Tratamiento de la fracción líquida del purín porcino en bio-reactores anaerobios de lecho fluidizado

[ES] Se ha llevado a cabo el estudio del proceso de degradación de la fracción líquida del purín porcino y del desarrollo de la biopelícula en dos reactores anaerobios de lecho fluidizado en el rango mesofílico de temperatura, empleando biolita y carbón activo granular como soportes. La reducción del carbono orgánico total alcanzada estuvo próxima a un 40%, trabajando con una velocidad de carga orgánica de 10 kg COT/m3.d, aunque este porcentaje se veía incrementado hasta el 90% si la carga orgánica de trabajo se reducía a 1-2 kg COT/m3.d. Estudios cinéticos revelan la existencia de una fracción orgánica remanente causada por la inhibición de la fase de hidrólisis en la depuración anaerobia del purín pocino. El efluente obtenido presenta mejores condiciones de aplicabilidad al terreno que el purín bruto al tener, a parte de un menor contenido en materia orgánica, menores cantidades de nutrientes (fósforo) y metales (hierro y cobre).CICYT (proyecto AMB1FD97-0644)Hidalgo, MD.; Álamo, JD.; Hernández, M.; Irusta, R. (2003). Tratamiento de la fracción líquida del purín porcino en bio-reactores anaerobios de lecho fluidizado. Ingeniería del agua. 10(2):127-133. https://doi.org/10.4995/ia.2003.2579OJS127133102APHA-AWWA-WPCF (1995). Standard Methods for de Examination of Water and Wastewater. 19th Edition. Washington D.C.De Mann, A.W.A. (1990). Anaerobic purification of raw sewage with the aid of granular sludge in UASB reactors. Report Agricultural University of Wageningen, The Netherlands.Farhan, M.H., Chinhong, P.H., Keenan, J.D., Shieh, W.K. (1997). Performance of anaerobic reactors during pseudo-steady-state operation. Journal. Chem. Tech. Biotech., 69 (1), 45-57.Holst, T.C., Truc, A., Pujol, R. (1997). Anaerobic fluidized beds: ten years of industrial experience. Wat. Sci.Tech., 36 (6/7), 415-422. JIH, C.-G., HUANG, J.-S. (1994).Effect of biofilm thickness distribution on substrate-inhibited kinetics. Wat. Res., 28 (4), 967-973.Jimeno, A., Bermúdez, J.J., Cánovas-Díaz, M., Manjón, A., Iborra, J.L. (1990). Methanogenic biofilm growth studies in an anaerobic fixed-film reactor. Enzyme Microb. Technol., 12, 387-393.Lettinga, G., Field, J., Van Lier, J., Zeeman, G., Pol, L.W.H. (1997).Advanced anaerobic wastewater treatment in the near future. Wat. Sci. Tech., 35 (10), 5-12). Perez, M., Romero, L.I., Sales, D. (1998).Comparative performance of high rate anaerobic thermophilic technologies treating industrial wastewater. Wat. Res., 32 (3), 559-564.Rozzi, A. (1988). Estado del arte sobre la depuración anaerobia en Europa. 4º Seminario D.A.A.R., Valladolid, 11-20.Ryhiner, G. B., Heinzle, E., Dunn, I.J. (1993). Modeling and simulation of anaerobic wastewater treatment and its application to control design: case whey. Biotechnol. Progress, 9 (3), 332-343.Wheatley, A.D., Johnson, K. A., Winstanley, C.I. (1990). The reliability of anaerobic digestion for the treatment of food processing effluents. Anaerobic Digestion, IAWPRC, 135-146.Zeeman, G. (1991). Mesophilic and psychrophilic digestión of liquid manure. Ph Thesis, University of Wageningen, The Netherlands

Kinetics of oxygen consumption, a key factor in the changes of young wines composition

Producción CientíficaThe oxygen that a wine receives during the winemaking process defines its properties. The aim of this work was to evaluate the oxygen consumption capacity of wines and its influence on the modification of their composition. This preliminary work evaluated the changes after 3 months in the chemical composition of twenty-seven Spanish commercial red, white and rosé wines after their air saturation and oxidation process at 35 °C for 7 days. All the wines studied were high oxygen consumers, while the white and rosé wines showed greater variability according to their chemical composition. Wines that consumed a lot of oxygen did so quickly or slowly, while wines that consumed little oxygen did so slowly. All the wines showed a significant decrease in ethyl esters of straight-chain fatty acids (50–58%), ethyl esters of branched-chain fatty acids (48–56%) and alcohol acetates (34–65%) content, and a significant increase in Strecker aldehydes (24%) because of oxygen consumption. This paper presents a preliminary approach to determine the oxidation tendency of different wines showing the importance of controlling the winemaking processes that can increase oxygen availability and of establishing the minimum appropriate level of free sulfur dioxide.Ministerio de Asuntos Económicos y Transformación Digital (AGL2017-87373-C3-2-R

