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HD235088 (TOI-1430) is a young star known to host a sub-Neptune-sized planet candidate. We validated the planetary nature of HD235088 b with multiband photometry, refined its planetary parameters, and obtained a new age estimate of the host star, placing it at 600-800 Myr. Previous spectroscopic observations of a single transit detected an excess absorption of He I coincident in time with the planet candidate transit. Here, we confirm the presence of He I in the atmosphere of HD235088 b with one transit observed with CARMENES. We also detected hints of variability in the strength of the helium signal, with an absorption of $-$0.91$\pm$0.11%, which is slightly deeper (2$\sigma$) than the previous measurement. Furthermore, we simulated the He I signal with a spherically symmetric 1D hydrodynamic model, finding that the upper atmosphere of HD235088 b escapes hydrodynamically with a significant mass loss rate of (1.5-5) $\times$10$^{10}$g s$^{-1}$, in a relatively cold outflow, with $T$=3125$\pm$375 K, in the photon-limited escape regime. HD235088 b ($R_{p}$ = 2.045$\pm$0.075 R$_{\oplus}$) is the smallest planet found to date with a solid atmospheric detection - not just of He I but any other atom or molecule. This positions it a benchmark planet for further analyses of evolving young sub-Neptune atmospheres., Comment: Accepted for publication in A&A. 17 pages, 18 figures

Aims. A transiting planet candidate with a sub-Neptune radius orbiting the nearby ($d$ = 51.9$\pm$0.07 pc) M1.5 V star TOI-1470 with a period of $\sim$2.5 d was announced by the NASA Transiting Exoplanet Survey Satellite (TESS), which observed the field of TOI-1470 in four different sectors. We aim to validate its planetary nature using precise radial velocities (RVs) taken with the CARMENES spectrograph. Methods. We obtained 44 RV measurements with CARMENES spanning eight months between 3 June 2020 and 17 January 2021. For a better characterization of the parent star activity, we also collected contemporaneous optical photometric observations at the Joan Or\'o and Sierra Nevada Observatories, and we retrieved archival photometry from the literature. We used ground-based photometric observations from MuSCAT and also from MuSCAT2 and MuSCAT3 to confirm the planetary transit signals. We performed a combined photometric and spectroscopic analysis by including Gaussian processes and Keplerian orbits to simultaneously account for the stellar activity and planetary signals. Results. We estimate that TOI-1470 has a rotation period of 29$\pm$3 d based on photometric and spectroscopic data. The combined analysis confirms the discovery of the announced transiting planet, TOI-1470 b, with an orbital period of 2.527093$\pm$0.000003 d, a mass of $7.32^{+1.21}_{-1.24}$ M$_{\oplus}$, and a radius of $2.18^{+0.04}_{-0.04}$ R$_{\oplus}$. We also discover a second transiting planet that was not announced previously by TESS, TOI-1470 c, with an orbital period of 18.08816$\pm$0.00006 d, a mass of $7.24^{+2.87}_{-2.77}$ M$_{\oplus}$, and a radius of $2.47^{+0.02}_{-0.02}$ R$_{\oplus}$. The two planets are placed on the same side of the radius valley of M dwarfs and lie between TOI-1470 and the inner border of its habitable zone., Comment: arXiv admin note: substantial text overlap with arXiv:2111.14602

We report the discovery of HN Lib b, a sub-Neptunian mass planet orbiting the nearby ($d \approx$ = 6.25 pc) M4.0 V star HN Lib detected by our CARMENES radial-velocity (RV) survey. We determined a planetary minimum mass of $M_\text{b}\sin i = $ 5.46 $\pm$ 0.75 $\text{M}_\oplus$ and an orbital period of $P_\text{b} = $ 36.116 $\pm$ 0.029 d, using $\sim$5 yr of CARMENES data, as well as archival RVs from HARPS and HIRES spanning more than 13 years. The flux received by the planet equals half the instellation on Earth, which places it in the middle of the conservative habitable zone (HZ) of its host star. The RV data show evidence for another planet candidate with $M_\text{[c]}\sin i = $ 9.7 $\pm$ 1.9 $\text{M}_\oplus$ and $P_\text{[c]} = $ 113.46 $\pm$ 0.20 d. The long-term stability of the signal and the fact that the best model for our data is a two-planet model with an independent activity component stand as strong arguments for establishing a planetary origin. However, we cannot rule out stellar activity due to its proximity to the rotation period of HN Lib, which we measured using CARMENES activity indicators and photometric data from a ground-based multi-site campaign as well as archival data. The discovery adds HN Lib b to the shortlist of super-Earth planets in the habitable zone of M dwarfs, but HN Lib [c] probably cannot be inhabited because, if confirmed, it would most likely be an icy giant.

Galactosemia is an autosomal recessive disease, caused by the deficit of any of the four enzymes involved in the metabolism of galactose, derived from the disaccharide lactose, on its way to becoming glucose. Knowledge of this pathology and a high index of suspicion will allow early diagnosis and treatment, thus decreasing the associated complications and even mortality. We will present a brief summary of the disease in the context of a patient treated in our neonatology service.

One of the main scientific goals of the TESS mission is the discovery of transiting small planets around the closest and brightest stars in the sky. Here, using data from the CARMENES, MAROON-X, and HIRES spectrographs, together with TESS, we report the discovery and mass determination of a planetary system around the M1.5 V star GJ 806 (TOI-4481). GJ 806 is a bright (V=10.8 mag, J=7.3 mag) and nearby (d=12 pc) M dwarf that hosts at least two planets. The innermost planet, GJ 806 b, is transiting and has an ultra-short orbital period of 0.93 d, a radius of 1.331+-0.023 Re, a mass of 1.90+-0.17 Me, a mean density of 4.40+-0.45 g/cm3, and an equilibrium temperature of 940+-10 K. We detect a second, non-transiting, super-Earth planet in the system, GJ 806c, with an orbital period of 6.6 d, a minimum mass of 5.80+-0.30 Me, and an equilibrium temperature of 490+-5 K. The radial velocity data also shows evidence for a third periodicity at 13.6 d, although the current dataset does not provide sufficient evidence to unambiguously distinguish between a third super-Earth mass (Msin(i)=8.50+-0.45 Me) planet or stellar activity. Additionally, we report one transit observation of GJ 806 b taken with CARMENES in search for a possible extended atmosphere of H or He, but we can only place upper limits to its existence. This is not surprising as our evolutionary models support the idea that any possible primordial H/He atmosphere that GJ 806 b might have had, would long have been lost. However, GJ 806b's bulk density makes it likely that the planet hosts some type of volatile atmosphere. In fact, with a transmission spectroscopy metrics (TSM) of 44 and an emission spectroscopy metrics (ESM) of 24, GJ 806 b the third-ranked terrestrial planet around an M dwarf suitable for transmission spectroscopy studies, and the most promising terrestrial planet for emission spectroscopy studies., Under second review in A&A. This paper is NOT yet accepted, but it is made openly available to the community due to the approaching JWST deadline

Full list of authors: Kemmer, J.; Dreizler, S.; Kossakowski, D.; Stock, S.; Quirrenbach, A.; Caballero, J. A.; Amado, P. J.; Collins, K. A.; Espinoza, N.; Herrero, E.; Jenkins, J. M.; Latham, D. W.; Lillo-Box, J.; Narita, N.; Pallé, E.; Reiners, A.; Ribas, I.; Ricker, G.; Rodríguez, E.; Seager, S.; Vanderspek, R.; Wells, R.; Winn, J.; Aceituno, F. J.; Béjar, V. J. S.; Barclay, T.; Bluhm, P.; Chaturvedi, P.; Cifuentes, C.; Collins, K. I.; Cortés-Contreras, M.; Demory, B. -O.; Fausnaugh, M. M.; Fukui, A.; Gómez Maqueo Chew, Y.; Galadí-Enríquez, D.; Gan, T.; Gillon, M.; Golovin, A.; Hatzes, A. P.; Henning, Th.; Huang, C.; Jeffers, S. V.; Kaminski, A.; Kunimoto, M.; Kürster, M.; López-González, M. J.; Lafarga, M.; Luque, R.; McCormac, J.; Molaverdikhani, K.; Montes, D.; Morales, J. C.; Passegger, V. M.; Reffert, S.; Sabin, L.; Schöfer, P.; Schanche, N.; Schlecker, M.; Schroffenegger, U.; Schwarz, R. P.; Schweitzer, A.; Sota, A.; Tenenbaum, P.; Trifonov, T.; Vanaverbeke, S.; Zechmeister, M., We report the discovery of GJ 3929 b, a hot Earth-sized planet orbiting the nearby M3.5 V dwarf star, GJ 3929 (G 180-18, TOI-2013). Joint modelling of photometric observations from TESS sectors 24 and 25 together with 73 spectroscopic observations from CARMENES and follow-up transit observations from SAINT-EX, LCOGT, and OSN yields a planet radius of Rb = 1.150 ± 0.040 R⊕, a mass of Mb = 1.21 ± 0.42 M⊕, and an orbital period of Pb = 2.6162745 ± 0.0000030 d. The resulting density of ρb = 4.4 ± 1.6 g cm−3 is compatible with the Earth’s mean density of about 5.5 g cm−3. Due to the apparent brightness of the host star (J = 8.7 mag) and its small size, GJ 3929 b is a promising target for atmospheric characterisation with the JWST. Additionally, the radial velocity data show evidence for another planet candidate with P[c] = 14.303 ± 0.035 d, which is likely unrelated to the stellar rotation period, Prot = 122 ± 13 d, which we determined from archival HATNet and ASAS-SN photometry combined with newly obtained TJO data. © ESO 2022., This paper is based on observations made with the MuSCAT3 instrument, developed by the Astrobiology Center and under financial supports by JSPS KAKENHI (JP18H05439) and JST PRESTO (JPMJPR1775), at Faulkes Telescope North on Maui, HI, operated by the Las Cumbres Observatory. This work includes observationscarried out at the Observatorio Astronómico Nacional on the Sierra de San Pedro Mártir (OAN-SPM), Baja California, México. We acknowledge financial support from the Agencia Estatal de Investigación of the Ministerio de Ciencia, Innovación y Universidades and the ERDF through projects PID2019-109522GB-C5[1:4], PID2019-107061GB-C64, PID2019-110689RB-100, ESP2017-87676-C5-1-R, and the Centre of Excellence “Severo Ochoa” and “María de Maeztu” awards to the Instituto de Astrofísica de Canarias (CEX2019-000920-S), Instituto de Astrofísica de Andalucía (SEV-2017-0709), and Centro de Astrobiología (MDM-2017-0737), the Swiss National Science Foundation (PP00P2-163967 and PP00P2-190080), the Centre for Space and Habitability of the University of Bern, the National Centre for Competence in Research PlanetS, supported by the Swiss National Science Foundation, the Deutsche Forschungsgemeinschaft priority program SPP 1992 “Exploring the Diversity of Extrasolar Planets” (JE 701/5-1), the Excellence Cluster ORIGINS, which is funded by the Deutsche Forschungsgemeinschaft under Germany’s Excellence Strategy (EXC-2094 – 390783311), NASA (NNX17AG24G), JSPS KAKENHI Grant Number JP18H05439, JST CREST Grant Number JPMJCR1761, the Astrobiology Center of National Institutes of Natural Sciences (NINS) (Grant Number AB031010), the UNAM-DGAPA PAPIIT (BG-101321), the “la Caixa” Foundation (100010434), the European Union Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie (No. 847648, fellowship code LCF/BQ/PI20/11760023), and the Generalitat de Catalunya/CERCA programme. Data were partly collected with the 90-cm telescope at Observatorio de Sierra Nevada (OSN), operated by the Instituto de Astrofísica de Andalucí a (IAA, CSIC). We deeply acknowledge the OSN telescope operators for their very appreciable support.

