First Results on Dark Matter Annual Modulation from the ANAIS-112 Experiment.

ANAIS is a direct detection dark matter experiment aiming at the testing of the DAMA/LIBRA annual modulation result, which, for about two decades, has neither been confirmed nor ruled out by any other experiment in a model independent way. ANAIS-112, consisting of 112.5 kg of sodium iodide crystals, has been taking data at the Canfranc Underground Laboratory, Spain, since August 2017. This Letter presents the annual modulation analysis of 1.5 years of data, amounting to 157.55 kg yr. We focus on the model independent analysis searching for modulation and the validation of our sensitivity prospects. ANAIS-112 data are consistent with the null hypothesis (p values of 0.67 and 0.18 for [2-6] and [1-6] keV energy regions, respectively). The best fits for the modulation hypothesis are consistent with the absence of modulation (S_{m}=-0.0044±0.0058 cpd/kg/keV and -0.0015±0.0063 cpd/kg/keV, respectively). They are in agreement with our estimated sensitivity for the accumulated exposure, which supports our projected goal of reaching a 3σ sensitivity to the DAMA/LIBRA result in five years of data taking.

Maresin 1 mitigates liver steatosis in ob/ob and diet-induced obese mice.

BACKGROUND/OBJECTIVES: The aim of this study was to characterize the effects of Maresin 1 (MaR1) in obesity-related liver steatosis and the mechanisms involved. METHODS: MaR1 effects on fatty liver disease were tested in ob/ob (2-10 µg kg-1 i.p., 20 days) and in diet-induced obese (DIO) mice (2 µg kg-1, i.p., or 50 µg kg-1, oral gavage for 10 days), as well as in cultured hepatocytes. RESULTS: In ob/ob mice, MaR1 reduced liver triglycerides (TG) content, fatty acid synthase (FAS) and stearoyl-CoA desaturase-1 protein expression, while increased acetyl-CoA carboxylase (ACC) phosphorylation and LC3II protein expression, in parallel with a drop in p62 levels. Similar effects on hepatic TG, ACC phosphorylation, p62 and LC3II were observed in DIO mice after MaR1 i.p. injection. Interestingly, oral gavage of MaR1 also decreased serum transaminases, reduced liver weight and TG content. MaR1-treated mice exhibited reduced hepatic lipogenic enzymes content (FAS) or activation (by phosphorylation of ACC), accompanied by upregulation of carnitine palmitoyltransferase (Cpt1a), acyl-coenzyme A oxidase (Acox1) and autophagy-related proteins 5 and 7 (Atg5-7) gene expression, along with increased number of autophagic vacuoles and reduced p62 protein levels. MaR1 also induced AMP-activated protein kinase (AMPK) phosphorylation in DIO mice and in primary hepatocytes, and AMPK inhibition completely blocked MaR1 effects on Cpt1a, Acox1, Atg5 and Atg7 expression. CONCLUSIONS: MaR1 ameliorates liver steatosis by decreasing lipogenic enzymes, while inducing fatty acid oxidation genes and autophagy, which could be related to AMPK activation. Thus, MaR1 may be a new therapeutic candidate for reducing fatty liver in obesity.

Demonstration of Single-Barium-Ion Sensitivity for Neutrinoless Double-Beta Decay Using Single-Molecule Fluorescence Imaging.

A new method to tag the barium daughter in the double-beta decay of ^{136}Xe is reported. Using the technique of single molecule fluorescent imaging (SMFI), individual barium dication (Ba^{++}) resolution at a transparent scanning surface is demonstrated. A single-step photobleach confirms the single ion interpretation. Individual ions are localized with superresolution (∼2 nm), and detected with a statistical significance of 12.9σ over backgrounds. This lays the foundation for a new and potentially background-free neutrinoless double-beta decay technology, based on SMFI coupled to high pressure xenon gas time projection chambers.

Demonstration of event position reconstruction based on diffusion in the NEXT-white detector.

