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.

Foundry sands as low-cost adsorbent material for Cr (VI) removal.

The potential of foundry sands, industrial waste from the iron foundry industry, was evaluated for the removal of Cr (VI) using discontinuous assays. Chemical foundry sands are composed of fine silica sand, furanic resins as binder, chemical catalyst and residual iron particles. The influence ofpH, agitation rate and metal concentration on the removal process was investigated. Kinetic and equilibrium tests were conducted to determine Cr (VI) removal from aqueous solutions at a temperature range of 25-55 degrees C. Cr (VI) removal of 40-100% for a range of pH 6-1.6 was obtained. This removal was attributed to the presence of a large number of protonated silanol and aluminol groups. Cr (VI) adsorption in foundry sands follows a pseudo-second-order kinetic reaction (Ho model, r2 > 0.999) reaching kinetic constants of 0.341, 0.551, 0.775 and 0.920 g/mg h at 25, 35, 45 and 55 degrees C, respectively. The adsorption data were fitted to the Langmuir adsorption isotherm model (r > 0.99) obtaining adsorption capacities (q(max)) of 1.99, 2.40, 2.50, and 3.14 mg Cr (VI)/g sand at 25, 35, 45 and 55 degrees C, respectively. Calculated Gibbs free energy change (deltaG0), adsorption energy (E) and activation energy (E(a)) values indicate that a physisorption mechanism governs Cr (VI) adsorption process in foundry sands.

Temporal evolution of linear alkylbenzene sulfonates and heavy metals in sludge from wastewater treatment plant.

Five homologues of linear alkylbenzene sulfonates (LAS)-LAS C-10, LAS C-11, LAS C-12, and LAS C-13 and total LAS-were monitored during a one-year period in primary, secondary, and digested sludge to evaluate their presence and temporal evolution. Extraction of LAS was carried out using microwaves energy, and determination was performed using high-performance liquid chromatographic- fluorescence (HPLC-FL). The results showed that concentrations of total LAS were between 9 337 mg/kg(-1) dry matter for primary sludge and 33.3 mg/kg(-1)(DM) for secondary sludge. Concentrations of total LAS were greater than 2 113 mg/kg(-1) in primary and digested sludge and were less than 260 mg/kg(-) in secondary sludge. On the other hand, the highest concentrations of LAS in primary sludge were found in summer, probably because of lack of rain during those months. Concentrations tend to be constant throughout the year in digested sludge. In addition heavy metals also were analyzed. Heavy metals, including zinc, copper, nickel, lead, and chromium are persistent environmental contaminants that cannot be destroyed. Biomagnification through the food-chain and potential accumulation in human tissues can cause both human health and environmental concerns. Concern regarding total heavy metal content of sludge limits sludge recycling for use on agricultural lands. This paper presents a comparative study of wastewater sludge that are going to be used as fertilizer based on the requirements of legislation proposed in the European Union. This research found that concentrations of total LAS in digested sludge are higher than the limits established in the proposed new draft.

Lactate activates hypothalamic POMC neurons by intercellular signaling.

Previous studies indicate that the activity of hypothalamic POMC neurons can be regulated by glucose via intracellular mechanisms, but its regulation by lactate is poorly understood. In addition to its energetic role, lactate acts as a signaling molecule. In this study, we evaluated the function and location of the lactate receptor, hydroxycarboxylic acid receptor 1 (HCAR1). We used a conditional genetic approach to label POMC neurons and evaluated their sensitivity to lactate using patch-clamp recordings. L-Lactate and 3-chloro-5-hydroxybenzoic acid (3Cl-HBA), HCAR1 specific agonist depolarized POMC neurons and the increase in excitability was abolished by pertussis toxin (PTX), indicating the involvement of Gαi/o-protein-coupled receptors. In addition, the depolarization of a subset of POMC neurons was sensitive to α-cyano-4-hydroxycinnamate (4-CIN), a lactate transporter blocker, suggesting that the depolarization induced by L-lactate can also occur by direct intracellular action. Surprisingly, HCAR1 was not detected in POMC neurons, but instead localized in astrocytes. These results suggest a new lactate-mediated mechanism for astrocyte-neuron intercellular communication.

