Investigating Inflammatory Pathways as Therapeutic Targets and Biomarkers using Functional Imaging and Pharmacological Interventions in Epilepsy Models.

Epilepsy is a neurological disorder that is characterised by spontaneous seizures. After various epileptogenic injuries, astrocytes become dysfunctional and experimental evidence indicates that these cells contribute to seizure mechanisms. The generation of inflammatory molecules in astrocytes appears to play a key pathogenic role in seizures. However, astrocytes may also contribute to repair the hyperexcitable neuronal networks underlying seizures. We focused our studies on understanding the role of astrocytes in epilepsy by (1) developing a new in vivo imaging method to monitor astrocytic cell activation during epileptogenesis and coupled this with their phenotypic characterization; (2) studying the role of Toll-like receptor 3 (TLR3) signaling in seizure mechanisms. We report that in vivo bioluminescence imaging is a powerful tool for monitoring astrocytic activation in diseased conditions. Characterization of astrocytic activation during epileptogenesis showed a rapid cell activation corresponding to their inflammatory phenotype while homeostatic (neuroprotective) mechanisms were activated with a delay. Moreover, we demonstrate that in vivo imaging of astrocyte activation allows to study the potential involvement of these cells in the therapeutic effects of anti-inflammatory drugs. We also show that priming TLR3 activation in astrocytes with the use of a synthetic agonist results in remarkable anti-inflammatory and anti-ictogenic effects. Mechanistic studies revealed that interferon regulatory factor (IRF)-3/Interferon-β mediated cascade is likely responsible for the inhibitory effects of TLR3 priming on seizures and neuronal excitability. In summary, astroglia activation during the critical epileptogenesis phase provides a potential target for interfering in a timely manner with the inflammatory phenotype of these cells contributing to seizures. Importantly, there are astrocytic cell functions that mediate decreased neuronal excitability and they should be carefully considered when developing treatments targeting these cells for therapeutic purposes

Innovative Magnetic Aggregates for the Removal of Transition Metals from Industrial Wastewater

A novel adsorbent material based on microaggregates of Fe3O4 magnetic nanoparticles functionalized with succinic acid has been developed. The magnetic aggregates (MA) were characterized in terms of the size distribution (master sizer analysis), morphology (TEM), chemical structure (IR-spectroscopy and XRD), magnetic properties (VSM), and Z-Potential. The effects of various parameters such as contact time, dosage of magnetic aggregates, the amount of succinic acid on the magnetic aggregates on the adsorption capacity, as well as the efficiency of the treatment in the adsorption of two transition metals, copper (Cu) and zinc (Zn) from real wastewater, were investigated. The kinetic behavior was analyzed by using the Lagergren pseudo-first-order, pseudo-second-order, and Elovich and intra-particle diffusion models. Langmuir and Freundlich’s models were applied to simulate the adsorption equilibrium. The magnetic aggregates reached the equilibrium condition relatively fast, within 10 min. Magnetic aggregates with a higher amount of succinic acid in their formulation showed a higher adsorption capacity of the two metals in all the experiments. This is consistent with the adsorption mechanism mainly based on electrostatic interaction between the metal ions and the negative charges on the surface of magnetic aggregates. A higher adsorption capacity for the removal of copper compared to zinc was found. Additionally, the electrochemical characterization of the magnetic aggregates was done as a preliminary study for proposing a regeneration method of the MA along with the extraction metals adsorbed based on an electrochemical process

Critical care admission following elective surgery was not associated with survival benefit: prospective analysis of data from 27 countries

This was an investigator initiated study funded by Nestle Health Sciences through an unrestricted research grant, and by a National Institute for Health Research (UK) Professorship held by RP. The study was sponsored by Queen Mary University of London

Prospective observational cohort study on grading the severity of postoperative complications in global surgery research

Background The Clavien–Dindo classification is perhaps the most widely used approach for reporting postoperative complications in clinical trials. This system classifies complication severity by the treatment provided. However, it is unclear whether the Clavien–Dindo system can be used internationally in studies across differing healthcare systems in high- (HICs) and low- and middle-income countries (LMICs). Methods This was a secondary analysis of the International Surgical Outcomes Study (ISOS), a prospective observational cohort study of elective surgery in adults. Data collection occurred over a 7-day period. Severity of complications was graded using Clavien–Dindo and the simpler ISOS grading (mild, moderate or severe, based on guided investigator judgement). Severity grading was compared using the intraclass correlation coefficient (ICC). Data are presented as frequencies and ICC values (with 95 per cent c.i.). The analysis was stratified by income status of the country, comparing HICs with LMICs. Results A total of 44 814 patients were recruited from 474 hospitals in 27 countries (19 HICs and 8 LMICs). Some 7508 patients (16·8 per cent) experienced at least one postoperative complication, equivalent to 11 664 complications in total. Using the ISOS classification, 5504 of 11 664 complications (47·2 per cent) were graded as mild, 4244 (36·4 per cent) as moderate and 1916 (16·4 per cent) as severe. Using Clavien–Dindo, 6781 of 11 664 complications (58·1 per cent) were graded as I or II, 1740 (14·9 per cent) as III, 2408 (20·6 per cent) as IV and 735 (6·3 per cent) as V. Agreement between classification systems was poor overall (ICC 0·41, 95 per cent c.i. 0·20 to 0·55), and in LMICs (ICC 0·23, 0·05 to 0·38) and HICs (ICC 0·46, 0·25 to 0·59). Conclusion Caution is recommended when using a treatment approach to grade complications in global surgery studies, as this may introduce bias unintentionally

The surgical safety checklist and patient outcomes after surgery: a prospective observational cohort study, systematic review and meta-analysis

© 2017 British Journal of Anaesthesia Background: The surgical safety checklist is widely used to improve the quality of perioperative care. However, clinicians continue to debate the clinical effectiveness of this tool. Methods: Prospective analysis of data from the International Surgical Outcomes Study (ISOS), an international observational study of elective in-patient surgery, accompanied by a systematic review and meta-analysis of published literature. The exposure was surgical safety checklist use. The primary outcome was in-hospital mortality and the secondary outcome was postoperative complications. In the ISOS cohort, a multivariable multi-level generalized linear model was used to test associations. To further contextualise these findings, we included the results from the ISOS cohort in a meta-analysis. Results are reported as odds ratios (OR) with 95% confidence intervals. Results: We included 44 814 patients from 497 hospitals in 27 countries in the ISOS analysis. There were 40 245 (89.8%) patients exposed to the checklist, whilst 7508 (16.8%) sustained ≥1 postoperative complications and 207 (0.5%) died before hospital discharge. Checklist exposure was associated with reduced mortality [odds ratio (OR) 0.49 (0.32–0.77); P\u3c0.01], but no difference in complication rates [OR 1.02 (0.88–1.19); P=0.75]. In a systematic review, we screened 3732 records and identified 11 eligible studies of 453 292 patients including the ISOS cohort. Checklist exposure was associated with both reduced postoperative mortality [OR 0.75 (0.62–0.92); P\u3c0.01; I2=87%] and reduced complication rates [OR 0.73 (0.61–0.88); P\u3c0.01; I2=89%). Conclusions: Patients exposed to a surgical safety checklist experience better postoperative outcomes, but this could simply reflect wider quality of care in hospitals where checklist use is routine