Noble element time projection chambers are a leading technology for rare event detection in physics, such as for dark matter and neutrinoless double beta decay searches. Time projection chambers typically assign event position in the drift direction using the relative timing of prompt scintillation and delayed charge collection signals, allowing for reconstruction of an absolute position in the drift direction. In this paper, alternate methods for assigning event drift distance via quantification of electron diffusion in a pure high pressure xenon gas time projection chamber are explored. Data from the NEXT-White detector demonstrate the ability to achieve good position assignment accuracy for both high- and low-energy events. Using point-like energy deposits from 83mKr calibration electron captures (E∼45 keV), the position of origin of low-energy events is determined to 2 cm precision with bias <1mm. A convolutional neural network approach is then used to quantify diffusion for longer tracks (E≥1.5 MeV), from radiogenic electrons, yielding a precision of 3 cm on the event barycenter. The precision achieved with these methods indicates the feasibility energy calibrations of better than 1% FWHM at Qßß in pure xenon, as well as the potential for event fiducialization in large future detectors using an alternate method that does not rely on primary scintillation.

LXR is a negative regulator of glucose uptake in human adipocytes.

AIMS/HYPOTHESIS: Obesity increases the risk of developing type 2 diabetes mellitus, characterised by impaired insulin-mediated glucose uptake in peripheral tissues. Liver X receptor (LXR) is a positive regulator of adipocyte glucose transport in murine models and a possible target for diabetes treatment. However, the levels of LXRα are increased in obese adipose tissue in humans. We aimed to investigate the transcriptome of LXR and the role of LXR in the regulation of glucose uptake in primary human adipocytes. METHODS: The insulin responsiveness of human adipocytes differentiated in vitro was characterised, adipocytes were treated with the LXR agonist GW3965 and global transcriptome profiling was determined by microarray, followed by quantitative RT-PCR (qRT-PCR), western blot and ELISA. Basal and insulin-stimulated glucose uptake was measured and the effect on plasma membrane translocation of glucose transporter 4 (GLUT4) was assayed. RESULTS: LXR activation resulted in transcriptional suppression of several insulin signalling genes, such as AKT2, SORBS1 and CAV1, but caused only minor changes (<15%) in microRNA expression. Activation of LXR impaired the plasma membrane translocation of GLUT4, but not the expression of its gene, SLC2A4. LXR activation also diminished insulin-stimulated glucose transport and lipogenesis in adipocytes obtained from overweight individuals. Furthermore, AKT2 expression was reduced in obese adipose tissue, and AKT2 and SORBS1 expression was inversely correlated with BMI and HOMA index. CONCLUSIONS/INTERPRETATION: In contrast to murine models, LXR downregulates insulin-stimulated glucose uptake in human adipocytes from overweight individuals. This could be due to suppression of Akt2, c-Cbl-associated protein and caveolin-1. These findings challenge the idea of LXR as a drug target in the treatment of diabetes.

An association between viral genes and human oncogenic alterations: the adenovirus E1A induces the Ewing tumor fusion transcript EWS-FLI1.

Malignant transformation of human cells requires the accumulation of multiple genetic alterations, such as the activation of oncogenes and loss of function of tumor suppressor genes or those related to genomic instability. Among the genetic alterations most frequently found in human tumors are chromosomal translocations that may result in the expression of chimeric products with transforming capability or are able to change the expression of oncogenes. We show here that the adenovirus early region 1A (E1A) gene can induce a specific human fusion transcript (EWS-FLI1) that is characteristic of Ewing tumors. This fusion transcript was detected by RT-PCR in normal human fibroblasts and keratinocytes after expression of the adenovirus E1A gene, as well as in human cell lines immortalized by adenoviruses. Cloning and sequencing of the RT-PCR product showed fusion points between EWS and FLI1 cDNA identical to those detected in Ewing tumors. In addition, we detected a chimeric protein by western blot analysis and immunoprecipitation and a t(11,22) by fluorescent in situ hybridization. This association between a single viral gene and a specific human fusion transcript indicates a direct link between viral genes and chromosome translocations, one of the hallmarks of many human tumors.

