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The NEXT experiment aims to observe the neutrinoless double beta decay of 136Xe in a high-pressure xenon gas TPC using electroluminescence (EL) to amplify the signal from ionization. One of the main advantages of this technology is the possibility to reconstruct the topology of events with energies close to Qββ. This paper presents the first demonstration that the topology provides extra handles to reject background events using data obtained with the NEXT-DEMO prototype. Single electrons resulting from the interactions of 22Na 1275 keV gammas and electronpositron pairs produced by conversions of gammas from the 228Th decay chain were used to represent the background and the signal in a double beta decay. These data were used to develop algorithms for the reconstruction of tracks and the identification of the energy deposited at the end-points, providing an extra background rejection factor of 24.3 ± 1.4 (stat.)%, while maintaining an efficiency of 66.7 ± 1.% for signal events.[Figure not available: see fulltext.]

The NEXT experiment aims to observe the neutrinoless double beta decay of 136Xe in a high-pressure xenon gas TPC using electroluminescence (EL) to amplify the signal from ionization. One of the main advantages of this technology is the possibility to reconstruct the topology of events with energies close to Qββ. This paper presents the first demonstration that the topology provides extra handles to reject background events using data obtained with the NEXT-DEMO prototype. Single electrons resulting from the interactions of 22Na 1275 keV gammas and electronpositron pairs produced by conversions of gammas from the 228Th decay chain were used to represent the background and the signal in a double beta decay. These data were used to develop algorithms for the reconstruction of tracks and the identification of the energy deposited at the end-points, providing an extra background rejection factor of 24.3 ± 1.4 (stat.)%, while maintaining an efficiency of 66.7 ± 1.% for signal events.[Figure not available: see fulltext.]

NEXT is an experiment dedicated to neutrinoless double beta decay searches in xenon. The detector is a TPC, holding 100 kg of high-pressure xenon enriched in the 136Xe isotope. It is under construction in the Laboratorio Subterráneo de Canfranc in Spain, and it will begin operations in 2015. The NEXT detector concept provides an energy resolutionbetter than 1% FWHM and a topological signal that can be used to reduce the background. Furthermore, the NEXT technology can be extrapolated to a 1 ton-scale experiment. © 2014 J. J. Gómez Cadenas et al.

NEXT is an experiment dedicated to neutrinoless double beta decay searches in xenon. The detector is a TPC, holding 100 kg of high-pressure xenon enriched in the 136Xe isotope. It is under construction in the Laboratorio Subterráneo de Canfranc in Spain, and it will begin operations in 2015. The NEXT detector concept provides an energy resolutionbetter than 1% FWHM and a topological signal that can be used to reduce the background. Furthermore, the NEXT technology can be extrapolated to a 1 ton-scale experiment. © 2014 J. J. Gómez Cadenas et al.

