C4BP(β-)-mediated immunomodulation attenuates inflammation in DSS-induced murine colitis and in myeloid cells from IBD patients

16 p.-9 fig.-1 tab.The most recent and promising therapeutic strategies for inflammatory bowel disease (IBD) have engaged biologics targeting single effector components involved in major steps of the immune-inflammatory processes, such as tumor necrosis factor, interleukins or integrins. Nevertheless, these molecules have not yet met expectations regarding efficacy and safety, resulting in a significant percentage of refractory or relapsing patients. Thus, novel treatment options are urgently needed. The minor isoform of the complement inhibitor C4b-binding protein, C4BP(β-), has been shown to confer a robust anti-inflammatory and immunomodulatory phenotype over inflammatory myeloid cells. Here we show that C4BP(β-)-mediated immunomodulation can significantly attenuate the histopathological traits and preserve the intestinal epithelial integrity in dextran sulfate sodium (DSS)-induced murine colitis. C4BP(β-) downregulated inflammatory transcripts, notably those related to neutrophil activity, mitigated circulating inflammatory effector cytokines and chemokines such as CXCL13, key in generating ectopic lymphoid structures, and, overall, prevented inflammatory immune cell infiltration in the colon of colitic mice. PRP6-HO7, a recombinant curtailed analogue with only immunomodulatory activity, achieved a similar outcome as C4BP(β-), indicating that the therapeutic effect is not due to the complement inhibitory activity. Furthermore, both C4BP(β-) and PRP6-HO7 significantly reduced, with comparable efficacy, the intrinsic and TLR-induced inflammatory markers in myeloid cells from both ulcerative colitis and Crohn’s disease patients, regardless of their medication. Thus, the pleiotropic anti-inflammatory and immunomodulatory activity of PRP6-HO7, able to “reprogram” myeloid cells from the complex inflammatory bowel environment and to restore immune homeostasis, might constitute a promising therapeutic option for IBD.We thank CERCA Programme/Generalitat de Catalunya for institutional support. This work was supported by the Ministerio de Ciencia, Innovación y Universidades (Madrid, Spain) (grants FIS-ISCIII PI20/00464, PI16/00377 and DTS20/00016), and the “Departament de Recerca i Universitats de la Generalitat de Catalunya” (grants 2019PROD00081, 2021INNOV00020, and 2021SGR00521), all co-funded by FEDER funds/European Regional Development Fund (ERDF)-a way to build Europe-. Additionally, the project that gave rise to these results has received funding from the “La Caixa” Foundation and the European Institute of Innovation and Technology, EIT (body of the European Union that receives support from the European Union’s Horizon 2020 research and innovation programme), under the grant agreement CI22–00230. Likewise, this study was financially promoted by the “hna Foundation”. Dr. Vega is supported by the Spanish “Ministerio de Ciencia, Innovación y Universidades/FEDER” [RTI2018–102242-B-I00]. Dr. Rodriguez de Córdoba is supported by the Spanish “Ministerio de Economia y Competitividad/FEDER [SAF2015–66287-R]. Dr. Vega and Dr. Rodriguez de Córdoba are also funded by the Autonomous Region of Madrid [S2022/BMD-7278] and the European Commission – NextGenerationEU through CSIC’s Global Health Platform (”PTI Salud Global”) [SGL2103020].Peer reviewe

Calpain-5 gene variants are associated with diastolic blood pressure and cholesterol levels

