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Summary The primary aim of this study was to determine the effect of oral antioxidant treatment (1500 mg of l‐Carnitine; 60 mg of vitamin C; 20 mg of coenzyme Q10; 10 mg of vitamin E; 10 mg of zinc; 200 μg of vitamin B9; 50 μg of selenium; 1 μg of vitamin B12) during a time period of 3 months upon the dynamics of sperm DNA fragmentation following varying periods of sperm storage (0 h, 2 h, 6 h, 8 h and 24 h) at 37 °C in a cohort of 20 infertile patients diagnosed with asthenoteratozoospermia. A secondary objective was to use the sperm chromatin dispersion test (SCD) to study antioxidant effects upon a specific subpopulation of highly DNA degraded sperm (DDS). Semen parameters and pregnancy rate (PR) were also determined. Results showed a significant improvement of DNA integrity at all incubation points (P < 0.01). The proportion of DDS was also significantly reduced (P < 0.05). Semen analysis data showed a significant increase in concentration, motility, vitality and morphology parameters. Our results suggest that antioxidant treatment improves sperm quality not only in terms of key seminal parameters and basal DNA damage, but also helps to maintain DNA integrity. Prior administration of antioxidants could therefore promote better outcomes following assisted reproductive techniques.

If Dark Matter is made of Weakly Interacting Massive Particles (WIMPs) with masses below ∼ 20 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 ∼ 0.300  kg of Ar at 10 bar, or alternatively ∼ 0.160 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.

Sperm DNA fragmentation can be produced in one (ssSDF) or both (dsSDF) DNA strands, linked to difficulties in naturally achieving a pregnancy and recurrent miscarriages, respectively. The techniques more frequently used to select sperm require centrifugation, which may induce sperm DNA fragmentation (SDF). The objective of this study was to assess whether the microfluidic-based device FertileChip ® (now ZyMot ® ICSI) can diminish the proportion of sperm with dsSDF. First, in a blinded split pilot study, the semen of nine patients diagnosed with ≥60% dsSDF, was divided into three aliquots: not processed, processed with FertileChip ® , and processed with swim up. The three aliquots were all analyzed using neutral COMET for the detection of dsSDF, resulting in a reduction of 46% ( P < 0.001) with FertileChip ® (dsSDF: 34.9%) compared with the ejaculate and the swim up (dsSDF: 65%). Thereafter, the FertileChip ® was introduced into clinical practice and a cohort of 163 consecutive ICSI cycles of patients diagnosed with ≥60% dsSDF was analyzed. Fertilization rate was 75.41%. Pregnancy rates after the first embryo transfer were 53.2% (biochemical), 37.8% (clinical), 34% (ongoing) and the live birth rate was 28.8%. Cumulative pregnancy rates after one (65.4% of patients), two (27.6% of patients) or three (6.4% of patients) transfers were 66% (biochemical), 56.4% (clinical), 53.4% (ongoing) and the live birth rate was 42%. The selection of spermatozoa using Fertile Chip ® significantly diminishes the percentage of dsSDF, compared with either the fresh ejaculate or after swim up. Its applicability in ICSI cycles of patients with high dsSDF resulted in good laboratory and clinical outcomes.

Background 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is one of the most abused recreational drugs. Its usual pattern of misuse includes repeated doses taken over a short time period that could influence MDMA pharmacology and toxicity. Objective This study aims to evaluate the pharmacokinetics and pharmacologically induced effects of two MDMA consecutive doses separated by 2 h. Methods A randomized, double-blind, crossover, and placebo-controlled trial included ten male volunteers participating in two experimental sessions. MDMA was administered as a single 100-mg dose or as a repeated dose (50 mg followed by 100 mg, administered at 2 h apart). Outcome variables included pharmacokinetics, physiological, subjective, and psychomotor effects. Results Following the repeated doses, plasma concentrations of MDMA were higher than those expected by simple dose accumulation (+16.2 % AUC; +12.8 % C max ), but those of HMMA and HMA were significantly lower (−29.8 % AUC; −38.2 % C max ). After the second dose, physiological effects, psychomotor performance, and subjective effects were lower than expected especially for euphoria and stimulation. MDMA-induced increases in diastolic and systolic arterial pressure and body temperature were in the range of those expected following MDMA concentrations. Conclusions MDMA pharmacokinetics and metabolic disposition following two doses separated by 2 h show that the contribution of the first dose to the MDMA-induced mechanism-based metabolic inhibition was already apparent. The concentrations of MDMA after the second dose were slightly higher than expected. The effects on blood pressure and temperature after the second administration were slightly higher than those following the first, but for heart rate and subjective variables these were lower than expected considering the MDMA concentrations achieved, suggesting a possible tolerance phenomenon.