This is an Open Access article, published by EDP Sciences, under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited., Context. Current exoplanet surveys using the radial velocity (RV) technique are targeting M dwarfs because any habitable zone terrestrial-mass planets will induce a high RV and orbit on shorter periods than for more massive stars. One of the main caveats is that M dwarfs show a wide range of activity levels from inactive to very active, which can induce an asymmetry in the line profiles and, consequently, a spurious RV measurement. Aims. We aim to benchmark the impact of stellar activity on high-precision RV measurements using regular-cadence CARMENES visible and near-infrared observations of the active M3.5 dwarf EV Lac. Methods. We used the newly developed technique of low-resolution Doppler imaging to determine the centre-of-light, or spot-induced RV component, for eight observational epochs. Results. We confirm a statistically significant and strong correlation between the independently measured centre-of-light and the chromatic index, which is a measure of the amplitude variation with wavelength of the RVs. We also find circular “closed-loop” relations of several activity indices with RV for a subset of data that covers only several rotation periods. We also investigate the implications of large phase gaps in the periodograms of activity indicators. Finally, by removing the spot-induced RV component we improve the planet-mass sensitivity by a factor of at least three. Conclusions. We conclude that for active M stars, a regular-cadence observing strategy is the most efficient way to identify and eliminate sources of correlated noise. © S. V. Jeffers et al. 2022., S.V.J. acknowledges the support of the German Science Foundation (DFG) priority program SPP 1992 “Exploring the Diversity of Extrasolar Planets” (JE 701/5-1). CARMENES is an instrument for the Centro Astronómico Hispano-Alemán de Calar Alto (CAHA, Almería, Spain). CARMENES was funded by the German Max-Planck-Gesellschaft (MPG), the Spanish Consejo Superior de Investigaciones Científicas (CSIC), the European Union through FEDER/ERF FICTS-2011-02 funds, and the members of the CARMENES Consortium (Max-Planck-Institut für Astronomie, Instituto de Astrofísica de Andalucía, Landessternwarte Königstuhl, Institut de Ciències de l’Espai, Institut für Astrophysik Göttingen, Universidad Complutense de Madrid, Thüringer Landessternwarte Tautenburg, Instituto de Astrofísica de Canarias, Hamburger Sternwarte, Centro de Astrobiología and Centro Astronómico Hispano-Alemán), with additional contributions by the Spanish Ministry of Economy, the German Science Foundation through the Major Research Instrumentation Programme and DFG Research Unit FOR2544 “Blue Planets around Red Stars”, the Klaus Tschira Stiftung, the states of Baden-Württemberg and Niedersachsen, and by the Junta de Andalucía. Based on data from the CARMENES data archive at CAB (INTA-CSIC). We acknowledge financial support from the Agencia Estatal de Investigación of the Ministerio de Ciencia, Innovación y Universidades and the ERDF through projects PID2019-109522GB-C5[1:4]/AEI/10.13039/501100011033, PID2019-107061GB-C64, PGC2018-098153-B-C33, AYA2016-79425-C3-1/2/3-P, BES-2017-080769, and the Centre of Excellence “Severo Ochoa” and “María de Maeztu” awards to the Instituto de Astrofísica de Canarias (CEX2019-000920-S, SEV-2015-0548-16-3), Instituto de Astrofísica de Andalucía (SEV-2017-0709), and Centro de Astrobiología (MDM-2017-0737), and the Generalitat de Catalunya/CERCA programme. This paper includes data collected by the TESS mission. Funding for the TESS mission is provided by the NASA’s Science Mission Directorate.

Introduction: Breast cancer is the most common neoplasia of women from all over the world especially women from Colombia. 5%­10% of all cases are caused by hereditary factors, 25% of those cases have mutations in the BRCA1/BRCA2 genes. Objective: The purpose of this study was to identify the mutations associated with the risk of familial breast and/or ovarian cancer in a population of Colombian pacific. Methods: 58 high-risk breast and/or ovarian cancer families and 20 controls were screened for germline mutations in BRCA1 and BRCA2, by Single Strand Conformation Polymorphism (SSCP) and sequencing. Results: Four families (6.9%) were found to carry BRCA1 mutations and eight families (13.8%) had mutations in BRCA2. In BRCA1, we found three Variants of Uncertain Significance (VUS), of which we concluded, using in silico tools, that c.81­12C>G and c.3119G>A (p.Ser1040Asn) are probably deleterious, and c.3083G>A (p.Arg1028His) is probably neutral. In BRCA2, we found three variants of uncertain significance: two were previously described and one novel mutation. Using in silico analysis, we concluded that c.865A>G (p.Asn289Asp) and c.6427T>C (p.Ser2143Pro) are probably deleterious and c.125A>G (p.Tyr42Cys) is probably neutral. Only one of them has previously been reported in Colombia. We also identified 13 polymorphisms (4 in BRCA1 and 9 in BRCA2), two of them are associated with a moderate increase in breast cancer risk (BRCA2 c.1114A>C and c.8755­66T>C). Conclusion: According to our results, the Colombian pacific population presents diverse mutational spectrum for BRCA genes that differs from the findings in other regions in the country.

It has been hypothesised that oral bacteria can migrate, through the blood, from the mouth to the arterial plaques, thus exacerbating atherosclerosis. This study compared bacteria present in the peripheral blood of individuals with and without coronary artery disease (CAD). RNA sequences obtained from blood were downloaded from GEO (GSE58150). Eight patients with coronary artery calcification (CAC) scoring > 500 and eight healthy individuals were analysed. After conducting quality control, the sequences were aligned to the hg38 reference genome using Hisat2. Bacterial taxa were analysed by inputting the unmapped sequences into Kraken. Ecological indices were calculated using Vegan. The package DESeq2 was used to compare the counts of bacteria per standard rank between groups. A total of 51 species were found only in patients with CAD and 41 were exclusively present in healthy individuals. The counts of one phylum, one class, three orders, two families and one genus were significantly different between the analysed groups (p Fusobacterium nucleatum was significantly less frequent in patients with CAD (p = 0.0012, FDR = 4.8%). Furthermore, the frequency of another 11 bacteria differed significantly among patients with CAD than that among healthy individuals (p

Open Access article, published by EDP Sciences, under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited., Context. Despite being a prominent subset of the exoplanet population discovered in the past three decades, the nature and provenance of sub-Neptune-sized planets is still one of the open questions in exoplanet science. Aims. For planets orbiting bright stars, precisely measuring the orbital and planet parameters of the system is the best approach to distinguish between competing theories regarding their formation and evolution. Methods. We obtained 69 new radial velocity observations of the mid-M dwarf G 9–40 with the CARMENES instrument to measure for the first time the mass of its transiting sub-Neptune planet, G 9–40 b, discovered in data from the K2 mission. Results. Combined with new observations from the TESS mission during Sectors 44, 45, and 46, we are able to measure the radius of the planet to an uncertainty of 3.4% (Rb = 1.900 ± 0.065 R⊕) and determine its mass with a precision of 16% (Mb = 4.00 ± 0.63 M⊕). The resulting bulk density of the planet is inconsistent with a terrestrial composition and suggests the presence of either a water-rich core or a significant hydrogen-rich envelope. Conclusions. G 9–40 b is referred to as a keystone planet due to its location in period-radius space within the radius valley. Several theories offer explanations for the origin and properties of this population and this planet is a valuable target for testing the dependence of those models on stellar host mass. By virtue of its brightness and small size of the host, it joins L 98-59 d as one of the two best warm (Teq ~ 400 K) sub-Neptunes for atmospheric characterization with JWST, which will probe cloud formation in sub-Neptune-sized planets and break the degeneracies of internal composition models. © R. Luque et al. 2022., This work was supported by the KESPRINT (www.kesprint.science.) collaboration, an international consortium devoted to the characterization and research of exoplanets discovered with space-based missions. This paper includes data collected by the Kepler and TESS missions, obtained from the MAST data archive at the Space Telescope Science Institute (STScI). Funding for the Kepler mission is provided by the NASA Science Mission Directorate. Funding for the TESS mission is provided by the NASA Explorer Program. STScI is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS 5–26555. We acknowledge the use of public TESS data from pipelines at the TESS Science Office and at the TESS Science Processing Operations Center. Resources supporting this work were provided by the NASA High-End Computing (HEC) Program through the NASA Advanced Supercomputing (NAS) Division at Ames Research Center for the production of the SPOC data products. This article is partly based on observations made with the MuSCAT2 instrument, developed by ABC, at Telescopio Carlos Sánchez operated on the island of Tenerife by the IAC in the Spanish Observatorio del Teide. CARMENES is an instrument at the Centro Astronómico Hispano-Alemán (CAHA) at Calar Alto (Almeria, Spain), operated jointly by the Junta de Andalucía and the Instituto de Astrofísica de Andalucía (CSIC). CARMENES was funded by the Max-Planck-Gesellschaft (MPG), the Consejo Superior de Investigaciones Científicas (CSIC), the Ministerio de Economia y Competitividad (MINECO) and the European Regional Development Fund (ERDF) through projects FICTS-2011-02, ICTS-2017-07-CAHA-4, and CAHA16-CE-3978, and the members of the CARMENES Consortium with additional contributions. IRD is operated by the Astrobiology Center of the National Institute of Natural Sciences of Japan. R.L. acknowledges funding from University of La Laguna through the Margarita Salas Fellowship from the Spanish Ministry of Universities ref. UNI/551/2021-May 26 under the EU Next Generation funds and from the Spanish Ministerio de Ciencia e Innovación, through project PID2019-109522GB-C52, and the Centre of Excellence “Severo Ochoa” award to the Instituto de Astrofísica de Andalucía (SEV-2017-0709). This work is partly supported by JSPS KAKENHI Grant Numbers 18H05442, 15H02063, 22000005, JP18H05439, JP21K20376 and JST CREST Grant Number JPMJCR1761. C.C. acknowledges financial support from the ERDF through project AYA2016-79425-C3-1/2/3-P. C.M.P. acknowledges the support of the Swedish National Space Agency (DNR 65/19). H.J.D. acknowledges support from the Spanish Research Agency of the Ministry of Science and Innovation (AEI-MICINN) under grant PID2019-107061GB-C66. P.K. acknowledges the support from the grant LTT-20015. K.W.F.L. was supported by Deutsche Forschungsgemeinschaft grants RA714/14-1 within the DFG Schwerpunkt SPP 1992, Exploring the Diversity of Extrasolar Planets. This work was supported by the DFG Research Unit FOR2544 “Blue Planets around Red Stars” G.M. has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 895525.

