Characterization fo the molecular mechanism of action of a new inhibitor of the complex cyclin-dependent kinase 2-cyclin A

Comunicaciones a congreso

Potential use of sewage sludge ash (SSA) as a cement replacement in precast concrete blocks

The present study explored the technological feasibility of re-using sewage sludge ash (SSA) as a Portland cement replacement in commercially manufactured pre cast concrete blocks. The blocks analysed were made to the guidelines laid down in Spain s National Plan for Waste Water Treatment Plant Sludge, 2001 2006, and European Union specifications (CE marking) for such products. Performance was compared in three families of blocks, with 0, 10 and 20% SSA. The findings proved that SSA is apt for pre cast concrete block manufacture and that, in addition to the economic and environmental benefits afforded, its use would improve certain of the properties of conventional block.This research was funded by the Spanish Ministry of the Environment under project A173/2007/304.4. The authors wish to thank Prefabricados Saval Hermanos, S. L. for the use of their pre cast concrete plant facilities to manufacture the blocks analysed in this study.Pérez-Carrión, M.; Baeza-Brotons, F.; Paya Bernabeu, JJ.; Saval, J.; Zornoza Gómez, EM.; Borrachero Rosado, MV.; Garcés, P. (2014). Potential use of sewage sludge ash (SSA) as a cement replacement in precast concrete blocks. Materiales de Construcción. 64(313):2-11. https://doi.org/10.3989/mc.2014.06312S21164313Inci, I., Schuurmans, M. M., Kestenholz, P., Schneiter, D., Hillinger, S., Opitz, I., … Weder, W. (2012). Long-term outcomes of bilateral lobar lung transplantation. European Journal of Cardio-Thoracic Surgery, 43(6), 1220-1225. doi:10.1093/ejcts/ezs541Artemiou, O., Wieselthaler, G., Zuckermann, A., Wisser, W., Wekerle, T., Senbaklavaci, O., … Klepetko, W. (1997). Downsizing of the donor lung: Peripheral segmental resections and lobar transplantation. Transplantation Proceedings, 29(7), 2899-2900. doi:10.1016/s0041-1345(97)00722-7Aigner, C. (2004). Lobar transplantation, split lung transplantation and peripheral segmental resection – reliable procedures for downsizing donor lungs. European Journal of Cardio-Thoracic Surgery, 25(2), 179-183. doi:10.1016/j.ejcts.2003.11.009Bisson, A., Bonnette, P., El Kadi, N. B., Leroy, M., & Colchen, A. (1994). Bilateral pulmonary lobe transplantation: Left lower and right middle and lower lobes. The Annals of Thoracic Surgery, 57(1), 219-221. doi:10.1016/0003-4975(94)90405-7Couetil, J.-P. A., Tolan, M. J., Loulmet, D. F., Guinvarch, A., Chevalier, P. G., Achkar, A., … Carpentier, A. F. (1997). Pulmonary bipartitioning and lobar transplantation: A new approach to donor organ shortage. The Journal of Thoracic and Cardiovascular Surgery, 113(3), 529-537. doi:10.1016/s0022-5223(97)70366-0Aigner, C., Winkler, G., Jaksch, P., Ankersmit, J., Marta, G., Taghavi, S., … Klepetko, W. (2004). Size-reduced lung transplantation: An advanced operative strategy to alleviate donor organ shortage. Transplantation Proceedings, 36(9), 2801-2805. doi:10.1016/j.transproceed.2004.09.066Hardy, J. D., Webb, W. R., Dalton, M. L., & Walker, G. R. (1963). Lung Homotransplantation in Man. JAMA, 186(12). doi:10.1001/jama.1963.63710120001010(1986). Unilateral Lung Transplantation for Pulmonary Fibrosis. New England Journal of Medicine, 314(18), 1140-1145. doi:10.1056/nejm1986050131418029. Helvaci A, Meydan B, Akin O, et al. Silikozis tanisiyla yapilan tek tarafli akciğer nakli: Türkiye'deki ilk başarili akciğer nakli olgusu. Türk Göğüs Kalp Damar Cerrahisi Dergisi. 2011;19:455-462.Oto, T., Date, H., Hayama, M., Ando, A., & Shimizu, N. (2005). Peripheral Lung Volume Reduction Improved Early Graft Function in Severe Size Mismatched Living Donor Lobar Lung Transplantation. Transplantation Proceedings, 37(10), 4515-4521. doi:10.1016/j.transproceed.2005.10.11911. Bowdish ME, Barr ML. Living lobar lung transplant. In: Lynch III JP, Ross JD, eds. Lung and Heart-Lung Transplant. New York, NY: Taylor & Francis; 2006:255-267

