Aportaciones hidrogeológicas al estudio arqueológico de los orígenes de la Edad del Bronce de La Mancha: la cueva monumentalizada de Castillejo del Bonete (Terrinches, Ciudad Real-España)

Estudios recientes indican que las motillas, asentamientos de la Edad del Bronce de La Mancha, pudieron ser las más antiguas captaciones de agua subterránea en la Península Ibérica. Pero ¿por qué no existen motivas en el Campo de Montiel, territorio ubicado tradicionalmente en esta área cultural? En Castillejo del Bonete, sitio arqueológico situado en esa comarca, existe una cueva que fue utilizada y sellada durante la Prehistoria Reciente. Se presenta ahora la primera investigación paleohidrogeológica interdisciplinar en La Mancha, que ha analizado manantiales y niveles de agua subterránea del acuífero de Campo de Montiel, así como el interior de la sima de Castillejo del Bonete. Las conclusiones avanzan una relación entre el sustrato hidrogeomorfológico y la distribución espacial de las motillas. Además permiten descartar que la sima de Castillejo del Bonete fuera utilizada como mina o como acceso al acuífero, dos de las hipótesis de trabajo planteadas. De ese modo cobra fuerza que Castillejo del Bonete fuera un excepcional monumento funerario y simbólico durante el Calcolítico y la Edad del Bronce, perteneciente a una nueva clase de asentamientos desconocidos hasta ahora en el grupo cultural de la Edad del Bronce de La Mancha

Ventricular Tachycardia and Early Fibrillation in Patients With Brugada Syndrome and Ischemic Cardiomyopathy Show Predictable Frequency-Phase Properties on the Precordial ECG Consistent With the Respective Arrhythmogenic Substrate

[EN] Background¿ Ventricular fibrillation (VF) has been proposed to be maintained by localized high-frequency sources. We tested whether spectral-phase analysis of the precordial ECG enabled identification of periodic activation patterns generated by such sources. Methods and Results¿Precordial ECGs were recorded from 15 ischemic cardiomyopathy and 15 Brugada syndrome (type 1 ECG) patients during induced VF and analyzed in the frequency-phase domain. Despite temporal variability, induced VF episodes lasting 19.6±7.9 s displayed distinctly high power at a common frequency (shared frequency, 5.7±1.1 Hz) in all leads about half of the time. In patients with Brugada syndrome, phase analysis of shared frequency showed a V1¿V6 sequence as would be expected from patients displaying a type 1 ECG pattern (P<0.001). Hilbert-based phases confirmed that the most stable sequence over the whole VF duration was V1¿V6. Analysis of shared frequency in ischemic cardiomyopathy patients with anteroseptal (n=4), apical (n=3), and inferolateral (n=4) myocardial infarction displayed a sequence starting at V1¿V2, V3¿V4, and V5¿V6, respectively, consistent with an activation origin at the scar location (P=0.005). Sequences correlated with the Hilbert-based phase analysis (P<0.001). Posterior infarction (n=4) displayed no specific sequence. On paired comparison, phase sequences during monomorphic ventricular tachycardia correlated moderately with VF (P<0.001). Moreover, there was a dominant frequency gradient from precordial leads facing the scar region to the contralateral leads (5.8±0.8 versus 5.4±1.1 Hz; P=0.004). Conclusions¿Noninvasive analysis of ventricular tachycardia and early VF in patients with Brugada syndrome and ischemic cardiomyopathy shows a predictable sequence in the frequency-phase domain, consistent with anatomic location of the arrhythmogenic substrate.This study was supported by the National Heart, Lung and Blood Institute (P01-HL039707, P01-HL087226 R01-HL118304); the Spanish Society of Cardiology, Arrhythmia and Electrophysiology Section; the Leducq Foundation, Paris, France; Centro Nacional de Investigaciones Cientificas, Madrid, Spain; Generalitat Valenciana, Valencia, Spain (PROMETEO/2012/030); VI Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica from the Ministerio de Economia y Competitividad of Spain (TIN2012-37546-C03-01); and the European Commission (European Regional Development Funds [ERDF]-FEDER)Calvo, D.; Atienza, F.; Saiz Rodríguez, FJ.; Martinez, L.; Ávila, P.; Rubín, J.; Herreros, B.... (2015). Ventricular Tachycardia and Early Fibrillation in Patients With Brugada Syndrome and Ischemic Cardiomyopathy Show Predictable Frequency-Phase Properties on the Precordial ECG Consistent With the Respective Arrhythmogenic Substrate. Circulation Arrhythmia and Electrophysiology. 8(5):1133-1143. https://doi.org/10.1161/CIRCEP.114.002717S1133114385Gray, R. A., Jalife, J., Panfilov, A. V., Baxter, W. T., Cabo, C., Davidenko, J. M., … Winfree, A. T. (1995). Mechanisms of Cardiac Fibrillation. Science, 270(5239), 1222-1222. doi:10.1126/science.270.5239.1222Keldermann, R. H., ten Tusscher, K. H. W. J., Nash, M. P., Bradley, C. P., Hren, R., Taggart, P., & Panfilov, A. V. (2009). A computational study of mother rotor VF in the human ventricles. American Journal of Physiology-Heart and Circulatory Physiology, 296(2), H370-H379. doi:10.1152/ajpheart.00952.2008Ten Tusscher, K. H. W. J., Mourad, A., Nash, M. P., Clayton, R. H., Bradley, C. P., Paterson, D. J., … Taggart, P. (2009). Organization of ventricular fibrillation in the human heart: experiments and models. Experimental Physiology, 94(5), 553-562. doi:10.1113/expphysiol.2008.044065CLAYTON, R. H., MURRAY, A., & CAMPBELL, R. W. F. (1995). Evidence for Electrical Organization During Ventricular Fibrillation in the Human Heart. Journal of Cardiovascular Electrophysiology, 6(8), 616-624. doi:10.1111/j.1540-8167.1995.tb00438.xCLAYTON, R. H., MURRAY, A., & CAMPBHLL, R. W. F. (1995). Analysis of the Body Surface ECG Measured in Independent Leads During Ventricular Fibrillation in Humans. Pacing and Clinical Electrophysiology, 18(10), 1876-1881. doi:10.1111/j.1540-8159.1995.tb03835.xArenal, A., del Castillo, S., Gonzalez-Torrecilla, E., Atienza, F., Ortiz, M., Jimenez, J., … Almendral, J. (2004). Tachycardia-Related Channel in the Scar Tissue in Patients With Sustained Monomorphic Ventricular Tachycardias. Circulation, 110(17), 2568-2574. doi:10.1161/01.cir.0000145544.35565.47Warren, M., Guha, P. 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Paleoecología y cultura material en el complejo tumular prehistórico de Castillejo del Bonete (Terrinches, Ciudad Real)