Geometric phase with nonunitary evolution in the presence of a quantum critical bath.

Geometric phases, arising from cyclic evolutions in a curved parameter space, appear in a wealth of physical settings. Recently, and largely motivated by the need of an experimentally realistic definition for quantum computing applications, the quantum geometric phase was generalized to open systems. The definition takes a kinematical approach, with an initial state that is evolved cyclically but coupled to an environment--leading to a correction of the geometric phase with respect to the uncoupled case. We obtain this correction by measuring the nonunitary evolution of the reduced density matrix of a spin one-half coupled to an environment. In particular we are interested in baths near a quantum phase transition, which are known to induce strong decoherence. The experiments are done with a NMR quantum simulator, where we emulate qualitatively the influence of a critical environment using a simple one-qubit model.

Sequential extraction of metals from mixed and digested sludge from aerobic WWTPs sited in the south of Spain.

The content of heavy metals is the major limitation to the application of sewage sludge in soil. However, assessment of the pollution by total metal determination does not reveal the true environmental impact. It is necessary to apply sequential extraction techniques to obtain suitable information about their bioavailability or toxicity. In this paper, sequential extraction of metals from sludge before and after aerobic digestion was applied to sludge from five WWTPs in southern Spain to obtain information about the influence of the digestion treatment in the concentration of the metals. The percentage of each metal as residual, oxidizable, reducible and exchangeable form was calculated. For this purpose, sludge samples were collected from two different points of the plants, namely, sludge from the mixture (primary and secondary sludge) tank (mixed sludge, MS) and the digested-dewatered sludge (final sludge, FS). Heavy metals, Al, Cd, Co, Cr, Cu, Fe, Hg, Mn, Mo, Ni, Pb, Ti and Zn, were extracted following the sequential extraction scheme proposed by the Standards, Measurements and Testing Programme of the European Commission and determined by inductively-coupled plasma atomic emission spectrometry. The total concentration of heavy metals in the measured sludge samples did not exceed the limits set out by European legislation and were mainly associated with the two less-available fractions (27-28% as oxidizable metal and 44-50% as residual metal). However, metals as Co (64% in MS and 52% in FS samples), Mn (82% in MS and 79% in FS), Ni (32% in MS and 26% in FS) and Zn (79% in MS and 62% in FS) were present at important percentages as available forms. In addition, results showed a clear increase of the concentration of metals after sludge treatment in the proportion of two less-available fractions (oxidizable and residual metal).

Silencing of the transcriptional factor ZEB1 alters the steroidogenic pathway, and increases the concentration of testosterone and DHT in DU145 cells.

Prostate cancer (PCa) is the second most common type of male malignancy worldwide. The transcription factor zinc finger E­box binding homeobox 1 (ZEB1) is associated with epithelial­mesenchymal transition and is also involved in regulation of androgen receptor (AR) expression, the main ligands of which are testosterone and dihydrotestosterone (DHT). These androgens are synthesized through the steroidogenic pathway within the prostate, and their synthesis is altered in PCa. The present study aimed to determine the ZEB1­induced alterations in androgen synthesis and AR expression in the DU145 PCa cell line. Reverse transcription­quantitative polymerase chain reaction, western blotting and immunocytochemistry were used to determine the mRNA and protein expression levels, and cellular localization of steroidogenic pathway enzymes in the DU145 cell line in response to ZEB1 silencing. Furthermore, the concentrations of testosterone and DHT were detected in cell culture medium using ELISA. ZEB1­silenced cells exhibited an increase in testosterone and DHT production, an increase in AR expression and an alteration in the steroidogenic pathway. In particular, steroidogenic acute regulatory protein and 5α­reductase 2 expression levels were decreased, whereas cytochrome P450 family 17 subfamily A member 1, 5α­reductase 1, aldo­keto reductase family 1 member D1 and aldo­keto reductase family 1 member C2 expression levels were increased. In conclusion, the present study provided novel information regarding the regulation of intratumoral androgen production in PCa, which is relevant for the progression of the disease to a castration­resistant form.