Effects of eicosapentaenoic acid (EPA) on adiponectin gene expression and secretion in primary cultured rat adipocytes.

Adiponectin, a hormone produced by adipocytes, is involved in glucose metabolism and insulin sensitivity. The production of this adipokine is impaired in obesity and insulin resistance. Eicosapentaenoic acid (EPA) is a dietary n-3 polyunsaturated fatty acid that improves insulin sensitivity in several models of obesity and diabetes, which has been suggested to be related to adiponectin induction. An increase in adiponectin production has been also associated with an up-regulation of the transcriptional factor PPARgamma. The aim of this trial was to evaluate the direct effects of EPA on adiponectin gene expression and protein secretion in isolated rat adipocytes as well as to explore the potential mechanisms involved. A comparative study with troglitazone, a PPARgamma agonist, was also performed. For these purposes, primary rat adipocytes were cultured with EPA (100 and 200 microM) and with troglitazone (10 microM) for 96 hours. Both EPA and troglitazone improved glucose utilization by adipocytes. As expected, troglitazone enhanced adiponectin secretion and increased PPARgamma gene expression. However, EPA significantly decreased adiponectin gene expression and protein secretion and reduced PPARy mRNA levels, suggesting that the inhibition of adiponectin by EPA is likely to be secondary to the down-regulation of this adipogenic transcription factor. Moreover, these results suggest that other mechanisms different from the direct stimulation of adiponectin by the fatty acid are underlying the insulin-sensitizing properties observed after EPA treatment in vivo.

TREX-DM: a low-background Micromegas-based TPC for low-mass WIMP detection.

If Dark Matter is made of Weakly Interacting Massive Particles (WIMPs) with masses below [Formula: see text] GeV, the corresponding nuclear recoils in mainstream WIMP experiments are of energies too close, or below, the experimental threshold. Gas Time Projection Chambers (TPCs) can be operated with a variety of target elements, offer good tracking capabilities and, on account of the amplification in gas, very low thresholds are achievable. Recent advances in electronics and in novel radiopure TPC readouts, especially micro-mesh gas structure (Micromegas), are improving the scalability and low-background prospects of gaseous TPCs. Here we present TREX-DM, a prototype to test the concept of a Micromegas-based TPC to search for low-mass WIMPs. The detector is designed to host an active mass of [Formula: see text] kg of Ar at 10 bar, or alternatively [Formula: see text] kg of Ne at 10 bar, with an energy threshold below 0.4 keVee, and is fully built with radiopure materials. We will describe the detector in detail, the results from the commissioning phase on surface, as well as a preliminary background model. The anticipated sensitivity of this technique may go beyond current experimental limits for WIMPs of masses of 2-8 GeV.

Hydrophilic surface modification of acrylate-based biomaterials.

Acrylic polymers have proved to be excellent with regard to cell adhesion, colonization and survival, in vitro and in vivo. Highly ordered and regular pore structures thereof can be produced with the help of polyamide templates, which are removed with nitric acid. This treatment converts a fraction of the ethyl acrylate side groups into acrylic acid, turning poly(ethyl acrylate) scaffolds into a more hydrophilic and pH-sensitive substrate, while its good biological performance remains intact. To quantify the extent of such a modification, and be able to characterize the degree of hydrophilicity of poly(ethyl acrylate), poly(ethyl acrylate) was treated with acid for different times (four, nine and 17 days), and compared with poly(acrylic acid) and a 90/10%wt. EA/AAc copolymer (P(EA-co-AAc)). The biological performance was also assessed for samples immersed in acid up to four days and the copolymer, and it was found that the incorporation of acidic units on the material surface was not prejudicial for cells. This surface modification of 3D porous hydrophobic scaffolds makes easier the wetting with culture medium and aqueous solutions in general, and thus represents an advantage in the manageability of the scaffolds.

