Prevention of ventilator-associated pneumonia: the multimodal approach of the spanish ICU pneumonia zero program.

Objectives: The “Pneumonia Zero” project is a nationwide multimodal intervention based on the simultaneous implementation of a comprehensive evidence-based bundle measures to prevent ventilator-associated pneumonia in critically ill patients admitted to the ICU. Design: Prospective, interventional, and multicenter study. Setting: A total of 181 ICUs throughout Spain. Patients: All patients admitted for more than 24 hours to the participating ICUs between April 1, 2011, and December 31, 2012. Intervention: Ten ventilator-associated pneumonia prevention measures were implemented (seven were mandatory and three highly recommended). The database of the National ICU-Acquired Infections Surveillance Study (Estudio Nacional de Vigilancia de Infecciones Nosocomiales [ENVIN]) was used for data collection. Ventilator-associated pneumonia rate was expressed as incidence density per 1,000 ventilator days. Ventilator-associated pneumonia rates from the incorporation of the ICUs to the project, every 3 months, were compared with data of the ENVIN registry (April–June 2010) as the baseline period. Ventilator-associated pneumonia rates were adjusted by characteristics of the hospital, including size, type (public or private), and teaching (postgraduate) or university-affiliated (undergraduate) status. Measurements and Main Results: The 181 participating ICUs accounted for 75% of all ICUs in Spain. In a total of 171,237 ICU admissions, an artificial airway was present on 505,802 days (50.0% of days of stay in the ICU). A total of 3,474 ventilator-associated pneumonia episodes were diagnosed in 3,186 patients. The adjusted ventilator-associated pneumonia incidence density rate decreased from 9.83 (95% CI, 8.42–11.48) per 1,000 ventilator days in the baseline period to 4.34 (95% CI, 3.22–5.84) after 19–21 months of participation. Conclusions: Implementation of the bundle measures included in the “Pneumonia Zero” project resulted in a significant reduction of more than 50% of the incidence of ventilator-associated pneumonia in Spanish ICUs. This reduction was sustained 21 months after implementation

Integrative multi-omics analysis identifies a prognostic miRNA signature and a targetable miR-21-3p/TSC2/ mTOR axis in metastatic pheochromocytoma/ paraganglioma

Rationale: Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that present variable outcomes. To date, no effective therapies or reliable prognostic markers are available for patients who develop metastatic PPGL (mPPGL). Our aim was to discover robust prognostic markers validated through in vitro models, and define specific therapeutic options according to tumor genomic features. Methods: We analyzed three PPGL miRNome datasets (n=443), validated candidate markers and assessed them in serum samples (n=36) to find a metastatic miRNA signature. An integrative study of miRNome, transcriptome and proteome was performed to find miRNA targets, which were further characterized in vitro. Results: A signature of six miRNAs (miR-21-3p, miR-183-5p, miR-182-5p, miR-96-5p, miR-551b-3p, and miR-202-5p) was associated with metastatic risk and time to progression. A higher expression of five of these miRNAs was also detected in PPGL patients’ liquid biopsies compared with controls. The combined expression of miR-21-3p/miR-183-5p showed the best power to predict metastasis (AUC=0.804, P=4.67·10-18), and was found associated in vitro with pro-metastatic features, such as neuroendocrine-mesenchymal transition phenotype, and increased cell migration rate. A pan-cancer multi-omic integrative study correlated miR-21-3p levels with TSC2 expression, mTOR pathway activation, and a predictive signature for mTOR inhibitor-sensitivity in PPGLs and other cancers. Likewise, we demonstrated in vitro a TSC2 repression and an enhanced rapamycin sensitivity upon miR-21-3p expression. Conclusions: Our findings support the assessment of miR-21-3p/miR-183-5p, in tumors and liquid biopsies, as biomarkers for risk stratification to improve the PPGL patients’ management. We propose miR-21-3p to select mPPGL patients who may benefit from mTOR inhibitors

Variación intraestacional en los visitantes florales de Erysimum mediohispanicum en Sierra Nevada