BACKGROUND: Genes implicated in common complex disorders such as obesity, type 2 diabetes mellitus (T2DM) or cardiovascular diseases are not disease specific, since clinically related disorders also share genetic components. Cysteine protease Calpain 10 (CAPN10) has been associated with T2DM, hypertension, hypercholesterolemia, increased body mass index (BMI) and polycystic ovary syndrome (PCOS), a reproductive disorder of women in which isunlin resistance seems to play a pathogenic role. The calpain 5 gene (CAPN5) encodes a protein homologue of CAPN10. CAPN5 has been previously associated with PCOS by our group. In this new study, we have analysed the association of four CAPN5 gene variants(rs948976A>G, rs4945140G>A, rs2233546C>T and rs2233549G>A) with several cardiovascular risk factors related to metabolic syndrome in general population. METHODS: Anthropometric measurements, blood pressure, insulin, glucose and lipid profiles were determined in 606 individuals randomly chosen from a cross-sectional population-based epidemiological survey in the province of Segovia in Central Spain (Castille), recruited to investigate the prevalence of anthropometric and physiological parameters related to obesity and other components of the metabolic syndrome. Genotypes at the four polymorphic loci in CAPN5 gene were detected by polymerase chain reaction (PCR). RESULTS: Genotype association analysis was significant for BMI (p ≤ 0.041), diastolic blood pressure (p = 0.015) and HDL-cholesterol levels (p = 0.025). Different CAPN5 haplotypes were also associated with diastolic blood pressure (DBP) (0.0005 ≤ p ≤ 0.006) and total cholesterol levels (0.001 ≤ p ≤ 0.029). In addition, the AACA haplotype, over-represented in obese individuals, is also more frequent in individuals with metabolic syndrome defined by ATPIII criteria (p = 0.029). CONCLUSION: As its homologue CAPN10, CAPN5 seems to influence traits related to increased risk for cardiovascular diseases. Our results also may suggest CAPN5 as a candidate gene for metabolic syndrome

Correction : Chaparro et al. Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain: Large-Scale Epidemiological Study. J. Clin. Med. 2021, 10, 2885

The authors wish to make the following corrections to this paper [...]

Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain : Large-Scale Epidemiological Study

(1) Aims: To assess the incidence of inflammatory bowel disease (IBD) in Spain, to describe the main epidemiological and clinical characteristics at diagnosis and the evolution of the disease, and to explore the use of drug treatments. (2) Methods: Prospective, population-based nationwide registry. Adult patients diagnosed with IBD-Crohn's disease (CD), ulcerative colitis (UC) or IBD unclassified (IBD-U)-during 2017 in Spain were included and were followed-up for 1 year. (3) Results: We identified 3611 incident cases of IBD diagnosed during 2017 in 108 hospitals covering over 22 million inhabitants. The overall incidence (cases/100,000 person-years) was 16 for IBD, 7.5 for CD, 8 for UC, and 0.5 for IBD-U; 53% of patients were male and median age was 43 years (interquartile range = 31-56 years). During a median 12-month follow-up, 34% of patients were treated with systemic steroids, 25% with immunomodulators, 15% with biologics and 5.6% underwent surgery. The percentage of patients under these treatments was significantly higher in CD than UC and IBD-U. Use of systemic steroids and biologics was significantly higher in hospitals with high resources. In total, 28% of patients were hospitalized (35% CD and 22% UC patients, p < 0.01). (4) Conclusion: The incidence of IBD in Spain is rather high and similar to that reported in Northern Europe. IBD patients require substantial therapeutic resources, which are greater in CD and in hospitals with high resources, and much higher than previously reported. One third of patients are hospitalized in the first year after diagnosis and a relevant proportion undergo surgery

Bronchoscopist's perception of the quality of the single-use bronchoscope (Ambu aScope4™) in selected bronchoscopies: a multicenter study in 21 Spanish pulmonology services

Background: The disposable bronchoscope is an excellent alternative to face the problem of SARS-CoV-2 and other cross infections, but the bronchoscopist’s perception of its quality has not been evaluated. Methods: To evaluate the quality of the Ambu-aScope4 disposable bronchoscope, we carried out a cross-sectional study in 21 Spanish pulmonology services. We use a standardized questionnaire completed by the bronchoscopists at the end of each bronchoscopy. The variables were described with absolute and relative frequencies, measures of cen‑ tral tendency and dispersion depending on their nature. The existence of learning curves was evaluated by CUSUM analysis. Results: The most frequent indications in 300 included bronchoscopies was bronchial aspiration in 69.3% and the median duration of these was 9.1 min. The route of entry was nasal in 47.2% and oral in 34.1%. The average score for ease of use, image, and aspiration quality was 80/100. All the planned techniques were performed in 94.9% and the bronchoscopist was satisfed in 96.6% of the bronchoscopies. They highlighted the portability and immediacy of the aScope4TM to start the procedure in 99.3%, the possibility of taking and storing images in 99.3%. The CUSUM analysis showed average scores>70/100 from the frst procedure and from the 9th procedure more than 80% of the scores exceeded the 80/100 score

