Treatment of hemorrhagic shock with hypertonic saline solution modulates the inflammatory response to live bacteria in lungs

Shock and resuscitation render patients more susceptible to acute lung injury due to an exacerbated immune response to subsequent inflammatory stimuli. To study the role of innate immunity in this situation, we investigated acute lung injury in an experimental model of ischemia-reperfusion (I-R) followed by an early challenge with live bacteria. Conscious rats (N = 8 in each group) were submitted to controlled hemorrhage and resuscitated with isotonic saline (SS, 0.9% NaCl) or hypertonic saline (HS, 7.5% NaCl) solution, followed by intratracheal or intraperitoneal inoculation of Escherichia coli. After infection, toll-like receptor (TLR) 2 and 4 mRNA expression was monitored by RT-PCR in infected tissues. Plasma levels of tumor necrosis factor α and interleukins 6 and 10 were determined by ELISA. All animals showed similar hemodynamic variables, with mean arterial pressure decreasing to nearly 40 mmHg after bleeding. HS or SS used as resuscitation fluid yielded equal hemodynamic results. Intratracheal E. coli inoculation per se induced a marked neutrophil infiltration in septa and inside the alveoli, while intraperitoneal inoculation-associated neutrophils and edema were restricted to the interseptal space. Previous I-R enhanced lung neutrophil infiltration upon bacterial challenge when SS was used as reperfusion fluid, whereas neutrophil influx was unchanged in HS-treated animals. No difference in TLR expression or cytokine secretion was detected between groups receiving HS or SS. We conclude that HS is effective in reducing the early inflammatory response to infection after I-R, and that this phenomenon is achieved by modulation of factors other than expression of innate immunity components.FAPESPFundação Faculdade de MedicinaCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES

Evidence of paleoecological changes and Mousterian occupations at the Galeria de las Estatuas site, Sierra de Atapuerca, northern Iberian plateau, Spain

Here we present a new site in the Sierra de Atapuerca (Burgos, Spain): Galeria de las Estatuas (GE), which provides new information about Mousterian occupations in the Iberian Plateau. The GE was an ancient entrance to the cave system, which is currently closed and sealed by a stalagmitic crust, below which a detritic sedimentary sequence of more than 2 m is found. This has been divided into five litostratigraphic units with a rich assemblage of faunal and lithic remains of clear Mousterian affinity. Radiocarbon dates provide minimum ages and suggest occupations older than 45 C-14 ka BP. The palynological analysis detected a landscape change to increased tree coverage, which suggests that the sequence recorded a warming episode. The macromammal assemblage is composed of both ungulates (mainly red deer and equids) and carnivores. Taphonomic analysis reveals both anthropic, and to a lesser extent, carnivore activities. The GE was occupied by Neanderthals and also sporadically by carnivores. This new site broadens the information available regarding different human occupations at the Sierra de Atapuerca, which emphasizes the importance of this site-complex for understanding human evolution in Western Europe

Theory and simulation of quantum photovoltaic devices based on the non-equilibrium Green's function formalism

This article reviews the application of the non-equilibrium Green's function formalism to the simulation of novel photovoltaic devices utilizing quantum confinement effects in low dimensional absorber structures. It covers well-known aspects of the fundamental NEGF theory for a system of interacting electrons, photons and phonons with relevance for the simulation of optoelectronic devices and introduces at the same time new approaches to the theoretical description of the elementary processes of photovoltaic device operation, such as photogeneration via coherent excitonic absorption, phonon-mediated indirect optical transitions or non-radiative recombination via defect states. While the description of the theoretical framework is kept as general as possible, two specific prototypical quantum photovoltaic devices, a single quantum well photodiode and a silicon-oxide based superlattice absorber, are used to illustrated the kind of unique insight that numerical simulations based on the theory are able to provide.Comment: 20 pages, 10 figures; invited review pape