Temporal evolution of polycyclic aromatic hydrocarbons (PAHs) in sludge from wastewater treatment plants: comparison between PAHs and heavy metals.

This paper presents results on the presence and temporal variability of the 16 PAHs recommended by the EPA in primary, secondary and digested sewage sludge over a year. The sewage sludges originated from the Guadalete wastewater treatment plant (WWTP) site in Jerez de la Frontera (Cádiz, Spain). These organic pollutants have been extracted from the sewage sludge by microwave energy. High performance liquid chromatography coupled with diode array (HPLC-DAD) or fluorescence (HPLC-FL) detectors have been used. The results showed that total PAHs concentration varied between 1,945 ng g(-1) dry matter (DM) for primary sludges collected in March and 10,100 ng g(-1) DM for primary sludge collected in June. Generally, concentrations of PAHs were higher in compost and digested sludge than in fresh one. On the other hand, the highest concentration of PAHs were found on summer. This thing is associated to the traffic increase from inland zones to the coast (Jerez de la Frontera is very near to beaches). Finally, this paper present a comparative study of the American an European legislation concluding that the limits of concentrations established are not exceeded. In addition heavy metals were analysed. The origin of PAHs and heavy metals seems to be different.

Fractionation of heavy metals in sludge from anaerobic wastewater stabilization ponds in southern Spain.

The analysis of heavy metals is a very important task to assess the potential environmental and health risk associated with the sludge coming from wastewater treatment plants (WWTPs). However, it is necessary to apply sequential extraction techniques to obtain suitable information about their bioavailability or toxicity. In this paper, a sequential extraction scheme according to the Standard, Measurements and Testing Programme of the European Commission was applied to sludge samples collected from ten anaerobic wastewater stabilization ponds (WSPs) located in southern Spain. Al, Cd, Co, Cr, Cu, Fe, Hg, Mn, Mo, Ni, Pb, Ti and Zn were determined in the sludge extracts by inductively coupled plasma atomic emission spectrometry. In relation to current international legislation for the use of sludge for agricultural purposes, none of the metal concentrations exceeded maximum permitted levels. Overall, heavy metals were mainly associated with the two less-available fractions (34% oxidizable metal and 55% residual metal). Only Mn and Zn showed the highest share of the available (exchangeable and reducible) fractions (25-48%).

[Effectiveness of a program of early instillation single chemotherapy in patients with bladder cancer]. / Efectividad de un programa de instilación de quimioterapia precoz en pacientes con cáncer de vejiga.

OBJECTIVE: To determine the effectiveness of early intravesical chemotherapy intervention for patients with non-muscle invasive bladder cancer, before and after a training and inter-professional communication plan. METHOD: Non-experimental prospective longitudinal study of a cohort of 349 patients with endoscopic diagnosis of a non-muscle invasive bladder tumour in Northern Area Health Management of Cadiz between 2010 and 2013 and amenable to postoperative treatment with mitomycin C. RESULTS: The mean rate of patients included in the program was 53.9%. The inclusion rate rose by 79.3% at 3 years. The absolute risk reduction of recurrence for patients receiving treatment is 18.1% (95% CI; 8.81% - 27.48%, p<.001), and the number of patients needed to treat was 5.5 (95% CI; 3.6 - 11.3, p<.001). CONCLUSIONS: A program of early postoperative chemotherapy that includes a plan for evaluation and dissemination of results has achieved a good level of adherence among professionals, obtaining the expected impact on the reduction of early recurrence of non-muscle invasive bladder cancer.

Elderly donor kidney transplant: factors involved in graft survival.