Impact of COVID-19 on the degree of compliance with hand hygiene: a repeated cross-sectional study

Hand hygiene (HH) is the paramount measure used to prevent healthcare associated infections. A repeated cross-sectional study was undertaken with direct observation of the degree of compliance on HH of healthcare personnel during the SARS-CoV-2 pandemic. Between, 2018-2019, 9,083 HH opportunities were considered, and 5,821 in 2020-2022. Chi squared tests were used to identify associations. The crude and adjusted odds ratios were used along with a logistic regression model for statistical analyses. Compliance on HH increased significantly (p < 0.001) from 54.5% (95% CI: 53.5, 55.5) to 70.1% (95% CI: 68.9, 71.2) during the COVID-19 pandemic. This increase was observed in four of the five key moments of HH established by the World Health Organization (WHO) (p<0.05), except at moment 4. The factors that were significantly and independently associated with compliance were the time period considered, type of healthcare-personnel, attendance at training sessions, knowledge of HH and WHO guidelines, and availability of hand disinfectant alcoholic solution in pocket format. Highest HH compliance occurred during the COVID-19 pandemic, reflecting a positive change in healthcare-personnel’s behavior regarding HH recommendations.We received funding through the Alicante Institute for Health and Biomedical Research (ISABIAL) plan for scientific and technical research and innovation project number 2021-0392

Evaluation of a program for updating recommendations about hand hygiene

Introducción. La higiene de manos (HM) es la medida más importante para prevenir las infecciones nosocomiales. El objetivo es evaluar el programa de actualización de las recomendaciones sobre HM implantado. Material y métodos. Intervenciones: marzo-octubre/2005 se realizaron sesiones de actualización sobre cuándo y cómo realizar la HM y mayo/2006 se repartió un tríptico explicativo a todos los trabajadores informando del grado de cumplimiento de las recomendaciones. Indicadores: nivel conocimientos (NC) medido con un cuestionario de cinco preguntas que se pasaba antes y después de las sesiones y se consideró respuesta inadecuada cuando se fallaban tres o más preguntas; el consumo soluciones alcohólicas (CSA) en ml/estancia agrupado en semestres desde 2004-2006; el grado cumplimiento de recomendaciones (GCR) sobre la HM medida por observación directa en dos momentos (diciembre/2005-febrero/2006 y octubre-noviembre/2006) y la prevalencia de infecciones nosocomiales (PI) y de pacientes con infección nosocomial (PPI) a partir estudios EPINE 2004-2005-2006. Resultados. La frecuencia de respuestas inadecuadas para evaluar NC pasó de un 57,5% antes a 18,9% después (p<0,001). El CSA para HM pasó de 3 ml/estancia en 2º semestre/2004 a 17 ml/estancia en 2º semestre/2006 (p<0,001). El GCR ha pasado del 31,0% al 55,6% (p<0,001). La PI y PPI han pasado del 11,4% y el 9,6% respectivamente en el 2004 al 9,4% y 8,9% en 2006 (N.S.). Conclusión. El programa está consiguiendo de manera progresiva sus objetivos ya que los tres indicadores de proceso (NC, CSA, GC) han mejorado de manera estadísticamente significativa, y los de resultado (PI y PPI) han mejorado aunque sin significación estadística.Background. Hand Hygiene (HH) is the most important measure in the prevention of nosocomial infections. The objective was to evaluate the program for updating recommendations on HH that had been introduced. Methods. Interventions: between March-October/2005 realisation of updating sessions about when and how to realize HH and May/2006 distribution of an explicative three-part document to all healthcare workers reporting on compliance with the recommendations. Indicators: level of knowledge (LK) measured with a questionnaire of five questions that was given to those attending before and after sessions, responses were considered inadequate when three or more questions were not answered; consumption of alcoholic solutions (CAS) on ml/stay grouped into semesters from 2004-2006; compliance (CO) with recommendations on HH was measured by direct observation at two times (December/2005-February/2006 and October-November/2006); and infections prevalence (IP) and patients with infection (IPP) for EPINE studies 2004-2005-2006. Results. The frequency of inadequate answers for evaluating LK has fallen from 57,5% before to 18,9% afterwards (p <0.001). The CAS for HH has passed from 3 ml/stay in 2nd semester/2004 to 17 ml/stay 2nd semester/2006 (p <0.001). The CO with HH has risen from 31,0% to 55,6% (p <0.001). The IP and IPP have risen respectively from 11,4% and 9,6% in 2004 to 9,4% and 8,9% in 2006 (N.S.). Conclusion. The program is progressively achieving its objectives as the three process indicators (LK, CAS, CO) have improved in a statistically significant way, and the indicators of results (IP and IPP) have improved but without achieving statistical significance.Proyecto de investigación financiado por el Fondo de Investigaciones Sanitarias del Ministerio de Sanidad, Nº Expte: PI0542075 y la Dirección General de Calidad de la Conselleria de Sanitat de la Generalitat Valenciana. Nº Expte: 12-2004

