Controversias: beneficios y mitos de la vacunación ante el avance del movimiento antivacunas Cortometraje documental científico

Trabajo Final para optar al grado académico de Licenciatura en Comunicación Social, Universidad Nacional de Córdoba (inédita). Calificación 10 (diez)Este Trabajo Final de Grado de la Licenciatura en Comunicación Social consiste en una producción de carácter documental que analiza la relación entre las creencias personales y las ideas científicas más aceptadas sobre la vacunación humana. Además reflexiona en torno a diferentes conceptos tales como la divulgación de la ciencia, la comunicación pública de la salud y el sistema de creencias asociado a la prevención sanitaria. Ante el avance global del escepticismo sobre la vacunación y sus beneficios, encarnado por el movimiento denominado “antivacunas”, este trabajo busca remarcar la importancia de la vacunación como práctica médica, destacando sus beneficios y refutando los principales mitos que surgen en torno a ella. Esta producción documental se inscribe en las formas del documental de divulgación científica y explora, mediante el testimonio de diferentes entrevistados, los motivos que llevan a una persona a dejar de vacunarse, la importancia de la inmunización dentro de una población, y cómo la información falsa se vincula de manera directa con la aparición de ciertas convicciones. Todo ello en el marco de una actual situación epidemiológica mundial. El corpus teórico se centra en las características del documental científico, la comunicación pública de la ciencia y el amplio universo referido de las vacunas y sus detractores. Este trabajo expone también una descripción de los procesos de preproducción, producción y postproducción del cortometraje documental Controversias: beneficios y mitos de la vacunación ante el avance del movimiento antivacunas.Fil: Coto Aubone, Guadalupe. Universidad Nacional de Córdoba. Facultad de Ciencias de la Comunicación. Argentina.Fil: Fortini, Nicolás. Universidad Nacional de Córdoba. Facultad de Ciencias de la Comunicación. Argentina.Fil: González Zugasti, Mateo. Universidad Nacional de Córdoba. Facultad de Ciencias de la Comunicación. Argentina

Calprotectin blockade inhibits long-term vascular pathology following peritoneal dialysis-associated bacterial infection

Bacterial infections and the concurrent inflammation have been associated with increased long-term cardiovascular (CV) risk. In patients receiving peritoneal dialysis (PD), bacterial peritonitis is a common occurrence, and each episode further increases late CV mortality risk. However, the underlying mechanism(s) remains to be elucidated before safe and efficient anti-inflammatory interventions can be developed. Damage-Associated Molecular Patterns (DAMPs) have been shown to contribute to the acute inflammatory response to infections, but a potential role for DAMPs in mediating long-term vascular inflammation and CV risk following infection resolution in PD, has not been investigated. We found that bacterial peritonitis in mice that resolved within 24h led to CV disease-promoting systemic and vascular immune-mediated inflammatory responses that were maintained up to 28 days. These included higher blood proportions of inflammatory leukocytes displaying increased adhesion molecule expression, higher plasma cytokines levels, and increased aortic inflammatory and atherosclerosis-associated gene expression. These effects were also observed in infected nephropathic mice and amplified in mice routinely exposed to PD fluids. A peritonitis episode resulted in elevated plasma levels of the DAMP Calprotectin, both in PD patients and mice, here the increase was maintained up to 28 days. In vitro, the ability of culture supernatants from infected cells to promote key inflammatory and atherosclerosis-associated cellular responses, such as monocyte chemotaxis, and foam cell formation, was Calprotectin-dependent. In vivo, Calprotectin blockade robustly inhibited the short and long-term peripheral and vascular consequences of peritonitis, thereby demonstrating that targeting of the DAMP Calprotectin is a promising therapeutic strategy to reduce the long-lasting vascular inflammatory aftermath of an infection, notably PD-associated peritonitis, ultimately lowering CV risk

A Novel Mouse Model of Peritoneal Dialysis: Combination of Uraemia and Long-Term Exposure to PD Fluid

Different animal models for peritoneal dialysis (PD) have been used in the past decades to develop PD fluids compatible with patient life and to identify markers of peritoneal fibrosis and inflammation. Only few of those studies have taken into account the importance of uraemia-induced alterations at both systemic and peritoneal levels. Moreover, some animal studies which have reported about PD in a uremic setting did not always entirely succeed in terms of uraemia establishment and animal survival. In the present study we induced uraemia in the recently established mouse PD exposure model in order to obtain a more clinically relevant mouse model for kidney patients. This new designed model reflected both the slight thickening of peritoneal membrane induced by uraemia and the significant extracellular matrix deposition due to daily PD fluid instillation. In addition the model offers the opportunity to perform long-term exposure to PD fluids, as it is observed in the clinical setting, and gives the advantage to knock out candidate markers for driving peritoneal inflammatory mechanisms.Marie Curie actionsPeer Reviewe