PURPOSE: To evaluate whether control of risk factors associated with worse results has improved graft survival, with respect of renal function quality and other factors influencing graft survival: recipient age, immunosuppressive therapy, cold ischemia time, acute tubular necrosis (ATN), acute rejection episodes (ARE) and 1-month creatinine levels. MATERIALS AND METHODS: Retrospective review of 147 patients who underwent kidney transplant between 1995 and 2001. Inclusion criteria were donor and recipient age older than 60 years, first renal transplant, follow-up period longer than 12 months, donor creatinine clearance higher than 75 mL/min, and less than 20% glomerulosclerosis observed in donor renal biopsy. RESULTS: Graft survivals were 87%, 83%, 78%, and 70% at first, second, third, and fifth year after transplantation, respectively. Mean serum creatinine levels were 2.3 mg/dL and mean follow-up time, 46 months. Multivariate analysis using a Cox regression model identified donor age, ARE, and serum creatinine levels 1 month after surgery as independent variables affecting graft survival. Recipient age, immunosuppressive therapy, and serum creatinine levels at 1 month after surgery were predictive variables of recipient survival. DISCUSSION: Renal transplantation is an accepted therapeutic option in elderly patients with chronic renal insufficiency, if both donor and recipient are carefully selected.

[High incidence of chromosome 8 monosomy and chromosome 7 trisomy in prostatic primary tumor and its related lymphatic metastasis. Preliminary results]. / Alta incidencia de la monosomia del cromosoma 8 y la trisomia del cromosoma 7 en el tumor primario prostático y su metástasis ganglionar asociada. Resultados preliminares.

INTRODUCTION: The research on tumoral aggressivity parameters in prostate cancer, such DNA ploidy detected by fluorescence in situ hybridization, has significant relevance to refine prognostic on an individualized patient. OBJECTIVES: To identify chromosome numeric alterations by FISH in primary prostate cancer focus and its corresponding lymph node metastases. b) To describe a cytogenetic tumoral progression pathway. METHODS: So far, we have retrospectively studies eight patients with prostate cancer and lymph node metastases performing FISH analysis on the primary prostate cancer focus and its metastatic lymph node. DNA probes for chromosomes 7, 8, 10 and 12 have been used for FISH analysis. RESULTS: a) Seven out of eight tumours (85%) were aneuploid when studied by FISH and the most frequent chromosome alterations found were monosomy 8 (100%) and trisomy 7 (85.7%). All the lymph nodes were aneuploid being monosomy 8 (87.5%) and trisomy 7 (62.5%) the most common chromosome alterations. b) Monosomy 8 and trisomy 7 appeared to be in the same cytogenetic tumoral progression pathway. CONCLUSION: Although we report about a preliminary study, monosomy of chromosome 8 and trisomy 7 are related with poor evolution, probably because of the loss of a suppressor gene or a proto-oncogen overexpression. The presence of any of them in a prostate cancer focus is related with poor prognosis.

DNA replication stress in CHK1-depleted tumour cells triggers premature (S-phase) mitosis through inappropriate activation of Aurora kinase B.

The disruption of DNA replication in cells triggers checkpoint responses that slow-down S-phase progression and protect replication fork integrity. These checkpoints are also determinants of cell fate and can help maintain cell viability or trigger cell death pathways. CHK1 has a pivotal role in such S-phase responses. It helps maintain fork integrity during replication stress and protects cells from several catastrophic fates including premature mitosis, premature chromosome condensation and apoptosis. Here we investigated the role of CHK1 in protecting cancer cells from premature mitosis and apoptosis. We show that premature mitosis (characterized by the induction of histone H3 phosphorylation, aberrant chromatin condensation, and persistent RPA foci in arrested S-phase cells) is induced in p53-deficient tumour cells depleted of CHK1 when DNA synthesis is disrupted. These events are accompanied by an activation of Aurora kinase B in S-phase cells that is essential for histone H3 Ser10 phosphorylation. Histone H3 phosphorylation precedes the induction of apoptosis in p53-/- tumour cell lines but does not appear to be required for this fate as an Aurora kinase inhibitor suppresses phosphorylation of both Aurora B and histone H3 but has little effect on cell death. In contrast, only a small fraction of p53+/+ tumour cells shows this premature mitotic response, although they undergo a more rapid and robust apoptotic response. Taken together, our results suggest a novel role for CHK1 in the control of Aurora B activation during DNA replication stress and support the idea that premature mitosis is a distinct cell fate triggered by the disruption of DNA replication when CHK1 function is suppressed.