Concurso creativo sobre derechos humanos en conmemoración del XXV aniversario de la Facultad de Ciencias Sociales

Memoria ID-0159. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2016-2017

BBB opening with focused ultrasound in nonhuman primates and Parkinson’s disease patients: Targeted AAV vector delivery and PET imaging

血液脳関門開放術による遺伝子治療法の開発 --身体を傷つけない脳疾患の治療を目指して--. 京都大学プレスリリース. 2023-04-20.Intracerebral vector delivery in nonhuman primates has been a major challenge. We report successful blood-brain barrier opening and focal delivery of adeno-associated virus serotype 9 vectors into brain regions involved in Parkinson’s disease using low-intensity focus ultrasound in adult macaque monkeys. Openings were well tolerated with generally no associated abnormal magnetic resonance imaging signals. Neuronal green fluorescent protein expression was observed specifically in regions with confirmed blood-brain barrier opening. Similar blood-brain barrier openings were safely demonstrated in three patients with Parkinson’s disease. In these patients and in one monkey, blood-brain barrier opening was followed by 18F-Choline uptake in the putamen and midbrain regions based on positron emission tomography. This indicates focal and cellular binding of molecules that otherwise would not enter the brain parenchyma. The less-invasive nature of this methodology could facilitate focal viral vector delivery for gene therapy and might allow early and repeated interventions to treat neurodegenerative disorders

Dissecting the role of TP53 alterations in del(11q) chronic lymphocytic leukemia

© 2021 The Authors.[Background]: Several genetic alterations have been identified as driver events in chronic lymphocytic leukemia (CLL) pathogenesis and oncogenic evolution. Concurrent driver alterations usually coexist within the same tumoral clone, but how the cooperation of multiple genomic abnormalities contributes to disease progression remains poorly understood. Specifically, the biological and clinical consequences of concurrent high-risk alterations such as del(11q)/ATM-mutations and del(17p)/TP53-mutations have not been established.[Methods]: We integrated next-generation sequencing (NGS) and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 techniques to characterize the in vitro and in vivo effects of concurrent monoallelic or biallelic ATM and/or TP53 alterations in CLL prognosis, clonal evolution, and therapy response.[Results]: Targeted sequencing analysis of the co-occurrence of high-risk alterations in 271 CLLs revealed that biallelic inactivation of both ATM and TP53 was mutually exclusive, whereas monoallelic del(11q) and TP53 alterations significantly co-occurred in a subset of CLL patients with a highly adverse clinical outcome. We determined the biological effects of combined del(11q), ATM and/or TP53 mutations in CRISPR/Cas9-edited CLL cell lines. Our results showed that the combination of monoallelic del(11q) and TP53 mutations in CLL cells led to a clonal advantage in vitro and in in vivo clonal competition experiments, whereas CLL cells harboring biallelic ATM and TP53 loss failed to compete in in vivo xenotransplants. Furthermore, we demonstrated that CLL cell lines harboring del(11q) and TP53 mutations show only partial responses to B cell receptor signaling inhibitors, but may potentially benefit from ATR inhibition.[Conclusions]: Our work highlights that combined monoallelic del(11q) and TP53 alterations coordinately contribute to clonal advantage and shorter overall survival in CLL.Spanish Fondo de Investigaciones Sanitarias, Grant/Award Numbers: PI15/01471, PI18/01500); Fundación Memoria Don Samuel Solórzano Barruso, Grant/Award Number: RD12/0036/006

Diagnostic Accuracy of Abdominal CT for Locally Advanced Colon Tumors: Can We Really Entrust Certain Decisions to the Reliability of CT?

Many different options of neoadjuvant treatments for advanced colon cancer are emerging. An accurate preoperative staging is crucial to select the most appropriate treatment option. A retrospective study was carried out on a national series of operated patients with T4 tumors. Considering the anatomo-pathological analysis of the surgical specimen as the gold standard, a diagnostic accuracy study was carried out on the variables T and N staging and the presence of peritoneal metastases (M1c). The parameters calculated were sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios, as well as the overall accuracy. A total of 50 centers participated in the study in which 1950 patients were analyzed. The sensitivity of CT for correct staging of T4 colon tumors was 57%. Regarding N staging, the overall accuracy was 63%, with a sensitivity of 64% and a specificity of 62%; however, the positive and negative likelihood ratios were 1.7 and 0.58, respectively. For the diagnosis of peritoneal metastases, the accuracy was 94.8%, with a sensitivity of 40% and specificity of 98%; in the case of peritoneal metastases, the positive and negative likelihood ratios were 24.4 and 0.61, respectively. The diagnostic accuracy of CT in the setting of advanced colon cancer still has some shortcomings for accurate diagnosis of stage T4, correct classification of lymph nodes, and preoperative detection of peritoneal metastases

