Las aguas de la Acequia Alta o de Mecina (Cogollos de Guadix). Los pleitos desde los siglos XII al XVIII. Algunas notas para su estudio

Los numerosos pleitos que tuvieron lugar desde el siglo XII al XVIII por las aguas de la Acequia Alta de Cogollos, entre las alquerías de Jerez y Cogollos, nos demuestran cómo se mantuvieron los derechos y costumbres que existían desde tiempos inmemoriales posiblemente desde época romana, como demuestra la abundante Toponimia latina de esta comarca. La sustitución de la alquería de Mecina, destruida, por Jerez hizo que Cogollos mantuviera el derecho sobre aquellas aguas. Los vecinos demostraron que ellos y sus antecesores abrieron la acequia, la cuidaban y limpiaban desde antes que se fundase Jerez en el siglo XII, segun afirmaciones de los testigos. La lucha por el agua fue una de las constantes desde antes de la formación del Reino Nazarí, pero se incrementó en este período y sobre todo con la llegada de los cristianos y, muy especialmente, tras la salida de la población morisca.The great amount of litigations from the XIIth to the XVIIIth century related to the water of the "Acequia Alta de Cogollos" between the villages of Jerez and Cogollos show the maintenance of ancient customs and rights, probably from the roman period, as the Latin Toponimy of that area shows. The replacement of the village of Mecina by Jerez meant the preeminence of Cogollos on the water of that canal. The neighbours of this village proved that they and their ancestors opened the canal and cleaned it before the foundation of Jerez in the XIIth century. The fights for the water were constant even before the birth of the Nasrid Kingdom of Granada, but they increased from the XIIIth century and, above all, after the Christian conquest and the Moorish expulsion

Granada Romana y Visigoda: estado de la cuestión arqueológica y bibliográfica

Cuando se realiza un atento repaso a la historia de la ciudad de Granada en el Bajo Imperio Romano y en los comienzos de la Edad Media se ponen de manifiesto lo limitados que son los conocimientos que se tienen sobre las grandes cuestiones que le afectan, pero también sobre los aspectos de detalle de la vida cotidiana de la ciudad en esa época. El gran número de publicaciones sobre estos temas no logra ocultar el poco interés que ha despertado, entre los investigadores unas veces y entre las autoridades otras, de modo que el balance final es bastante pobre: aunque abundan los trabajos que dan noticia de los diferentes descubrimientos arqueológicos, apenas hay estudios de detalle de aspectos parciales de la investigación y, en definitiva, los trabajos sobre este tema apenas han avanzado desde el siglo XIX, constituyendo las más de las veces más motivo de curiosidad que de estudio.Quand on réalise une attentive révision de l’histoire de Grenade à la fin de l’Empire Roman et au commencement du Moyen Age on voit les limitées connaisances des grandes problèmes que lui affectent, mais aussi sur les aspects de détail de la vie quotidienne de la cité en cette époque. Le grand nombre de publications ne peut cacher le peu intérêt que cet thème a éveillé chez les chercheurs quelques fois et chez les autorités quelques autres, de tel façon que le bilan final est assez pauvre: malgré l’abondance des oeuvres sur les différentes découvertes archéologiques, il n’y a presque des études détaillés sur aspects partiels de la recherche et, bref, les travails sur cet thème presque n’ont pas avancé depuis le XIXéme siècle, et elles sont plus motif de curiosité que d’étude.When one review watchfully the history of Granada in the late Roman Empire and in the early Middle Ages we realize the limited knowledge we have on the main questions related to this town, and also on details of its everyday life in this age. Large amount of publications can not hide little interest of researchers and authorities on this topic, so the final result is rather poor: in spite of the works on different archeological discoveries, it does not almost exist detailed studies on partial aspects of the research and, in short, works on this topic have nearly not progress from XIXth century, and they are more curious than interesting

Estudios sobre la ciudad de Baza en época musulmana y morisca: los efectos del terremoto de 1531 en la estructura urbana