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

We report the discovery of a Neptune-like planet (LP 714-47 b, P = 4.05204 d, mb = 30.8 ± 1.5Mpdbl, Rb = 4.7 ± 0.3 Rpdbl) located in the "hot Neptune desert". Confirmation of the TESS Object of Interest (TOI 442.01) was achieved with radial-velocity follow-up using CARMENES, ESPRESSO, HIRES, iSHELL, and PFS, as well as from photometric data using TESS, Spitzer, and ground-based photometry from MuSCAT2, TRAPPIST-South, MONET-South, the George Mason University telescope, the Las Cumbres Observatory Global Telescope network, the El Sauce telescope, the TÜBITAK National Observatory, the University of Louisville Manner Telescope, and WASP-South. We also present high-spatial resolution adaptive optics imaging with the Gemini Near-Infrared Imager. The low uncertainties in the mass and radius determination place LP 714-47 b among physically well-characterised planets, allowing for a meaningful comparison with planet structure models. The host star LP 714-47 is a slowly rotating early M dwarf (Teff = 3950 ± 51 K) with a mass of 0.59 ± 0.02Mpdbl and a radius of 0.58 ± 0.02Rpdbl. From long-term photometric monitoring and spectroscopic activity indicators, we determine a stellar rotation period of about 33 d. The stellar activity is also manifested as correlated noise in the radial-velocity data. In the power spectrum of the radial-velocity data, we detect a second signal with a period of 16 days in addition to the four-day signal of the planet. This could be shown to be a harmonic of the stellar rotation period or the signal of a second planet. It may be possible to tell the difference once more TESS data and radial-velocity data are obtained. © ESO 2020., CARMENES is an instrument for the Centro Astronomico Hispano-Aleman de Calar Alto (CAHA, Almeria, Spain). CARMENES is funded by the German Max-Planck-Gesellschaft (MPG), the Spanish Consejo Superior de Investigaciones Cientificas (CSIC), the European Union through FEDER/ERF FICTS-2011-02 funds, and the members of the CARMENES Consortium (Max-Planck-Institut fur Astronomie, Instituto de Astrofisica de Andalucia, Landessternwarte Konigstuhl, Institut de Ciencies de l'Espai, Institut fur Astrophysik Gottingen, Universidad Complutense de Madrid, Thuringer Landessternwarte Tautenburg, Instituto de Astrofisica de Canarias, Hamburger Sternwarte, Centro de Astrobiologia and Centro Astronomico Hispano-Aleman), with additional contributions by the Spanish Ministry of Economy, the German Science Foundation through the Major Research Instrumentation Programme and DFG Research Unit FOR2544 "Blue Planets around Red Stars", the Klaus Tschira Stiftung, the states of Baden-Wurttemberg and Niedersachsen, and by the Junta de Andalucia. Based on data from the CARMENES data archive at CAB (INTA-CSIC). We acknowledge the use of public TESS Alert data from pipelines at the TESS Science Office and at the TESS Science Processing Operations Center. This research has made use of the Exoplanet Follow-up Observation Program website, which is operated by the California Institute of Technology, under contract with the National Aeronautics and Space Administration under the Exoplanet Exploration Program. Resources supporting this work were provided by the NASA High-End Computing (HEC) Program through the NASA Advanced Supercomputing (NAS) Division at Ames Research Center for the production of the SPOC data products. Some of the observations in the paper made use of the High-Resolution Imaging instrument Zorro. Zorro was funded by the NASA Exoplanet Exploration Program and built at the NASA Ames Research Center by Steve B. Howell, Nic Scott, Elliott P. Horch, and Emmett Quigley. Zorro was mounted on the Gemini South telescope of the international Gemini Observatory, a program of NSF's OIR Lab, which is managed by the Association of Universities for Research in Astronomy (AURA) under a cooperative agreement with the National Science Foundation. on behalf of the Gemini partnership: the National Science Foundation (United States), National Research Council (Canada), Agencia Nacional de Investigacion y Desarrollo (Chile), Ministerio de Ciencia, Tecnologia e Innovacion (Argentina), Ministerio da Ciencia, Tecnologia, Inovacoes e Comunicacoes (Brazil), and Korea Astronomy and Space Science Institute (Republic of Korea). This work makes use of observations from the LCOGT network. This article is based on observations made with the MuSCAT2 instrument, developed by ABC, at Telescopio Carlos Sanchez operated on the island of Tenerife by the IAC in the Spanish Observatorio del Teide. This paper is also based on observations made in the Observatorios de Canarias del IAC with the Nordic Optical Telescope operated on the island of La Palma by NOTSA in the Observatorio del Roque de los Muchachos. Data were partly obtained with the MONET/South telescope of the MOnitoring NEtwork of Telescopes, funded by the Alfried Krupp von Bohlen und Halbach Foundation, Essen, and operated by the Georg-August-Universitat Gottingen, the McDonald Observatory of the University of Texas at Austin, and the South African Astronomical Observatory. This research has made use of the NASA Exoplanet Archive, which is operated by the California Institute of Technology, under contract with the National Aeronautics and Space Administration under the Exoplanet Exploration Program. This research made use of Lightkurve, a Python package for Kepler and TESS data analysis (Lightkurve Collaboration 2018). We acknowledge financial support from the Spanish Agencia Estatal de Investigacion of the Ministerio de Ciencia, Innovacion y Universidades and the European FEDER/ERF funds through projects AYA2015-69350-C3-2-P, PGC2018098153-B-C31/C33, AYA2016-79425-C3-1/2/3-P, AYA2018-84089, BES-2017080769, ESP2016-80435-C2-1/2-R, ESP2017-87676-C5-1/2/5-R, Instituto de Astrofisica de Andalucia (SEV-2017-0709), the Generalitat de Catalunya through CERCA programme, the UK Science and Technology Facilities Council through grant ST/P000592/1, the JSPS KAKENHI through grants 17H04574, JP18H01265, and 18H05439, and the JST PRESTO through grant JPMJPR1775, the "la Caixa" INPhINIT Fellowship Grant LCF/BQ/IN17/11620033 for Doctoral studies at Spanish Research Centres of Excellence, V.M.P. acknowledges support from NASA Grant NNX17AG24G, Support for this work was provided to J.K.T. by NASA through Hubble Fellowship grant HST-HF2-51399.001 awarded by the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., for NASA, under contract NAS5-26555. The research leading to these results has received funding from the ARC grant for Concerted Research Actions, financed by the Wallonia-Brussels Federation. TRAPPIST is funded by the Belgian Fund for Scientific Research (Fond National de la Recherche Scientifique, FNRS) under the grant FRFC 2.5.594.09.F, with the participation of the Swiss National Science Foundation (SNF). M.G. and E.J. are FNRS Senior Research Associates. S.D. acknowledges support from the Deutsche Forschungsgemeinschaft under Research Unit FOR2544 "Blue Planets around Red Stars", project no. RE 281/32-1. M.Z. acknowledges support from the Deutsche Forschungsgemeinschaft under DFG RE 1664/12-1 and Research Unit FOR2544 "Blue Planets around Red Stars", project no. RE 1664/14-1. M.S. was supported by the DFG Research Unit FOR2544 "Blue Planets around Red Stars", project no. RE 2694/4-1. I.J.M.C. and E.M. acknowledge support from the National Science Foundation through grant AST-1824644. B.B. thanks the European Research Council (ERC Starting Grant 757 448-PAMDORA) for their financial support. D.D. acknowledges support from NASA through Caltech/JPL grant RSA-1006130 and through the TESS Guest Investigator Program Grant 80NSSC19K1727. P.P. acknowledges support from NASA (16-APROBES16-0020 and the Exoplanet Exploration Program) and the National Science Foundation (Astronomy and Astrophysics grant 1716202), the Mt Cuba Astronomical Foundation, and George Mason University start-up and instructional equipment funds. The NASA Infrared Telescope Facility is operated by the University of Hawaii under contract NNH14CK55B with the National Aeronautics and Space Administration. M.R.K is supported by the NSF Graduate Research Fellowship, grant No. DGE 1 339 067. M.Y. and H.V.S. thank to TUB.ITAK for a partial support in using T100 telescope with project number 19AT100-1474. J.N.W. thanks the Heising-Simons Foundation for support. D.H. acknowledges support from the Alfred P. Sloan Foundation, the National Aeronautics and Space Administration (80NSSC18K1585, 80NSSC19K0379), and the National Science Foundation (AST-1 717 000). T.D. acknowledges support from MIT's Kavli Institute as a Kavli postdoctoral fellow. This work made use of tpfplotter (developed by J. Lillo-Box, which also made use of the python packages astropy, lightkurve, matplotlib and numpy. Part of this research was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration (NASA). The authors wish to recognise and acknowledge the very significant cultural role and reverence that the summit of Mauna Kea has always had within the indigenous Hawaiian community. We are most fortunate to have the opportunity to conduct observations from this mountain. Finally, we thank the referee for detailed and helpful comments.

International audience; We report the discovery of two planetary systems, namely G 264–012, an M 4.0 dwarf with two terrestrial planets ( M b sin i =2.50 −0.30 +0.29 M ⊕ and M c sin i =3.75 −0.47 +0.48 M ⊕ ), and Gl 393, a bright M 2.0 dwarf with one terrestrial planet ( M b sin i = 1.71 ± 0.24 M ⊕ ). Although both stars were proposed to belong to young stellar kinematic groups, we estimate their ages to be older than about 700 Ma. The two planets around G 264–012 were discovered using only radial-velocity (RV) data from the CARMENES exoplanet survey, with estimated orbital periods of 2.30 d and 8.05 d, respectively.Photometric monitoring and analysis of activity indicators reveal a third signal present in the RV measurements, at about 100 d,caused by stellar rotation. The planet Gl 393 b was discovered in the RV data from the HARPS, CARMENES, and HIRES instruments. Its identification was only possible after modelling, with a Gaussian process (GP), the variability produced by the magnetic activity of the star. For the earliest observations, this variability produced a forest of peaks in the periodogram of the RVs at around the 34 d rotation period determined from Kepler data, which disappeared in the latestepochs. After correcting for them with this GP model, a significant signal showed at a period of 7.03 d. No significant signals in any of our spectral activity indicators or contemporaneous photometry were found at any of the planetary periods. Given the orbital and stellar properties, the equilibrium temperatures of the three planets are all higher than that for Earth. Current planet formation theories suggest that these two systems represent a common type of architecture. This is consistent with formation following the core accretion paradigm.

