P2X7 receptor in epilepsy; role in pathophysiology and potential targeting for seizure control.

The P2X7 receptor is an ATP-gated non-selective cation-permeable ionotropic receptor selectively expressed in neurons and glia in the brain. Activation of the P2X7 receptor has been found to modulate neuronal excitability in the hippocampus and it has also been linked to microglia activation and neuroinflammatory responses. Accordingly, interest developed on the P2X7 receptor in disorders of the nervous system, including epilepsy. Studies show that expression of the P2X7 receptor is elevated in damaged regions of the brain after prolonged seizures (status epilepticus) in both neurons and glia. P2X7 receptor expression is also increased in the hippocampus in experimental epilepsy. Recent data show that mice lacking the P2X7 receptor display altered susceptibility to status epilepticus and that drugs targeting the P2X7 receptor have potent anticonvulsant effects. Together, this suggests that P2X7 receptor ligands may be useful adjunctive treatments for refractory status epilepticus or perhaps pharmacoresistant epilepsy. This review summarizes the evidence of P2X7 receptor involvement in the pathophysiology of epilepsy and the potential of drugs targeting this receptor for seizure control

Treatment of a Complex Distal Triceps Tendon Rupture With a New Technique: A Case Report

Introduction: The distal triceps tendon rupture is an uncommon injury. The acute treatment is well-defined, but when a delayed diagnosis is made or when a tendon retraction is present the alternatives or reconstruction are limited and sometimes complex. Case Presentation: In this case, we report on a 28-year-old man who presented with a chronic disruption of the distal triceps tendon with a gap of approximately 15 cm. The patient was diagnosed in another center with an inveterate breakage of the distal triceps tendon and was initially treated with an Achilles allograft that was complicated by a wound infection and required more than ten surgeries. Nearly 22 months after the initial trauma, and 12 months after the first surgery, we performed a reconstruction with an Achilles tendon allograft using the new technique of distal attachment. At the 12-month follow-up the patient presented a joint balance from -5º to 110º and presented with no pain. Conclusions: The use of an Achilles tendon allograft provides excellent results in complex distal triceps tendon ruptures. We report the use of a new technique to anchor a distal Achilles allograft

Co-application of activated carbon and compost to contaminated soils: toxic elements mobility and PAH degradation and availability

This work assesses the suitability of three commercial activated carbons (ACs) and their combination with olive mill waste compost (AC + C) as amendments for the remediation of two different contaminated soils. The treatments were applied to a mining soil, and their ability to immobilize trace elements was evaluated. Besides, the efficiency of the amendments to degrade and reduce the availability of polycyclic aromatic hydrocarbons (PAHs) was investigated in a soil from a wood creosote treatment plant. To this aim, trace elements mobility and PAH degradation and availability were evaluated. Ecotoxicological assays were performed to assess potential toxicity risks in the untreated and the amended soils. In the mining soil, the ACs were able to immobilize metals and As, but the AC + C treatments were more effective than AC. In the PAH-polluted soil, AC treatments promoted the degradation of high molecular weight PAH, but the AC + C amendments further enhanced the degradation of total PAH and reduced the availability of those with 3-rings. The ecotoxicological tests demonstrated an improvement of soil quality when AC and compost were applied together. In conclusion, the co-application of AC and compost reduces the mobility of potentially toxic elements in the polluted mine soil and enhances PAH degradation and reduces PAH availability in the creosote-contaminated soilThis work was fnancially supported by the Ministry of Economy and Competitiveness of Spain, projects CTM2013-47874-C2-R and CTM2013-48697-C2-

Mortality attributable to extreme temperatures in Spain: A comparative analysis by city