Eicosapentaenoic acid promotes mitochondrial biogenesis and beige-like features in subcutaneous adipocytes from overweight subjects.

Eicosapentaenoic acid (EPA), a n-3 long-chain polyunsaturated fatty acid, has been reported to have beneficial effects in obesity-associated metabolic disorders. The objective of the present study was to determine the effects of EPA on the regulation of genes involved in lipid metabolism, and the ability of EPA to induce mitochondrial biogenesis and beiging in subcutaneous adipocytes from overweight subjects. Fully differentiated human subcutaneous adipocytes from overweight females (BMI: 28.1-29.8kg/m2) were treated with EPA (100-200 µM) for 24 h. Changes in mRNA expression levels of genes involved in lipogenesis, fatty acid oxidation and mitochondrial biogenesis were determined by qRT-PCR. Mitochondrial content was evaluated using MitoTracker® Green stain. The effects on peroxisome proliferator-activated receptor gamma, co-activator 1 alpha (PGC-1α) and AMP-activated protein kinase (AMPK) were also characterized. EPA down-regulated lipogenic genes expression while up-regulated genes involved in fatty acid oxidation. Moreover, EPA-treated adipocytes showed increased mitochondrial content, accompanied by an up-regulation of nuclear respiratory factor-1, mitochondrial transcription factor A and cytochrome c oxidase IV mRNA expression. EPA also promoted the activation of master regulators of mitochondrial biogenesis such as sirtuin 1, PGC1-α and AMPK. In parallel, EPA induced the expression of genes that typify beige adipocytes such as fat determination factor PR domain containing 16, uncoupling protein 1 and cell death-inducing DFFA-like effector A, T-Box protein 1 and CD137. Our results suggest that EPA induces a remodeling of adipocyte metabolism preventing fat storage and promoting fatty acid oxidation, mitochondrial biogenesis and beige-like markers in human subcutaneous adipocytes from overweight subjects.

[Injecting drug users from Eastern Europe in Barcelona, Spain]. / Ciudadanos del este de Europa consumidores de drogas en Barcelona.

From May 1999 to May 2001, we made contact with injecting drug users from Eastern Europe in the healthcare and prevention service of the Red Cross (servicio de atención y prevención sociosanitaria [SAPS]) in Barcelona (Spain). The users attended free therapeutic centers, but paid approximately 500 e for the trip. The users were aged between 18 and 30 years old and maintained family contact. The knew the risk of disease transmission, but often exchanged needles. The prevalence of hepatitis C (92%) and B (62%) was high but less than that of HIV (19%). If they did not stop taking drugs their return would be a failure and they would have difficulties in following methadone and antiretroviral treatments in their countries of origin. The healthcare provided in these centers should respond to user' needs: cultural mediation should be sought, as well as information from users' countries of origin. Centers receiving users from other countries should be supervised and alternatives should be designed for users who abandon treatment. International cooperation and programs to reduce the risk of drug consumption should be developed. Treatment should be prevented from becoming a business.

[Costs of accidental punctures in hospital health personnel]. / Costes de las inoculaciones accidentales en personal sanitario de un hospital.

OBJECTIVES: The aim of this study was to calculate the average cost of each hepatitis B, C and HIV follow-up carried out in the health personnel that have suffered an exposure to blood and body fluids and to estimate the cost for each of the different types of sources as well as to identify the items that account for the main part of the cost. METHODS: A cost analysis was carried out. The post-exposure programme was modelled in a decision tree combining probabilities (percentage of each type of source in dependence of its positivity for the three viruses and immunization state of the health personnel against hepatitis B) and monetary costs (pesetas from 1994). Costs included: salaries, laboratory, chemist, energy, cleaning, telephone, medical and office equipment, amortization and lost productivity. A sensitivity analysis was carried out with the real fulfillment of the programme. RESULTS: The average cost was 39,564 ptas. (29,750 ptas. applying the sensitivity analysis), with a range from 86,864 ptas. (source positive for the three viruses and injured subject not immunized) to 23,074 ptas. (source negative for the three viruses). If the source was hepatitis B positive, the average cost was 86,093 ptas. when the injured subject was not immunized and 53,232 ptas. if he was immunized. Serologic tests account for the main part of the cost (range from 72.8% to 87.7%). CONCLUSIONS: High cost suggests an appropriate risk evaluation in order to avoid unnecessary follow-ups. The model used allows to know the cost of each potentially avoided episode and it could be used for any hospital in order to make an economical evaluation of new preventive devices.