TREX-DM (TPC Rare Event eXperiment for Dark Matter) is intended to look for low mass WIMPs in the Canfranc Underground Laboratory (LSC) in Spain, using light elements (Ne, Ar) as target in a high pressure TPC equipped with Micromegas readouts. Here, a description of the detector, the first results from commissioning data and the expected sensitivity from the developed background model are briefly presented.

Summary There is an interest in the nuclear degraded sperm subpopulation because, although it is present in a low percentage in all semen samples, patient groups such as varicocele and rearranged genome carriers show high levels of these degraded spermatozoa. This study is designed with two objectives in mind: first, incubations of H2O2 and nuclease on DTT‐treated and untreated samples to show the aetiology of this subpopulation and second, assessment of the correlation between the protamine ratio and nuclear degraded spermatozoa. A very high increase in the nuclear degraded subpopulation has been found with nuclease incubation, and it is even higher when it has been merged with nuclear decompaction using DTT. Alternatively, incubation with H2O2 with and without DTT did not show such a significant increase in nuclear degraded spermatozoa. The protamine ratio correlated with this subpopulation, showing, in patients, that poor nuclear compaction would turn the sperm susceptible to degradation. Then, the assessment of nuclear degraded spermatozoa might not be only a measure of DNA degradation but also an indicator of chromatin compaction in the spermatozoa. Different patient groups would fit this model for sperm nuclear degradation, such as varicocele patients, who show a high percentage of immature spermatozoa and nuclear degraded spermatozoa, and reorganised genome carriers, where reorganisation might also cause poor chromatin compaction on the sperm nucleus.

3,4-Methylenedioxymethamphetamine (MDMA, \"ecstasy\") is increasingly used by young people for its euphoric and empathic effects. MDMA presents non-linear pharmacokinetics, probably by inhibition of cytochrome P450 isoform 2D6. Users are known to often take more than one dose per session. This practice could have serious implications for the toxicity of MDMA. To evaluate the pharmacological effects and pharmacokinetics of MDMA following the administration of two repeated doses of MDMA (24 h apart). A randomised, double-blind, cross-over, placebo controlled trial was conducted in nine healthy male subjects. Variables included physiological, psychomotor performance, subjective effects, endocrine response and pharmacokinetics. MDMA 100 mg or placebo was administered in two successive doses separated by an interval of 24 h. MDMA produced the prototypical effects of the drug. Following a second dose, plasma concentrations of MDMA increased (AUC 77% and Cmax 29%) in comparison with the first. The increase is greater than those expected by simple accumulation and indicates metabolic inhibition. The pharmacological effects after the second dose were slightly higher than those observed after the first in the majority of variables including blood pressure, heart rate, most subjective effects and cortisol concentrations. The effects were similar in the case of pupil diameter, esophoria and prolactin. Pharmacological effects after the second administration were higher than those following the first but lower than expected. A disproportionate increase in plasma concentrations in MDMA and MDA was observed most likely due to metabolic inhibition. This inhibition lasts at least 24 h. Further experiments need to be conducted to evaluate its duration.

TREX-DM (TPC Rare Event eXperiment for Dark Matter) is a high-pressure Micromegas-based TPC designed to host a few hundreds of grams of light nuclei (argon or neon) with energy thresholds potentially at the level of 0.4 keVee or below. Preliminary background studies suggest that the levels expected are of the order of 1-10 counts keV−1 kg−1 d−1, making TREX-DM competitive in the search for low mass WIMPs (<10 GeV). The experiment has been approved by the LSC (Laboratorio Subterrneo de Canfranc) and the last months have been devoted to its installation underground. Here we will report on the first commissioning phase.

The most compelling candidates for Dark Matter to day are WIMPs and axions. The applicability of gasesous Time Projection Chambers (TPCs) with Micromesh Gas Structures (Micromegas) to the search of these particles is explored within this work. Both particles would produce an extremely low rate at very low energies in particle detectors. Micromegas detectors can provide both low background rates and low energy threshold, due to the high granularity, radiopurity and uniformity of the readout. Small (few cm wide) Micromegas detectors are used to image the axion-induced x-ray signal expected in the CERN Axion Solar Telescope (CAST) experiment. We show the background levels obtained in CAST and the prospects to further reduce them to the values required by the Internation Axion Observatory (IAXO). We also present TREX-DM, a scaled-up version of the Micromegas used in axion research, but this time dedicated to the low-mass WIMP detection. TREX-DM is a high-pressure Micromegas-based TPC designed to host a few hundreds of grams of light nuclei (argon or neon) with energy thresholds potentially at the level of 100 eV. The detector is described in detail, as well as the results of the commissioning and characterization phase on surface. Besides, the background model of TREX-DM is presented, along with the anticipated sensitivity of this search, which could go beyond current experimental limits.

Inferences about gender differences and socioeconomic status in Chronic Non-Cancer Pain (CNCP) management may shape health care. This can be a particularly relevant issue for women, who continue to more often assume reproductive gender roles. The objective of this study was to explore the gendered impact of CNCP on low-and middle-income women and men through text mining analysis.