Radical cystectomy, hysterectomy with double adnexectomy and bilateral nephroureterectomy with transvaginal extraction.

OBJECTIVES: The onset of synchronous urothelial carcinoma in the upper or lower urinary tract is uncommon. Even more uncommon is the onset the bilateral form. The aim of this article is to describe the surgical technique of complete laparoscopic exeresis of the urinary apparatus and to add several variants of the technique that improve the patient's hemodynamics during surgery. MATERIAL AND METHODS: We present the technique of cystectomy with bilateral nephroureterectomy, hysterectomy with double adnexectomy and bilateral ilio-obturator lymphadenectomy by laparoscopy and transvaginal extraction of specimens from a 58-year-old patient with multiple prior vesical resections of high-grade urothelial carcinoma. The patient currently presents bladder recurrence and bilateral ureteropelvic tumor. The technique consists first of the hysterectomy and double adnexectomy along with the lymphadenectomy and cystectomy, maintaining the urethrovesical, ureterovesical and uterovaginal junctions. After changing the patient's position, both nephroureterectomies were performed. Lastly, we completed the resection of the previously mentioned segments to extract the specimens transvaginally. RESULTS: The histological result was high-grade urothelial carcinoma that affected the bladder and both ureteropelvic junctions, along with endometrial carcinoma. After reviewing the literature, we found less than 10 cases in which complete exeresis of the urinary apparatus was performed and none with the technical description presented in this article. In most cases described in the literature, surgery was performed at 2 separate times and without preserving renal function until the end of the complete exeresis. CONCLUSION: This technique helps maintain diuresis for a longer time during surgery and thereby facilitates the work of the anesthesiologist and improves the patient's circulatory dynamics. Additionally, the technique prevents any type of handling of the urinary tract, thereby avoiding the passage of tumor cells to the peritoneal cavity, given that the specimens are extracted whole through the vagina.

Initial experience with abiraterone acetate in patients with castration-resistant prostate cancer.

OBJECTIVE: To describe the results obtained in 25 males with metastatic castration-resistant prostate cancer (MCRPC) treated with abiraterone (AA). A comparative analysis of abiraterone effectiveness and safety between our results and data published in the literature was conducted. MATERIAL AND METHOD: Bi-institutional prospective analysis of 25 consecutive patients with MCRPC undergoing treatment with abiraterone, with a mean follow-up 7.9 (3-15) months was carried out. Treatment effectiveness and safety analyses regarding baseline characteristics of patients (age, prior treatments, basal PSA, performance status, pain, metastasis) were conducted. RESULTS: At 13.6 months of follow-up, the overall survival is 80% (CI 95%: 11.8-15.4). Clinical and radiological-free progression survival is 9.5 ± 1 months (CI 95%: 7.7-11.3) and biochemical response is 6.8 ± 1 months (CI 95%: 5-8.7). Only the treatment with chemotherapy impaired significantly the response time to AA [6.4 months for radiological-free progression survival (CI 95%: 4.2-8,6) and 4.3 months for biochemical-free progression survival (CI 95%: 2.6-6)]. The incidence of adverse drug events was 36%, all of them grade 1-2/4 and, in no case, suspension or reduction of the dose of AA was needed. CONCLUSIONS: The treatment with AA has been effective in our series, with a tolerability considerably higher than what other studies published.

Pre-chemotherapy abiraterone acetate. A proposal of a treatment algorithm in castration resistant prostate cancer.

