38 research outputs found

    Guia d'ús no sexista del llenguatge : 10 punts per visibilitzar les dones en el llenguatge

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    Podeu consultar la guia completa a: http://hdl.handle.net/11703/113697Una guia que proposa deu punts per acabar amb els estereotips que fomenten la desigualtat mitjançant l’ús del llenguatge

    Cell-penetrating peptide-conjugated copper complexes for redox-mediated anticancer therapy

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    Metal-based chemotherapeutics like cisplatin are widely employed in cancer treatment. In the last years, the design of redox-active (transition) metal complexes, such as of copper (Cu), has attracted high interest as alternatives to overcome platinum-induced side-effects. However, several challenges are still faced, including optimal aqueous solubility and efficient intracellular delivery, and strategies like the use of cell-penetrating peptides have been encouraging. In this context, we previously designed a Cu(II) scaffold that exhibited significant reactive oxygen species (ROS)-mediated cytotoxicity. Herein, we build upon the promising Cu(II) redox-active metallic core and aim to potentiate its anticancer activity by rationally tailoring it with solubility- and uptake-enhancing functionalizations that do not alter the ROS-generating Cu(II) center. To this end, sulfonate, arginine and arginine-rich cell-penetrating peptide (CPP) derivatives have been prepared and characterized, and all the resulting complexes preserved the parent Cu(II) coordination core, thereby maintaining its reported redox capabilities. Comparative in vitro assays in several cancer cell lines reveal that while specific solubility-targeting derivatizations (i.e., sulfonate or arginine) did not translate into an improved cytotoxicity, increased intracellular copper delivery via CPP-conjugation promoted an enhanced anticancer activity, already detectable at short treatment times. Additionally, immunofluorescence assays show that the Cu(II) peptide-conjugate distributed throughout the cytosol without lysosomal colocalization, suggesting potential avoidance of endosomal entrapment. Overall, the systematic exploration of the tailored modifications enables us to provide further understanding on structure-activity relationships of redox-active metal-based (Cu(II)) cytotoxic complexes, which contributes to rationalize and improve the design of more efficient redox-mediated metal-based anticancer therapy

    The value of repeat biopsy in lupus nephritis flares

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    Whether a repeat renal biopsy is helpful during lupus nephritis (LN) flares remains debatable. In order to analyze the clinical utility of repeat renal biopsy in this complex situation, we retrospectively reviewed our series of 54 LN patients who had one or more repeat biopsies performed only on clinical indications. Additionally, we reviewed 686 well-documented similar cases previously reported (PubMed 1990-2015). The analysis of all patients reviewed showed that histological transformations are common during a LN flare, ranging from 40% to 76% of cases. However, the prevalence of transformations and the clinical value of repeat biopsy vary when they are analyzed according to proliferative or nonproliferative lesions. The great majority of patients with class II (78% in our series and 77.5% in the literature review) progressed to a higher grade of nephritis (classes III, IV, or V), resulting in worse renal prognosis. The frequency of pathological conversion in class V is lower (33% and 43%, respectively) but equally clinically relevant, since almost all cases switched to a proliferative class. Therefore, repeat biopsy is highly advisable in patients with nonproliferative LN at baseline biopsy, because these patients have a reasonable likelihood of switch to a proliferative LN that may require more aggressive immunosuppression. In contrast, the majority of patients (82% and 73%) with proliferative classes in the reference biopsy (III, IV or mixed III/IV + V), remained into proliferative classes on repeat biopsy. Although rebiopsy in this group does not seem as necessary, it is still advisable since it will allow us to identify the 18% to 20% of patients that switch to a nonproliferative class. In addition, consistent with the reported clinical experience, repeat biopsy might also be helpful to identify selected cases with clear progression of proliferative lesions despite the initial treatment, for whom it is advisable to intensify inmunosuppression. Thus, our experience and the literature data support that repeat biopsy also brings more advantges than threats in this group. The results of the repeat biopsy led to a change in the immunosuppresive treatment in more than half of the patients on average, intensifying it in the majority of the cases, but also reducing it in 5% to 30%

    Optimización del circuito de medicación de Farmacia a Hospitalización a Domicilio en un hospital urbano