El estudio de las catástrofes naturales que afectan a ciudades y pueblos trata de conocer un poco mejor el funcionamiento de estos centros en momentos tan dramáticos. El terremoto que sufrió Baza en 1531 nos sirve de marco para profundizar en la estructura urbana de esta ciudad y los efectos que produjo en ella, desde las medidas de protección y de emergencia hasta los tipos de edificios afectados, además de tener en cuenta el tipo de documentación que contienen estos datos. En el caso de los terremotos, además, se puede acceder a una: información que, convenientemente tratada, puede ser utilizada por otros científicos para determinar factores de riesgo sísmico y las posibilidades de recurrencia de terremotos destructores.The study of natural disasters that affected towns and villages tries to know a little better the working of these centres in moments so drama tic. The 1531 Baza earthquake is the background of an study on the urban structure of this town and the effects the earthquake caused, from protection and emergency measures tothe types of buildings affected; we also consider the different documents that contain these infonnations. Earthquakes also can provide us sorne data that others scientists can treat and use in order to determine seismic risk factors and the recurrence of destructive earthquakes

Las aguas de la Acequia Alta o de Mecina (Cogollos de Guadix). Los pleitos desde los siglos XII al XVIII. Algunas notas para su estudio

The great amount of litigations from the XIIth to the XVIIIth century related to the water of the "Acequia Alta de Cogollos" between the villages of Jerez and Cogollos show the maintenance of ancient customs and rights, probably from the roman period, as the Latin Toponimy of that area shows.The replacement of the village of Mecina by Jerez meant the preeminence of Cogollos on the water of that canal. The neighbours of this village proved that they and their ancestors opened the canal and cleaned it before the foundation of Jerez in the Xllth century. The lights for the water were constant even before the birth of the Nasrid Kingdom of Granada, but they increased from the XIIlth century and, above all, after the Christian conques! and the Moorish expulsion.Los numerosos pleitos que tuvieron lugar desde el siglo XII al XVIII por las aguas de la Acequia Alta de Cogollos, entre las alquerías de Jerez y Cogollos, nos demuestran cómo se mantuvieron los derechos y costumbres que existían desde tiempos inmemoriales, posiblemente desde época romana, como demuestra la abundante Toponimia latina de esta comarca.La sustitución de la alquería de Mecina, destruida, por Jerez hizo que Cogollos mantuviera el derecho sobre aquellas aguas. Los vecinos demostraron que ellos y sus antecesores abrieron la acequia, la cuidaban y limpiaban desde antes que se fundase Jerez en el siglo XII, segun afirmaciones de los testigos. La lucha por el agua fue una de las constantes desde antes de la formación del Reino Nazarí, pero se incrementó en este período y sobre todo con la llegada de los cristianos y, muy especialmente, tras la salida de la población morisca

Medina Elvira. 4. Anillos romanos y visigodos de la necrópolis de Marugán y alrededores

Los numerosos hallazgos de materiales arqueológicos de Sierra Elvira han proporcionado objetos muy estimados para la Cultura material y el conocimiento de la vida de aquellas poblaciones, entre los que destacan por su interés los anillos.En el presente trabajo estudiamos los ejemplares que han llegado hasta nosotros en distintas épocas y circunstancias. Los anillos de Sierra Elvira de época romana y visigoda se han relacionado con otros ejemplares de laPenínsula y de otras tierras conquistadas por los pueblos germánicos. Se incide en la particularidad de éstas piezas, coincidencia y discrepancias, arte, epigrafía, materiales, técnicas, uso, etc.The discovery of numerous archeological relics from Sierra Elvira has provided interesting evidence as to the culture and way of life of the people who inhabited the area. Especially interesting are the rings which have been found.In this paper we examine samples of rings from different epochs and social contexts. The Roman and Yisigoth rings from Sierra Elvira are compared to other examples from the lberian Península and other lands conqueredby the Germanic peoples. The si milarities and differences evident in these pieces are analysed, together with their art, epigraphy, the materials and techniques employed, etc