BACKGROUND: The Low Temperature Days (LTD) have attracted far less attention than that of High Temperature Days (HTD), though its impact on mortality is at least comparable. This lower degree of attention may perhaps be due to the fact that its influence on mortality is less pronounced and longer-term, and that there are other concomitant infectious winters factors. In a climate-change scenario, the studies undertaken to date report differing results. The aim of this study was to analyse mortality attributable to both thermal extremes in Spain's 52 provinces across the period 2000-2009, and estimate the related economic cost to show the benefit or "profitability" of implementing prevention plans against LTD. METHODS: Previous studies enabled us: to obtain the maximum daily temperature above which HTD occurred and the minimum daily temperature below which LTD occurred in the 52 provincial capitals analysed across the same study period; and to calculate the relative and attributable risks (%) associated with daily mortality in each capital. These measures of association were then used to make different calculations to obtain the daily mean mortality attributable to both thermal extremes. To this end, we obtained a summary of the number of degrees whereby the temperature exceeded (excess °C) or fell short (deficit °C) of the threshold temperature for each capital, and calculated the respective number of extreme temperatures days. The economic estimates rated the prevention plans as being 68% effective. RESULTS: Over the period considered, the number of HTD (4373) was higher than the number of LTD (3006) for Spain as a whole. Notwithstanding this, in every provincial capital the mean daily mortality attributable to heat was lower (3deaths/day) than that attributable to cold (3.48deaths/day). In terms of the economic impact of the activation of prevention plans against LTD, these could be assumed to avoid 2.37 deaths on each LTD, which translated as a saving of €0.29M. Similarly, in the case of heat, 2.04 deaths could be assumed to be avoided each day on which the prevention plan against HTD was activated, amounting to a saving of €0.25M. While the economic cost of cold-related mortality across the ten-year period 2000-2009 was €871.7M, that attributable to heat could be put at €1093.2M. CONCLUSION: The effect of extreme temperatures on daily mortality was similar across the study period for Spain overall. The lower number of days with LTD meant, however, that daily cold-related mortality was higher than daily heat-related mortality, thereby making prevention plans against LTD more "profitable" prevention plans against HTD in terms of avoidable mortality.This study was supported by grants FIS ENPY 1001/13 & SEPY 1037/14 from Spain's Health Research Fund.S

Economic burden of air pollution in Colombia

To estimate indirect costs related to the loss of productivity due to premature mortality associated with air quality risk factors in Colombia, 2016. We estimated potential productivity years of life lost (PPYLL) related to indoor (biomass fuels) and outdoor pollution (PM2.5 and ozone). We analyzed deaths records of the Departamento Administrativo Nacional de Estadística, 2016, with the following basic causes of death related to air quality risk factors: isquemic hearth disease (IHD), cardiovascular disease (CD), lower respiratory tract infections (LRTI), lung cancer (LC) and chronic obstructive pulmonary disease(COPD), according to ICD-10. PPYLL were valued considering the productive age in Colombia, which ranges from 18-57 years for women and up to 62 for men. Three scenarios were built: lower loss (minimum legal wage), average loss [one per capita gross domestic product (GDPpc)] and higher loss (three GDPpc). PPYLL for the mentioned causes were multiplied by the fraction attributable to each air risk factor. The latest were estimated from IDEAM (outdoor) and the survey of Quality of Life 2016 and systematic reviews (indoor pollution). Costs were reported in American dollars, using the December 31 (2016) exchange rate: 1USD=3,000.7 Colombian Pesos. The economic burden due to premature deaths caused by the analyzed diseases was US$845,967,999 ($444,320,058-$2,537,903,997). From this burden, 17.8$150,585,143 ($79,090,461-451,755,428). Regarding to the studied diseases, IHD deaths caused by air quality risk factors accounted US$83.007.582. The second with the highest economic burden attributable to air quality risk factors was CD (US$32,750,315), followed by LRTI (US$22,077,091), LC (US$6,909,659) and COPD (US$5,840,495). The exposure to PM2.5 particulate matter represented the largest share of the economic burden attributable to air quality risk factors. Our estimations suggest that premature deaths caused by exposure to air qualityrisk factors represented 0.052% of GDP for 2016