The specificity of antibodies (Ab) is essential for the precise recognition of foreign or dangerous molecules. We have shown that mice infected with non-pathogenic Lactate Dehydrogenase Elevating Virus (LDV) inoculated with human growth hormone (hGH) or Ovalbumin (OVA), exhibit modified specificity of anti-hGH or anti-OVA Ab associated with the secretion of IFN-γ, IL-13, and IL-17. Cytokines are directly or indirectly involved in the isotypes, specificity, and affinity of Ab. Accordingly, here we investigated the effect of IL-17 neutralization on Ab specificities to OVA and Diphtheria Toxoid (DTx) in a mouse model of viral infection. Thereby, we employed an anti-cytokine "auto-vaccination" with an OVA/IL-17A complex or a Monoclonal Ab (MAb) anti-IL-17A (MM17/F3). Competitive ELISA assays were used to estimate the quality of the humoral immune response and the amount of Abs to conformational versus linear antigenic determinants. Results indicated that the OVA/IL-17A complex increased Abs levels to conformational epitopes of OVA, while LDV prolonged antibodies for a longer period. Mice treated with MM17F3 MAb showed an increase in Abs to conformational epitopes of OVA. A similar effect, confirmed by a competitive Western-blot assay, was produced by LDV. Moreover, an increased level of IgM, IgG1, and IgG2a was found in infected animals. Similarly, MAb anti-IL-17A treatment increased the proportion of Ab to conformational epitopes of DTx in uninfected mice, while LDV decreased this parameter. In conclusion, our findings demonstrate a correlation between IL-17A neutralization and a change in Ab specificity to OVA or DTx, presenting a novel strategy for obtaining Abs with higher specificity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Obesity increases the risk of arterial hypertension in young adults and favors an early-onset cardiomyopathy by generating oxidative stress. In this sense, indiscriminate consumption of sucrose and fructose sweetened beverages from early ages causes obesity, however its consequences on the heart when there is a genetic predisposition to develop hypertension are not clear. We compared the effects of sucrose, fructose, and their combination in weanling male spontaneously hypertensive rats to determine the relationship between genetic hypertension, obesity, and consumption of these sugars on the degree of cardiac hypertrophy, oxidative stress and Ca 2+ /calmodulin dependent protein kinase II delta oxidation. Histological, biochemical, and Western blot studies were performed 12 weeks after treatment initiation. We found that chronic consumption of sucrose or fructose leads to obesity, exacerbates genetic arterial hypertension-induced metabolic alterations, and increases cardiac oxidative stress, Ca 2+ /calmodulin dependent protein kinase II delta oxidation and cardiac hypertrophy. Nonetheless, when sucrose and fructose are consumed together, metabolic alterations worsen and are accompanied by dilated cardiomyopathy. These data suggest that sucrose and fructose combined consumption starting from maternal weaning in rats with genetic predisposition to arterial hypertension accelerates the progression of cardiomyopathy resulting in an early dilated cardiomyopathy., Competing Interests: No potential conflicts of interest were disclosed., (Copyright © 2023 JCBN.)

The migration of the biocides: 2-methyl-2H-isothiazol-3-one (MIT), 1,2-benzisothiazol-3(2H)-one (BIT) and 2-phenoxyethanol (PHE) from spiked paperboard into the simulants Tenax ® , water and acetic acid (3%) has been studied and compared with that into the vegetables: red cabbage, lettuce and cauliflower. The migration of the biocides into the vegetables is significant and it shows the trend BIT > PHE > MIT, at both 4 °C and room temperature (RT), whatever tested foodstuff and with the highest value corresponding to BIT into cauliflower at RT (71%). Differences up to one order of magnitude between the biocides migration into Tenax ® (<4.3%) and that into the vegetables indicate that Tenax ® is not a suitable food simulant to mimic the selected vegetables in terms of the migration of the studied biocides. Water has been shown to be the most appropriate food simulant in the cases under study.

In a previous work we demonstrated that inhibition of mouse indoleamine 2,3-dioxygenase (IDO) by methyltryptophan (MT) exacerbated the pathological actions of mouse hepatitis virus (MHV-A59) infection, suggesting that tryptophan (TRP) catabolism was involved in viral effects. Since there is a second enzyme that dioxygenates TRP, tryptophan-2, 3-dioxygenase (TDO), which is mainly located in liver, we decided to study its role in our model of MHV-infection. Results showed that in vivo TDO inhibition by LM10, a derivative of 3-(2-(pyridyl) ethenyl) indole, resulted in a decrease of anti- MHV Ab titers induced by the virus infection. Besides, a reduction of some alarmin release, i.e, uric acid and high-mobility group box1 protein (HMGB1), was observed. Accordingly, since alarmin liberation was related to the expression of autoantibodies (autoAb) to fumarylacetoacetate hydrolase (FAH), these autoAb also diminished. Moreover, PCR results indicated that TDO inhibition did not abolish viral replication. Furthermore, histological liver examination did not reveal strong pathologies, whereas mouse survival was hundred percent in control as well as in MHV-infected mice treated with LM10. Data presented in this work indicate that in spite of the various TDO actions already described, specific TDO blockage could also restrain some MHV actions, mainly suppressing autoimmune reactions. Such results should prompt further experiments with various viruses to confirm the possible use of a TDO inhibitor such as LM-10 to treat either viral infections or even autoimmune diseases triggered by a viral infection., (Copyright © 2019 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.)