Radial-velocity (RV) jitter caused by stellar magnetic activity is an important factor in state-of-the-art exoplanet discovery surveys such as CARMENES. Stellar rotation, along with heterogeneities in the photosphere and chromosphere caused by activity, can result in false-positive planet detections. Hence, it is necessary to determine the stellar rotation period and compare it to any putative planetary RV signature. Long-term measurements of activity indicators such as the chromospheric emission in the Ca II H&K lines enable the identification of magnetic activity cycles. In order to determine stellar rotation periods and study the long-term behavior of magnetic activity of the CARMENES guaranteed time observations (GTO) sample, it is advantageous to extract Ca II H&K time series from archival data, since the CARMENES spectrograph does not cover the blue range of the stellar spectrum containing the Ca II H&K lines. We have assembled a catalog of 11634 archival spectra of 186 M dwarfs acquired by seven different instruments covering the Ca II H&K regime: ESPADONS, FEROS, HARPS, HIRES, NARVAL, TIGRE, and UVES. The relative chromospheric flux in these lines was directly extracted from the spectra by rectification with PHOENIX synthetic spectra via narrow passbands around the Ca ii H&K line cores. The combination of archival spectra from various instruments results in time series for 186 stars from the CARMENES GTO sample. As an example of the use of the catalog, we report the tentative discovery of three previously unknown activity cycles of M dwarfs. We conclude that the method of extracting Ca II H&K fluxes with the use of model spectra yields consistent results for different instruments and that the compilation of this catalog will enable the analysis of long-term activity time series for a large number of M dwarfs., 11 pages, 9 figures

Introduction: Breast cancer is the most common neoplasia of women from all over the world especially women from Colombia. 5%­10% of all cases are caused by hereditary factors, 25% of those cases have mutations in the BRCA1/BRCA2 genes. Objective: The purpose of this study was to identify the mutations associated with the risk of familial breast and/or ovarian cancer in a population of Colombian pacific. Methods: 58 high-risk breast and/or ovarian cancer families and 20 controls were screened for germline mutations in BRCA1 and BRCA2, by Single Strand Conformation Polymorphism (SSCP) and sequencing. Results: Four families (6.9%) were found to carry BRCA1 mutations and eight families (13.8%) had mutations in BRCA2. In BRCA1, we found three Variants of Uncertain Significance (VUS), of which we concluded, using in silico tools, that c.81­12C>G and c.3119G>A (p.Ser1040Asn) are probably deleterious, and c.3083G>A (p.Arg1028His) is probably neutral. In BRCA2, we found three variants of uncertain significance: two were previously described and one novel mutation. Using in silico analysis, we concluded that c.865A>G (p.Asn289Asp) and c.6427T>C (p.Ser2143Pro) are probably deleterious and c.125A>G (p.Tyr42Cys) is probably neutral. Only one of them has previously been reported in Colombia. We also identified 13 polymorphisms (4 in BRCA1 and 9 in BRCA2), two of them are associated with a moderate increase in breast cancer risk (BRCA2 c.1114A>C and c.8755­66T>C). Conclusion: According to our results, the Colombian pacific population presents diverse mutational spectrum for BRCA genes that differs from the findings in other regions in the country.

Background: HIV-2 is a neglected virus despite estimates of 1–2 million people being infected worldwide. The virus is naturally resistant to some antiretrovirals used to treat HIV-1 and therapeutic options are limited for patients with HIV-2. Methods: In this retrospective observational study, we analysed all HIV-2-infected individuals treated with inte- grase strand transfer inhibitors (INSTIs) recorded in the Spanish HIV-2 cohort. Demographics, treatment modal- ities, laboratory values, quantitative HIV-2 RNA and CD4 counts as well as drug resistance were analysed. Results: From a total of 354 HIV-2-infected patients recruited by the Spanish HIV-2 cohort as of December 2017, INSTIs had been given to 44, in 18 as first-line therapy and in 26 after failing other antiretroviral regimens. After a median follow-up of 13 months of INSTI-based therapy, undetectable viraemia for HIV-2 was achieved in 89% of treatment-naive and in 65.4% of treatment-experienced patients. In parallel, CD4 gains were 82 and 126cells/mm3, respectively. Treatment failure occurred in 15 patients, 2 being treatment-naive and 13 treatment-experienced. INSTI resistance changes were recognized in 12 patients: N155H (5), Q148H/R (3), Y143C/G (3) and R263K (1). Conclusions: Combinations based on INSTIs are effective and safe treatment options for HIV-2-infected individ- uals. However, resistance mutations to INSTIs are selected frequently in failing patients, reducing the already limited treatment options.

We present the discovery and characterisation of two transiting planets observed by the Transiting Exoplanet Survey Satellite (TESS) orbiting the nearby (d∗ ≈ 22 pc), bright (J ≈ 9 mag) M3.5 dwarf LTT 3780 (TOI-732). We confirm both planets and their association with LTT 3780 via ground-based photometry and determine their masses using precise radial velocities measured with the CARMENES spectrograph. Precise stellar parameters determined from CARMENES high-resolution spectra confirm that LTT 3780 is a mid-M dwarf with an effective temperature of Teff = 3360 ± 51 K, a surface gravity of log g∗ = 4.81 ± 0.04 (cgs), and an iron abundance of [Fe/H] = 0.09 ± 0.16 dex, with an inferred mass of M∗ = 0.379 ± 0.016M· and a radius of R∗ = 0.382 ± 0.012R·. The ultra-short-period planet LTT 3780 b (Pb = 0.77 d) with a radius of 1.35-0.06+0.06 R·, a mass of 2.34-0.23+0.24 M·, and a bulk density of 5.24-0.81+0.94 g cm-3 joins the population of Earth-size planets with rocky, terrestrial composition. The outer planet, LTT 3780 c, with an orbital period of 12.25 d, radius of 2.42-0.10+0.10 R·, mass of 6.29-0.61+0.63 M·, and mean density of 2.45-0.37+0.44 g cm-3 belongs to the population of dense sub-Neptunes. With the two planets located on opposite sides of the radius gap, this planetary system is anexcellent target for testing planetary formation, evolution, and atmospheric models. In particular, LTT 3780 c is an ideal object for atmospheric studies with the James Webb Space Telescope (JWST).

Two kidney transplant recipients from a single donor became infected with HTLV-1 (human T-lymphotropic virus type 1) in Spain. One developed myelopathy 8 months following surgery despite early prescription of antiretroviral therapy. The allograft was removed from the second recipient at month 8 due to rejection and immunosuppressors discontinued. To date, 3 years later, this patient remains infected but asymptomatic. HTLV-1 infection was recognized retrospectively in the donor, a native Spaniard who had sex partners from endemic regions. Our findings call for a reappraisal of screening policies on donor-recipient organ transplantation. Based on the high risk of disease development and the large flux of persons from HTLV-1 endemic regions, pre-transplant HTLV-1 testing should be mandatory in Spain.

Introduction: Breast cancer is the most common neoplasia of women from all over the world especially women from Colombia. 5%10% of all cases are caused by hereditary factors, 25% of those cases have mutations in the BRCA1/BRCA2 genes. Objective: The purpose of this study was to identify the mutations associated with the risk of familial breast and/or ovarian cancer in a population of Colombian pacific. Methods: 58 high-risk breast and/or ovarian cancer families and 20 controls were screened for germline mutations in BRCA1 and BRCA2, by Single Strand Conformation Polymorphism (SSCP) and sequencing. Results: Four families (6.9%) were found to carry BRCA1 mutations and eight families (13.8%) had mutations in BRCA2. In BRCA1, we found three Variants of Uncertain Significance (VUS), of which we concluded, using in silico tools, that c.8112C>G and c.3119G>A (p.Ser1040Asn) are probably deleterious, and c.3083G>A (p.Arg1028His) is probably neutral. In BRCA2, we found three variants of uncertain significance: two were previously described and one novel mutation. Using in silico analysis, we concluded that c.865A>G (p.Asn289Asp) and c.6427T>C (p.Ser2143Pro) are probably deleterious and c.125A>G (p.Tyr42Cys) is probably neutral. Only one of them has previously been reported in Colombia. We also identified 13 polymorphisms (4 in BRCA1 and 9 in BRCA2), two of them are associated with a moderate increase in breast cancer risk (BRCA2 c.1114A>C and c.875566T>C). Conclusion: According to our results, the Colombian pacific population presents diverse mutational spectrum for BRCA genes that differs from the findings in other regions in the country. Resumen Introducción: El cáncer de mama es la neoplasia más común en mujeres de todo el mundo, y, también de Colombia. 5% a 10% de todos los casos son causados por factores hereditarios; 25% de estos casos tienen mutaciones en los genes BRCA1/BRCA2. Objetivo: El propósito de este estudio fue el de identificar mutaciones asociadas con riesgo de cáncer de mama y/u ovario familiar en pacientes del pacífico colombiano. Métodos: Fueron revisados para mutaciones en BRCA1 y BRCA2 de línea germinal mediante SSCP y secuenciación 58 familias de alto riesgo para cáncer de mama y/u ovario y 20 controles Resultados: cuatro familias (6.9%) presentaron mutaciones en BRCA1 y ocho familias (13.8%) en BRCA2. En BRCA1, encontramos tres variantes de significado clínico desconocido (VUS), de las cuales concluimos, usando herramientas bioinformáticas, que c.8112C>G y c.3119G>A (p.Ser1040Asn) son probablemente deletéreas, y c.3083G>A (p.Arg1028His) es probablemente neutral. En BRCA2, encontramos tres VUS: una mutación nueva y dos previamente descritas, usando análisis bioinformáticos, concluimos que c.865A>G (p.Asn289Asp) y c.6427T>C (p.Ser2143Pro) son probablemente deletéreas y c.125A>G (p.Tyr42Cys) es probablemente neutral. Solo una de ellas ha sido reportada previamente en Colombia. También identificamos 13 polimorfismos (4 en BRCA1 y 9 en BRCA2), dos de ellos asociados con un moderado incremento del riesgo para cáncer de mama (BRCA2 c.1114A>C and c.875566T>C). Conclusión: de acuerdo con nuestros resultados, la población del suroccidente colombiano presenta un espectro mutacional diverso para los genes BRCA que difiere de lo encontrado en otras regiones del país.

