Effect of corticosteroids on the clinical course of community-acquired pneumonia: a randomized controlled trial

Introduction The benefit of corticosteroids as adjunctive treatment in patients with severe community-acquired pneumonia (CAP) requiring hospital admission remains unclear. This study aimed to evaluate the impact of corticosteroid treatment on outcomes in patients with CAP. Methods This was a prospective, double-blind and randomized study. All patients received treatment with ceftriaxone plus levofloxacin and methyl-prednisolone (MPDN) administered randomly and blindly as an initial bolus, followed by a tapering regimen, or placebo. Results Of the 56 patients included in the study, 28 (50%) were treated with concomitant corticosteroids. Patients included in the MPDN group show a more favourable evolution of the pO2/FiO2 ratio and faster decrease of fever, as well as greater radiological improvement at seven days. The time to resolution of morbidity was also significantly shorter in this group. Six patients met the criteria for mechanical ventilation (MV): five in the placebo group (22.7%) and one in the MPDN group (4.3%). The duration of MV was 13 days (interquartile range 7 to 26 days) for the placebo group and three days for the only case in the MPDN group. The differences did not reach statistical significance. Interleukin (IL)-6 and C-reactive protein (CRP) showed a significantly quicker decrease after 24 h of treatment among patients treated with MPDN. No differences in mortality were found among groups. Conclusions MPDN treatment, in combination with antibiotics, improves respiratory failure and accelerates the timing of clinical resolution of severe CAP needing hospital admission

Effect of corticosteroids on the clinical course of community-acquired pneumonia: a randomized controlled trial

Introduction The benefit of corticosteroids as adjunctive treatment in patients with severe community-acquired pneumonia (CAP) requiring hospital admission remains unclear. This study aimed to evaluate the impact of corticosteroid treatment on outcomes in patients with CAP. Methods This was a prospective, double-blind and randomized study. All patients received treatment with ceftriaxone plus levofloxacin and methyl-prednisolone (MPDN) administered randomly and blindly as an initial bolus, followed by a tapering regimen, or placebo. Results Of the 56 patients included in the study, 28 (50%) were treated with concomitant corticosteroids. Patients included in the MPDN group show a more favourable evolution of the pO2/FiO2 ratio and faster decrease of fever, as well as greater radiological improvement at seven days. The time to resolution of morbidity was also significantly shorter in this group. Six patients met the criteria for mechanical ventilation (MV): five in the placebo group (22.7%) and one in the MPDN group (4.3%). The duration of MV was 13 days (interquartile range 7 to 26 days) for the placebo group and three days for the only case in the MPDN group. The differences did not reach statistical significance. Interleukin (IL)-6 and C-reactive protein (CRP) showed a significantly quicker decrease after 24 h of treatment among patients treated with MPDN. No differences in mortality were found among groups. Conclusions MPDN treatment, in combination with antibiotics, improves respiratory failure and accelerates the timing of clinical resolution of severe CAP needing hospital admission

Patient-Derived Xenograft Models for Endometrial Cancer Research

Endometrial cancer (EC) is the most common malignancy of the genital tract among women in developed countries. Recently, a molecular classification of EC has been performed providing a system that, in conjunction with histological observations, reliably improves EC classification and enhances patient management. Patient-derived xenograft models (PDX) represent nowadays a promising tool for translational research, since they closely resemble patient tumour features and retain molecular and histological features. In EC, PDX models have already been used, mainly as an individualized approach to evaluate the efficacy of novel therapies and to identify treatment-response biomarkers; however, their uses in more global or holistic approaches are still missing. As a collaborative effort within the ENITEC network, here we describe one of the most extensive EC PDX cohorts developed from primary tumour andmetastasis covering all EC subtypes. Ourmodels are histologically andmolecularly characterized and represent an excellent reservoir of EC tumour samples for translational research. This review compiles the information on current methods of EC PDX generation and their utility and provides new perspectives for the exploitation of these valuable tools in order to increase the success ratio for translating results to clinical practice.This work was supported by CIBERONC (CB16/12/00328), the “Fondo Europeo de Desarrollo Regional” FEDER (RTC-2015-3821-1), Grups consolidats de la Generalitat de Catalunya (2017 SGR-1661) and the Instituto de Salud Carlos III (PI14/02043; PI17/02071). An AGAUR grant funded CL-G (2018FI_B_00573), and a PERIS grant funded EC (SLT002/16/00315) from Generalitat de Catalunya. The present work has been also funded by the “Fonds National de la Recherche du Luxembourg” (FNR) via the PEARL-CPIL program to BD and an AFR grant to AL (PDR 2013-2, Project Reference 6835664)