Misperception of the cardiovascular risk in patients with rheumatoid arthritis

ABSTRACT: The risk of cardiovascular (CV) disease and mortality is increased by rheumatoid arthritis (RA). However, data on how RA patients perceive their own CV risk and their adherence to CV prevention factors are scarce. We conducted an observational study on 266 patients with RA to determine whether the perceived CV risk correlates to the objective CV risk, and if it influences their compliance with a Mediterranean diet and physical exercise. The objective CV risk was calculated according to the modified European League Against Rheumatism (EULAR) Systematic Coronary Risk Evaluation (SCORE). The perceived CV risk did not correlate to the objective CV risk. The correlation was even lower when carotid ultrasound was used. Notably, 64.62% of patients miscalculated their CV risk, with 43.08% underestimating it. Classic CV risk factors, carotid ultrasound markers and ESR and CRP showed significant correlation with the objective CV risk. However, only hypertension and RA disease features showed association with the perceived CV risk. Neither the objective CV risk nor the perceived CV risk were associated with the accomplishment of a Mediterranean diet or physical activity. In conclusion, RA patients tend to underestimate their actual CV risk, giving more importance to RA features than to classic CV risk factors. They are not concerned enough about the beneficial effects of physical activity or diet.This work was partially supported by RETICS Programs, RD08/0075 (RIER), RD12/0009/0013 and RD16/0012 from “Instituto de Salud Carlos III” (ISCIII) (Spain). However, this research did not receive any specific grant from funding agencies in the commercial or not-for-profit sectors

Novel aspects of the immune response involved in the peritoneal damage in chronic Kkdney disease patients under dialysis

Chronic kidney disease (CKD) incidence is growing worldwide, with a significant percentage of CKD patients reaching end-stage renal disease (ESRD) and requiring kidney replacement therapies (KRT). Peritoneal dialysis (PD) is a convenient KRT presenting benefices as home therapy. In PD patients, the peritoneum is chronically exposed to PD fluids containing supraphysiologic concentrations of glucose or other osmotic agents, leading to the activation of cellular and molecular processes of damage, including inflammation and fibrosis. Importantly, peritonitis episodes enhance peritoneum inflammation status and accelerate peritoneal injury. Here, we review the role of immune cells in the damage of the peritoneal membrane (PM) by repeated exposure to PD fluids during KRT as well as by bacterial or viral infections. We also discuss the anti-inflammatory properties of current clinical treatments of CKD patients in KRT and their potential effect on preserving PM integrity. Finally, given the current importance of coronavirus disease 2019 (COVID-19) disease, we also analyze here the implications of this disease in CKD and KRTThis research was funded by grants from the Instituto de Salud Carlos III (ISCIII) and Fondos FEDER European Union (PI20/00140, PI19/00815, and DTS20/00083). Red de Investi gación Renal REDINREN: RD16/0009/0003 to M.R-O and RICORS2040; RD21/0005/0002 funded by European Union—NextGenerationEU, Sociedad Española de Nefrología. Innovation programme under the Marie Skłodowska-Curie grant of the European Union’s Horizon 2020 (IMPROVE-PD ID: 812699) to M.R-O. E.K. was supported by the grant from the Narodowe Centrum Nauki (NCN, Polish National Science Centre; 2018/29/N/NZ3/02504). R.S. was supported by Ministry for Health of Italy (Ricerca Corrente). This work was also supported by a grant (PID 2019-110132RB I00/AEI/10.13039/501100011033) from the Spanish Ministry of Science and Innovation/Fondo Europeo de Desarrollo Regional (MICINN/FEDER) to M.L.-C

Paricalcitol reduces peritoneal fibrosis in mice through the activation of regulatory T cells and reduction in IL-17 production