Effectiveness of influenza vaccine against laboratory-confirmed influenza, in the late 2011-2012 season in Spain, among population targeted for vaccination

Background: In Spain, the influenza vaccine effectiveness (VE) was estimated in the last three seasons using the observational study cycEVA conducted in the frame of the existing Spanish Influenza Sentinel Surveillance System. The objective of the study was to estimate influenza vaccine effectiveness (VE) against medically attended, laboratory-confirmed influenza-like illness (ILI) among the target groups for vaccination in Spain in the 2011-2012 season. We also studied influenza VE in the early (weeks 52/2011-7/2012) and late (weeks 8-14/2012) phases of the epidemic and according to time since vaccination. Methods: Medically attended patients with ILI were systematically swabbed to collect information on exposure, laboratory outcome and confounding factors. Patients belonging to target groups for vaccination and who were swabbed 4 months, respectively, since vaccination. A decrease in VE with time since vaccination was only observed in individuals aged ≥ 65 years. Regarding the phase of the season, decreasing point estimates were only observed in the early phase, whereas very low or null estimates were obtained in the late phase for the shortest time interval. Conclusions: The 2011-2012 influenza vaccine showed a low-to-moderate protective effect against medically attended, laboratory-confirmed influenza in the target groups for vaccination, in a late season and with a limited match between the vaccine and circulating strains. The suggested decrease in influenza VE with time since vaccination was mostly observed in the elderly population. The decreasing protective effect of the vaccine in the late part of the season could be related to waning vaccine protection because no viral changes were identified throughout the season

Salidas profesionales y desarrollo de carreras relacionadas con la titulación estudiada

El objetivo de este proyecto es la mejora de la empleabilidad de los alumnos del grado de Comercio. El proyecto consiste en un ciclo de conferencias con directivos que tienen responsabilidades en áreas comerciales de empresas, con el objetivo de que conozcan las posibilidades de trabajo y las competencias y habilidades que se exigen.Depto. de Organización de EmpresasFac. de Ciencias Económicas y EmpresarialesFALSEsubmitte

La Presencia Salesiana en Ecuador: Perspectivas históricas y sociales

Este libro recoge los resultados de un programa de investigación sobre las siguientes dimensiones de la presencia salesiana en el país: desarrollo comunitario, inclusión social, niñez y adolescencia; educación salesiana, con énfasis en la educación técnica; conformación de identidades e interculturalidad. Esta investigación fue realizada por un equipo de la Universidad Politécnica Salesiana en convenio con la Sociedad Salesiana en el Ecuador. Participaron profesionales que aportaron sus propias visiones desde diversas ciencias sociales (historia, sociología y antropología) y de la educación. Por lo tanto, se trata de una obra interdisciplinaria que busca profundizar el diálogo entre la herencia espiritual-pedagógica salesiana, la ciencia y las expectativas de los pueblos y culturas de hoy en momento de complejidad creciente de la sociedad ecuatoriana sujeta a transformaciones radicales cargadas de desafíos para la comunidad salesiana y la misma Iglesia

Radiaciones ionizantes y su impacto Primer Simposio Internacional sobre Medioambiente (ISE 2017)

Son ya varias las décadas en las que en América Latina se ha trabajado arduamente sobre las radiaciones ionizantes; tanto en las ionizantes directas, tales como las partículas beta positivas y negativas, las partículas alfa, los protones, los mesones cargados, los muones y los iones pesados, así como también en las ionizantes indirectas (las producidas por partículas sin cargas), como las generadas por fotones con energías superiores a los 10 keV y los neutrones. Por otro lado, las radiaciones no ionizantes también han sido objeto de detallados estudios, y muy especialmente las provenientes del Sol, como el factor natural más influyente sobre la Tierra. En esta obra se presentan algunos de los avances en los que han participado reconocidos científicos latinoamericanos, como el Dr. Héctor Vega Carrillo, Dr. Daniel Palacios, Dra. Patrizia Pereyra, Dra. Sheila Serrano, y el Dr. Manuel Ernesto Delgado, entre otros. Esta obra puede ser de interés para profesionales del área de la protección radiológica, la ingeniería ambiental, física de la atmósfera y áreas afines, así como para estudiantes