IV consenso mexicano sobre Helicobacter pylori

Desde el último consenso mexicano para el diagnóstico y tratamiento de la infección por Helicobacter pylori (H. pylori) en el 2007, han existido avances importantes al respecto. Por tal motivo, la Asociación Mexicana de Gastroenterología convocó a 20 expertos para la realización del «IV consenso mexicano sobre H. pylori». Durante febrero y junio del 2017 se organizaron 4 mesas de trabajo, una revisión de la literatura y 3 rondas de votaciones donde se establecieron 32 enunciados para discusión y consenso. Dentro de las recomendaciones se destaca el reconocer a México como un país con riesgo de cáncer gástrico bajo a intermedio a pesar de la alta prevalencia de infección por H. pylori. Se corrobora que enfermedad ulcerosa péptica, presencia de lesiones premalignas, antecedentes de cáncer gástrico y linfoma asociado a la mucosa deben considerarse indicaciones claras para erradicación. La relación del H. pylori con los síntomas dispépticos sigue siendo controversial. La triple terapia de erradicación con amoxicilina, claritromicina y un inhibidor de la bomba de protones ya no debe ser considerada la primera línea de tratamiento. En su lugar, se proponen 2 opciones: la terapia cuádruple con bismuto (inhibidor de la bomba de protones, subcitrato de bismuto, tetraciclina y metronidazol) y la terapia cuádruple sin bismuto (inhibidor de la bomba de protones, amoxicilina, claritromicina y metronidazol). Se establece la necesidad de la realización de sensibilidad antimicrobiana ante la falla a 2 tratamientos de erradicación. Finalmente, se proponen campañas de educación respecto al diagnóstico y tratamiento del H. pylori para médicos de primer contacto y población general. Abstract Important advances have been made since the last Mexican consensus on the diagnosis and treatment of Helicobacter pylori (H. pylori) infection was published in 2007. Therefore, the Asociación Mexicana de Gastroenterología summoned 20 experts to produce ‘‘The Fourth Mexican Consensus on Helicobacter pylori’’. From February to June 2017, 4 working groups were organized, a literature review was performed, and 3 voting rounds were carried out, resulting in the formulation of 32 statements for discussion and consensus. From the ensuing recommendations, it was striking that Mexico is a country with an intermediate-to-low risk for gastric cancer, despite having a high prevalence of H. pylori infection. It was also corroborated that peptic ulcer disease, premalignant lesions, and histories of gastric cancer and mucosaassociated lymphoid tissue lymphoma should be considered clear indications for eradication. The relation of H. pylori to dyspeptic symptoms continues to be controversial. Eradication triple therapy with amoxicillin, clarithromycin, and a proton pump inhibitor should no longer be considered first-line treatment, with the following 2 options proposed to take its place: quadruple therapy with bismuth (proton pump inhibitor, bismuth subcitrate, tetracycline, and metronidazole) and quadruple therapy without bismuth (proton pump inhibitor, amoxicillin, clarithromycin, and metronidazole). The need for antimicrobial sensitivity testing when 2 eradication treatments have failed was also established. Finally, the promotion of educational campaigns on the diagnosis and treatment of H. pylori for both primary care physicians and the general population were proposed

Milagro limits and HAWC sensitivity for the rate-density of evaporating Primordial Black Holes

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Association of a single nucleotide polymorphism combination pattern of the Klotho gene with non-cardiovascular death in patients with chronic kidney disease

Chronic kidney disease (CKD) is associated with an elevated risk of all-cause mortality, with cardiovascular death being extensively investigated. However, non-cardiovascular mortality represents the biggest percentage, showing an evident increase in recent years. Klotho is a gene highly expressed in the kidney, with a clear influence on lifespan. Low levels of Klotho have been linked to CKD progression and adverse outcomes. Single nucleotide polymorphisms (SNPs) of the Klotho gene have been associated with several diseases, but studies investigating the association of Klotho SNPs with noncardiovascular death in CKD populations are lacking. The main aim of this study was to assess whether 11 Klotho SNPs were associated with non-cardiovascular death in a subpopulation of the National Observatory of Atherosclerosis in Nephrology (NEFRONA) study (n ¼ 2185 CKD patients). After 48 months of follow-up, 62 cardiovascular deaths and 108 non-cardiovascular deaths were recorded. We identified a high non-cardiovascular death risk combination of SNPs corresponding to individuals carrying the most frequent allele (G) at rs562020, the rare allele (C) at rs2283368 and homozygotes for the rare allele (G) at rs2320762 (rs562020 GG/AG þ rs2283368 CC/CT þ rs2320762 GG). Among the patients with the three SNPs genotyped (n ¼ 1016), 75 (7.4%) showed this combination. Furthermore, 95 (9.3%) patients showed a low-risk combination carrying all the opposite genotypes (rs562020 AA þ rs2283368 TT þ rs2320762 GT/TT). All the other combinations [n ¼ 846 (83.3%)] were considered as normal risk. Using competing risk regression analysis, we confirmed that the proposed combinations are independently associated with a higher fhazard ratio [HR] 3.28 [confidence interval (CI) 1.51-7.12]g and lower [HR 6 × 10- (95% CI 3.3 × 10--1.1 × 10-)] risk of suffering a non-cardiovascular death in the CKD population of the NEFRONA cohort compared with patients with the normal-risk combination. Determination of three SNPs of the Klotho gene could help in the prediction of non-cardiovascular death in CKD

Association of candidate gene polymorphisms with chronic kidney disease : Results of a case-control analysis in the NEFRONA cohort