Fibrosis is a significant health problem associated with a chronic inflammatory reaction. The precise mechanisms involved in the fibrotic process are still poorly understood. However, given that inflammation is a major causative factor, immunomodulation is a possible therapeutic approach to reduce fibrosis. The vitamin D receptor (VDR) that is present in all hematopoietic cells has been associated with immunomodulation. We investigated whether the intraperitoneal administration of paricalcitol, a specific activator of the VDR, modulates peritoneal dialysis fluid (PDF)-induced peritoneal fibrosis. We characterized the inflammatory process in the peritoneal cavity of mice treated or not treated with paricalcitol and analyzed the ensuing fibrosis. The treatment reduced peritoneal IL-17 levels, which strongly correlated with a significantly lower peritoneal fibrotic response. In vitro studies demonstrate that both CD4+ and CD8+ regulatory T cells appear to impact the regulation of IL-17. Paricalcitol treatment resulted in a significantly increased frequency of CD8+ T cells showing a regulatory phenotype. The frequency of CD4+ Tregs tends to be increased, but it did not achieve statistical significance. However, paricalcitol treatment increased the number of CD4+ and CD8+ Treg cells in vivo. In conclusion, the activation of immunological regulatory mechanisms by VDR signaling could prevent or reduce fibrosis, as shown in peritoneal fibrosis induced by PDF exposure in mice.This study was supported by RETICS 06/0016 (VFM, RS) and FIS PI 09/0064 (RS) from the Fondo de Investigaciones Sanitarias (Health Research Fund). MLC was funded by SAF 2013-47611-R, SAF 2010-21249, and SAF 2007-61201 from the Ministerio de Economía y competitividad. MRO was supported by RETICS 12/0021,S2012DMD2321 from the Comunidad Autónoma de Madrid, PI 11/01854 from Fondo Investigaciones Sanitarias. GTGM was supported by Renal Foundation Íñigo Álvarez de Toledo, FIBHULP, and by Severo Ochoa FoundationPeer Reviewe

Targeting toll-like receptors with soluble toll-like receptor 2 prevents peritoneal dialysis solution-induced fibrosis

Peritoneal membrane failure due to fibrosis limits the use of peritoneal dialysis (PD). Peritoneal fibrosis may potentially be induced by sterile inflammation caused by ongoing cellular stress due to prolonged exposure to PD solutions (PDS). Effective therapies to prevent this process remain to be developed. Toll-like receptors (TLRs) mediate sterile inflammation by recognizing damage-associated molecular patterns (DAMPs) released by cellular stress. We evaluated the involvement of TLRs and DAMPs in PDS-induced fibrosis models and the therapeutic potential of TLR-DAMP targeting for preventing fibrosis. A range of PDS elicited pro-inflammatory and fibrotic responses from PD patient peritoneal leukocytes, mesothelial cells and mouse peritoneal leukocytes. TLR2/4 blockade of human peritoneal cells or TLR2/4 knockouts inhibited these effects. PDS did not induce rapid ERK phosphorylation or IκB-α degradation, suggesting that they do not contain components capable of direct TLR activation. However, PDS increased the release of Hsp70 and hyaluronan, both TLR2/4 DAMP ligands, by human and mouse peritoneal cells, and their blockade decreased PDS-driven inflammation. Soluble TLR2, a TLR inhibitor, reduced PDS-induced pro-inflammatory and fibrotic cytokine release ex vivo. Daily catheter infusion of PDS in mice caused peritoneal fibrosis, but co-administration of soluble TLR2 prevented fibrosis, suppressed pro-fibrotic gene expression and pro-inflammatory cytokine production, reduced leukocyte/neutrophil recruitment, recovered Treg cell levels and increased the Treg:Th17 ratio. Thus, TLR2/4, Hsp70 and hyaluronan showed major roles in PDS-induced peritoneal inflammation and fibrosis. The study demonstrates the therapeutic potential of a TLR-DAMP targeting strategy to prevent PDS-induced fibrosis

Tamoxifen ameliorates peritoneal membrane damage by blocking mesothelial to mesenchymal transition in peritoneal dialysis

