Evaluation of a Commercial Enzyme Linked Immunosorbent Assay (ELISA) for the Determination of the Neurotoxin BMAA in Surface Waters

The neurotoxin ß-N-methylamino-L-alanine (BMAA) is suspected to play a role in Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. Because BMAA seems to be produced by cyanobacteria, surface waters are screened for BMAA. However, reliable analysis of BMAA requires specialized and expensive equipment. In 2012, a commercial enzyme-linked immunosorbent assay (ELISA) for determination of BMAA in surface waters was released. This kit could enable fast and relatively cheap screening of surface waters for BMAA. The objective of this study was to determine whether the BMAA ELISA kit was suitable for the determination of BMAA concentrations in surface waters. We hypothesised that the recovery of spiked samples was close to 100% and that the results of unspiked sample analysis were comparable between ELISA and liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. However, we found that recovery was higher than 100% in most spiked samples, highest determined recovery was over 400%. Furthermore, the ELISA gave a positive signal for nearly each tested sample while no BMAA could be detected by LC-MS/MS. We therefore conclude that in its current state, the kit is not suitable for screening surface waters for BMAA

Perturbation theory for very long-range potentials

Systems with very long-range interactions (that decay at large distances like $U(r)\sim r^{-l}$ with $l\le d$ where $d$ is the space dimensionality) are difficult to study by conventional statistical mechanics perturbation methods. Examples of these systems are gravitational and charged (non-electroneutral). In this work we propose two alternative methodologies to avoid these difficulties and capture some of the properties of the original potential. The first one consists in expressing the original potential in terms of a finite sum of hard-core Yukawa potentials. In the second one, the potential is rewritten as a damped potential, using a damping function with a parameter that controls the range of the interaction. These new potentials, which mimic the original one, can now be treated by conventional statistical mechanics methods.Comment: 25 pages, 11 figure

Combination of KIR2DS4 and FcγRIIa polymorphisms predicts the response to cetuximab in KRAS mutant metastatic colorectal cancer

Cetuximab is a standard-of-care treatment for RAS wild-type metastatic colorectal cancer (mCRC) but not for those harbor a KRAS mutation since MAPK pathway is constitutively activated. Nevertheless, cetuximab also exerts its effect by its immunomodulatory activity despite the presence of RAS mutation. The aim of this study was to determine the impact of polymorphism FcγRIIIa V158F and killer immunoglobulin-like receptor (KIR) genes on the outcome of mCRC patients with KRAS mutations treated with cetuximab. This multicenter Phase II clinical trial included 70 mCRC patients with KRAS mutated. We found KIR2DS4 gene was significantly associated with OS (HR 2.27; 95% CI, 1.08–4.77; P = 0.03). In non-functional receptor homozygotes the median OS was 2.6 months longer than in carriers of one copy of full receptor. Multivariate analysis confirmed KIR2DS4 as a favorable prognostic marker for OS (HR 6.71) in mCRC patients with KRAS mutation treated with cetuximab. These data support the potential therapeutic of cetuximab in KRAS mutated mCRC carrying non-functional receptor KIR2DS4 since these patients significantly prolong their OS even after heavily treatment. KIR2DS4 typing could be used as predictive marker for identifying RAS mutated patients that could benefit from combination approaches of anti-EGFR monoclonal antibodies and other immunotherapies to overcome the resistance mediated by mutation in RAS.This clinical trial was approved and supported by Merck S.L., an affiliate of Merck KGaA, Darmstadt. Germany [research project number 2010-023580-18, date: 05-06-2014

Why don't we treat chronic hepatitis C in HIV patients? Results from a cohort of HIV-HCV coinfected patients from the southeast of Spain