Chronic kidney disease (CKD) is a major risk factor for end-stage renal disease, cardiovascular disease and premature death. Despite classical clinical risk factors for CKD and some genetic risk factors have been identified, the residual risk observed in prediction models is still high. Therefore, new risk factors need to be identified in order to better predict the risk of CKD in the population. Here, we analyzed the genetic association of 79 SNPs of proteins associated with mineral metabolism disturbances with CKD in a cohort that includes 2,445 CKD cases and 559 controls. Genotyping was performed with matrix assisted laser desorption ionization-time of flight mass spectrometry. We used logistic regression models considering different genetic inheritance models to assess the association of the SNPs with the prevalence of CKD, adjusting for known risk factors. Eight SNPs (rs1126616, rs35068180, rs2238135, rs1800247, rs385564, rs4236, rs2248359, and rs1564858) were associated with CKD even after adjusting by sex, age and race. A model containing five of these SNPs (rs1126616, rs35068180, rs1800247, rs4236, and rs2248359), diabetes and hypertension showed better performance than models considering only clinical risk factors, significantly increasing the area under the curve of the model without polymorphisms. Furthermore, one of the SNPs (the rs2248359) showed an interaction with hypertension, being the risk genotype affecting only hypertensive patients. We conclude that 5 SNPs related to proteins implicated in mineral metabolism disturbances (Osteopontin, osteocalcin, matrix gla protein, matrix metalloprotease 3 and 24 hydroxylase) are associated to an increased risk of suffering CKD

Epidemiological trends of HIV/HCV coinfection in Spain, 2015-2019

Altres ajuts: Spanish AIDS Research Network; European Funding for Regional Development (FEDER).Objectives: We assessed the prevalence of anti-hepatitis C virus (HCV) antibodies and active HCV infection (HCV-RNA-positive) in people living with HIV (PLWH) in Spain in 2019 and compared the results with those of four similar studies performed during 2015-2018. Methods: The study was performed in 41 centres. Sample size was estimated for an accuracy of 1%. Patients were selected by random sampling with proportional allocation. Results: The reference population comprised 41 973 PLWH, and the sample size was 1325. HCV serostatus was known in 1316 PLWH (99.3%), of whom 376 (28.6%) were HCV antibody (Ab)-positive (78.7% were prior injection drug users); 29 were HCV-RNA-positive (2.2%). Of the 29 HCV-RNA-positive PLWH, infection was chronic in 24, it was acute/recent in one, and it was of unknown duration in four. Cirrhosis was present in 71 (5.4%) PLWH overall, three (10.3%) HCV-RNA-positive patients and 68 (23.4%) of those who cleared HCV after anti-HCV therapy (p = 0.04). The prevalence of anti-HCV antibodies decreased steadily from 37.7% in 2015 to 28.6% in 2019 (p < 0.001); the prevalence of active HCV infection decreased from 22.1% in 2015 to 2.2% in 2019 (p < 0.001). Uptake of anti-HCV treatment increased from 53.9% in 2015 to 95.0% in 2019 (p < 0.001). Conclusions: In Spain, the prevalence of active HCV infection among PLWH at the end of 2019 was 2.2%, i.e. 90.0% lower than in 2015. Increased exposure to DAAs was probably the main reason for this sharp reduction. Despite the high coverage of treatment with direct-acting antiviral agents, HCV-related cirrhosis remains significant in this population

Review of Kaon Physics at CERN and in Europe

The Kaon physics program at CERN and in Europe will be presented. I will first give a short review of recent results form the NA48/2 and NA62 experiments, with special emphasis to the measurement of RK , the ratio of Kaon leptonic decays rates, K → eν and K → μν, using the full minimum bias data sample collected in 2007-2008. The main subject of the talk will be the study of the highly suppressed decay K → πνν. While its rate can be predicted with minimal theoretical uncertainty in the Standard Model (BR ∼ 8 × 10−11), the smallness of BR and the challenging experimental signature make it very difficult to measure. The branching ratio for this decay is thus a sensitive probe of the flavour sector of the SM. The aim of NA62 is the measurement of the K → πνν BR with ∼ 10% precision in two years of data taking. This will require the observation of 10K decays in the experiment's fiducial volume, as well as the use of high-performance systems for precision tracking, particle identification, and photon vetoing. These aspects of the experiment will also allow NA62 to carry out a rich program of searches for lepton flavour and/or number violating K decays. Data taking will start in October 2014. The physics prospects and the status of the construction and commissioning of the NA62 experiment will be presented. In the last part of the talk I will report on Kaon physics results and prospects from other experiments at CERN (e.g. LHCb) and in Europe (e.g. KLOE and KLOE-2) and briefly mention the status in US