[Early mitochondrial encephalomyopathy due to complex IV deficiency consistent with Alpers-Huttenlocher syndrome: report of two cases]. / Encefalomiopatía mitocondrial precoz por deficiencia aislada del complejo IV compatible con el síndrome de Alpers-Huttenlocher: a propósito de dos observaciones.

INTRODUCTION: Complex IV or cytochrome c oxidase (COX) deficiency is the most common disorder involving complexes of the respiratory chain in the pediatric age. Exceptionally, it has been reported in association with Alpers syndrome or Alpers disease, and with its variant named progressive neuronal degeneration with liver disease or Alpers-Huttenlocher syndrome. OBJECTIVE: To report the cases of two infants with mitochondrial encephalomyopathy due to COX deficiency in whom the clinical, biochemical, neurophysiologic and neuroimaging characterization suggested an associated Alpers-Huttenlocher syndrome. CLINICAL CASES: Two no-related males, one with noncontributory family history and the other with third-grade consanguineous parents developed refractory seizures from age 20 and 60 days, respectively. Additionally, myoclonic fits accounted on evolution of the condition. In the first case, serial EEG recordings showed low amplitude polyspikes, polyspike waves and very slow waves of high amplitude alternating with a trace of burst-suppression activity. In the second case, a right preponderant but also bilateral low amplitude polyspikes, polyspike waves and occasional desynchronization of basal trace were recorded. In both, a rapidly progressive cerebral atrophy, neurological deterioration with pyramidal signs, and tendency to microcephaly, ensued. Accompanying to this clinical picture, minor hepatic dysfunction, elevated protein levels in the CSF, lactic acidosis and COX deficiency in muscle homogenate were demonstrated. In the first case, moreover, cortical blindness and severe hepatic failure occurred while receiving valproate, in spite of concomitant L-carnitine therapy. CONCLUSIONS: We believe that the reported cases are consisted with Alpers-Huttenlocher syndrome associated with mitochondrial encephalomyopathy due to COX deficiency. Nevertheless, early myoclonic encephalopathy, a condition related in same cases with poliodistrophy, must be keep in mind as a possible diagnosis in case 1.

Hypoglycaemia and somnambulism: a case report.

Sleepwalking (somnambulism) is a sleep disorder classified as a parasomnia. Sleepwalkers develop motor activities that may be simple or complex: they can get out of bed, walk, urinate and even leave the house while remaining unconscious and unable to communicate. It is difficult to wake a sleepwalker, but it is not dangerous - as many people think. Sleepwalking cases have been caused by jet lag, the consumption of narcotics, sedatives and alcohol, cardiac problems such as arrhythmias, and other medical conditions, including epilepsy, asthma and apnoea. In a quick search of the literature, only one case due to hypoglycaemia has been reported, describing a patient with type 1 diabetes whose sleepwalking was triggered by nocturnal hypoglycaemia. Our present case was similar, and our report also describes how it occurred and how the condition was remedied.

Sp1-mediated transcription is involved in the induction of leptin by insulin-stimulated glucose metabolism.

