Relationship between maximum clot firmness in ROTEM® and postoperative bleeding after coronary artery bypass graft surgery in patients using clopidogrel

Background: The aim of the present study was to investigate the relationship between maximum clot firmness (MCF) in rotational thromboelastometry (ROTEM®) and postoperative bleeding in patients on clopidogrel after emergency coronary artery bypass graft surgery (CABG). Methods: This observational study recruited 60 patients posted for emergency CABG following unsuccessful primary percutaneous coronary intervention (PCI) while on 600 mg of clopidogrel. The study population was divided into 2 groups on the basis of their MCF in the extrinsically activated thromboelastometric (EXTEM) component of the (preoperative) ROTEM® test: patients with MCF <50 mm (n = 16) and those with MCF �50 mm (n = 44). Postoperative chest tube drainage amount, need for blood product transfusion, postoperative complications, and duration of mechanical ventilation after CABG were recorded. Results: No significant differences were observed between the two groups regarding duration of surgery, cardiopulmonary bypass, and aortic cross-clamp time. Chest tube drainage at 6, 12, and 24 h after Intensive Care Unit admission were significantly higher in the patients with MCF below 50 mm. The need for blood product transfusion was higher in the group with MCF <50 mm. In patients who experienced postoperative bleeding of 1000 mL or more, the ROTEM® parameters of INTEM (Intrinsically activated thromboelastomery) and MCF, EXTEM and MCF, and HEPTEM (INTEM assay performed in the presence of heparinase) MCF (but not FIBTEM (Thromboelastometric assay for the fibrin part of the clot) values) were significantly lower than those with postoperative bleeding <1000 mL (P � 0.05). Conclusions: When platelet aggregometry is not available, the ROTEM® test could be useful for the prediction of increased risk bleeding after emergency CABG in patients who have received a loading dose of clopidogrel. © 2018 Annals of Cardiac Anaesthesia | Published by Wolters Kluwer - Medknow

Increased function of pronociceptive TRPV1 at the level of the joint in a rat model of osteoarthritis pain

Objectives Blockade of transient receptor potential vanilloid 1 (TRPV1) with systemic antagonists attenuates osteoarthritis (OA) pain behaviour in rat models, but on-target-mediated hyperthermia has halted clinical trials. The present study investigated the potential for targeting TRPV1 receptors within the OA joint in order to produce analgesia. Methods The presence of TRPV1 receptors in human synovium was detected using western blotting and immunohistochemistry. In a rat model of OA, joint levels of an endogenous ligand for TRPV1, 12- ydroxyeicosatetraenoic acid (12-HETE), were quantified using liquid chromatography-tandem mass spectrometry (LCMS/MS). Effects of peripheral administration of the TRPV1 receptor antagonist JNJ-17203212 on afferent fibre activity, pain behaviour and core body temperature were investigated. Effects of a spinal administration of JNJ-17203212 on dorsal horn neuronal responses were studied. Results We demonstrate increased TRPV1 immunoreactivity in human OA synovium, confirming the diseased joint as a potential therapeutic target for TRPV1-mediated analgesia. In a model of OA pain, we report increased joint levels of 12-HETE, and the sensitisation of joint afferent neurones to mechanical stimulation of the knee. Local administration of JNJ- 17203212 reversed this sensitisation of joint afferents and inhibited pain behaviour (weight-bearing asymmetry), to a comparable extent as systemic JNJ- 17203212, in this model of OA pain, but did not alter core body temperature. There was no evidence for increased TRPV1 function in the spinal cord in this model of OA pain. Conclusions Our data provide a clinical and mechanistic rationale for the future investigation of the therapeutic benefits of intra-articular administration of TRPV1 antagonists for the treatment of OA pain

EMA-amplicon-based sequencing informs risk assessment analysis of water treatment systems