Mice infected with mouse hepatitis virus A59 (MHV-A59) develop hepatitis and autoantibodies (autoAb) to liver and kidney fumarylacetoacetate hydrolase (FAH), a fact closely related to the release of alarmins such as uric acid and/or high-mobility group box protein 1 (HMGB1). We studied the effect of neutralizing monoclonal antibodies (MAb) against IL-17A in our model of mouse MHV-A59-infection. MAb anti-IL-17F and anti-IFNγ were used to complement the study. Results showed that transaminase levels markedly decreased in MHV-A59-infected mice treated with MAb anti-IL-17A whereas plasmatic Ig concentration sharply increased. Conversely, MAb anti-IL-17F enhanced transaminase liberation and did not affect Ig levels. Serum IFNγ was detected in mice infected with MHV-A59 and its concentration increased after MAb anti-IL-17A administration. Besides, MAb anti-IFNγ greatly augmented transaminase plasmatic levels. IL-17A neutralization did not affect MHV-A59-induction of HMGB1 liberation and slightly augmented plasmatic uric acid concentration. However, mice treated with the MAb failed to produce autoAb to FAH. The above results suggest a reciprocal regulation of Th1 and Th17 cells acting on the different MHV-A59 effects. In addition, it is proposed that IL-17A is involved in alarmins adjuvant effects leading to autoAb expression.

A silicon calcium phosphate cement (Si-CPC) was developed to produce a composite of calcium phosphate and calcium silicate. The silicon cements prepared with low silicon (Si) content were composed of crystalline phases of brushite and silicocarnotite. However, the cements prepared with high Si content were mainly composed of amorphous phases of silicocarnotite, hydroxyapatite and calcium silicate. The cement porosity was about 40% with a shift of the average pore diameter to the nanometric range with increasing Si content. Interestingly, this new cement system provides a matrix with a high specific surface area of up to 29 m(2) g(-1). The cytocompatibility of the new Si-doped cements was tested with a human osteoblast-like cell line (MG-63) showing an enhancement of cell proliferation (up to threefold) when compared with unsubstituted material. Cements with a high silica content also improved the cell attachment. The in vivo results indicated that Si-CPCs induce the formation of new bone tissue, and modify cement resorption. We conclude that this cement provides an optimal environment to enhance osteoblast growth and proliferation that could be of interest in bone engineering.

Lactate dehydrogenase-elevating virus (LDV) is an apparently innocuous and persistent virus that can modify mouse immune reactions. We have shown that LDV-infected mice immunized with human growth hormone (hGH) showed a deep modification of the specificity of the anti-hGH antibodies (Ab) in CBA/Ht mice but not BALB/c animals. The aim of this work was to extend the previous observations to another mouse strain, C57BL/6, as well as to an antigen unrelated to hGH, ovalbumin (OVA), and to explore at the same time the production of various cytokines at serum and cellular levels. The amount of Ab directed to hGH or OVA native antigenic determinants versus the concentration of Ab to cryptic epitopes was evaluated by ELISA competition experiments. Results indicated that LDV infection affected Ab specificity solely in CBA/Ht mice. In CBA/Ht the virus infection was associated with a reduction of the Ab titers to hGH native epitopes and with a decrease of IL-13 and IL-17 serum levels, but Ab to native OVA epitopes were increased with a simultaneous increase of IL-17. Accordingly, only lymph node cells from infected CBA/Ht mice immunized with OVA were found to produce INF-γ, IL-13 and IL-17. Thus, a correlation of cytokine production with a change in Ab specificity after a viral infection was found, although this phenomenon was restricted to a given antigen and to the genetic background of immunized animals. These observations suggest that an apparent harmless virus can affect some immunological mechanisms, which could lead, for example, to inflammatory or autoimmune disorders., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Previous works from our laboratory demonstrated that the monoclonal antibody (MAb) called R7B4 is directed to an epitope shared by various receptors corresponding to the type I cytokine receptor family, containing the common motif WSXWS or the homologous F(Y)GEFS. Later a consensus peptide significantly recognized by the MAb was identified and synthesized (sequence HGYWSEWSPE). In the present work, an homologous of the consensus sequence (HHGYWSEWSPE) was conjugated to PADRE adjuvant to produce Ab that could simulate theMAb activity, that is, acting as hormone and/or cytokine antagonists. The covalently conjugated peptide-PADRE was a better immunogen than the consensus peptide alone according to the reactivity of sera from C57BL/6 immunized mice and, besides, no Ab to PADRE were detected. Furthermore, Ab to consensus peptide elicited after peptide-PADRE inoculation into mice behaved as immunomodulatory agents, since they improved the humoral response to a foreign antigen (in this case ovalbumin). In addition, the Ab inhibited the in vitro proliferation of various cell lines, mainly cells derived from human and mouse breast cancer. Thus, immunization with the conjugate peptide-PADRE prepared under the experimental conditions described herein originated immunomodulatory Ab that, in the future, could be tested in some pathological conditions.