New Route for Valorization of Oil Mill Wastes: Isolation of Humic-Like Substances to be Employed in Solar-Driven Processes for Pollutants Removal

[EN] The valorization of olive oil mill solid wastes (OMW) has been addressed by considering it as a possible source of humic-like substances (HLSs), to be used as auxiliary substances for photo-Fenton, employing caffeine as a target pollutant to test the efficiency of this approach. The OMW-HLS isolation encompassed the OMW basic hydrolysis, followed by ultrafiltration and drying. OMW-HLS structural features have been investigated by means of laser light scattering, fluorescence, size exclusion chromatography, and thermogravimetric analysis; moreover, the capability of OMW-HLS to generate reactive species under irradiation has been investigated using spin-trap electronic paramagnetic resonance. The caffeine degradation by means of photo-Fenton process driven at pH = 5 was significantly increased by the addition of 10 mg/L of OMW-HLS. Under the mechanistic point of view, it could be hypothesized that singlet oxygen is not playing a relevant role, whereas other oxidants (mainly OH center dot radicals) can be considered as the key species in promoting caffeine degradation.Authors want to acknowledge the financial support of Spanish Ministerio de Economia y Competitividad (CTQ2015-69832-C04) and European Union (645551-RISE-2014, MAT4-TREAT).García-Ballesteros, S.; Grimalt, J.; Berto, S.; Minella, M.; Laurenti, E.; Vicente Candela, R.; López Pérez, MF.... (2018). New Route for Valorization of Oil Mill Wastes: Isolation of Humic-Like Substances to be Employed in Solar-Driven Processes for Pollutants Removal. ACS Omega. 3(10):13073-13080. https://doi.org/10.1021/acsomega.8b01816S130731308031

Calcium-dependent conformational changes of membrane-bound Ebola fusion peptide drive vesicle fusion

The fusogenic subdomain of the Ebola virus envelope glycoprotein is an internal sequence located ca. 20 residues downstream the N‐terminus of the glycoprotein transmembrane subunit. Partitioning of the Ebola fusion peptide into membranes containing phosphatidylinositol in the absence of Ca2+ stabilizes an α‐helical conformation, and gives rise to vesicle efflux but not vesicle fusion. In the presence of millimolar Ca2+ the membrane‐bound peptide adopts an extended β‐structure, and induces inter‐vesicle mixing of lipids. The peptide conformational polymorphism may be related to the flexibility of the virus-cell intermembrane fusogenic complex

Predictores de riesgo en una cohorte española con cardiolaminopatías. Registro REDLAMINA

