1,701 research outputs found

    Prevalence, characteristics, and impact of adverse events in 34 Madrid hospitals. The ESHMAD study

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    Introduction: Adverse Events (AE) are one of the main problems in healthcare. Therefore, many policies have been developed worldwide to mitigate their impact. The Patient Safety Incident Study in Hospitals in the Community of Madrid (ESHMAD) measures the results of them in the region. Methods: Cross-sectional study, conducted in May 2019, in hospitalised patients in 34 public hospitals using the Harvard Medical Practice Study methodology. A logistic regression model was carried out to study the association of the variables with the presence of AE, calibrated and adjusted by patient. Results: A total of 9975 patients were included, estimating a prevalence of AE of 11.9%. A higher risk of AE was observed in patients with surgical procedures (OR[CI95%]: 2.15[1.79 to 2.57], vs. absence), in Intensive Care Units (OR[CI95%]: 1.60[1.17 to 2.17], vs. Medical) and in hospitals of medium complexity (OR[CI95%]: 1.45[1.12 to 1.87], vs. low complexity). A 62.6% of AE increased the length of the stay or it was the cause of admission, and 46.9% of AE were considered preventable. In 11.5% of patients with AE, they had contributed to their death. Conclusions: The prevalence of AE remains similar to the previously estimated one in studies developed with the same methodology. AE keep leading to longer hospital stays, contributing to patient's death, showing that it is necessary to put focus on patient safety again. A detailed analysis of these events has enabled the detection of specific areas for improvement according to the type of care, centre and patient

    Cyclin B1-Cdk1 facilitates MAD1 release from the nuclear pore to ensure a robust spindle checkpoint.

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    How the cell rapidly and completely reorganizes its architecture when it divides is a problem that has fascinated researchers for almost 150 yr. We now know that the core regulatory machinery is highly conserved in eukaryotes, but how these multiple protein kinases, protein phosphatases, and ubiquitin ligases are coordinated in space and time to remodel the cell in a matter of minutes remains a major question. Cyclin B1-Cdk is the primary kinase that drives mitotic remodeling; here we show that it is targeted to the nuclear pore complex (NPC) by binding an acidic face of the kinetochore checkpoint protein, MAD1, where it coordinates NPC disassembly with kinetochore assembly. Localized cyclin B1-Cdk1 is needed for the proper release of MAD1 from the embrace of TPR at the nuclear pore so that it can be recruited to kinetochores before nuclear envelope breakdown to maintain genomic stability

    A cancer-associated, genome protective programme engaging PKCε.

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    Associated with their roles as targets for tumour promoters, there has been a long-standing interest in how members of the protein kinase C (PKC) family act to modulate cell growth and division. This has generated a great deal of observational data, but has for the most part not afforded clear mechanistic insights into the control mechanisms at play. Here, we review the roles of PKCε in protecting transformed cells from non-disjunction. In this particular cell cycle context, there is a growing understanding of the pathways involved, affording biomarker and interventional insights and opportunities

    FNDC5 is produced in the stomach and associated to body composition

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    The fibronectin type III domain-containing protein 5 (FNDC5) discovered in 2002 has recently gained attention due to its potential role in protecting against obesity. In rat, no data exist regarding FNDC5 production and regulation in the stomach. The aim of the present work was to determine the expression of FNDC5 in the rat stomach and its potential regulation by body composition. The present data shows FNDC5 gene expression in the gastric mucosa. Immunohistochemical studies found FNDC5 immunopositivity in chief cells of gastric tissue. By the use of three different antibodies FNDC5 was found expressed in gastric mucosa and secreted by the stomach. The rate of gastric FNDC5 secretion parallels the circulating levels of FNDC5. The body fat mass increase after intervention with high fat diet coincided with a decrease in the secretion of FNDC5 from the stomach and a diminution in the FNDC5 circulating levels. In summary, the present data shows, for the first time, the expression of FNDC5 in the stomach of rats and its regulation by body composition, suggesting a potential role of gastric FNDC5 in energy homeostasishis work has been supported by grants from Instituto de Salud Carlos III (PI1202021 and PI15/01272) cofounded by FEDER, Xunta de Galicia (10 PXIB 918 273PR) and Fundación Mutua Madrileña. SB-F is funded by Xunta de Galicia and Universidade de Santiago de Compostela, CF by IDIS (Instituto de Investigación Sanitaria de Santiago de Compostela), CC by Ciber obn and OA-M is funded by the ISCIII/SERGAS thought a research contract “Sara Borrell” (CD14/00091). MP is funded by ISCIII/SERGAS through a research contract “Miguel Servet II”. LMS is a SERGAS-I3SNS researcher. Centro de Investigacion Biomedica en Red Fisiopatología de la Obesidad y Nutrición (CIBERobn) is a iniciative of the Instituto de Salud Carlos III (ISCIII) of Spain which is supported by FEDER fundsS