Mouse hepatitis virus A59 (MHV A59) induces autoantibodies (autoAb) to fumarylacetoacetate hydrolase (FAH), a soluble cytosolic enzyme present in the liver and kidneys, in various mouse strains. The aim of this work was to amplify and diversify the autoimmune response restricted to FAH through the use of the exogenous adjuvant called PADRE. Accordingly, C57BL/6 mice were chosen, because these animals respond to PADRE better than other mouse strains. Results presented herein indicate that, surprisingly, C57BL/6 mice developed signs of autoimmune hepatitis-like disease (AIH), including transient hypergammaglobulinemia, elevated transaminases, autoAb directed against different liver proteins and hepatic cellular infiltrates, indicating that a new model of experimental AIH could be generated by a viral inoculation. Furthermore, PADRE administration amplified the MHV effect, extending the duration of hypergammaglobulinemia and increasing the binding of autoAb as well as the degree of hepatic infiltrates. However, the adjuvant did not expand the time of the symptoms. Additionally, since plasmatic uric acid and high-mobility group box protein 1 (HGMB1) concentrations augmented in MHV- and/or PADRE-treated mice, it is suggested that both alarmins were probably involved in the spreading of the immune response induced by the viral infection and the adjuvant administration., (Copyright © 2011. Published by Elsevier B.V.)

The effect of using potassium lactate, sodium metasilicate, acidified sodium chlorite, or peroxyacetic acid as a single antimicrobial intervention on ground beef instrumental color, sensory color and odor characteristics, and lipid oxidation was evaluated. Prior to grinding, beef trimmings (90/10) were treated with 3% potassium lactate (KL), 4% sodium metasilicate (NMS), 200-ppm peroxyacetic acid (PAA), 1000-ppm acidified sodium chlorite (ASC), or left untreated (CON). Ground beef under simulated retail display was measured at 0, 1, 2, 3, and 7 of display for instrumental color, sensory characteristics, TBARS values, and pH to evaluate the impact of the treatments. The KL, NMS, PAA, and ASC were redder (a(∗); P<0.05) than CON. All treatments were scored by sensory panelists to have a brighter (P<0.05) red color than CON during days 1-3 of display. All treatments had less (P<0.05) lipid oxidation than CON on days 0, 3, and 7 of display. These results suggest that the use of these antimicrobial compounds on beef trimmings prior to grinding may not adversely affect, and may improve bulk packaged ground beef quality characteristics.

We have shown that mice infected with mouse hepatitis virus A59 (MHV-A59) develop autoantibodies (autoAb) to liver and kidney fumarylacetoacetate hydrolase (FAH). The autoAb recognized conformational as well as linear antigenic determinants in the enzyme, and the autoimmune response was not entirely restricted to molecular mimicry and/or epitope spreading. Since the N- and C-terminal portions of the enzyme were the most reactive with autoAb, the fine specificity of these Ab was investigated. Immobilized 15-mer linear peptides (overlapping by 14 amino acids) spanning the N-terminal FAH sequence 1-49 were recognized by Ab from MHV-infected mice. The pattern of reactivity indicated the existence of two major epitope cores (i.e., sequences 9-23 and 30-44), and sequence comparison permitted the identification of two minimal epitopes, DSDFPIQ (amino acids 9-15) and IGDQILD (amino acids 36-42). Mutational analysis of sequences 9-23 and 30-44 indicated that residues 9-12 (DSDF) from the first major N-terminal epitope, and residue 36 (I) from the second, were the key amino acids energetically important for Ab contact. Interestingly, those residues were inside the two minimal epitopes previously predicted. The C-terminal portion of the enzyme (sequence 390-419) presented only one major epitope, located between residues 390 and 409. In this case, the minimal epitope had nine amino acids, CQGDGYRVG, corresponding to the FAH sequence 396-404 that outlines a loop specific for the enzyme. Data indicated that neither the FAH minimal epitopes nor the key residues important for binding to Ab from MHV-infected mice have their counterparts in the viral proteins. However, location of the energetically important residues in the tertiary structure of the enzyme originates a virtual conformational epitope. Such hypothetical B-cell epitopes could be present in any viral protein, originating a cross-reaction leading to the autoimmune response induced by MHV.

