Perinatal Tuberculosis: Is it a Forgotten Disease?

Perinatal tuberculosis is an uncommon condition but with a high mortality and a challenging diagnosis. We present four cases of perinatal tuberculosis managed between 1991-2014 in a Spanish Tertiary Hospital. The infection should be considered in patients with progressive respiratory symptoms and with a poor response to conventional antibiotic therapy, especially in those with positive epidemiologic risk. Bronchoscopy can be a useful tool for diagnosis

The nucleotidohydrolases DCTPP1 and dUTPase are involved in the cellular response to decitabine

Decitabine (5-aza-2acute;-deoxycytidine, aza-dCyd) is an anticancer drug used clinically for the treatment of myelodysplastic syndromes and acute myeloid leukemia that can act as a DNA-demethylating or genotoxic agent in a dose-dependent manner. On the other hand, DCTPP1 and dUTPase are two "house-cleaning" nucleotidohydrolases involved in the elimination of non-canonical nucleotides. Here we show that exposure of HeLa cells to decitabine up-regulates the expression of several pyrimidine metabolic enzymes including DCTPP1, dUTPase, dCMP deaminase and thymidylate synthase thus suggesting their contribution to the cellular response to this anticancer nucleoside. We present several lines of evidence supporting that, in addition to the formation of aza-dCTP, an alternative cytotoxic mechanism for decitabine may involve the formation of aza-dUMP, a potential thymidylate synthase inhibitor. Indeed, dUTPase or DCTPP1 down-regulation enhanced the cytotoxic effect of aza-dCyd producing an accumulation of nucleoside triphosphates containing uracil as well as uracil misincorporation and double-strand breaks in genomic DNA. Moreover, DCTPP1 hydrolyzes the triphosphate form of decitabine with similar kinetic efficiency than its natural substrate dCTP and prevents decitabine-induced global DNA demethylation. The data suggest that the nucleotidohydrolases DCTPP1 and dUTPase are factors involved in the mode of action of decitabine with potential value as enzymatic targets to improve decitabine-based chemotherapy

Binary frequency of planet-host stars at wide separations: A new brown dwarf companion to a planet-host star

The aim of the project is to improve our knowledge on the multiplicity of planet-host stars at wide physical separations. We cross-matched approximately 6200 square degree area of the Southern sky imaged by the Visible Infrared Survey Telescope for Astronomy (VISTA) Hemisphere Survey (VHS) with the Two Micron All Sky Survey (2MASS) to look for wide common proper motion companions to known planet-host stars. We complemented our astrometric search with photometric criteria. We confirmed spectroscopically the co-moving nature of seven sources out of 16 companion candidates and discarded eight, while the remaining one stays as a candidate. Among these new wide companions to planet-host stars, we discovered a T4.5 dwarf companion at 6.3 arcmin (~9000 au) from HIP70849, a K7V star which hosts a 9 Jupiter mass planet with an eccentric orbit. We also report two new stellar M dwarf companions to one G and one metal-rich K star. We infer stellar and substellar binary frequencies for our complete sample of 37 targets of 5.4+/-3.8% and 2.7+/-2.7% (1 sigma confidence level), respectively, for projected physical separations larger than ~60-160 au assuming the range of distances of planet-host stars (24-75 pc). These values are comparable to the frequencies of non planet-host stars. We find that the period-eccentricity trend holds with a lack of multiple systems with planets at large eccentricities (e > 0.2) for periods less than 40 days. However, the lack of planets more massive than 2.5 Jupiter masses and short periods (<40 days) orbiting single stars is not so obvious due to recent discoveries by ground-based transit surveys and space missions.Comment: Accepted for publication in A&A, 13 pages, 5 figures, 3 tables, optical spectra will be available at CDS Strasbour

Polypyrrole and polyaniline nanocomposites with high photothermal conversion efficiency

The simple and scalable synthesis of poly[2-(methacryloyloxy)ethyl phosphorylcholine] (PMPC)-coated conducting polymer (CP) nanocomposites is described. These functional nanocomposites exhibit tunable absorption in the near-infrared region with relatively high photothermal efficiencies. More importantly, their potential for bio-imaging and therapeutic treatment is proven by cellular uptake and cytotoxicity studies

Búsqueda de dianas en Podosphaera Xanthii para el desarrollo de nuevas fitoterapias antifúngicas