[Abstract] Introduction and objectives. According to sudden cardiac death guidelines, an implantable cardioverter-defibrillator (ICD) should be considered in patients with LMNA-related dilated cardiomyopathy (DCM) and ≥ 2 risk factors: male sex, left ventricular ejection fraction (LVEF) < 45%, nonsustained ventricular tachycardia (NSVT), and nonmissense genetic variants. In this study we aimed to describe the clinical characteristics of carriers of LMNA genetic variants among individuals from a Spanish cardiac-laminopathies cohort (REDLAMINA registry) and to assess previously reported risk criteria. Methods. The relationship between risk factors and cardiovascular events was evaluated in a cohort of 140 carriers (age ≥ 16 years) of pathogenic LMNA variants (54 probands, 86 relatives). We considered: a) major arrhythmic events (MAE) if there was appropriate ICD discharge or sudden cardiac death; b) heart failure death if there was heart transplant or death due to heart failure. Results. We identified 11 novel and 21 previously reported LMNA-related DCM variants. LVEF < 45% (P = .001) and NSVT (P < .001) were related to MAE, but not sex or type of genetic variant. The only factor independently related to heart failure death was LVEF < 45% (P < .001). Conclusions. In the REDLAMINA registry cohort, the only predictors independently associated with MAE were NSVT and LVEF < 45%. Therefore, female carriers of missense variants with either NSVT or LVEF < 45% should not be considered a low-risk group. It is important to individualize risk stratification in carriers of LMNA missense variants, because not all have the same prognosis.[Resumen] Introducción y objetivos. Según las guías de muerte súbita, se debe considerar un desfibrilador automático implantable (DAI) para los pacientes con miocardiopatía dilatada debida a variantes en el gen de la lamina (LMNA) con al menos 2 factores: varones, fracción de eyección del ventrículo izquierdo (FEVI) < 45%, taquicardia ventricular no sostenida (TVNS) y variantes no missense. Nuestro objetivo es describir las características clínicas de una cohorte española de pacientes con cardiolaminopatías (registro REDLAMINA) y evaluar los criterios de riesgo vigentes. Métodos. Se evaluó la relación entre factores de riesgo y eventos cardiovasculares en una cohorte de 140 portadores de variantes en LMNA (54 probandos, 86 familiares, edad ≥ 16 años). Se consideró: a) evento arrítmico mayor (EAM) si hubo descarga apropiada del DAI o muerte súbita, y b) muerte por insuficiencia cardiaca, incluidos los trasplantes. Resultados. Se identificaron 11 variantes nuevas y 21 previamente publicadas. La FEVI < 45% (p = 0,001) y la TVNS (p < 0,001) se relacionaron con los EAM, pero no el sexo o el tipo de variante (missense frente a no missense). La FEVI < 45% (p < 0,001) fue el único factor relacionado con la muerte por insuficiencia cardiaca. Conclusiones. En el registro REDLAMINA, los únicos 2 predictores asociados con EAM fueron la TVNS y la FEVI < 45%. No se debería considerar grupo de bajo riesgo a las portadoras de variantes missense con TVNS o FEVI < 45%. Es importante individualizar la estratificación del riesgo de los portadores de variantes missense en LMNA, porque no todas tienen el mismo pronóstico.This study received a grant from the Proyecto de investigación de la Sección de Insuficiencia Cardiaca 2017 from the Spanish Society of Cardiology and grants from the Instituto de Salud Carlos III (ISCIII) [PI14/0967, PI15/01551, AC16/0014] and ERA-CVD Joint Transnational Call 2016 (Genprovic). Grants from the ISCIII and the Ministerio de Economía y Competitividad de España (Spanish Department of Economy and Competitiveness) are supported by the Plan Estatal de I+D+i 2013-2016: Fondo Europeo de Desarrollo Regional (FEDER) “Una forma de hacer Europa”

Amidase-responsive controlled release of antitumoral drug into intracellular media using gluconamide-capped mesoporous silica nanoparticles