Mesothelial-to-mesenchymal transition (MMT) is an auto-regulated physiological process of tissue repair that in uncontrolled conditions such as peritoneal dialysis (PD) can lead to peritoneal fibrosis. The maximum expression of peritoneal fibrosis induced by PD fluids and other peritoneal processes is the encapsulating peritoneal sclerosis (EPS) for which no specific treatment exists. Tamoxifen, a synthetic estrogen, has successfully been used to treat retroperitoneal fibrosis and EPS associated with PD. Hence, we used in vitro and animal model approaches to evaluate the efficacy of Tamoxifen to inhibit the MMT as a trigger of peritoneal fibrosis. In vitro studies were carried out using omentum-derived mesothelial cells (MCs) and effluent-derived MCs. Tamoxifen blocked the MMT induced by transforming growth factor (TGF)-β1, as it preserved the expression of E-cadherin and reduced the expression of mesenchymal-associated molecules such as snail, fibronectin, collagen-I, α-smooth muscle actin, and matrix metalloproteinse-2. Tamoxifen-treatment preserved the fibrinolytic capacity of MCs treated with TGF-β1 and decreased their migration capacity. Tamoxifen did not reverse the MMT of non-epitheliod MCs from effluents, but it reduced the expression of some mesenchymal molecules. In mice PD model, we demonstrated that MMT progressed in parallel with peritoneal membrane thickness. In addition, we observed that Tamoxifen significantly reduced peritoneal thickness, angiogenesis, invasion of the compact zone by mesenchymal MCs and improved peritoneal function. Tamoxifen also reduced the effluent levels of vascular endothelial growth factor and leptin. These results demonstrate that Tamoxifen is a therapeutic option to treat peritoneal fibrosis, and that its protective effect is mediated via modulation of the MMT processThis work was supported by grant SAF2010-21249 from the ‘‘Ministerio de Economia y Competitividad’’ to MLC and by grant S2010/BMD-2321 from ‘‘Comunidad Autónoma de Madrid’’ to MLC and RS. This work was also partially supported by grants PI 09/0776 from ‘‘Fondo de Investigaciones Sanitarias’’ to AA, and RETICS 06/0016 (REDinREN, Fondos FEDER, EU) to R

Alanyl-Glutamine Restores Tight Junction Organization after Disruption by a Conventional Peritoneal Dialysis Fluid

Understanding and targeting the molecular basis of peritoneal solute and protein transport is essential to improve peritoneal dialysis (PD) efficacy and patient outcome. Supplementation of PD fluids (PDF) with alanyl-glutamine (AlaGln) increased small solute transport and reduced peritoneal protein loss in a recent clinical trial. Transepithelial resistance and 10 kDa and 70 kDa dextran transport were measured in primary human endothelial cells (HUVEC) exposed to conventional acidic, glucose degradation products (GDP) containing PDF (CPDF) and to low GDP containing PDF (LPDF) with and without AlaGln. Zonula occludens-1 (ZO-1) and claudin-5 were quantified by Western blot and immunofluorescence and in mice exposed to saline and CPDF for 7 weeks by digital imaging analyses. Spatial clustering of ZO-1 molecules was assessed by single molecule localization microscopy. AlaGln increased transepithelial resistance, and in CPDF exposed HUVEC decreased dextran transport rates and preserved claudin-5 and ZO-1 abundance. Endothelial clustering of membrane bound ZO-1 was higher in CPDF supplemented with AlaGln. In mice, arteriolar endothelial claudin-5 was reduced in CPDF, but restored with AlaGln, while mesothelial claudin-5 abundance was unchanged. AlaGln supplementation seals the peritoneal endothelial barrier, and when supplemented to conventional PD fluid increases claudin-5 and ZO-1 abundance and clustering of ZO-1 in the endothelial cell membrane.This work is part of the IMPROVE-PD project that has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie grant agreement number 812699. M.B. is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—Projektnummer 419826430. R.H. was supported by a research fellowship of the European Renal Association and European Dialysis and Transplant Association (ERA-EDTA). E.L. was supported by the ÚNKP-18-2 New National Excellence Program of the Ministry of Human Capacities, Hungary. E.L. and H.J. were supported by Jellinek-Harry scholarship. S.G.Z. acknowledges the Alexander von Humboldt Stiftung/Foundation for an Experienced Researcher Fellowship (2019–2021) and the International Peritoneal Dialysis Society (ISPD) for an International Cooperation Research Grant (2019–2021). C.P.S. has obtained funding from European Nephrology and Dialysis Institute (ENDI).Peer reviewe

Covid-19: la malinterpretación de los datos de la pandemia daña la confianza del público

Dos cartas publicadas en The Lancet y The Lancet Public Health en los últimos meses defienden la necesidad de evaluar de forma independiente la respuesta española ante la covid-19. Estamos de acuerdo, pero nos gustaría complementarlas con tres puntos que nos acercan a la ciencia abierta. Nos referimos a la confusión terminológica, la calidad de los datos y su disponibilidad