Las interacciones planta-polinizador han sido tradicionalmente un tema de gran interés en el área de la ecología y la biología evolutiva, tanto por los servicios ecosistémicos que ofrecen como por la complejidad que presentan como sistema. La comunidad de visitantes florales de una especie vegetal puede ser muy diversa en plantas generalistas pero muy reducida en plantas especialistas, siendo los sistemas generalistas una realidad más común de lo que tradicionalmente se ha pensado. Además, esta comunidad puede presentar importantes fluctuaciones espacio-temporales en composición y abundancia. Esta variabilidad está sujeta a factores intrínsecos y extrínsecos a la planta, y podría afectar notoriamente a diversos aspectos poblacionales. En el presente trabajo estudiamos la variación temporal de la comunidad de visitantes florales en composición, abundancia y diversidad en dos parcelas experimentales de Erysimum mediohispanicum Polatschek (Brassicaceae), una especie típicamente generalista. Para centrarnos en las variaciones temporales en la comunidad hemos homogeneizado la distribución espacial y las condiciones microambientales de las plantas. Durante el periodo de floración censamos diariamente los insectos a nivel de morfoespecie, agrupándolos en 16 grupos funcionales basándonos en características morfológicas y comportamentales. Nuestros resultados muestran una gran diversidad en la comunidad de visitantes florales para ambas parcelas así como importantes fluctuaciones temporales en composición y abundancia relativa tanto para morfoespecies como para grupos funcionales. Esta variación temporal en abundancia de los visitantes florales de E. mediohispanicum puede tener importantes implicaciones ecológicas y evolutivas

Ionic interactions: Comparative topological approach

International audienc

Human milk oligosaccharides: Functionality in infants Oligosacaridos de la leche materna: Evidencia de su funcionalidad en lactantes

Human milk is a very complex fluid that contains numerous bioactive compounds. Among them, it includes very high con-centrations of oligosaccharides (human milk oligosaccharides [HMOs]) that group more than a hundred complex sugars. We present an extensive review of the composition and functions of the HMOs, highlighting the influence of the maternal genotype FUT2 on the type and concentration, being the latter much higher in FUT secretory women. The HMOs are non digestible in the intestine of the infant, therefore, they provide a substrate for the development of an intestinal microbiota, mainly rich in bifidobacteria. In addition, since some of these HMOs share some structural sequences with receptors for intestinal pathogens, they act as decoy blocking these receptors prevent-ing their adhesion and proliferation. The benefits of the con-sumption of these HMOs are considered unique, therefore the synthesis of HMOs structurally identical to those found in breast milk and with similar functionality demonstrated through clinical studies, opens a very interesting line of re-search in the field of infant nutrition. The first clinical studies conducted with HMOs are analyzed, considering necessary new clinical intervention trials in infants to confirm these ef-fects on the immune system and reducing the frequency of re-spiratory and gastrointestinal infections

Highly photoactive TiO2 microspheres for photocatalytic production of hydrogen

[EN] In this study, the photocatalytic activity in hydrogen production of a TiO catalyst with hierarchical structure and microsphere morphology was tested. This catalyst was synthesised by hydrolysis and condensation processes from a Ti(OBut) precursor and calcined at 150 °C, 400 °C and 630 °C. Hydrogen production of the subsequent photocatalysts rose by two and three orders of magnitude after the incorporation of Au or Pt particles by photodeposition. The microspheres with and without metal modification were characterised by scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX), X-ray diffraction (XRD), Raman, Brunauer–Emmett–Teller (BET) surface area, Fourier transform infrared spectroscopy (FTIR) and diffuse reflectance measurements. The highest production rates were obtained for the metal-modified photocatalysts calcined at 400 °C. Hydrogen production increased with Au loading, attaining a rate of 1118 μmol·h for the 1.5 wt% Au photocatalyst. However, the highest production rate in the case of Pt was attained with just 0.27 wt% and was almost twice as high as that obtained with Au, 2125 μmol·h. When compared with previous studies by our team under the same conditions, this high production rate, obtained with a very low Pt loading, was only exceeded by the reference Aeroxide P25 TiO catalyst with a Pt loading greater than 1.5 wt%.This work was supported by the Spanish Ministry of Science and Innovation through the project IPT-120000-2010-033(GESHTOS). We would also like to thank the Spanish Ministry of Science and Innovation for the UNLP10-3E-726 infra-structure, co-financed with ERDF funds. T. Jardiel alsoacknowledges the financial support of the MAT2014-59210-JIN project of MINECO. M. Nereida Suárez would also like to thankthe University of Las Palmas de Gran Canaria for its fundingthough the PhD Grant Program