Consortia on behalf of the Spanish HTLV Network: C. Rodríguez, M. Vera, J. del Romero, G. Marcaida, M. D. Ocete, E. Caballero, I. Molina, A. Aguilera, J. J. Rodríguez-Calviño, D. Navarro, C. Rivero, M. D. Vilariño, R. Benito, S. Algarate, J. Gil, R. Ortiz de Lejarazu, S. Rojo, J. M. Eirós, A. San Miguel, C. Manzardo, J. M. Miró, J. García, I. Paz, E. Poveda, E. Calderón, D. Escudero, M. Trigo, J. Diz, M. García-Campello, M. Rodríguez Iglesias, A. Hernández Betancor, A. M. Martín, J. M. Ramos, A. Gimeno, F. Gutiérrez, J. C. Rodríguez, V. Sánchez, C. Gómez Hernando, G. Cilla, E. Pérez Trallero, J. López Aldeguer, L. Fernández Pereira, J. Niubó, M. Hernández, A. M. López Lirola, J. L. Gómez Sirvent, L. Force, C. Cifuentes, S. Pérez, L. Morano, C. Raya, A. González Praetorius, J. L. Pérez, M. Peñaranda, S. Hernáez Crespo, J. M. Montejo, L. Roc, A. Martínez Sapiña, I. Viciana, T. Cabezas, A. Lozano, J. M. Fernández, I. García-Bermejo, G. Gaspar, R. García, M. Górgolas, C. Vegas, J. Blas, P. Miralles, M. Valeiro, T. Aldamiz, N. Margall, C. Guardia, E. do Pico, I. Polo, A. Aguinaga, C. Ezpeleta, S. Sauleda, M. Pirón, R. González, L. Barea, A. Jiménez, L. Blanco, A. Suárez, I. Rodríguez Avial, A. Pérez Rivilla, P. Parra, M. Fernández, M. Fernández Alonso, A. Treviño, S. Requena, L. Benítez Gutiérrez, V. Cuervas Mons, C. de Mendoza, P. Barreiro, V. Soriano, O. Corral & F. Gómez-Gallego, [Background]: HTLV-1 infection is a neglected disease, despite infecting 10–15 million people worldwide and severe illnesses develop in 10% of carriers lifelong. Acknowledging a greater risk for developing HTLV-1 associated illnesses due to immunosuppression, screening is being widely considered in the transplantation setting. Herein, we report the experience with universal HTLV testing of donors and recipients of solid organ transplants in a survey conducted in Spain., [Methods]: All hospitals belonging to the Spanish HTLV network were invited to participate in the study. Briefly, HTLV antibody screening was performed retrospectively in all specimens collected from solid organ donors and recipients attended since the year 2008., [Results]: A total of 5751 individuals were tested for HTLV antibodies at 8 sites. Donors represented 2312 (42.2%), of whom 17 (0.3%) were living kidney donors. The remaining 3439 (59.8%) were recipients. Spaniards represented nearly 80%. Overall, 9 individuals (0.16%) were initially reactive for HTLV antibodies. Six were donors and 3 were recipients. Using confirmatory tests, HTLV-1 could be confirmed in only two donors, one Spaniard and another from Colombia. Both kidneys of the Spaniard were inadvertently transplanted. Subacute myelopathy developed within 1 year in one recipient. The second recipient seroconverted for HTLV-1 but the kidney had to be removed soon due to rejection. Immunosuppression was stopped and 3 years later the patient remains in dialysis but otherwise asymptomatic., [Conclusion]: The rate of HTLV-1 is low but not negligible in donors/recipients of solid organ transplants in Spain. Universal HTLV screening should be recommended in all donor and recipients of solid organ transplantation in Spain. Evidence is overwhelming for very high virus transmission and increased risk along with the rapid development of subacute myelopathy.

Two kidney transplant recipients from a single donor became infected with HTLV-1 (human T-lymphotropic virus type 1) in Spain. One developed myelopathy 8 months following surgery despite early prescription of antiretroviral therapy. The allograft was removed from the second recipient at month 8 due to rejection and immunosuppressors discontinued. To date, 3 years later, this patient remains infected but asymptomatic. HTLV-1 infection was recognized retrospectively in the donor, a native Spaniard who had sex partners from endemic regions. Our findings call for a reappraisal of screening policies on donor–recipient organ transplantation. Based on the high risk of disease development and the large flux of persons from HTLV-1 endemic regions, pre-transplant HTLV-1 testing should be mandatory in Spain.

Background. Although only 8%-10% of persons infected with human T-cell leukemia virus type 1 (HTLV-1) may develop virus-associated diseases lifelong, misdiagnosis of asymptomatic infected carriers frequently leads to late diagnoses. Methods. A nationwide HTLV-1 register was created in Spain in 1989. A total of 351 infected persons had been reported by the end of 2017. We examined all new HTLV-1 diagnoses during the last decade and compared their clinical presentation. Results. A total of 247 individuals with HTLV-1 infection had been reported in Spain since year 2008. The incidence has remained stable with 20-25 new diagnoses yearly. Women represented 62%. Only 12% were native Spaniards, most of whom were foreigners from Latin America (72.5%). Up to 57 (23%) individuals presented clinically with HTLV-1-associated conditions, including subacute myelopathy (n = 24; 42.1%), T-cell lymphoma (n = 19; 33.3%), or Strongyloides stercoralis infestation (n = 8; 14%). Human T-cell leukemia virus type 1 diagnosis had been made either at blood banks (n = 109; 44%) or at clinics (n = 138; 56%). It is interesting to note that Spaniards and especially Africans were overrepresented among patients presenting with HTLV-1-associated illnesses, suggesting that misdiagnosis and late presentation are more frequent in these populations compared to Latin Americans. Conclusions. Given that 23% of new HTLV-1 diagnoses in Spain are symptomatic, underdiagnosis must be common. Although screening in blood banks mostly identifies asymptomatic Latin American carriers, a disproportionately high number of Spaniards and Africans are unveiled too late, that is, they already suffer from classic HTLV-1 illnesses.

Objectives The aim of the study was to assess the rates of discontinuation of integrase inhibitor regimens because of any neuropsychiatric adverse event (NPAE) and the factors associated with discontinuation. Methods A population-based, prospective, multicentre cohort study was carried out. Treatment-naive subjects starting therapy with a regimen containing integrase inhibitors, or those switching to such a regimen, with plasma HIV-1 RNA < 50 HIV-1 RNA copies/mL in 14 hospitals in Catalonia or the Balearic Islands (Spain) were included in the study. Every discontinuation because of adverse events (AEs) was double-checked directly with treating physicians. Multivariable Cox models identified factors correlated with discontinuation. Results A total of 4165 subjects (37% treatment-naive) started regimens containing dolutegravir (n = 1650; 91% with abacavir), raltegravir (n = 930) or elvitegravir/cobicistat (n = 1585). There were no significant differences among regimens in the rate of discontinuation because of any AE. Rates of discontinuation because of NPAEs were low but higher for dolutegravir/abacavir/lamivudine [2.1%; 2.9 (95% confidence interval (CI) 2.0, 4.2) discontinuations/100 patients/year] versus elvitegravir/cobicistat (0.5%; 0.8 (95% CI 0.3, 1.5) discontinuations/100 patients/year], with significant differences among centres for dolutegravir/abacavir/lamivudine and NPAEs (P = 0.003). We identified an association of female gender and lower CD4 count with increased risk of discontinuation because of any AE [Incidence ratio (IR) 2.3 (95% CI 1.4, 4.0) and 1.8 (95% CI 1.1, 2.8), respectively]. Female gender, age > 60 years and abacavir use were not associated with NPAE discontinuations. NPAEs were commonly grade 1-2, and had been present before and improved after drug withdrawal. Conclusions In this large prospective cohort study, patients receiving dolutegravir, raltegravir or elvitegravir/cobicistat did not show significant differences in the rate of discontinuation because of any toxicity. The rate of discontinuations because of NPAEs was low, but was significantly higher for dolutegravir than for elvitegravir/cobicistat, with significant differences among centres, suggesting that greater predisposition to believe that a given adverse event is caused by a given drug of some treating physicians might play a role in the discordance seen between cohorts.

Background: Human retroviruses HIV and HTLV share transmission routes. HIV widely spread in Spain during the 80 s through injection drug use and sex, and nowadays HIV rates in Spain account for one of the largest in Europe. In contrast, HTLV-1 is not endemic in Spain, despite hosting huge numbers of migrants from highly endemic regions. Herein, we report the rate and main features of the HIV-HTLV co-infected population in Spain. Methods: A national registry exists in Spain for HTLV since year 1989. Data from standardized case report forms and one centralized lab repository were reviewed, especially for the subset with HTLV-HIV co-infection. Results: Up to December 2018, a total of 369 individuals with HTLV-1 had been diagnosed in Spain. 64% of the population were females, and Latin American individuals accounted for 64.5%. Classical HTLV-associated illnesses were found in 12.7% (myelopathy) and 7.6% (leukemia). HIV coinfection was found in 12 (3.2%). Of those, 3 patients (25%) were female and 39 (75%) were of non Spanish origin. All but two harbored HIV-1 subtype B, being non-B variants found in the two West Africans. Exposure had been sexual in most cases, being 4 homosexual men. Seven HTLV-HIV co-infected patients had developed AIDS and two had developed myelopathy. There was no evidence for increased HTLV-1 clinical pathogenicity due to HIV coinfection. Conclusion: HIV coinfection is infrequent (< 5%) among HTLV-1 carriers in Spain. More than half of co-infected patients come from Latin America. Sexual contact is the most frequent risk behavior, being MSM one third of cases. Late diagnosis explains the high rate (9/12) of clinical manifestations in our HIV-HTLV co-infected population.

Background: Whereas HIV-1 has spread globally, HIV-2 is mainly found in West Africa where dual HIV-1/HIV-2 coinfection is nowadays uncommon. Herein, we report the rate, main characteristics, and treatment outcomes of all dually infected patients living in Spain. Methods: We identified retrospectively all persons coinfected with HIV-1 recorded at the Spanish HIV-2 registry. Dual infection had been confirmed using PCR in plasma and/or cells, and/or using discriminatory serological tests. Results: From a total of 373 individuals with HIV-2 recorded at the Spanish registry, 34 (9.1%) were coinfected with HIV-1. Compared with HIV-2 monoinfected persons, dually infected patients were more often male (67.6%), presented with lower median CD4(+) cell counts (204 cells/mu l), and had developed more frequently AIDS events (26.5%). Although 61.7% came from West Africa, 6 (17.6%) were native Spaniards. HIV-1 non-B subtypes were recognized in 75% of coinfected patients, being the most prevalent CRF02_AG. At baseline, 45% of dually infected patients had undetectable plasma HIV-2 RNA. After a median follow-up of 32 (13-48) months on antiretroviral therapy, dually infected patients achieved undetectable viremia in 85% for HIV-1, in 80% for HIV-2; and in 70% for both viruses. Median CD4(+) cell counts reached up to 418 cells/mu l. Conclusion: Roughly 9% of individuals with HIV-2 infection living in Spain are coinfected with HIV-1. Overall, 70% of dually infected patients achieved viral suppression for both viruses under antiretroviral therapy. Given the relatively large population of West Africans living in Spain and the continuous migration flow from HIV-2 endemic areas, HIV-1/HIV-2 coinfection should always be excluded at first diagnosis in all HIV-seroreactive persons. Copyright (C) 2019 Wolters Kluwer Health, Inc. All rights reserved.

This study using the Catalan PISCIS cohort explores risk factors of migrants' late presentation and the impact of late presentation on their health outcomes. We analyse 9590 new HIV diagnoses enrolled in the cohort between 2004 and 2016. Univariate and multivariate logistic regression models are used to identify risk factors associated with late presentation among migrants, giving crude and adjusted odds ratios and their 95% confidence intervals. Cox regression models are estimated to identify risk factors associated with AIDS/death, and crude and adjusted hazard ratios and 95% confidence intervals are reported. Late presentation is higher in migrants than non-migrants. Among migrants, region of origin is associated with late presentation and AIDS/death during follow-up. The results highlight persisting inequalities in HIV diagnosis and care among migrants in Catalonia. Targeted interventions addressed to specific subgroups in the migrant population are needed.