Illumina amplicon-based sequencing was coupled with ethidium monoazide bromide (EMA) pre-treatment to monitor the total viable bacterial community and subsequently identify and prioritise the target organisms for the health risk assessment of the untreated rainwater and rainwater treated using large-volume batch solar reactor prototypes installed in an informal settlement and rural farming community. Taxonomic assignments indicated that Legionella and Pseudomonas were the most frequently detected genera containing opportunistic bacterial pathogens in the untreated and treated rainwater at both sites. Additionally, Mycobacterium, Clostridium sensu stricto and Escherichia/Shigella displayed high (≥80%) detection frequencies in the untreated and/or treated rainwater samples at one or both sites. Numerous exposure scenarios (e.g. drinking, cleaning) were subsequently investigated and the health risk of using untreated and solar reactor treated rainwater in developing countries was quantified based on the presence of L. pneumophila, P. aeruginosa and E. coli. The solar reactor prototypes were able to reduce the health risk associated with E. coli and P. aeruginosa to below the 1 × 10−4 annual benchmark limit for all the non-potable uses of rainwater within the target communities (exception of showering for E. coli). However, the risk associated with intentional drinking of untreated or treated rainwater exceeded the benchmark limit (E. coli and P. aeruginosa). Additionally, while the solar reactor treatment reduced the risk associated with garden hosing and showering based on the presence of L. pneumophila, the risk estimates for both activities still exceeded the annual benchmark limit. The large-volume batch solar reactor prototypes were thus able to reduce the risk posed by the target bacteria for non-potable activities rainwater is commonly used for in water scarce regions of sub-Saharan Africa. This study highlights the need to assess water treatment systems in field trials using QMRA

Characterisation of a Peripheral Neuropathic Component of the Rat Monoiodoacetate Model of Osteoarthritis

Joint degeneration observed in the rat monoiodoacetate (MIA) model of osteoarthritis shares many histological features with the clinical condition. The accompanying pain phenotype has seen the model widely used to investigate the pathophysiology of osteoarthritis pain, and for preclinical screening of analgesic compounds. We have investigated the pathophysiological sequellae of MIA used at low (1 mg) or high (2 mg) dose. Intra-articular 2 mg MIA induced expression of ATF-3, a sensitive marker for peripheral neuron stress/injury, in small and large diameter DRG cell profiles principally at levels L4 and 5 (levels predominated by neurones innervating the hindpaw) rather than L3. At the 7 day timepoint, ATF-3 signal was significantly smaller in 1 mg MIA treated animals than in the 2 mg treated group. 2 mg, but not 1 mg, intra-articular MIA was also associated with a significant reduction in intra-epidermal nerve fibre density in plantar hindpaw skin, and produced spinal cord dorsal and ventral horn microgliosis. The 2 mg treatment evoked mechanical pain-related hypersensitivity of the hindpaw that was significantly greater than the 1 mg treatment. MIA treatment produced weight bearing asymmetry and cold hypersensitivity which was similar at both doses. Additionally, while pregabalin significantly reduced deep dorsal horn evoked neuronal responses in animals treated with 2 mg MIA, this effect was much reduced or absent in the 1 mg or sham treated groups. These data demonstrate that intra-articular 2 mg MIA not only produces joint degeneration, but also evokes significant axonal injury to DRG cells including those innervating targets outside of the knee joint such as hindpaw skin. This significant neuropathic component needs to be taken into account when interpreting studies using this model, particularly at doses greater than 1 mg MIA

Synthesis of silver nanoparticles and its synergistic effects in combination with imipenem and two biocides against biofilm producing Acinetobacter baumannii

Objectives: Biofilms are communities of bacteria attached to surfaces through an external polymeric substances matrix. In the meantime, Acinetobacterbaumanniiis the predominant species related to nosocomial infections. In the present study, the effect of silver nanoparticles alone and in combination with biocides and imipenem against planktonic and biofilms of A. baumannii was assessed. Materials and Methods: Minimum inhibitory concentrations (MICs) of 75 planktonic isolates of A. baumannii were determined by using the microdilution method as described via clinical and laboratory standards institute (CLSI). Among all strains, 10 isolates which formed strong biofilms were selected and exposed to silver nanoparticles alone and in combination with imipenem, bismuth ethandithiol (BisEDT) and bismuth propanedithiol (BisPDT) to determine minimum biofilm inhibitory concentrations (MBIC). Subsequently, minimum biofilm eradication concentrations (MBECs) of silver nanoparticles alone and in combination with imipenem against mature biofilm of the isolates were evaluated. Results: Results showed that 29.3% of isolates were susceptible to silver nanoparticles and could inhibit the growth and eradicate biofilms produced by the isolates. For this reason, ∑FIC, ∑FBIC and ∑FBEC ≤ 0.05 were reported which shows synergism between silver nanoparticles and imipenem against not only planktonic cells but also inhibition and eradication of biofilms. The results of ∑FBIC >2 indicated to antagonistic impacts between silver nanoparticles and BisEDT/BisPDT against biofilms. Conclusion: It can be concluded that silver nanoparticles alone can inhibit biofilm formation but in combination with imipenem are more effective against A. baumannii in planktonic and biofilm forms