Tailoring electromechanical properties of natural rubber vitrimers by cross-linkers

The growing demand for smart polymeric transducers such as dielectric elastomer actuators and energy harvesters has urged the use of sustainable and recyclable elastomeric materials. Vitrimer chemistry has shed light on future reprocessable and recyclable thermosets and elastomers. In this work, epoxidized natural rubber (ENR) vitrimers were prepared using diacid or triacid cross-linkers and formed covalently cross-linking networks via thermally triggered reversible β-hydroxy ester bonds. The cross-linked ENR elastomers exhibited Arrhenius-type viscoelastic behavior with a complete stress relaxation between 140 and 160 °C, that is, vitrimer characteristics, which were highly dependent on the cross-linking temperature. The mechanical and dielectric properties of the ENR vitrimers can be tuned by varying the molecular structure and concentration of the cross-linkers. Among the diacid and triacid cross-linkers, Pripol 1017 fatty polyacid (P1017) and 3,3′-dithiopropionic acid (DTPA) had similar effects on the cross-linking density and mechanical properties of the ENR vitrimers. The highest tensile strength of 8.70 ± 1.9 or 15.6 ± 2.6 MPa was obtained at 6 mol % of P1017 or DTPA, respectively. While for diamide-based diacid cross-linker (DME), 8 mol % was needed to reach the highest tensile strength of 13.1 ± 2.7 MPa for the elastomer. The three ENR vitrimers showed increased relative permittivity ε′ = 5∼7 at 1 kHz while maintaining low dielectric losses compared to traditional dicumyl peroxide-cured ENR, with ε′ = 3.57 at 1 kHz. With the optimized acidic cross-linker concentrations of P1017 at 6 mol %, DTPA at 6 mol %, and DME at 8 mol %, the ENR vitrimers exhibited improved actuation capabilities at lower electrical fields. Utilizing dynamic cross-linkers to tune the electromechanical properties of dielectric elastomers and the reversibly cross-linked polymer networks will open new opportunities for smart and sustainable dielectric elastomer devices

HST hot Jupiter transmission spectral survey: detection of water in HAT-P-1b from WFC3 near-IR spatial scan observations

We present Hubble Space Telescope near-infrared transmission spectroscopy of the transiting hot-Jupiter HAT-P-1b. We observed one transit with Wide Field Camera 3 using the G141 low-resolution grism to cover the wavelength range 1.087–1.678 μm. These time series observations were taken with the newly available spatial-scan mode that increases the duty cycle by nearly a factor of 2, thus improving the resulting photometric precision of the data. We measure a planet-to-star radius ratio of Rp/R* = 0.117 09 ± 0.000 38 in the white light curve with the centre of transit occurring at 245 6114.345 ± 0.000 133 (JD). We achieve S/N levels per exposure of 1840 (0.061 per cent) at a resolution of Δλ = 19.2 nm (R ∼ 70) in the 1.1173–1.6549 μm spectral region, providing the precision necessary to probe the transmission spectrum of the planet at close to the resolution limit of the instrument. We compute the transmission spectrum using both single target and differential photometry with similar results. The resultant transmission spectrum shows a significant absorption above the 5σ level matching the 1.4 μm water absorption band. In solar composition models, the water absorption is sensitive to the ∼1 m bar pressure levels at the terminator. The detected absorption agrees with that predicted by a 1000 K isothermal model, as well as with that predicted by a planetary-averaged temperature model

Hubble Space Telescope hot Jupiter transmission spectral survey: a detection of Na and strong optical absorption in HAT-P-1b