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    Introduction: Severe inefficiencies were detected in the circuits between the Hospitalary Pharmacy Service (HPS) and the Home Hospital at Home Service (HaH), which led to an analysis, with the support of Quality, and the definition and subsequent implementation of various improvement actions. Method: Analysis of the flow of medication between HPS and HaH at Hospital Dos de Maig. The proposed objectives were to reduce interruptions to professionals, increase the efficiency of circuits, and ensure the availability of medication. Inefficiencies were identified in the system of requesting and dispensing medication, and mismatches in the supply and review of the stock. A change of dispensation model was agreed, the stock was adjusted, revisions of the same were expedited, and a new application tool was applied via computer medication. Results: The HaH team achieved greater autonomy, interruptions between both services were reduced and dispensing became safer. The overall dispensing of out-of-stock drugs decreased by 61%, and HPS technicians gained almost half an hour a day. Conclusions: The change in logistics between HPS and HaH has been very positive, obtaining important achievements, which have a positive impact on the organization and the safety of the patient, with a flow of medications more fluid and efficient, and the systematic recording of deliveries which increases the security of dispensing.Introducción: Se detectaron severas ineficiencias en los circuitos entre el Servicio de Farmacia Hospitalaria (SFH) y el Servicio de Hospitalización a Domicilio (HAD), lo que motivó la realización de un análisis, con el soporte de Calidad, y la definición e implementación posterior de varias acciones de mejora. Método: Análisis del flujo de medicación entre los SFH y HAD del Hospital Dos de Maig. Los objetivos propuestos fueron reducir las interrupciones a los profesionales, aumentar la eficiencia de los circuitos, y garantizar la disponibilidad de la medicación. Se identificaron ineficiencias en el sistema de solicitud y dispensación de medicación, y desajustes en la dotación y revisión del stock. Se acordó un cambio de modelo de dispensación, se ajustó la dotación del stock, se agilizaron las revisiones del mismo, y se aplicó una nueva herramienta de solicitud vía informática de medicación. Resultados: El equipo de HAD consiguió mayor autonomía, se redujeron las interrupciones entre ambos servicios y la dispensación ganó en seguridad. La dispensación global de fármacos fuera de stock disminuyó en un 61%, y los técnicos del SFH ganaron casi media hora diaria. Conclusiones: El cambio en la logística entre el SFH y HAD ha sido muy positivo, obteniendo unos logros importantes, que repercuten positivamente en la organización y en la seguridad del paciente, con un flujo de medicación más fluido y eficiente, y el registro sistemático de las entregas que incrementa la seguridad en la dispensación

    Copper(II) N, N, O -Chelating Complexes as Potential Anticancer Agents

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    Altres ajuts: Acord transformatiu CRUE-CSICThree novel dinuclear Cu(II) complexes based on a N,N,O-chelating salphen-like ligand scaffold and bearing varying aromatic substituents (−H, −Cl, and −Br) have been synthesized and characterized. The experimental and computational data obtained suggest that all three complexes exist in the dimeric form in the solid state and adopt the same conformation. The mass spectrometry and electron paramagnetic resonance results indicate that the dimeric structure coexists with the monomeric form in solution upon solvent (dimethyl sulfoxide and water) coordination. The three synthesized Cu(II) complexes exhibit high potentiality as ROS generators, with the Cu(II)/Cu(I) redox potential inside the biological redox window, and thus being able to biologically undergo Cu(II)/Cu(I) redox cycling. The formation of ROS is one of the most promising reported cell death mechanisms for metal complexes to offer an inherent selectivity to cancer cells. In vitro cytotoxic studies in two different cancer cell lines (HeLa and MCF7) and in a normal fibroblast cell line show promising selective cytotoxicity for cancer cells (IC50 about 25 μM in HeLa cells, which is in the range of cisplatin and improved with respect to carboplatin), hence placing this N,N,O-chelating salphen-like metallic core as a promising scaffold to be explored in the design of future tailor-made Cu(II) cytotoxic compounds

    Pragmatic, open-label, single-center, randomized, phase II clinical trial to evaluate the efficacy and safety of methylprednisolone pulses and tacrolimus in patients with severe pneumonia secondary to COVID-19: the TACROVID trial protocol