Out-of-pocket health expenditures in Colombia: a systematic review

Objectives To review the evidence of out-of-pocket (OOPE) and catastrophic expenditures (CHE) in health in Colombia. Methods Systematic review of the literature (SLR). Searches were performed in PubMed, Scopus, Scielo and Google Scholar. We used the MESH terms: out-of-pocket, catastrophic health expenditure, health and Colombia. We included cost description or cost analysis studies. Cost-effectiveness analysis of health technologies and qualitative studies were excluded. Data about period of analysis, type of study, costing perspective, OOPE, and CHE were extracted. Studies were classified as macroeconomic, microeconomic, and diseases analysis. All costs were indexed to 2018 and reported in Colombian pesos (COP)

Serum melatonin levels during the first seven days of severe sepsis diagnosis are associated with sepsis severity and mortality

Objective: Higher serum melatonin levels have previously been found in patients with severe sepsis who died within 30 days of diagnosis than in survivors. The objective of our study were to determine whether serum melatonin levels during the first seven days of severe sepsis diagnosis could be associated with sepsis severity and mortality. Methods: Multicentre study in eight Spanish Intensive Care Units which enrolled 308 patients with severe sepsis. We determined serum levels of melatonin, malondialdehyde (as biomarker of lipid peroxidation) and tumor necrosis factor-alpha at days 1, 4 and 8 of severe sepsis diagnosis. The study's primary endpoint was 30-day mortality. Results: A total of 103 patients had died and 205 survived at 30 days of severe sepsis diagnosis, with the non-survivors presenting higher serum melatonin levels at days 1 (p<0.001), 4 (p<0.001) and 8 (p<0.001) of severe sepsis diagnosis than the survivor patient group. The multiple logistic regression analysis found that serum melatonin levels at days 1, 4 and 8 of severe sepsis diagnosis (p<0.001, p = 0.01 and p = 0.001, respectively) were associated with mortality adjusted for age, serum lactic acid, SOFA score and diabetes mellitus. Conclusions: The novel and more interesting findings of our study were that serum melatonin levels during the first seven days of severe sepsis diagnosis are associated with sepsis severity and mortality. (C) 2017 Elsevier Espana, S.L.U. and Sociedad Espanola de Enfermedades lnfecciosas y Microbiologia Clinica

Metalloproteinase-dependent TLR2 ectodomain shedding is involved in soluble toll-like receptor 2 (sTLR2) production

Toll-like receptor (TLR) 2, a type I membrane receptor that plays a key role in innate immunity, recognizes conserved molecules in pathogens, and triggering an inflammatory response. It has been associated with inflammatory and autoimmune diseases. Soluble TLR2 (sTLR2) variants have been identified in human body fluids, and the TLR2 ectodomain can negatively regulate TLR2 activation by behaving as a decoy receptor. sTLR2 generation does not involve alternative splicing mechanisms, indicating that this process might involve a post-translational modification of the full-length receptor; however, the specific mechanism has not been studied. Using CD14+ peripheral human monocytes and the THP-1 monocytic leukemia-derived cell line, we confirm that sTLR2 generation increases upon treatment with pro-inflammatory agents and requires a post-translational mechanism. We also find that the constitutive and ligand-induced release of sTLR2 is sensitive to pharmacological metalloproteinase activator and inhibitors leading us to conclude that metalloproteinase TLR2 shedding contributes to soluble receptor production. By expressing human TLR2 in ADAM10- or ADAM17-deficient MEF cells, we find both enzymes to be implicated in TLR2 ectodomain shedding. Moreover, using a deletion mutant of the TLR2 juxtamembrane region, we demonstrate that this domain is required for sTLR2 generation. Functional analysis suggests that sTLR2 generated by metalloproteinase activation inhibitsTLR2-induced cytokine production by this monocytic leukemia-derived cell line. The identification of the mechanisms involved in regulating the availability of soluble TLR2 ectodomain and cell surface receptors may contribute further research on TLR2-mediated processes in innate immunity and inflammatory disorders