Cytotoxicity of BP-3 and BP-4: Blockage of Extrusion Pumps, Oxidative Damage and Programmed Cell Death on Chlamydomonas reinhardtii

Financiado para publicación en acceso aberto: Universidade da Coruña/CISUG[Abstract] The health concern associated with the dangers related to exposure to UV radiation has led to an increase in the use of sunscreens containing UV-filters that can reach aquatic environments and possibly affect ecosystems. Benzophenone-3 (BP-3) and benzophenone-4 (BP-4) are two of the most used UV-filters. In the present work, the microalga Chlamydomonas reinhardtii was exposed to several concentrations of both chemicals. To evaluate their potential cytotoxicity on microalgal cells, different parameters were analysed including fast response biomarkers (increase in intracellular free Ca2+) as well as biomarkers related with the presence of oxidative stress (lipid peroxidation), energy metabolism (photosynthetic yield and cytoplasmic lipid accumulations), cell division (proliferation and F-actin content), programmed cell death (PCD) (caspase activation and DNA fragmentation) and possible mechanisms of resistance to xenobiotics (operation of extrusion pumps and presence of autophagic vacuoles). Results showed an increment of the percentage of cells with cytosolic free Ca2+ that could act as a secondary messenger in response to the stress. A decrease in photosynthetic yield and an increase in cytoplasmic lipid accumulations and lipid peroxidation levels were also detected. In addition, a decrease in cell proliferation was observed, linked to a decrease in the percentage of cells with F-actin. The increase observed in the microalgal population with caspase activity, together with the DNA fragmentation and the alterations in the cytoskeleton, suggested the induction of processes linked to PCD. Moreover, a blockage of extrusion pumps, which could be related to the toxicity mechanism of these compounds, and an increase in autophagic vacuoles, as an attempt to repair the damage caused by benzophenones, were detected. Overall, these biomarkers indicate that both UV-filters can be a serious threat to non-target photosynthetic microorganisms in aquatic environments, although BP-3 affected C. reinhardtii more markedly.This research has been funded by Spanish “Ministerio de Economía, Industria y Competitividad” (CTM2017- 88668-R). M. S. and M. E. were funded by a grant from “Diputación Provincial de A Coruña

Análisis preliminar a la toma de una posición en investigación evaluativa.

n.d.Fil: Anido de López, Mercedes . Facultad de Ciencias Económicas y Estadística - Universidad Nacional de Rosario - Argentin

Evaluation of Lu-177-Dotatate treatment in patients with metastatic neuroendocrine tumors and prognostic factors

BACKGROUND: (177)Lu peptide receptor radionuclide therapy (PRRT) is a recently approved therapy in Spain that has been demonstrated to be a well-tolerated therapy for positive somatostatin receptor advanced gastroenteropancreatic neuroendocrine tumors. AIM: To determine the impact of PRRT on quality of life, radiologic and metabolic response, overall survival, prognostic factors and toxicity. METHODS: Thirty-six patients treated with (177)Lu-PRRT from 2016 to 2019 were included. The most frequent location of the primary tumor was the gastrointestinal tract (52.8%), pancreas (27.8%), and nongastropancreatic neuroendocrine tumor (11.1%). The liver was the most common site of metastasis (91.7%), followed by distant nodes (50.0%), bone (27.8%), peritoneum (25.0%) and lung (11.1%). Toxicity was evaluated after the administration of each dose. Treatment efficacy was evaluated by two parameters: stable disease and disease progression in response evaluation criteria in solid tumors 1.1 criterion and prognostic factors were tested. RESULTS: From 36 patients, 55.6% were men, with a median age of 61.1 +/- 11.8 years. Regarding previous treatments, 55.6% of patients underwent surgery of the primary tumor, 100% of patients were treated with long-acting somatostatin analogues, 66.7% of patients were treated with everolimus, 27.8% of patients were treated with tyrosine kinase inhibitor, and 27.8% of patients were treated with interferon. One patient received radioembolization, three patients received chemoembolization, six patients received chemotherapy. Hematological toxicity was registered in 14 patients (G1-G2: 55.5% and G3: 3.1%). Other events presented were intestinal suboclusion in 4 cases, cholestasis in 2 cases and carcinoid crisis in 1 case. The median follow-up time was 3 years. Currently, 24 patients completed treatment. Nineteen are alive with stable disease, two have disease progression, eight have died, and nine are still receiving treatment. The median overall survival was 12.5 mo (95% confidence interval range: 9.8-15.2), being inversely proportional to toxicity in previous treatments (P < 0.02), tumor grade (P < 0.01) and the presence of bone lesions (P = 0.009) and directly proportional with matching lesion findings between Octreoscan and computed tomography pre-PRRT (P < 0.01), , primary tumor surgery (P = 0.03) and metastasis surgery (P = 0.045). In a multivariate Cox regression analysis, a high Ki67 index (P = 0.003), a mismatch in the lesion findings between Octreoscan and computed tomography pre-PRRT (P < 0.01) and a preceding toxicity in previous treatments (P < 0.05) were risk factors to overall survival. CONCLUSION: Overall survival was inversely proportional to previous toxicity, tumor grade and the presence of bone metastasis and directly proportional to matching lesion findings between Octreoscan and computed tomography pre-PRRT and primary tumor and metastasis surgery