CONTEXT: Prostate cancer treatment remains a challenge for the urologist. Medical control in locally advanced or metastatic prostate cancer is usually performed with LHRH analogues and/or antiandrogens. Different treatments have been proposed when there is biochemical and clinical progression of the disease and other new ones have changed the patients' perspective and life expectancy. OBJECTIVE: This review has aimed to establish the current role of Abiraterone Acetate in the treatment of castration-resistant prostate cancer and facilitate decision-making by the Urologist by means of a Treatment Algorithm. ACQUISITION OF THE EVIDENCE: A search of current evidence on Abiraterone treatment in patients with castration- resistant metastatic prostate cancer was performed in PubMed, mainly analyzing those studies designed as clinical trials. In addition, we reviewed and updated the role of hormone therapy and androgen receptors in prostate cancer. EVIDENCE SYNTHESIS: There are currently basically two clinical trials that demonstrate the effectiveness of Abiraterone in metastatic prostate cancer compared to placebo. The study COU-AA 302 shows a clear benefit with Abiraterone prior to chemotherapy in patients with castration-resistant prostate cancer, this making it possible to establish an algorithm for initial treatment that facilitates decision-making by the urologist. CONCLUSION: Abiraterone is a pre-chemotherapy treatment option in selected patients with castration resistant metastatic prostate cancer, although it is necessary to improve the cost and to design more multicenter clinical trials to optimize the cost/benefit ratio.

Assessment of a process to degrade metal working fluids using Pseudomonas stutzeri CECT 930 and indigenous microbial consortia.

The development of a novel biological process to treat metal working fluids (MWFs)-containing effluents at bioreactor scale was pursued in this work. The bacteria Pseudomonas stutzeri CECT 930 was investigated for the first time as an alternative agent for MWF degradation. An adequate medium design and mixing and aeration system, as well as an appropriate microorganism proved to be crucial for reaching high levels of degradation by P. stutzeri and by an indigenous consortium (about 70% and 50% of reduction in total petroleum hydrocarbon content in less than 2 wk, respectively). Additionally, as there is no information in literature trying to kinetically characterize an MWF-polluted effluent degradation process, all the experimental data were fitted to logistic and Luedeking and Piret models, that allowed to elucidate the growth-associated character of the biodegradation process.

[Gastrocolocutaneous fistula: an uncommon complication of percutaneous endoscopic gastrostomy]. / Fístula gastrocolocutánea: una infrecuente complicación de la gastrostomía endoscópica percutánea.

Endoscopic percutaneous gastrostomy is a safe technique although with potential complications before which the clinician has to be on alert in order to early detect them even after a long period of normal functioning. Most of them represent minor problems. Gastrocolocutaneous fistula is a rare but severe complication favored by some risk factors such as previous post-surgical adherences, deformities of the spine, or excessive gastric inflation at the time of performing the technique. We present the case of a patient with PEG with this complication that occurred after the first tube replacement. Our goal was in two senses: on the one hand, to analyze the preventive aspects and basic guidelines for a safe PEG placement to minimize the risks; on the other hand, to alert on the possible presence of this entity to prevent a progressive nutritional impairment. This complication ought to be included in the differential diagnosis of the diarrhea syndrome in the patient carrying a PEG. The diagnostic techniques of choice are radiologic tests such as CT scan and contrast media administration through the tube. Surgical therapy should be reserved to patients with acute peritonitis in order to perform a new gastrostomy.

[Toxicity of intravesical gemcitabine in superficial bladder cancer treatment]. / Toxicidad de la gemcitabina intravesical en el tratamiento del cáncer de vejiga superficial.

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Effect of cannabis on enzyme induction by phenobarbital.

Cannabis extracts in olive oil administered s.c. to male adult rats decreases oxidizing microsomal enzymes measured as TPNH disappearance and AHH activity in liver postmitochondrial fraction (93.06% and 25.54% maximum inhibition respectively in chronic treatments). Simultaneous administration of single doses of cannabis extracts (330 mg/kg s.c.) and phenobarbital (100 mg/kg i.p.) causes impairment of total microsomal oxidases (86.83% inhibition) and decreases AHH (31.86% inhibition), thus blocking the enzyme induction by phenobarbital.