Impact of SARS-CoV-2 RNAemia and other risk factors on long-COVID: A prospective observational multicentre cohort study

As the COVID-19 pandemic has progressed, long-COVID has emerged as a major problem that poses a significant challenge for attending physicians and health care policy makers. Therefore, we read with much interest the recently published unicentre study in the Journal of Infection by Righi et al.,1 carried out on 465 adult COVID-19 patients (235 [50.5%] hospital-admitted) followed-up during nine months, concluding that those with advanced age, intensive care unit (ICU) admission, and multiple symptoms at onset were more likely to have long-term COVID-19 symptoms, with negative impact on physical and mental wellbeing. Other studies have found that female gender, age, longer hospital stay, pre-existing hypertension, cardiovascular disease, diabetes, chronic obstructive pulmonary disease, smoking, obesity, and chronic alcoholism increase the likelihood of long-COVID.2,3 It is known that SARS-CoV-2 RNAemia is a predictor of COVID-19 severity and in-hospital complications.4,5 However, to the best of our knowledge, only two studies have assessed, up to one or three months after the acute COVID-19 onset, whether SARS-CoV-2 RNAemia may have an impact on long-COVID,6,7 both finding that RNAemia at presentation might predict the persistence of symptoms. However, these studies did not provide information regarding long-COVID symptoms nor the association with SARS-CoV-2 RNAemia beyond three months, and could not differentiate between “true” long-COVID and the convalescence phase of the SARS-CoV-2 infection.A.R. has received a predoctoral research grant from the Instituto de Salud Carlos III, Spanish Ministry of Science, Innovation and Universities, (PFIS grant FI18/00183). G.A.A. reports a predoctoral research grant from the 201808-10 project, funded by La Marató de TV3. This study was supported by the Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, the Spanish Network for Research in Infectious Diseases (REIPI, RD16/0016/0001, RD16/0016/0005, RD16/0016/0009, RD16/0016/0013)-co-financed by the European Development Regional Fund, A way to achieve Europe, Operative program Intelligent Growth 2014-2020, and the Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC) [CB21/13/00009; CB21/13/00006], Madrid, Spain. J.S.C. and E.C. received grants from the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, Proyectos de Investigación sobre el SARS-CoV-2 y la enfermedad COVID-19 (COV20/00580; COV20/00370). J.S.C. is a researcher belonging to the program “Nicolás Monardes” (C-0059–2018), Servicio Andaluz de Salud, Junta de Andalucía, Spain. Samples and data from patients included in this study from the Hospital Universitario Cruces (Bizkaia, Spain) were provided by the Basque Biobank (www.biobancovasco.org) and were processed following standard operation procedures with appropriate approval of the Ethical and Scientific Committees.Peer reviewe

An Off-Target Nucleostemin RNAi Inhibits Growth in Human Glioblastoma-Derived Cancer Stem Cells

Glioblastomas (GBM) may contain a variable proportion of active cancer stem cells (CSCs) capable of self-renewal, of aggregating into CD133+ neurospheres, and to develop intracranial tumors that phenocopy the original ones. We hypothesized that nucleostemin may contribute to cancer stem cell biology as these cells share characteristics with normal stem cells. Here we report that nucleostemin is expressed in GBM-CSCs isolated from patient samples, and that its expression, conversely to what it has been described for ordinary stem cells, does not disappear when cells are differentiated. The significance of nucleostemin expression in CSCs was addressed by targeting the corresponding mRNA using lentivirally transduced short hairpin RNA (shRNA). In doing so, we found an off-target nucleostemin RNAi (shRNA22) that abolishes proliferation and induces apoptosis in GBM-CSCs. Furthermore, in the presence of shRNA22, GBM-CSCs failed to form neurospheres in vitro or grow on soft agar. When these cells are xenotransplanted into the brains of nude rats, tumor development is significantly delayed. Attempts were made to identify the primary target/s of shRNA22, suggesting a transcription factor involved in one of the MAP-kinases signaling-pathways or multiple targets. The use of this shRNA may contribute to develop new therapeutic approaches for this incurable type of brain tumor

Effectiveness of a strategy that uses educational games to implement clinical practice guidelines among Spanish residents of family and community medicine (e-EDUCAGUIA project):A clinical trial by clusters