Mouse hepatitis virus strain A59 (MHV-A59) triggers various pathologies in several mouse strains, including hypergammaglobulinaemia, hepatitis and thymus involution. We reported previously the presence of autoantibodies (autoAb) to liver and kidney fumarylacetoacetate hydrolase (FAH) in sera from mice infected with MHV-A59. Long-term MHV-infected mice represented a good model of non-pathogenic autoimmune response since the animals were apparently healthy in spite of the presence of autoAb. The aim of this work was to see whether a severe liver injury, which releases endogenous adjuvants, i.e. danger signals, could elicit a broader spectrum of autoAb and perhaps signs of autoimmune hepatitis. Carbon tetrachloride (CCl(4)) was injected into mice 30 days after MHV infection, and serum was assayed for autoAb and total IgG 20 days later. The association of MHV infection with the toxic effects of CCl(4) resulted in hypergammaglobulinaemia and the production of autoAb to various liver and kidney proteins. Histological examination of liver samples showed tissue damages but without significant differences between the animals submitted to MHV+CCl(4) and controls, which were either infected by MHV without CCl(4), or poisoned by CCl(4) in the absence of MHV infection. Those results show that liver injury after viral infection may lead to the spreading of the immune response and to an increase of serum IgG, suggesting that the procedure used herein could simulate the onset of autoimmune hepatitis.

Beef trimmings were treated with 3% potassium lactate (KL), 4% sodium metasilicate (NMS), 0.02% peroxyacetic acid (PAA) or 0.1% acidified sodium chlorite (ASC) or left untreated (CON). Beef trimmings were ground, pattied, and sampled for 7 days. Under simulated retail display, instrumental color, sensory characteristics, TBARS, pH, and Lee-Kramer shear force were measured to evaluate the impact of the treatments on the quality attributes. The NMS and PAA patties were redder (a(∗), P<0.05) than CON on days 0-3. Panelists found KL, NMS, PAA, and ASC patties to have less (P<0.05) or similar (P>0.05) off odor to CON on days 0-3. The NMS and PAA treated patties had lower (P<0.05) lipid oxidation than the CON at days 0, 3, and 7. Therefore, KL, NMS, PAA, and ASC treatments on beef trimmings can potentially improve or maintain quality attributes of beef patties.

In the last twenty years Spain has turned into one of the principal countries recipients of foreign population. As consequence of this massive entry of people, our country is among the first ones of Europe for interannual increase of population. The concept of immigrant child is very wide and includes minors of very diverse characteristics, as the proceeding from international adoptions, the children coming from developing countries or those that come from other developed countries. The immigrant children do not represent health risk for the autochthonous population, on the contrary, they are in situation of defenselessness for their scanty vaccination coverages, their situation of marginality and the precarious sanitary systems of the countries of origin. At the moment of offering medical paediatric attention to foreign children, we must individualize our actions in conformity with the characteristics of each patient. It is not possible to simplify in one unique protocol the best studies to resolve a problem of health in an immigrant child. The attention of these children implies an overstrain for the pediatrician and the sanitary personnel that receives them, because it is necessary to conquer idiomatic, cultural and social barriers to optimize the level of health of these patients. The syndromic initial description can help to prioritize the studies in each case (according to the most probable diagnoses). The children who return to the native land of their parents meet in a special situation of risk, for not being prepared to resist the attack of pathogen that do not exist or are rare in Spain.