Usefulness of bone turnover markers as predictors of mortality risk, disease progression and skeletal-related events appearance in patients with prostate cancer with bone metastases following treatment with zoledronic acid: TUGAMO study

Owing to the limited validity of clinical data on the treatment of prostate cancer (PCa) and bone metastases, biochemical markers are a promising tool for predicting survival, disease progression and skeletal-related events (SREs) in these patients. The aim of this study was to evaluate the predictive capacity of biochemical markers of bone turnover for mortality risk, disease progression and SREs in patients with PCa and bone metastases undergoing treatment with zoledronic acid (ZA). Methods: This was an observational, prospective and multicenter study in which ninety-eight patients were included. Patients were treated with ZA (4mg every 4 weeks for 18 months). Data were collected at baseline and 3, 6, 9, 12, 15 and 18 months after the beginning of treatment. Serum levels of bone alkaline phosphtase (BALP), aminoterminal propeptide of procollagen type I (P1NP) and beta-isomer of carboxiterminal telopeptide of collagen I (b-CTX) were analysed at all points in the study. Data on disease progression, SREs development and survival were recorded. Results: Cox regression models with clinical data and bone markers showed that the levels of the three markers studied were predictive of survival time, with b-CTX being especially powerful, in which a lack of normalisation in visit 1 (3 months after the beginning of treatment) showed a 6.3-times more risk for death than in normalised patients. Levels of these markers were also predictive for SREs, although in this case BALP and P1NP proved to be better predictors. We did not find any relationship between bone markers and disease progression. Conclusion: In patients with PCa and bone metastases treated with ZA, b-CTX and P1NP can be considered suitable predictors for mortality risk, while BALP and P1NP are appropriate for SREs. The levels of these biomarkers 3 months after the beginning of treatment are especially importantThis study was supported by Novartis Oncology Spai

An algorithm based on discrete response regression models suitable to correct the bias of non-response in surveys with several capture tries

The use of survey plans, which contemplate several tries or call-backs when endeavouring to capture individual data, may supply unarguable information in certain sampling situations with non-ignorable non-response. This paper presents an algorithm whose final aim is the estimation of the individual non-response probabilities from a general perspective of discrete response regression models, which includes the well known probit and logit models. It will be assumed that the respondents supply all the variables of interest when they are captured. Nevertheless, the call-backs continue. even after previous captures, for a small number of tries, r, which has been fixed beforehand only for estimating purposes. The different retries or call-backs are supposed to be carried out with different capture intensities. As mentioned above. the response probabilities, which may vary from one individual to another, are sought by discrete response regression models, whose parameters are estimated from conditioned likelihoods evaluated on the respondents only. The algorithm, quick and easy to implement, may be used even when the capture indicator matrix has been partially recorded. Finally, the practical performance of the proposed procedure is tested and evaluated from empirical simulations whose results are undoubtedly encouraging

Analysis of variance with general errors and grouped and non-grouped data: Some iterative algorithms

In this paper we consider some iterative estimation algorithms, which are valid to analyse the variance of data, which may be either non-grouped or grouped with different classification intervals. This situation appears, for instance, when data is collected from different sources and the grouping intervals differ from one source to another. The analysis of variance is carried out by means of general linear models, whose error terms may be general. An initial procedure in the line of the EM, although it does not necessarily agree with it, opens the paper and gives rise to a simplified version where we avoid the double iteration, which implicitly appears in the EM and, also, in the initial procedure mentioned above. The asymptotic stochastic properties of the resulting estimates have been investigated in depth and used to test ANOVA hypothesis.62F10 62F15 Iterative estimation Stochastic approximation ANOVA with grouped or censored data Conditional imputation techniques Consistency Asymptotic distributions

Revista de estilos de aprendizaje

Resumen basado en el de la publicaciónSe sintetiza un proceso de producción colaborativa de material didáctico realizado por docentes universitarios. Se focalizan y detallan los criterios para la estandarización de un cuestionario evaluativo de los mismos. En referencia al problema de transposición didáctica del saber, que se realiza vía los materiales didácticos, se responde a las siguientes cuestiones: ¿cómo presentar los temas para despertar un mayor interés?, ¿qué problemas y actividades seleccionar que contemplen los distintos Estilos de Aprendizaje de los alumnos?, ¿qué criterios tener en cuenta para evaluar los materiales didácticos?, ¿se cuenta con instrumentos de evaluación fiables y válidos en el tema?, ¿cómo se construyen?, y ¿qué variables utilizar? Se encuentra una correlación entre la evaluación del material didáctico realizada por los alumnos, y sus respectivos Estilos de Aprendizaje.MadridES

Analysis of variance with general errors and grouped and non-grouped data: Some iterative algorithms

In this paper we consider some iterative estimation algorithms, which are valid to analyse the variance of data, which may be either non-grouped or grouped with different classification intervals. This situation appears, for instance, when data is collected from different sources and the grouping intervals differ from one source to another. The analysis of variance is carried out by means of general linear models, whose error terms may be general. An initial procedure in the line of the EM, although it does not necessarily agree with it, opens the paper and gives rise to a simplified version where we avoid the double iteration, which implicitly appears in the EM and, also, in the initial procedure mentioned above. The asymptotic stochastic properties of the resulting estimates have been investigated in depth and used to test ANOVA hypothesi