Background: Human retroviruses HIV and HTLV share transmission routes. HIV widely spread in Spain during the 80 s through injection drug use and sex, and nowadays HIV rates in Spain account for one of the largest in Europe. In contrast, HTLV-1 is not endemic in Spain, despite hosting huge numbers of migrants from highly endemic regions. Herein, we report the rate and main features of the HIV-HTLV co-infected population in Spain. Methods: A national registry exists in Spain for HTLV since year 1989. Data from standardized case report forms and one centralized lab repository were reviewed, especially for the subset with HTLV-HIV co-infection. Results: Up to December 2018, a total of 369 individuals with HTLV-1 had been diagnosed in Spain. 64% of the population were females, and Latin American individuals accounted for 64.5%. Classical HTLV-associated illnesses were found in 12.7% (myelopathy) and 7.6% (leukemia). HIV coinfection was found in 12 (3.2%). Of those, 3 patients (25%) were female and 39 (75%) were of non Spanish origin. All but two harbored HIV-1 subtype B, being non-B variants found in the two West Africans. Exposure had been sexual in most cases, being 4 homosexual men. Seven HTLV-HIV co-infected patients had developed AIDS and two had developed myelopathy. There was no evidence for increased HTLV-1 clinical pathogenicity due to HIV coinfection. Conclusion: HIV coinfection is infrequent (< 5%) among HTLV-1 carriers in Spain. More than half of co-infected patients come from Latin America. Sexual contact is the most frequent risk behavior, being MSM one third of cases. Late diagnosis explains the high rate (9/12) of clinical manifestations in our HIV-HTLV co-infected population.

Background: HIV-2 is a neglected virus despite estimates of 1-2 million people being infected worldwide. The virus is naturally resistant to some antiretrovirals used to treat HIV-1 and therapeutic options are limited for patients with HIV-2. Methods: In this retrospective observational study, we analysed all HIV-2-infected individuals treated with integrase strand transfer inhibitors (INSTIs) recorded in the Spanish HIV-2 cohort. Demographics, treatment modalities, laboratory values, quantitative HIV-2 RNA and CD4 counts as well as drug resistance were analysed. Results: From a total of 354 HIV-2-infected patients recruited by the Spanish HIV-2 cohort as of December 2017, INSTIs had been given to 44, in 18 as first-line therapy and in 26 after failing other antiretroviral regimens. After a median follow-up of 13 months of INSTI-based therapy, undetectable viraemia for HIV-2 was achieved in 89% of treatment-naive and in 65.4% of treatment-experienced patients. In parallel, CD4 gains were 82 and 126 cells/mm(3), respectively. Treatment failure occurred in 15 patients, 2 being treatment-naive and 13 treatment-experienced. INSTI resistance changes were recognized in 12 patients: N155H (5), Q148H/R (3), Y143C/G (3) and R263K (1). Conclusions: Combinations based on INSTIs are effective and safe treatment options for HIV-2-infected individuals. However, resistance mutations to INSTIs are selected frequently in failing patients, reducing the already limited treatment options.

In the quest for Earth-sized exoplanets, M dwarfs are stars of increasing interest during the last two decades. Their small sizes and masses as compared to our Sun make them specially suitable targets to look for the signatures of planetary companions, as their habitable zones fall closer to their host star. Despite being the most abundant stars in our Galaxy, it still exists large uncertainty about basic physical properties of M dwarfs. In particular, determining properties such as luminosities and effective temperatures is essential to characterize their planetary companions, since their properties are derived from those of their host stars. This means that the larger the uncertainties in these fundamental stellar properties, the broader is the span of compatible planetary compositions and parameters. CARMENES is a next-generation spectrograph, built and operated by the homonymous German-Spanish consortium of eleven institutions, which monitorizes bright nearby M dwarfs using the radial velocity method. Carmencita, its input catalog, contains dozens of parameters for about 2200 M dwarfs, from M0.0 to M7.0, including photometric data in a broad range, from UV to mid-infrared. These photometric date, compiled and updated for 18 broadband filters, FUV, NUV, u', B_T, B, g', V_T, G, V, r', i', J, H, Ks, W1, W2, W3, W4, have made possible the determination of important stellar properties using the Virtual Observatory SED Analyzer (VOSA).

Background HTLV-1 infection is a neglected disease, despite infecting 10-15 million people worldwide and severe illnesses develop in 10% of carriers lifelong. Acknowledging a greater risk for developing HTLV-1 associated illnesses due to immunosuppression, screening is being widely considered in the transplantation setting. Herein, we report the experience with universal HTLV testing of donors and recipients of solid organ transplants in a survey conducted in Spain. Methods All hospitals belonging to the Spanish HTLV network were invited to participate in the study. Briefly, HTLV antibody screening was performed retrospectively in all specimens collected from solid organ donors and recipients attended since the year 2008. Results A total of 5751 individuals were tested for HTLV antibodies at 8 sites. Donors represented 2312 (42.2%), of whom 17 (0.3%) were living kidney donors. The remaining 3439 (59.8%) were recipients. Spaniards represented nearly 80%. Overall, 9 individuals (0.16%) were initially reactive for HTLV antibodies. Six were donors and 3 were recipients. Using confirmatory tests, HTLV-1 could be confirmed in only two donors, one Spaniard and another from Colombia. Both kidneys of the Spaniard were inadvertently transplanted. Subacute myelopathy developed within 1 year in one recipient. The second recipient seroconverted for HTLV-1 but the kidney had to be removed soon due to rejection. Immunosuppression was stopped and 3 years later the patient remains in dialysis but otherwise asymptomatic. Conclusion The rate of HTLV-1 is low but not negligible in donors/recipients of solid organ transplants in Spain. Universal HTLV screening should be recommended in all donor and recipients of solid organ transplantation in Spain. Evidence is overwhelming for very high virus transmission and increased risk along with the rapid development of subacute myelopathy.

Background. Although only 8%-10% of persons infected with human T-cell leukemia virus type 1 (HTLV-1) may develop virus-associated diseases lifelong, misdiagnosis of asymptomatic infected carriers frequently leads to late diagnoses. Methods. A nationwide HTLV-1 register was created in Spain in 1989. A total of 351 infected persons had been reported by the end of 2017. We examined all new HTLV-1 diagnoses during the last decade and compared their clinical presentation. Results. A total of 247 individuals with HTLV-1 infection had been reported in Spain since year 2008. The incidence has remained stable with 20-25 new diagnoses yearly. Women represented 62%. Only 12% were native Spaniards, most of whom were foreigners from Latin America (72.5%). Up to 57 (23%) individuals presented clinically with HTLV-1-associated conditions, including subacute myelopathy (n = 24; 42.1%), T-cell lymphoma (n = 19; 33.3%), or Strongyloides stercoralis infestation (n = 8; 14%). Human T-cell leukemia virus type 1 diagnosis had been made either at blood banks (n = 109; 44%) or at clinics (n = 138; 56%). It is interesting to note that Spaniards and especially Africans were overrepresented among patients presenting with HTLV-1-associated illnesses, suggesting that misdiagnosis and late presentation are more frequent in these populations compared to Latin Americans. Conclusions. Given that 23% of new HTLV-1 diagnoses in Spain are symptomatic, underdiagnosis must be common. Although screening in blood banks mostly identifies asymptomatic Latin American carriers, a disproportionately high number of Spaniards and Africans are unveiled too late, that is, they already suffer from classic HTLV-1 illnesses.

International audience; Despite their activity, low-mass stars are of particular importance for the search of exoplanets by the means of Doppler spectroscopy, as planets with lower masses become detectable. We report on the discovery of a planetary companion around HD 180617, a bright (J = 5.58 mag), low-mass (M = 0.45M⊙) star of spectral type M2.5 V. The star, located at a distance of 5.9 pc, is the primary of the high proper motion binary system containing vB 10, a star with one of the lowest masses known in most of the twentieth century. Our analysis is based on new radial velocity (RV) measurements made at red-optical wavelengths provided by the high-precision spectrograph CARMENES, which was designed to carry out a survey for Earth-like planets around M dwarfs. The available CARMENES data are augmented by archival Doppler measurements from HIRES and HARPS. Altogether, the RVs span more than 16 yr. The modeling of the RV variations, with a semi-amplitude of K = 2.85-0.25+0.16 m s-1, yields a Neptune-like planet with a minimum mass of 12.2-1.4+1.0 M⊕ on a 105.90-0.10+0.09 d circumprimary orbit, which is partly located in the host star's habitable zone. The analysis of time series of common activity indicators does not show any dependence on the detected RV signal. The discovery of HD 180617 b not only adds information to a currently hardly filled region of the mass-period diagram of exoplanets around M dwarfs, but the investigated system becomes the third known binary consisting of M dwarfs and hosting an exoplanet in an S-type configuration. Its proximity makes it an attractive candidate for future studies. The RV data (Table C.1) are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/618/A115

The system WDS 16329+0315 is an old, nearby quintuple physical system in the thick Galactic disc formed by a close-resolved, triple primary of solar metallicity, namely HD 149162, and a very wide, common proper motion, secondary pair, formed by the mid-M dwarf G-17-23 and the white dwarf LSPM J1633+0311S. We present an exhaustive astrometric and photometric data compilation of the system, including Gaia DR2 parallaxes and proper motions, and the first analysis of the nature of the faintest component. LSPM J1633+0311S (HD 149162 C) is a very cool white dwarf with an effective temperature of only about 5500 K, near the coolest end of the grid of theoretical models., The Observatory, in press, to appear in December 2018

BACKGROUND: Screening strategies based on interferon-? release assays in tuberculosis contact tracing may reduce the need for preventive therapy without increasing subsequent active disease. METHODS: We conducted an open-label, randomized trial to test the noninferiority of a 2-step strategy with the tuberculin skin test (TST) followed by QuantiFERON-TB Gold In-Tube (QFT-GIT) as a confirmatory test (the TST/QFT arm) to the standard TST-alone strategy (TST arm) for targeting preventive therapy in household contacts of patients with tuberculosis. Participants were followed for 24 months after randomization. The primary endpoint was the development of tuberculosis, with a noninferiority margin of 1.5 percentage points. RESULTS: A total of 871 contacts were randomized. Four contacts in the TST arm and 2 in the TST/QFT arm developed tuberculosis. In the modified intention-to-treat analysis, this accounted for 0.99% in the TST arm and 0.51% in the TST/QFT arm (-0.48% difference; 97.5% confidence interval [CI], -1.86% to 0.90%); in the per-protocol analysis, the corresponding rates were 1.67% and 0.82% in the TST and TST/QFT arms, respectively (-0.85% difference; 97.5% CI, -3.14% to 1.43%). Of the 792 contacts analyzed, 65.3% in the TST arm and 42.2% in the TST/QFT arm were diagnosed with tuberculosis infection (23.1% difference; 95% CI, 16.4% to 30.0%). CONCLUSIONS: In low-incidence settings, screening household contacts with the TST and using QFT-GIT as a confirmatory test is not inferior to TST-alone for preventing active tuberculosis, allowing a safe reduction of preventive treatments. CLINICAL TRIALS REGISTRATION: NCT01223534.