Purpose of the study: To know the different reasons why we decide not to treat or to delay the antiviral treatment against HCV in HIV coinfected patients. Methods: Prospective cohort of HIV and HCV coinfected patients, followed in the Infectious Diseases Department of the Santa Lucia Universitary Hospital (Cartagena, Spain) between 1/12/2011 and 28/02/2012 in which we made transitory elastography. We evaluated the main reasons that moved us to decide not to treat or to delay the antiviral treatment against HCV: social-familiar-laboral reasons; neuro-psychiatric severe diseases; patient decision; low grade hepatic fibrosis; previous failure to pegylated interferon (IFN) and ribavirin (RBV) in no-1 genotype patients; delay in the approval of the triple therapy with INF-RBV and a protease inhibitor (boceprevir or telaprevir) by the Regional Sanitary Authority; active alcohol abuse; active diseases that contraindicate the antiviral treatment, incomplete study of HCV (VL of HCV, genotype, ILB28, abdominal ecography); previous intolerance against IFN-RBV and severe thrombocytopenia (<50×109/L). Summary of results: The cohort included 109 patients, being 27 of them females (25%) and 82 males (75%), with a median of age of 45.8 years (SD: 6.2). In 98 patients (90%) we decided not to treat or to delay the antiviral treatment against HCV for one or more of the following reasons: 37 (34%) presented low grade hepatic fibrosis (<9.5 kpascal or F0-F2); 19 (17%) had neuro-psychiatric diseases; 18 (16.5%) were waiting for the approval of triple therapy by the Regional Sanitary Authority; 10 (9.2%) did not want to be treated; 10 (9.2%) had failure to IFN-RBV in no-1 genotype; 6 (5.5%) had social-familiar-laboral reasons; 6 (5.5%) presented active severe diseases; 4 (3.7%) were waiting to complete HCV study; 3 (2.8%) presented active alcohol abuse; 3 (2.8%) had previous intolerance against IFN-RBV treatment and 2 (2%) had severe thrombocytopenia. Conclusions: In our cohort of HIV-HCV coinfected patients it was decided to delay or not to treat chronic hepatitis C in a significant proportion of subjects. The low grade of hepatic fibrosis measured with transitory elastography was the main reason for delaying the HCV antiviral treatment. The neuro-psychiatric disease was the main clinical reason to not treat HCV. The delay of the approval of triple therapy treatment by the Regional Sanitary Authority was the most relevant non- clinical reason in our prospective study

Radiaciones ionizantes y su impacto Primer Simposio Internacional sobre Medioambiente (ISE 2017)

Son ya varias las décadas en las que en América Latina se ha trabajado arduamente sobre las radiaciones ionizantes; tanto en las ionizantes directas, tales como las partículas beta positivas y negativas, las partículas alfa, los protones, los mesones cargados, los muones y los iones pesados, así como también en las ionizantes indirectas (las producidas por partículas sin cargas), como las generadas por fotones con energías superiores a los 10 keV y los neutrones. Por otro lado, las radiaciones no ionizantes también han sido objeto de detallados estudios, y muy especialmente las provenientes del Sol, como el factor natural más influyente sobre la Tierra. En esta obra se presentan algunos de los avances en los que han participado reconocidos científicos latinoamericanos, como el Dr. Héctor Vega Carrillo, Dr. Daniel Palacios, Dra. Patrizia Pereyra, Dra. Sheila Serrano, y el Dr. Manuel Ernesto Delgado, entre otros. Esta obra puede ser de interés para profesionales del área de la protección radiológica, la ingeniería ambiental, física de la atmósfera y áreas afines, así como para estudiantes

Adipose tissue concentrations of persistent organic pollutants and total cancer risk in an adult cohort from Southern Spain: Preliminary data from year 9 of the follow-up

There is an increasing trend in the incidence of cancer worldwide, and it has been accepted that environmental factors account for an important proportion of the global burden. The present paper reports preliminary findings on the influence of the historical exposure to a group of persistent organic pollutants on total cancer risk, at year 9 in the follow-up of a cohort from Southern Spain. A cohort of 368 participants (median age 51 years) was recruited in 2003. Their historical exposure was estimated by analyzing residues of persistent organic pollutants in adipose tissue. Estimation of cancer incidence was based on data from a population-based cancer registry. Statistical analyses were performed using multivariable Cox-regression models. In males, PCB 153 concentrations were positively associated with total cancer risk, with an adjusted hazard ratio (95% confidence interval) of 1.20 (1.01–1.41) for an increment of 100 ng/g lipid. Our preliminary findings suggest a potential relationship between the historical exposure to persistent organic pollutants and the risk of cancer in men. However, these results should be interpreted with caution and require verification during the future follow-up of this cohort.This study was supported in part by research grants from the Spanish Ministry of Health (FIS 02/974, EUS2008-03574), CIBER de Epidemiología; Junta de Andalucía (01/264, P09-CTS-5488 Project of Excellence, PI-0675-2010, and PI-0513-2012), and the Instituto de Salud Carlos III (FIS PI11/0610)