We have previously demonstrated that insulin-stimulated glucose metabolism, and not insulin per se, mediates the effects of insulin to increase the transcriptional activity of the leptin promoter in adipocytes. Here, we sought to identify the specific cis-acting DNA elements required for the upregulation of leptin gene transcription in response to insulin-mediated glucose metabolism. To accomplish this, 3T3-L1 cells and primary rat adipocytes were transfected with a series of luciferase reporter genes containing portions of the mouse leptin promoter. Using this method, we identified an element between -135 and -95 bp (relative to the transcriptional start site) that mediated transcription in response to insulin-stimulated glucose metabolism in adipocytes. This effect was abolished by incubation with 2-deoxy-d-glucose, a competitive inhibitor of glucose metabolism. Gel shift electrophoretic mobility shift assays confirmed that the stimulatory effect of insulin-mediated glucose metabolism on leptin transcription was mediated by a previously identified Sp1 site. Consistent with these findings, incubation of primary rat adipocytes with WP631, a specific inhibitor of specificity protein (Sp)1-dependent transcription, inhibited glucose- and insulin-stimulated, but not basal, leptin secretion. Together, these findings support a key role for Sp1 in the transcriptional activation of the leptin gene promoter by insulin-mediated glucose metabolism.

New limit on the neutrinoless betabeta decay of 130Te.

We report the present results of CUORICINO, a search for neutrinoless double-beta (0nu betabeta) decay of 130Te. The detector is an array of 62 TeO2 bolometers with a total active mass of 40.7 kg. The array is cooled by a dilution refrigerator shielded from environmental radioactivity and energetic neutrons, operated at approximately 8 mK in the Gran Sasso Underground Laboratory. No evidence for (0nu betabeta) decay was found and a new lower limit, T(1/2)(0nu) > or = 1.8 x 10(24) yr (90% C.L.) is set, corresponding to [m(nu)] < or = 0.2 to 1.1 eV, depending on the theoretical nuclear matrix elements used in the analysis.

First results from the CERN axion solar telescope.

Hypothetical axionlike particles with a two-photon interaction would be produced in the sun by the Primakoff process. In a laboratory magnetic field ("axion helioscope"), they would be transformed into x-rays with energies of a few keV. Using a decommissioned Large Hadron Collider test magnet, the CERN Axion Solar Telescope ran for about 6 months during 2003. The first results from the analysis of these data are presented here. No signal above background was observed, implying an upper limit to the axion-photon coupling g(agamma)<1.16x10(-10) GeV-1 at 95% C.L. for m(a) less, similar 0.02 eV. This limit, assumption-free, is comparable to the limit from stellar energy-loss arguments and considerably more restrictive than any previous experiment over a broad range of axion masses.

[Cost-effectiveness analysis of the treatment of moderate benign prostatic hyperplasia]. / Análisis coste-efectividad del tratamiento de la hiperplasia prostática benigna de grado moderado.

OBJECTIVES: To estimate the most cost-effective alternative of treatment of moderate benign prostatic hyperplasia and to learn whether the outcome can be varied by changing the cost or effectiveness of the alternatives. DESIGN: The study is made by a decision tree in order to test the cost-effectiveness (CE) rate of three treatment strategies: a) watchful waiting; if there is no response a drug is administered and if there is no response transurethral resection of the prostate (TURP) is done, b) pharmacological treatment, and if there is no response TURP is done, and c) to apply TURP initially. The treatment is simulated taking 1000 patients with MBPH and testing the outcome of events and probabilities in a two-year treatment and from the point of view of the health system as services supplier. MEASUREMENTS AND RESULTS: Effectiveness is obtained from an american experts' consensus. Only the direct fangible costs are taken into account, in constant 1998 pts. An univariant simple sensitivity analysis is made considering the cost variables of TURP and from the drugs in an acceptable range of +/- 20%, and the effectiveness of the watchful waiting and the pharmacological treatment. The lower cost alternative per improved patient (IP) is the watchful waiting (77,069 pts./IP) followed by the drug treatment (118,656 pts./IP) and lastly the TURP (456,642 pts./IP). Variations in the variable values make no difference in the relative positions of the tested alternatives. CONCLUSIONS: From the pharmacoeconomics point of view the MBPH treatment must be iniciated by watchful waiting, proceeding to drug administration only if there is a positive response and to make use of TURP when the pharmacological procedures have not been effective.