Anti-Corruption Campaign
China's Happiest Day, Hong Kong's Dark Cloud
The Latest Game-Changing Chinese Innovation
Liang Fan's Reverence for the Chinese National Flag
The Greater Significance of the Forced Abortion Photo
What We Can Learn from China's Soccer Corruption
A Curious Sense of Justice
Foxconn: A Very Quiet Riot
One (Very Tiny) Reason to be Thankful for China's Censorship
Foreigners in China: Weibo vs. Reality
China's Bash Foreigner Free-for-all
Chinese Culture (28)
Posted: August 11, 2014 in media
Tags: China, journalism, media
Over the past few months, those who thought the state of Chinese journalism couldn't possibly get any worse have sadly been proven wrong. A few weeks ago China's chief censorship agency told Chinese reporters that they can't pass information on to their foreign counterparts, nor can they independently publicize stories they find through their work. This is on top of newly required courses in Marxist journalism (AKA journalism that props up the Party). While it's unlikely these regulations can or will be universally enforced, the intended message to journalists is clear: fall in line and keep your heads down.
This all fits with Xi Jinping's overall approach since assuming power of squashing every hint of potential challenge. In the Telegraph, a well-known journalism professor recently estimated that "the number of journalists responsible for 'independent, public-interest, negative or sensitive' reports has fallen by 66 percent in the last three years." This fits exactly with what I've seen. Among all the Chinese reporters I knew who were doing real investigative journalism two years ago, all but a few have shifted to more vanilla beats or left the field altogether.
Once upon a time, it was good to be an investigative journalist in China. In the late 1990s and early 2000s, we saw arguably the best officially sanctioned media atmosphere in PRC history. Muckraking private outlets like Caijing and Economic Observer sprouted up. Investigative journalist Wang Keqin came to prominence with stories on AIDS villages and securities fraud. And the Southern Media Group did a series of hard-hitting reports that actually prompted changes to long-standing government policies.
However, when Hu Jintao came to power in 2002, a gradual regression began to take shape. New rules against cross-provincial reporting emerged that culled watchdog media; a few editors in the Southern Media Group were slapped with lengthy prison sentences on trumped up charges; Caijing was put under pressure, prompting its star editor-in-chief Hu Shuli to jump ship; and Wang Keqin was unceremoniously pushed out of two separate newspapers.
Xi Jinping's new government now appears to be accelerating this trend. But politics is only half of the story in the regression of Chinese journalism.
The internet has had the same disruptive effect on traditional media in China that it has in much of the rest of the world. Weibo, WeChat and a host of other social media sites, blogs and pseudo media have sprung up, grabbing market share from the traditional press. This is coupled with independent watchdog papers being watered down. The same provocative stories officials don't want printed are usually the same ones that make people buy the papers. When repressive politics meet disruptive technology, it means tight budgets for independent papers that don't get government subsidies. This trickles down to journalists who see their income squeezed and jobs cut.
One implication of this is journalists from respected independent media getting funneled out and ending up at state media (where they can have more money and better resources, but more ideological oversight and censorship). I've known of a few journalists that couldn't bring themselves to leave journalism – either out of passion or because they lacked the skillset to go into another industry – so they reluctantly took jobs at state media after work at independent outlets dried up.
But what looks to be an even more acute implication of the current media atmosphere is good reporters getting pushed out of the industry completely. One of my former Economic Observer bosses, who's been reporting for the past two decades, recently reflected on trends of the past few years saying that we're seeing perhaps the biggest media brain drain ever. "People with dignity and passion get driven out of the newspaper business," he told me.
In 2012, Jian Guanzhou, the reporter who'd broken the Sanlu milk powder scandal four years earlier, drove this point home when he finally decided to call it quits. "I have been at the Oriental Morning Post for 10 years, during which I have poured the most precious years of my youth, my sorrow, my dreams and feelings into the purest of ideals," he wrote on Weibo. "Now my ideal is dead, so I'll get going. Take care, brothers!"
Working within China's tightening media system entails an endless stream of moral dilemmas. If a story could be killed for political reasons, for instance, it might make a reporter think twice about pursuing it in the first place. In most cases, they get paid based on how much they publish. If the story isn't published, they don't get paid for it. Even if they're willing to risk their necks to investigate and print these sensitive stories, the scope of allowable topics is shrinking, leading to moral and financial frustration. Many just can't do it anymore and quit journalism to go into something more stable or morally straightforward. On the grand scale, as this happens and honest reporters with a moral compass get sifted out, corrupt and sycophantic peers take over.
There are no meaningful statistics, but in talking to several Chinese journalist friends over the past few months, there seems to be a feeling that the entire industry is getting dirtier. Making money through good honest reporting is a lot harder than it once was, meaning the allure of taking bribes and colluding with (or extorting) special interests becomes greater. So there may be some semblance of legitimacy to the government's ostensible drive to "clean up" the media.
A sullying of the industry may be the downside, but this atmosphere is certainly conducive to keeping the CCP unchallenged. The days when the Party had to seriously worry about shutting down watchdog newspapers and clipping the wings of renegade reporters might be drawing to a close. Instead, it can just watch the papers struggle to stay afloat and the journalists sort themselves into less threatening positions…or out of the industry completely.
There are of course plenty of fantastic Chinese reporters still out there pushing what they can for the pittance they get in return. One friend reporting in the Southern Media Group recently told me that the tightening atmosphere makes him regret not pushing harder in earlier years when things were more open. But this is the new reality, which only looks to hold more heartbreak ahead. "For us reporters, new changes must happen," he told me. "I just don't know how they'll go."
Daniel Bouysou says:
Sad, good journalist do not give up.
Does this new style of repressive journalism have anything to do with the closing of 70+ newsstands in the CBD?
justrecently says:
Deutsche Welle, on the other hand, is absolutely mesmerized about the opportunities in the PRC.


Join Pastor Stu for a 13-week class that is open to anyone wanting to learn more on the foundations of theology. The class starts March 8th and will run on Wednesday nights at 7pm through the end of May. It will require outside reading and preparation.