Las mezclas asfálticas con RAP (pavimento asfaltico reciclado) tienen muchas ventajas relacionadas a la reutilización de este material. Pero sin el adecuado tratamiento, estas mezclas tienen asociados problemas de durabilidad debido a la perdida de propiedades que sufre este material con el paso del tiempo. La utilización de escorias de cobre puede ayudar a solventar parte de estos problemas gracias sus propiedades físicas-químicas, como la elevada angulosidad, el contenido de cal en su composición y su bajo contenido en sílice, aportando fricción y adhesividad elevada. A su vez, también se reduce el volumen de escorias de cobre acopiadas y la lixiviación asociada a éstas. Este trabajo muestra los resultados obtenidos en mezclas asfálticas con porcentajes de RAP de 0 a 40% combinados con porcentajes de escoria de cobre del 0 al 35%. Se realizaron 16 combinaciones de materiales con las que se elaboraron probetas Marshall para su análisis mediante ensayos de estabilidad y fluencia, tracción indirecta y módulo resiliente por compresión diametral. La utilización de escorias de cobre provoca una mejora en el comportamiento de mezclas asfálticas con RAP. Con cantidades de escorias de cobre del 15% en volumen, los valores de estabilidad y fluencia se estabilizan, mejorando el índice de rigidez Marshall. También se mejoran los valores de tracción indirecta y módulo resiliente para porcentajes de RAP mayores al 20%, especialmente en mezclas con porcentajes altos de RAP (40%). Estos resultados ayudan a potenciar la utilización de RAP en aplicaciones que requieran parámetros más exigentes. Asphalt mixes with Reclaimed Asphalt Pavement (RAP) offer many advantages when reusing this material. But without the adequate treatment, these mixtures present durability problems due to the material’s loss of properties over time. The use of copper slag can reduce these problems through its physical-chemical properties, such as highly angular characteristics, lime content in its composition and low silica content, while contributing with friction and strong adhesive characteristics. On the other hand, the amount of copper slag stockpiles and their associated lixiviation are also reduced. This work presents the results obtained in asphalt mixes with RAP percentages from 0 to 40%, combined with copper slag percentages ranging from 0 to 35%. Sixteen (16) combinations of materials were used to prepare Marshall specimens in order to carry out stability and flow tests, indirect tensile strength tests and resilient modulus by diametral compression. The use of copper slag improves the performance of asphalt mixes with RAP. With 15% copper slag amounts by mass, the stability and flow values are stabilized, thereby improving the Marshall stiffness index. The values for indirect tensile strength and resilient modulus with RAP percentages over 20% are also improved, especially in mixtures with high RAP percentage (40%). These results favor the use of RAP in applications that require more demanding parameters.

RESUMENObjetivo. Evaluar el efecto de dos inductores hormonales en la reproducción inducida de nicuro Pimelodus blochii. Materiales y métodos. Para los procesos experimentales fueron utilizados adultos sexualmente maduros, sometidos a tres tratamientos aplicados vía intramuscular, en dosis única de 0.25 mL/kg Ovaprim® (OVAP) (T1), 0.5 mL/kg de OVAP (T2) y 6.25 mg/kg de Extracto de Hipófisis de Carpa (EHC) (T3), para este último tratamiento la inyección fue dividida en 20 y 80%, con un intervalo de 12 h entre aplicaciones. Previo a la extracción de los gametos, los animales fueron tranquilizados por inmersión en una solución de Metanosulfonato de Tricaina (90 mg/L). El desempeño reproductivo fue evaluado mediante el índice de ovulación (hembras ovuladas/hembras tratadas), fecundidad absoluta (Fa) (ovocitos/hembra), fecundidad relativa (Fr) en función del número de ovocitos desovados por gramo de peso. La fecundación se realizó en seco y seis horas post-fecundación (HPF) se determinó la tasa de fertilidad. Resultados. La ovulación (ºh) para el T1 fue a las 297.1±30.0, T2 294.6±32.9 y T3 247.3±13.1 ºh. En todos los tratamientos se obtuvieron hembras ovuladas, donde los mayores índices de ovulación fueron obtenidos con Ovaprim® (T1 y T2) con 36.4 y 50%, respectivamente. Las tasas de fecundación obtenidas fueron mayores a un 50%, para el tratamiento 1 y 2, con valores de 74.5 y 32.7%, respectivamente. Conclusiones. El uso de inductores hormonales puede ser efectivo para garantizar la reproducción inducida del nicuro, en dosis única de 0.25 y 0.5 mL/kg de Ovaprim®.

Background: BRCA1 and BRCA2 have been identified as high-penetrance breast cancer predisposition genes, but they only account for a small fraction of the inherited component of breast cancer. To explain the remaining cases, a polygenic model with a large number of low- to moderate-penetrance genes have been proposed; one of these, is the CHEK2 gene (Checkpoint Kinase 2). The objective of this study was to determine the role of the CHEK2 gene, specifically the c.1100delC mutation in familial breast cancer susceptibility in Colombian patients. Methods: We screened 131 high-risk breast and/or ovarian cancer patients (negative for mutations in BRCA1 and BRCA2) and 131 controls for the germline mutation CHEK2 c.1100delC by allele-specific PCR. Results: None of the cases or controls showed the CHEK2 c.1100delC mutation, neither as a homozygote nor as a heterozygote. Conclusions: Our results suggest that the CHEK2 c.1100delC mutation is not a risk factor for genetic susceptibility to familial breast or ovarian cancer in the Colombian population. The absence of the CHEK2 c.1100delC mutation in our population show the importance of considering ethnic background before offering a genetic test.

Nonketotic hyperglycinemia is an inborn error of metabolism resulting from a defect in the glycine cleavage enzyme system, is inherited as an autosomal recessive trait. It is characterized by elevated concentrations of glycine in blood and central nervous system. Accumulation of glycine in the brain is thought to cause excessive stimulation of the inhibitory and excitatory receptors presenting apnea, hipcus, seizures and brain damage. We report a full-term male newborn with encephalopathy in the first days of life. He did not present hypoglicemia, metabolic acidosis, non hyperammonemia cetosis. The brain ultrasonography was normal. At six days of age he presents respiratory failure and needs mecanic ventilation. Thin layer chromatography shows glycine in plasma and urine. He was treated with sodium benzoate, diazepam and a low-protein diet. He improved and at 42 days of age he was discharged with the same treatment. The acylcarnitine profile does in Santiago de Compostela was normal. The concentrations of amino acids does in CEDEM was found elevated glycine in plasma and cerebrospinal fluid and the glycine ratio LCR/plasma establish the diagnosis of Typical Neonatal non-ketotic hyperglycinemia. We revised the etiology of neonatal encephalopathy and proposed diagnostic secuency.

HIV-2 and HTLV-1 infections are globally less frequent than those produced by HIV-1, the classical AIDS agent. In Spain and up to the end of 2014, a total of 310 cases of HIV-2, 274 of HTLV-1, and 776 of HTLV-2 infections had been reported. No cases of HTLV-3 or HTLV-4 infections have been identified so far in Spain. Most persons infected with HIV-2 or HTLV-1 acknowledge epidemiological risk factors for contagion, such as originating from or living in endemic regions and/or having had sexual partners from those areas. However, risk factors could not be recognized in up to 20-25% of carriers in Spain. Thus, it seems worth keeping a high level of clinical suspicion in order to identify earlier these neglected human retroviral infections, since diagnostic procedures and antiviral treatment are specific for each of these agents. In this article we summarize the major contributions reported at the meeting of the Spanish Group for HIV-2/HTLV held in Madrid in December 2014

Background: There is little information on the incidence of AIDS-defining events which have been reported in the literature to be associated with immune reconstitution inflammatory syndrome (IRIS) after combined antiretroviral therapy (cART) initiation. These events include tuberculosis, mycobacterium avium complex (MAC), cytomegalovirus (CMV) retinitis, progressive multifocal leukoencephalopathy (PML), herpes simplex virus (HSV), Kaposi sarcoma, non-Hodgkin lymphoma (NHL), cryptococcosis and candidiasis.Methods: We identified individuals in the HIV-CAUSAL Collaboration, which includes data from six European countries and the US, who were HIV-positive between 1996 and 2013, antiretroviral therapy naive, aged at least 18 years, hadCD4+ cell count and HIV-RNA measurements and had been AIDS-free for at least 1 month between those measurements and the start of follow-up. For each AIDS-defining event, we estimated the hazard ratio for no cART versus less than 3 and at least 3 months since cART initiation, adjusting for time-varying CD4+ cell count and HIV-RNA via inverse probability weighting.Results: Out of 96 562 eligible individuals (78% men) with median (interquantile range) follow-up of 31 [13,65] months, 55 144 initiated cART. The number of cases varied between 898 for tuberculosis and 113 for PML. Compared with non-cART initiation, the hazard ratio (95% confidence intervals) up to 3 months after cART initiation were 1.21 (0.90-1.63) for tuberculosis, 2.61 (1.05-6.49) for MAC, 1.17 (0.34-4.08) for CMV retinitis, 1.18 (0.62-2.26) for PML, 1.21 (0.83-1.75) for HSV, 1.18 (0.87-1.58) for Kaposi sarcoma, 1.56 (0.82-2.95) for NHL, 1.11 (0.56-2.18) for cryptococcosis and 0.77 (0.40-1.49) for candidiasis.Conclusion: With the potential exception of mycobacterial infections, unmasking IRIS does not appear to be a common complication of cART initiation in high-income countries.