We present an optical to near-infrared transmission spectrum of the hot Jupiter HAT-P-1b, based on Hubble Space Telescope observations, covering the spectral regime from 0.29 to 1.027 μm with Space Telescope Imaging Spectrograph (STIS), which is coupled with a recent Wide Field Camera 3 (WFC3) transit (1.087 to 1.687 μm). We derive refined physical parameters of the HAT-P-1 system, including an improved orbital ephemeris. The transmission spectrum shows a strong absorption signature shortward of 0.55 μm, with a strong blueward slope into the near-ultraviolet. We detect atmospheric sodium absorption at a 3.3σ significance level, but find no evidence for the potassium feature. The red data imply a marginally flat spectrum with a tentative absorption enhancement at wavelength longer than ∼ 0.85 μm. The STIS and WFC3 spectra differ significantly in absolute radius level (4.3 ± 1.6 pressure scaleheights), implying strong optical absorption in the atmosphere of HAT-P-1b. The optical to near-infrared difference cannot be explained by stellar activity, as simultaneous stellar activity monitoring of the G0V HAT-P-1b host star and its identical companion show no significant activity that could explain the result. We compare the complete STIS and WFC3 transmission spectrum with theoretical atmospheric models which include haze, sodium and an extra optical absorber. We find that both an optical absorber and a supersolar sodium to water abundance ratio might be a scenario explaining the HAT-P-1b observations. Our results suggest that strong optical absorbers may be a dominant atmospheric feature in some hot Jupiter exoplanets

Elevated α-Ketoglutaric Acid Concentrations and a Lipid-Balanced Signature Are the Key Factors in Long-Term HIV Control

Long-term elite controllers (LTECs) are a fascinating small subset of HIV individuals with viral and immunological HIV control in the long term that have been designated as models of an HIV functional cure. However, data on the LTEC phenotype are still scarce, and hence, the metabolomics and lipidomics signatures in the LTEC-extreme phenotype, LTECs with more than 10 years of viral and immunological HIV control, could be pivotal to finding the keys for functional HIV remission. Metabolomics and lipidomics analyses were performed using high-resolution mass spectrometry (ultra-high-performance liquid chromatography-electrospray ionization-quadrupole time of flight [UHPLC-(ESI) qTOF] in plasma samples of 13 patients defined as LTEC-extreme, a group of 20 LTECs that lost viral and/or immunological control during the follow-up study (LTEC-losing) and 9 EC patients with short-term viral and immunological control (less than 5 years; no-LTEC patients). Long-term viral and immunological HIV-1 control was found to be strongly associated with elevated tricarboxylic acid (TCA) cycle function. Interestingly, of the nine metabolites identified in the TCA cycle, α-ketoglutaric acid (p = 0.004), a metabolite implicated in the activation of the mTOR complex, a modulator of HIV latency and regulator of several biological processes, was found to be a key metabolite in the persistent control. On the other hand, a lipidomics panel combining 45 lipid species showed an optimal percentage of separation and an ability to differentiate LTEC-extreme from LTEC-losing, revealing that an elevated lipidomics plasma profile could be a predictive factor for the reignition of viral replication in LTEC individuals.This work was supported by the Fondo de Investigación Sanitaria [PI13/0796, PI16/00503, PI16/0684, PI18/1532, PI19/00004, PI19/01127, PI19/01337 PI16/001769, PI19/00973, and PI20/00326]-ISCIII-FEDER (co-funded by the European Regional Development Fund/European Social Fund; “A way to make Europe”/”Investing in your future”); Programa de Suport als Grups de Recerca AGAUR (2017SGR948); Gilead Fellowship Program GLD14/293; The SPANISH AIDS Research Network [RD16/0002/0001, RD16/0002/0002, RD16/0025/0006, RD16/0025/0013, and RD16/0025/0020]-ISCIII-FEDER (Spain); and the Centro de Investigación Biomédica en Red de Enfermedades Infecciosas-ISCIII [CB21/13/00015, CB21/13/00020, and CB21/13/00044], Madrid, Spain. JM is supported by the Universitat Rovira I Virgili under grant agreement “2019PMF-PIPF-18,” through the call “Martí Franquès Research Fellowship Programme.” NR is a Miguel Servet researcher from the ISCIII [CPII19/00025]. EY is supported by the Instituto de Salud Carlos III (ISCIII) under grant agreement “FI20/0011800” through the program “Contratos Predoctorales de Formación en Investigación en Salud.” ER-M was supported by the Spanish National Research Council (CSIC). FV is supported by grants from the Programa de Intensificación de Investigadores (INT20/00031)-ISCIII and by “Premi a la Trajectòria Investigadora als Hospitals de l’ICS 2018.” AR is supported by IISPV through the project “2019/IISPV/05” (Boosting Young Talent), by GeSIDA through the “III Premio para Jóvenes Investigadores 2019,” and by the Instituto de Salud Carlos III (ISCIII) under grant agreement “CP19/00146” through the Miguel Servet Program.S