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    Introduction: Some COVID-19 patients evolve to severe lung injury and systemic hyperinflammatory syndrome triggered by both the coronavirus infection and the subsequent host-immune response. Accordingly, the use of immunomodulatory agents has been suggested but still remains controversial. Our working hypothesis is that methylprednisolone pulses and tacrolimus may be an effective and safety drug combination for treating severe COVID-19 patients. Methods: and analysis: TACROVID is a randomized, open-label, single-center, phase II trial to evaluate the ef- ficacy and safety of methylprednisolone pulses and tacrolimus plus standard of care (SoC) versus SoC alone, in patients at advanced stage of COVID-19 disease with lung injury and systemic hyperinflammatory response. Patients are randomly assigned (1:1) to one of two arms (42 patients in each group). The primary aim is to assess the time to clinical stability after initiating randomization. Clinical stability is defined as body temperature≤37.5 ◦C, and PaO2/FiO2 > 400 and/or SatO2/FiO2 > 300, and respiratory rate ≤24 rpm; for 48 consecutive hours. Discussion: Methylprednisolone and tacrolimus might be beneficial to treat those COVID-19 patients progressing into severe pulmonary failure and systemic hyperinflammatory syndrome. The rationale for its use is the fast effect of methylprednisolone pulses and the ability of tacrolimus to inhibit both the CoV-2 replication and the secondary cytokine storm. Interestingly, both drugs are low-cost and can be manufactured on a large scale; thus, if effective and safe, a large number of patients could be treated in developed and developing countries

    Methylprednisolone Pulses Plus Tacrolimus in Addition to Standard of Care vs. Standard of Care Alone in Patients With Severe COVID-19. A Randomized Controlled Trial

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    Introduction: Severe lung injury is triggered by both the SARS-CoV-2 infection and the subsequent host-immune response in some COVID-19 patients. Methods: We conducted a randomized, single-center, open-label, phase II trial with the aim to evaluate the efficacy and safety of methylprednisolone pulses and tacrolimus plus standard of care (SoC) vs. SoC alone, in hospitalized patients with severe COVID-19. The primary outcome was time to clinical stability within 56 days after randomization. Results: From April 1 to May 2, 2020, 55 patients were prospectively included for subsequent randomization; 27 were assigned to the experimental group and 28 to the control group. The experimental treatment was not associated with a difference in time to clinical stability (hazard ratio 0.73 [95% CI 0.39-1.37]) nor most secondary outcomes. Median methylprednisolone cumulative doses were significantly lower (360 mg [IQR 360-842] vs. 870 mg [IQR 364-1451]; p = 0.007), and administered for a shorter time (median of 4.00 days [3.00-17.5] vs. 18.5 days [3.00-53.2]; p = 0.011) in the experimental group than in the control group. Although not statistically significant, those receiving the experimental therapy showed a numerically lower all-cause mortality than those receiving SoC, especially at day 10 [2 (7.41%) vs. 5 (17.9%); OR 0.39 (95% CI 0.05-2.1); p = 0.282]. The total number of non-serious adverse events was 42 in each the two groups. Those receiving experimental treatment had a numerically higher rate of non-serious infectious adverse events [16 (38%) vs. 10 (24%)] and serious infectious adverse events [7 (35%) vs. 3 (23%)] than those receiving SoC. Conclusions: The combined use of methylprednisolone pulses plus tacrolimus, in addition to the SoC, did not significantly improve the time to clinical stability or other secondary outcomes compared with the SoC alone in severe COVID-19. Although not statistically significant, patients receiving the experimental therapy had numerically lower all-cause mortality than those receiving SoC, supporting recent non-randomized studies with calcineurin inhibitors. It is noteworthy that the present trial had a limited sample size and several other limitations. Therefore, further RCTs should be done to assess the efficacy and safety of tacrolimus to tackle the inflammatory stages of COVID-19

    Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

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    Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

    Estudi de les arts del cos en el museu del segle XXI: un art efímer i viu dins del museu

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    L’objectiu principal d’aquesta investigació és analitzar per què les arts de cos estan tan presents en els museus del segle XXI. Per fer-ho, ens centrarem primer en conèixer la història de les arts del cos des dels seus inicis al carrer o galeries alternatives fins a l’entrada al museu. En segon lloc, farem una aproximació a l’evolució dels museus centrant-nos en els segles XX i XXI. En tercer lloc, investigarem com les arts del cos entren als museus i farem una recerca d’aquestes arts en el museu del segle XXIThe main objective of this research is to analyze why the body arts (performance art, etc.) are so present nowadays in museums. So firstly, we will focus in knowing the history of body arts from its beginnings in street, then in galleries, and finally in the museums. Secondly, we will approach the development of museums focusing on the 20th and 21st centuries. Thirdly, we will investigate how the body arts go into museums and we will do a research about these arts in the 21th century museum
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