Producción Científica, Background:HIV-2 infection is characterized by low plasma viraemia and slower progression to AIDS in compari-son with HIV-1 infection. However, antiretroviral therapy in patients with HIV-2 is less effective and often fails toprovide optimal CD4 recovery.Methods:We examined viral tropism in persons with HIV-2 infection enrolled in the HIV-2 Spanish cohort. Viraltropism was estimated based on V3 sequences obtained from plasma RNA and/or proviral DNA.Results:From a total of 279 individuals with HIV-2 infection recorded in the Spanish national register, 58 V3sequences belonging to 42 individuals were evaluated. X4 viruses were recognized in 14 patients (33%).Patients with X4 viruses had lower median CD4+cell counts than patients with R5 viruses [130 (17 – 210) versus359 (180 – 470) cells/mm3;P¼0.007]. This was true even considering only the subset of 19 patients on antiretro-viral therapy [94 (16 – 147) versus 184 (43 – 368) cells/mm3;P¼0.041]. In multivariate analysis, significant differ-ences in CD4+cell counts between patients with X4 and R5 viruses remained after adjusting for age, gender,antiretroviral therapy and viral load.Conclusions:The presence of X4-tropic viruses in HIV-2 infection is associated with low CD4+cell counts, regard-less of antiretroviral treatment. Along with CD4+cell counts, viral tropism testing may assist decisions aboutwhen to initiate antiretroviral therapy in HIV-2-infected individuals., Fundación Investigación y Educación en Sida. (RIS, ISCIII-RETICRD/12/0017/0031), Fondo de Investigación Sanitaria (FIS, PI10/00520), Ministerio de Salud Consumo y Bienestar Social (EC10/277), Ministerio de Ciencia e Innovación (MICINN, SAF2010/22232), El proyecto Europeo CHAIN (FP7-223131)

Background: There is little information on the incidence of AIDS-defining events which have been reported in the literature to be associated with immune reconstitution inflammatory syndrome (IRIS) after combined antiretroviral therapy (cART) initiation. These events include tuberculosis, mycobacterium avium complex (MAC), cytomegalovirus (CMV) retinitis, progressive multifocal leukoencephalopathy (PML), herpes simplex virus (HSV), Kaposi sarcoma, non-Hodgkin lymphoma (NHL), cryptococcosis and candidiasis. Methods: We identified individuals in the HIV-CAUSAL Collaboration, which includes data from six European countries and the US, who were HIV-positive between 1996 and 2013, antiretroviral therapy naive, aged at least 18 years, hadCD4+ cell count and HIV-RNA measurements and had been AIDS-free for at least 1 month between those measurements and the start of follow-up. For each AIDS-defining event, we estimated the hazard ratio for no cART versus less than 3 and at least 3 months since cART initiation, adjusting for time-varying CD4+ cell count and HIV-RNA via inverse probability weighting. Results: Out of 96 562 eligible individuals (78% men) with median (interquantile range) follow-up of 31 [13,65] months, 55 144 initiated cART. The number of cases varied between 898 for tuberculosis and 113 for PML. Compared with non-cART initiation, the hazard ratio (95% confidence intervals) up to 3 months after cART initiation were 1.21 (0.90-1.63) for tuberculosis, 2.61 (1.05-6.49) for MAC, 1.17 (0.34-4.08) for CMV retinitis, 1.18 (0.62-2.26) for PML, 1.21 (0.83-1.75) for HSV, 1.18 (0.87-1.58) for Kaposi sarcoma, 1.56 (0.82-2.95) for NHL, 1.11 (0.56-2.18) for cryptococcosis and 0.77 (0.40-1.49) for candidiasis. Conclusion: With the potential exception of mycobacterial infections, unmasking IRIS does not appear to be a common complication of cART initiation in high-income countries. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Hepatitis C virus (HCV) is one of the major causes of chronic hepatitis, cirrhosis, and hepatocellular carcinoma, and the development of HCV-related disease is accelerated in individuals coinfected with human immunodeficiency-1 virus (HIV). In the present study, we correlated different host single-nucleotide polymorphisms (SNPs) in the IL28B, CTLA4, LDLr, and HFE genes and mitochondrial DNA (mtDNA) haplogroups with the outcome of HCV infection and the response to pegylated-interferon plus ribavirin (pegIFN-RBV) treatment. Our study population consisted of 63 Majorcan patients coinfected with HCV and HIV and 59 anonymous unrelated controls. Whereas the population frequency of IL28B alleles was similar to that found in a North-American cohort of European descent, the frequency of the rs12979860 C allele was lower than that determined in other cohorts from Spain. The frequencies of CTLA4 and LDLr polymorphisms were comparable to those reported in other populations. Significant differences between cases and control cohorts occurred only for the H63D mutation of the HFE gene. There were no other differences in the frequencies of other polymorphisms or mtDNA haplogroups. The IL28B rs12979860 CC genotype was shown to be associated with a rapid virological response, and the spontaneous viral clearance rate for HCV was higher in patients with the CTLA4+49 G allele. There was no relationship between SNPs in the LDLr and HFE genes and mtDNA haplogroups and the response to treatment. Our results suggest that the host genetic background plays a significant role in the pegIFN-RBV response of patients coinfected with HCV and HIV.

Background:CHEK2(Checkpoint Kinase 2) encodes CHK2, a serine/threonine kinase involved in maintaining the G1/S and G2/M checkpoints and repair of double-strand DNA breaks via homologous recombination. Functions of CHK2 include the prevention of damaged cells from going through the cell cycle or proliferating and the maintenance of chromosomal stability.CHEK2mutations have been reported in a variety of cancers including glioblastoma, ovarian, prostate, colorectal, gastric, thyroid, and lung cancer in studies performed mainly in White populations. The most studied mutation inCHEK2is c.1100delC, which was associated with increased risk of breast cancer. The objective of this study was to compile mutations inCHEK2identified in cancer genomics studies in different populations and especially in Latin American individuals.Methods:A revision of cancer genomics data repositories and a profound literature review of Latin American studies was performed.Results:Mutations with predicted high impact inCHEK2were reported in studies from Australia, Japan, United States, among other countries. The TCGA cancer types with most mutations inCHEK2were breast, colorectal, and non-small cell lung cancer. The most common mutation found was E321* in three patients with uterine cancer. In Latin American individuals nine mutations were found in melanoma, lymphoma, and head and neck cohorts from TCGA and ICGC. Latin American studies have been restricted to breast and colorectal cancer and only two mutations out of four that have been interrogated in this population were identified, namely c.1100delC and c.349A>G.Conclusions:This study presents a compilation of mutations inCHEK2with high impact in different cancer types in White, Hispanic and other populations. We also show the necessity of screeningCHEK2mutations in Latin American in cancer types different than breast and colorectal.

La sífilis congénita es un problema de salud pública mundial, la mayoría de los neonatos infectados no presenta manifestaciones clínicas de la enfermedad y la determinación de Ig M específica utilizada para el diagnóstico es de bajo rendimiento, por lo que el diagnóstico en el recién nacido depende del diagnóstico de sífilis en la gestante. Presentamos la historia clínica de una recién nacida, hija de una madre con sífilis gestacional inadecuadamente tratada. Durante su hospitalización se evidenció compromiso hepático con aumento de la aspartato amino transferasa e hiperbilirrubinemia con aumento de la fracción conjugada. Se descartó compromiso de SNC. Los cultivos para gérmenes comunes de sangre y orina fueron negativos. Las determinaciones de Ig M para CMV, rubeola, toxoplasma , Herpes I y II fueron negativas. Las ecografías transfontanelar, cardiaca, renal y de vías urinarias y hepatobiliar fueron normales. Durante la hospitalización, a los 9 días de vida presentó un episodio de infección bacteriana asociada. Recibió tratamiento con penicilina cristalina durante 14 días con normalización de los niveles de bilirrubina y de aspartato aminotransferasa. El seguimiento clínico y serológico a los 3 meses de edad mostró patrón de crecimiento y desarrollo normal y VDRL no reactiva. Congenital syphilis is a global public health problem. The majority of infected children have no clinical manifestations of the disease and the specific IgM determination in newborns has low diagnostic performance. The diagnosis depends mostly of the diagnosis in mothers before birth. We report a newborn that was inadequately treated prenatally. At birth, the liver involvement was detected, with increase in aspartate amino transferase and of conjugated fractions of bilirubin. CNS involvement was ruled out and cultures of blood and urine were negative for bacteria. Determinations for IgM of CMV, rubella, toxoplasmosis and herpes I and II, were negative. Transfontanellar, heart, kidney, urinary tract and hepatobiliary ultrasound examinations were normal. Crystalline penicillin treatment for 14 days was undertaken, obtaining normal levels of bilirubin and aspartate aminotransferase at the end of treatment. The clinical and serological follow-up after 3 months showed a normal growth and development pattern with non-reactive VDRL tests.

Objetivo. Evaluar el efecto de dos inductores hormonales en la reproducción inducida de nicuro Pimelodus blochii. Materiales y métodos. Para los procesos experimentales fueron utilizados adultos sexualmente maduros, sometidos a tres tratamientos aplicados vía intramuscular, en dosis única de 0.25 mL/kg Ovaprim® (OVAP) (T1), 0.5 mL/kg de OVAP (T2) y 6.25 mg/kg de Extracto de Hipófisis de Carpa (EHC) (T3), para este último tratamiento la inyección fue dividida en 20 y 80%, con un intervalo de 12 h entre aplicaciones. Previo a la extracción de los gametos, los animales fueron tranquilizados por inmersión en una solución de Metanosulfonato de Tricaina (90 mg/L). El desempeño reproductivo fue evaluado mediante el índice de ovulación (hembras ovuladas/hembras tratadas), fecundidad absoluta (Fa) (ovocitos/hembra), fecundidad relativa (Fr) en función del número de ovocitos desovados por gramo de peso. La fecundación se realizó en seco y seis horas post-fecundación (HPF) se determinó la tasa de fertilidad. Resultados. La ovulación (°h) para el T1 fue a las 297.1±30.0, T2 294.6±32.9 y T3 247.3±13.1 °h. En todos los tratamientos se obtuvieron hembras ovuladas, donde los mayores índices de ovulación fueron obtenidos con Ovaprim® (T1 y T2) con 36.4 y 50%, respectivamente. Las tasas de fecundación obtenidas fueron mayores a un 50%, para el tratamiento 1 y 2, con valores de 74.5 y 32.7%, respectivamente. Conclusiones. El uso de inductores hormonales puede ser efectivo para garantizar la reproducción inducida del nicuro, en dosis única de 0.25 y 0.5 mL/kg de Ovaprim®. Objective. Evaluate the effect of two hormonal inducers in induced breeding of nicuro Pimelodus blochii. Materials and methods. The experimental process used sexually mature adults exposed to three intramuscular treatments, a single dose of 0.25 mL/g Ovaprim® (OVAP) (T1), 0.5 mL/kg of OVAP (T2) and 6.25 mg/kg of pituitary carp extract (EPC) (T3), for the latter treatment the injection was divided into 20 and 80%, with an interval of 12 hours between applications. Prior to the removal of gametes, the animals were tranquilized by immersion in a Tricaine Methanesulfonate (90 mg/L) solution. Reproductive performance was evaluated using ovulation rates (females ovulated/treated females), fertility (Fa) (eggs/female), relative fertility (Fr) depending on the number of eggs spawned per gram of weight. The dry method of fertilization was used and the fertility rate was determined six hours post-fertilization (HPF). Results. The Ovulation (°h) was: for T1 297.1±30.0, T2 294.6±32.9 and T3 247.3±13.1°h. Ovulated females were obtained in all treatments, where the highest rates of ovulation were obtained with Ovaprim ® (T1 and T2) with 36.4 and 50% respectively. Fertilization rates were higher than 50% for treatments 1 and 2, with values of 74.5 and 32.7% respectively. Conclusions. The use of hormonal inducers may be effective to ensure nicuro induced reproduction with a single dose of 0.25 and 0.5 mL/kg Ovaprim®.