Castillejo del Bonete es un complejo tumular situado en el borde meridional de la Meseta Ibérica, ocupado en fechas calcolíticas y de la Edad del Bronce, vinculado a la Cultura de las Motillas. Materiales arqueológicos muy diversos han sido recuperados asociados a las arquitecturas del lugar (túmulos, corredores, potentes muros, etc.). Se presenta un avance de la investigación paleoecológica sobre las colecciones de carbón, polen y microvertebrados. Además se presentan cuentas de piedra y madera, colgantes de concha, material lítico, la colección cerámica, nuevas metalografías e industria metálica y botones de marfil. El conjunto de estas evidencias arqueológicas pone de manifiesto la celebración ritual de banquetes y ofrendas durante la Prehistoria Reciente en una cueva monumentalizada mediante túmulos en el interior de la Península Ibérica

Adherence to recommendations by infectious disease consultants and its influence on outcomes of intravenous antibiotic-treated hospitalized patients

BACKGROUND: Consultation to infectious diseases specialists (ID), although not always performed by treating physicians, is part of hospital's daily practice. This study analyses adherence by treating physicians to written ID recommendations (inserted in clinical records) and its effect on outcome in hospitalized antibiotic-treated patients in a tertiary hospital in Spain. METHODS: A prospective, randomized, one-year study was performed. Patients receiving intravenous antimicrobial therapy prescribed by treating physicians for 3 days were identified and randomised to intervention (insertion of written ID recommendations in clinical records) or non-intervention. Appropriateness of empirical treatments (by treating physicians) was classified as adequate, inadequate or unnecessary. In the intervention group, adherence to recommendations was classified as complete, partial or non-adherence. RESULTS: A total of 1173 patients were included, 602 in the non-intervention and 571 in the intervention group [199 (34.9%) showing complete adherence, 141 (24.7%) partial adherence and 231 (40.5%) non-adherence to recommendations]. In the multivariate analysis for adherence (R2 Cox=0.065, p=0.009), non-adherence was associated with prolonged antibiotic prophylaxis (p=0.004; OR=0.37, 95%CI=0.19-0.72). In the multivariate analysis for clinical failure (R2 Cox=0.126, p<0.001), Charlson index (p<0.001; OR=1.19, 95%CI=1.10-1.28), malnutrition (p=0.006; OR=2.00, 95%CI=1.22-3.26), nosocomial infection (p<0.001; OR=4.12, 95%CI=2.27-7.48) and length of hospitalization (p<0.001; OR=1.01, 95%CI=1.01-1.02) were positively associated with failure, while complete adherence (p=0.001; OR=0.35, 95%CI=0.19-0.64) and adequate initial treatment (p=0.010; OR=0.39, 95%CI=0.19-0.80) were negatively associated. CONCLUSIONS: Adherence to ID recommendations by treating physicians was associated with favorable outcome, in turn associated with shortened length of hospitalization. This may have important health-economic benefits and stimulates further investigation. TRIAL REGISTRATION: Current Controlled Trials ISRCTN83234896. http://www.controlled-trials.com/isrctn/sample_documentation.asp

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field