La resistencia a fungicidas en uno de los principales problemas de la agricultura y esto es especialmente patente en el caso de los oídios. En España y en las principales áreas productoras del mundo, el oídio de las cucurbitáceas es una amenaza muy grave, y Podosphaera xanthii es considerado como el principal agente causante de la enfermedad. Hasta la fecha, la aplicación de fungicidas y el uso de variedades resistentes son las principales herramientas para el control de la enfermedad. En cualquier caso, el oídio sigue imponiendo serias limitaciones en la producción agrícola, siendo necesario el desarrollo de nuevas estrategias de control. En este estudio se pretende proporcionar información sobre las bases moleculares de P. xanthii que pueda ser de utilidad para el desarrollo de nuevas herramientas de fitoprotección. Para lograr este objetivo, estamos centrando nuestra atención en un conjunto de proteínas fúngicas carentes de función, determinado en un estudio anterior. Ante la falta de homología con proteínas funcionalmente anotadas, para conocer la posible función de dichas proteínas, en primer lugar, llevamos a cabo un análisis in silico detallado de las proteínas que incluye modelado 3D, predicción de posibles ligandos e identificación de dominios funcionales. En segundo lugar, para la identificación de proteínas clave para la patogénesis de P. xanthii, silenciamos proteínas del hongo con función predicha bioinformáticamente mediante silenciamiento génico inducido por hospedador (HIGS) empleando Agrobacterium tumefaciens como vector para la expresión transitoria de construcciones de silenciamiento en células de melón, y desde ellas, al hongo diana. Finalmente, las proteínas con un fenotipo claro de silenciamiento serán seleccionadas para la caracterización de su actividad biológica. En este congreso se mostrarán los resultados más relevantes obtenidos hasta la fecha, relativos a la asimilación de azufre.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. Este trabajo ha sido financiado por una ayuda del Programa Estatal de I+D+i Orientada a los Retos de la Sociedad (AGL2016-76216-C2-1-R), cofinanciada con fondos FEDER (UE). Los autores agredecen además ayudas del Plan Propio de Investigación de la Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Macrophage Targeting pH Responsive Polymersomes for Glucocorticoid Therapy

Glucocorticoid (GC) drugs are the cornerstone therapy used in the treatment of inflammatory diseases. Here, we report pH responsive poly(2-methacryloyloxyethyl phosphorylcholine)–poly(2-(diisopropylamino)ethyl methacrylate) (PMPC–PDPA) polymersomes as a suitable nanoscopic carrier to precisely and controllably deliver GCs within inflamed target cells. The in vitro cellular studies revealed that polymersomes ensure the stability, selectivity and bioavailability of the loaded drug within macrophages. At molecular level, we tested key inflammation-related markers, such as the nuclear factor-κB, tumour necrosis factor-α, interleukin-1β, and interleukin-6. With this, we demonstrated that pH responsive polymersomes are able to enhance the anti-inflammatory effect of loaded GC drug. Overall, we prove the potential of PMPC–PDPA polymersomes to efficiently promote the inflammation shutdown, while reducing the well-known therapeutic limitations in GC-based therapy

The ALMA Early Science View of FUor/EXor Objects - V. Continuum Disc Masses and Sizes

Low-mass stars build a significant fraction of their total mass during short outbursts of enhanced accretion known as FUor and EXor outbursts. FUor objects are characterized by a sudden brightening of ∼5 mag at visible wavelengths within 1 yr and remain bright for decades. EXor objects have lower amplitude outbursts on shorter time-scales. Here we discuss a 1.3 mm Atacama Large Millimeter/submillimeter Array (ALMA) mini-survey of eight outbursting sources (three FUors, four EXors, and the borderline object V1647 Ori) in the Orion Molecular Cloud. While previous papers in this series discuss the remarkable molecular outflows observed in the three FUor objects and V1647 Ori, here we focus on the continuum data and the differences and similarities between the FUor and EXor populations. We find that FUor discs are significantly more massive (∼80–600 MJup) than the EXor objects (∼0.5–40 MJup). We also report that the EXor sources lack the prominent outflows seen in the FUor population. Even though our sample is small, the large differences in disc masses and outflow activity suggest that the two types of objects represent different evolutionary stages. The FUor sources seem to be rather compact (Rc \u3c 20–40 au) and to have a smaller characteristic radius for a given disc mass when compared to T Tauri stars. V1118 Ori, the only known close binary system in our sample, is shown to host a disc around each one of the stellar components. The disc around HBC 494 is asymmetric, hinting at a structure in the outer disc or the presence of a second disc

Switching from natalizumab to fingolimod: an observational study

Background – Multiple sclerosis patients who discontinue using natalizumab are at risk of a rebound in disease activity. However, the optimal alternative therapy is not currently known. Aims of the study – We report on clinical and MRI data and patient safety in a group of relapsing–remitting multiple sclerosis patients who tested seropositive for the JC virus and who have switched from natalizumab to fingolimod because of concerns regarding PML risks. Methods – The test for JC virus antibodies was performed in 18 relapsing–remitting multiple sclerosis patients who were being treated with natalizumab for more than 1 year. Eight seropositive patients switched to fingolimod while the seronegative patients continued with natalizumab. Results – After switching to fingolimod, five of eight patients (63%) experienced clinical relapses, and MRI activity was detected in six of eight patients (75%). Neither clinical relapses nor MRI activity was observed in the patients who continued with natalizumab. No serious adverse effects were detected. Conclusions – Natalizumab is an effective treatment for relapsing–remitting multiple sclerosis, but its discontinuation continues to be a complex problem. All of the therapies tried thus far, including fingolimod, have been unable to control the reactivation of the disease. Further studies addressing alternative therapies after natalizumab discontinuation are necessary

Hysteroscopic Management of an Interstitial Ectopic Pregnancy

We report a case of an interstitial ectopic pregnancy successfully managed by hysteroscopy. We highlight the benefits of using hysteroscopy, a non-invasive procedure, to preserve fertility