Background: HCV was initially identified in 1989 when it was found to be the primary causative agent of non-A, non-B hepatitis,a condition associated with high rates of progressive and end-stage liver disease, cirrhosis, and hepatocellular carcinoma. Since then, appreciation of the significant worldwide health impact of HCV infection has grown. HCV infection was identified as a public health problem in Cuba in the 1990s. Despite universal blood donor screening, which was achieved in 1995 using the Cuban immunoassay system UMELISA HCV, the infection is still found in multi-transfused patients., Objectives: To determine the magnitude of HCV, HBV and HIV-1&2 infections among Cuban blood recipients and to assess the role of potential risk factors., Study Design: Cross-sectional study of 318 patients from Havana City, Pinar del Río and Villa Clara, who had been previously treated with 10 or more units of allogenic blood or blood components in at least two different occasions. The patients were evaluated for HCV Ab, HBsAg, anti-HBc Ab, and HIV-1&2 Ab. Data management and statistical analysis were performed using EpiInfo and SSPS software., Results: Prevalence rates were 51.6% for HCV Ab; 5.3% for HBsAg; 45.0% for anti-HBc and 0% for HIV-1&2 Ab. Ten (3.1%) patients were co-infected with HCV and HBV Blood transfusion was not identified as the main risk factor for HCV transmission. The number of blood units received by the patients was not statistically associated with the HCV Ab prevalence., Conclusions: Infection with HCV was identified more frequently than HBV and HIV among our study population. Patients undergoing hemodialysis were at the highest risk of becoming infected. Medical procedures including surgery, transplantation, invasive odontology, and sharing or reuse of needles and syringes, are associated with higher HCV Ab seroprevalences compared with blood transfusion alone.

We report a clinic case of renal-cell carcinoma presenting as sinistral portal hypertension; a clinical syndrome consisting of esplenic vein thrombosis manifested as isolated gastric varices with patent portal vein and normal hepatic function. The most frequent cause of this syndrome is pancreatic pathology. Renal-cell carcinoma is characterized by a wide variety of symptoms as initial manifestation. In our case, the patient developed a massive gastrointestinal bleeding secondary to isolated gastric varices caused by splenic vein thrombosis due to extrinsic compression by a hypernephroma that infiltrated the pancreas.

Background: We analysed the trend in seroprevalence for human immunodeficiency virus (HIV) in homosexual or bisexual men who voluntary requested the test in a sexually transmitted disease/HIV clinic in Madrid., Patients and Methods: We studied 5,424 homo/bisexual non-injecting drug user (non-IDU) men, who came for the first time since 1986 to 1995. We analysed the HIV seroprevalence taken into account the year, age and exchange of sex by money. A hundred and thirty-six IDU homo/bisexual men were also attended during the same period and they were compared with non-IDU., Results: HIV seroprevalence among the 5,424 non-IDU homo/bisexual men were 20.2%, rising from 19.6% in 1986 to 29.6% in 1990. After then, the trend decreased to 15.3% in 1995 (chi 2 for trend, 66.8; p < 0.0001). Average age was three years higher among seropositives (p < 0.0001), and showed an upward trend from 29.9 in 1986 to 34.6 in 1995 (p = 0.0059). Seroprevalence among homosexuals younger than 25 fell in the last years. One percent of individuals had ever practiced the prostitution. They were younger (average age, 27.6), and their HIV seroprevalence were 25.9%. A hundred and thirty-six IDU homo/bisexual men were also attended for the first time, being 2.4% of overall homo/bisexual men. They had a higher seroprevalence (48.5%) than non-IDU (p < 0.0001), and did not show any significative time-trend., Conclusions: A favourable evolution can be observed in HIV seroprevalence among homo/bisexual from Madrid, Spain, men who came to be tested, especially among the youngest. Prevention programs should make an effort to maintain this trend.

The adequation of the current theories for calculating activity coefficients has been studied for a series of ionic equilibria in analytical chemistry: the water ionic product as well as two reactions of complex formation and oxidation-reduction. In all the cases, the specific interaction theory (SIT) has proved to be adequate and simple to apply in a restricted interval (0.5-3M), whereas Pitzer's theory is outstanding for its high precision in reproducing experimental behaviour and to correlate values of equilibrium constants for different conditions and media.