    Inhibiting HER3 Hyperphosphorylation in HER2‐Overexpressing Breast Cancer through Multimodal Therapy with Branched Gold Nanoshells

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    Treatment failure in breast cancers overexpressing human epidermal growth factor receptor 2 (HER2) is associated mainly to the upregulation of human epidermal growth factor receptor 3 (HER3) oncoprotein linked to chemoresitence. Therefore, to increase patient survival, here a multimodal theranostic nanoplatform targeting both HER2 and HER3 is developed. This consists of doxorubicin-loaded branched gold nanoshells functionalized with the near-infrared (NIR) fluorescent dye indocyanine green, a small interfering RNA (siRNA) against HER3, and the HER2-specific antibody Transtuzumab, able to provide a combined therapeutic outcome (chemo- and photothermal activities, RNA silencing, and immune response). In vitro assays in HER2+/HER3+ SKBR-3 breast cancer cells have shown an effective silencing of HER3 by the released siRNA and an inhibition of HER2 oncoproteins provided by Trastuzumab, along with a decrease of the serine/threonine protein kinase Akt (p-AKT) typically associated with cell survival and proliferation, which helps to overcome doxorubicin chemoresistance. Conversely, adding the NIR light therapy, an increment in p-AKT concentration is observed, although HER2/HER3 inhibitions are maintained for 72 h. Finally, in vivo studies in a tumor-bearing mice model display a significant progressively decrease of the tumor volume after nanoparticle administration and subsequent NIR light irradiation, confirming the potential efficacy of the hybrid nanocarrierE.V.-A. and I.G.-C. contributed equally to this work. This work was sup ported by the Agencia Estatal de Investigación (AEI) through Project No. PID2019-109517RB-I00) and from the Xunta de Galicia, Project No. ED431C2022/18. European Regional Development Funds are also ac knowledged. A.A.-M. and P.T. also thank the International Scientific Part nership Program ISSP at King Saud University for additional funding of this research through Grant No. ISPP-144. This work also received fi nancial support from the ISCIII, Ministerio de Economía y Competitivi dad (Grant No. PI15/01129; J.A.C.), and the AEI (Grant No. PID2020- 113501RB-I00; J.A.C.). I.-G.C. thanks for financial support through Grant No. PRE/2011/131, and the Centro Singular de Investigación de Galicia accreditation Grant No. 2016–2019 ED431G/05)S

    From tsunami risk assessment to disaster risk reduction the case of Oman

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    Oman is located in an area of high seismicity, facing the Makran Subduction Zone, which is the major source of earthquakes in the eastern border of the Arabian plate. These earthquakes, as evidenced by several past events, may trigger a tsunami event. The aim of this work is to minimize the consequences that tsunami events may cause in coastal communities by integrating tsunami risk assessment and risk reduction measures as part of the risk-management preparedness strategy. An integrated risk assessment approach and the analysis of site-specific conditions permitted to propose target-oriented risk reduction measures. The process included a participatory approach, involving a panel of local stakeholders and international experts. One of the main concerns of this work was to obtain a useful outcome for the actual improvement of tsunami risk management in Oman. This goal was achieved through the development of comprehensive and functional management tools such as the Tsunami Hazard, Vulnerability and Risk Atlas and the Risk Reduction Measures Handbook, which will help to design and plan a roadmap towards risk reduction. The integrated tsunami risk assessment performed showed that the northern area of Oman would be the most affected, considering both the hazard and vulnerability components. This area also concentrates nearly 50% of the hot spots identified throughout the country, 70% of them are located in areas with a very high risk class, in which risk reduction measures were selected and prioritized.The authors thank the Ministry of Transport and Communications of the Government of the Sultanate of Oman (MOTC), the Public Authority for Civil Aviation (PACA) and the Directorate General of Meteorology (DGMET), for supporting and funding the project “Assessment of Coastal Hazards, Vulnerability and Risk for the Coast of Oman” during the period 2014–2016. We also thank and appreciate the collaboration of the International Oceanographic Commission of the United Nations Educational, Scientific and Cultural Organization personnel (IOC-UNESCO)
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