MCM-41 silica nanoparticles were used as inorganic scaffolding to prepare a nanoscopic-capped hybrid material S1, which was able to release an entrapped cargo in the presence of certain enzymes, whereas in the absence of enzymes, a zero release system was obtained. S1 was prepared by loading nanoparticles with Safranine O dye and was then capped with a gluconamide derivative. In the absence of enzymes, the release of the dye from the aqueous suspensions of S1 was inhibited as a result of the steric hindrance imposed by the bulky gluconamide derivative, the polymerized gluconamide layer and the formation of a dense hydrogen-bonded network around the pore outlets. Upon the addition of amidase and pronase enzymes, delivery of Safranine O dye was observed due to the enzymatic hydrolysis of the amide bond in the anchored gluconamide derivative. S1 nanoparticles were not toxic for cells, as demonstrated by cell viability assays using HeLa and MCF-7 cell lines, and were associated with lysosomes, as shown by confocal microscopy. Finally, the S1¿CPT material loaded with the cytotoxic drug camptothecin and capped with the gluconamide derivative was prepared. The HeLa cells treated with S1¿CPT underwent cell death as a result of material internalization, and of the subsequent cellular enzyme-mediated hydrolysis and aperture of the molecular gate, which induced the release of the camptothecin cargo.We thank the Spanish Government (Project MAT2009-14564-C04 and SAF2010-15512) and the Generalitat Valenciana (Project PROMETEO/2009/016and/2010/005) for support. I. C. thanks the Universitat Politecnica de Valencia for her fellowship. L. M. thanks the Generalitat Valenciana for her post-doctoral VALi+d contract. E. A. and C. T. also thank the CIBER-BBN for contracts. We thank Eva Maria Lafuente Villarreal and Alberto Hernandez Cano from the Confocal Microscopy service of CIPF and the Electronic Microscopy service of UPV for their technical support.Candel Busquets, I.; Aznar Gimeno, E.; Mondragón Martínez, L.; De La Torre Paredes, C.; Martínez Mañez, R.; Sancenón Galarza, F.; Marcos Martínez, MD.... (2012). Amidase-responsive controlled release of antitumoral drug into intracellular media using gluconamide-capped mesoporous silica nanoparticles. Nanoscale. 4(22):7237-7245. https://doi.org/10.1039/c2nr32062bS7237724542

Risk of Cancer in Cases of Suspected Lynch Syndrome Without Germline Mutation

Background & Aims: Colorectal cancers (CRCs) with microsatellite instability (MSI) and a mismatch repair (MMR) immunohistochemical deficit without hypermethylation of the MLH1 promoter are likely to be caused by Lynch syndrome. Some patients with these cancers have not been found to have pathogenic germline mutations and are considered to have Lynch-like syndrome (LLS). The aim of this study was to determine the risk of cancer in families of patients with LLS. Methods: We studied a population-based cohort of 1705 consecutive patients, performing MSI tests and immunohistochemical analyses of MMR proteins. Patients were diagnosed with Lynch syndrome when they were found to have pathogenic germline mutations. Patients with MSI and loss of MSH2 and/or MSH6 expression, isolated loss of PMS2 or loss of MLH1 without MLH1 promoter hypermethylation, and no pathogenic mutation were considered to have LLS. The clinical characteristics of patients and the age- and sex-adjusted standardized incidence ratios (SIRs) of cancer in families were compared between groups. Results: The incidence of CRC was significantly lower in families of patients with LLS than in families with confirmed cases of Lynch syndrome (SIR for Lynch syndrome, 6.04; 95% confidence interval [CI], 3.58–9.54; SIR for LLS, 2.12; 95% CI, 1.16–3.56; P < .001). However, the incidence of CRC was higher in families of patients with LLS than in families with sporadic CRC (SIR for sporadic CRC, 0.48; 95% CI, 0.27–0.79; P < .001). Conclusions: The risk of cancer in families with LLS is lower that of families with Lynch syndrome but higher than that of families with sporadic CRC. These results confirm the need for special screening and surveillance strategies for these patients and their relatives.This work was supported by grants from Instituto de Salud Carlos III (PI-080726, INT-09/208, and PI11/026030), the Fondo de Investigación Sanitaria/FEDER (PS09/02368, 10/00384, 10/00918, 11/00219, and 11/00681), Fundació Olga Torres (CRP) and FP7 CHIBCHA Consortium (SCB and ACar), the Ministerio de Economía y Competitividad (SAF2010-19273), and Agència de Gestió d’Ajuts Universitaris i de Recerca (2009 SGR 849). SCB is supported by a contract from the Fondo de Investigación Sanitaria (CP03-0070). CIBERER and CIBERehd are funded by the Instituto de Salud Carlos III