This study was funded by the Fondo de Investigaciones Sanitarias FIS Grant Number PI11/0477 ISCIII.-REDISSEC Proyecto RD12/0001/0012 AND FEDER Funding.Background: Clinical practice guidelines (CPGs) have been developed with the aim of helping health professionals, patients, and caregivers make decisions about their health care, using the best available evidence. In many cases, incorporation of these recommendations into clinical practice also implies a need for changes in routine clinical practice. Using educational games as a strategy for implementing recommendations among health professionals has been demonstrated to be effective in some studies; however, evidence is still scarce. The primary objective of this study is to assess the effectiveness of a teaching strategy for the implementation of CPGs using educational games (e-learning EDUCAGUIA) to improve knowledge and skills related to clinical decision-making by residents in family medicine. The primary objective will be evaluated at 1 and 6months after the intervention. The secondary objectives are to identify barriers and facilitators for the use of guidelines by residents of family medicine and to describe the educational strategies used by Spanish teaching units of family and community medicine to encourage implementation of CPGs. Methods/design: We propose a multicenter clinical trial with randomized allocation by clusters of family and community medicine teaching units in Spain. The sample size will be 394 residents (197 in each group), with the teaching units as the randomization unit and the residents comprising the analysis unit. For the intervention, both groups will receive an initial 1-h session on clinical practice guideline use and the usual dissemination strategy by e-mail. The intervention group (e-learning EDUCAGUIA) strategy will consist of educational games with hypothetical clinical scenarios in a virtual environment. The primary outcome will be the score obtained by the residents on evaluation questionnaires for each clinical practice guideline. Other included variables will be the sociodemographic and training variables of the residents and the teaching unit characteristics. The statistical analysis will consist of a descriptive analysis of variables and a baseline comparison of both groups. For the primary outcome analysis, an average score comparison of hypothetical scenario questionnaires between the EDUCAGUIA intervention group and the control group will be performed at 1 and 6months post-intervention, using 95% confidence intervals. A linear multilevel regression will be used to adjust the model. Discussion: The identification of effective teaching strategies will facilitate the incorporation of available knowledge into clinical practice that could eventually improve patient outcomes. The inclusion of information technologies as teaching tools permits greater learning autonomy and allows deeper instructor participation in the monitoring and supervision of residents. The long-term impact of this strategy is unknown; however, because it is aimed at professionals undergoing training and it addresses prevalent health problems, a small effect can be of great relevance. Trial registration: ClinicalTrials.gov: NCT02210442.Publisher PDFPeer reviewe

Efficacy and safety of baricitinib in hospitalized adults with severe or critical COVID‑19 (Bari‑SolidAct): a randomised, double‑blind, placebo‑controlled phase 3 trial

Background Baricitinib has shown efcacy in hospitalized patients with COVID-19, but no placebo-controlled trials have focused specifcally on severe/critical COVID, including vaccinated participants. Methods Bari-SolidAct is a phase-3, multicentre, randomised, double-blind, placebo-controlled trial, enrolling participants from June 3, 2021 to March 7, 2022, stopped prematurely for external evidence. Patients with severe/ critical COVID-19 were randomised to Baricitinib 4 mg once daily or placebo, added to standard of care. The primary endpoint was all-cause mortality within 60 days. Participants were remotely followed to day 90 for safety and patient related outcome measures. Results Two hundred ninety-nine patients were screened, 284 randomised, and 275 received study drug or placebo and were included in the modifed intent-to-treat analyses (139 receiving baricitinib and 136 placebo). Median age was 60 (IQR 49–69) years, 77% were male and 35% had received at least one dose of SARS-CoV2 vaccine. There were 21 deaths at day 60 in each group, 15.1% in the baricitinib group and 15.4% in the placebo group (adjusted absolute diference and 95% CI −0.1% [−8·3 to 8·0]). In sensitivity analysis censoring observations after drug discontinuation or rescue therapy (tocilizumab/increased steroid dose), proportions of death were 5.8% versus 8.8% (−3.2% [−9.0 to 2.7]), respectively. There were 148 serious adverse events in 46 participants (33.1%) receiving baricitinib and 155 in 51 participants (37.5%) receiving placebo. In subgroup analyses, there was a potential interaction between vaccination status and treatment allocation on 60-day mortality. In a subsequent post hoc analysis there was a signifcant interac‑ tion between vaccination status and treatment allocation on the occurrence of serious adverse events, with more respiratory complications and severe infections in vaccinated participants treated with baricitinib. Vaccinated partici‑ pants were on average 11 years older, with more comorbidities. Conclusion This clinical trial was prematurely stopped for external evidence and therefore underpowered to con‑ clude on a potential survival beneft of baricitinib in severe/critical COVID-19. We observed a possible safety signal in vaccinated participants, who were older with more comorbidities. Although based on a post-hoc analysis, these fnd‑ ings warrant further investigation in other trials and real-world studies