Vitamin D Endocrine System and COVID-19. Treatment with Calcifediol

The COVID-19 pandemic is the greatest challenge facing modern medicine and public health systems. The viral evolution of SARS-CoV-2, with the emergence of new variants with in-creased infectious potential, is a cause for concern. In addition, vaccination coverage remains in-sufficient worldwide. Therefore, there is a need to develop new therapeutic options, and/or to optimize the repositioning of drugs approved for other indications for COVID-19. This may include the use of calcifediol, the prohormone of the vitamin D endocrine system (VDES) as it may have potential useful effects for the treatment of COVID-19. We review the aspects associating COVID-19 with VDES and the potential use of calcifediol in COVID-19. VDES/VDR stimulation may enhance innate antiviral effector mechanisms, facilitating the induction of antimicrobial peptides/autophagy, with a critical modulatory role in the subsequent host reactive hyperinflammatory phase during COVID-19: By decreasing the cytokine/chemokine storm, regulating the renin–angiotensin–bradykinin system (RAAS), modulating neutrophil activity and maintaining the integrity of the pulmonary epithelial barrier, stimulating epithelial repair, and directly and indirectly decreasing the increased coagulability and prothrombotic tendency associated with severe COVID-19 and its complications. Available evidence suggests that VDES/VDR stimulation, while maintaining optimal serum 25OHD status, in patients with SARS-CoV-2 infection may significantly reduce the risk of acute respiratory distress syndrome (ARDS) and severe COVID-19, with possible beneficial effects on the need for mechanical ventilation and/or intensive care unit (ICU) admission, as well as deaths in the course of the disease. The pharmacokinetic and functional characteristics of calcifediol give it superiority in rapidly optimizing 25OHD levels in COVID-19. A pilot study and several observational intervention studies using high doses of calcifediol (0.532 mg on day 1 and 0.266 mg on days 3, 7, 14, 21, and 28) dramatically decreased the need for ICU admission and the mortality rate. We, therefore, propose to use calcifediol at the doses described for the rapid correction of 25OHD deficiency in all patients in the early stages of COVID-19, in association, if necessary, with the new oral antiviral agents

Flavonoid Phloretin Inhibits Adipogenesis and Increases OPG Expression in Adipocytes Derived from Human Bone-Marrow Mesenchymal Stromal-Cells

Phloretin (a flavonoid abundant in apple), has antioxidant, anti-inflammatory, and glucose-transporter inhibitory properties. Thus, it has interesting pharmacological and nutraceutical potential. Bone-marrow mesenchymal stem cells (MSC) have high differentiation capacity, being essential for maintaining homeostasis and regenerative capacity in the organism. Yet, they preferentially differentiate into adipocytes instead of osteoblasts with aging. This has a negative impact on bone turnover, remodeling, and formation. We have evaluated the effects of phloretin on human adipogenesis, analyzing MSC induced to differentiate into adipocytes. Expression of adipogenic genes, as well as genes encoding OPG and RANKL (involved in osteoclastogenesis), protein synthesis, lipid-droplets formation, and apoptosis, were studied. Results showed that 10 and 20 µM phloretin inhibited adipogenesis. This effect was mediated by increasing beta-catenin, as well as increasing apoptosis in adipocytes, at late stages of differentiation. In addition, this chemical increased OPG gene expression and OPG/RANKL ratio in adipocytes. These results suggest that this flavonoid (including phloretin-rich foods) has interesting potential for clinical and regenerative-medicine applications. Thus, such chemicals could be used to counteract obesity and prevent bone-marrow adiposity. That is particularly useful to protect bone mass and treat diseases like osteoporosis, which is an epidemic worldwide

PAX4 preserves endoplasmic reticulum integrity preventing beta cell degeneration in a mouse model of type 1 diabetes mellitus

[Aims/hypothesis]: A strategy to enhance pancreatic islet functional beta cell mass (BCM) while restraining inflammation, through the manipulation of molecular and cellular targets, would provide a means to counteract the deteriorating glycaemic control associated with diabetes mellitus. The aims of the current study were to investigate the therapeutic potential of such a target, the islet-enriched and diabetes-linked transcription factor paired box 4 (PAX4), to restrain experimental autoimmune diabetes (EAD) in the RIP-B7.1 mouse model background and to characterise putative cellular mechanisms associated with preserved BCM. [Methods]: Two groups of RIP-B7.1 mice were genetically engineered to: (1) conditionally express either PAX4 (BPTL) or its diabetes-linked mutant variant R129W (mutBPTL) using doxycycline (DOX); and (2) constitutively express luciferase in beta cells through the use of RIP. Mice were treated or not with DOX, and EAD was induced by immunisation with a murine preproinsulin II cDNA expression plasmid. The development of hyperglycaemia was monitored for up to 4 weeks following immunisation and alterations in the BCM were assessed weekly by non-invasive in vivo bioluminescence intensity (BLI). In parallel, BCM, islet cell proliferation and apoptosis were evaluated by immunocytochemistry. Alterations in PAX4- and PAX4R129W-mediated islet gene expression were investigated by microarray profiling. PAX4 preservation of endoplasmic reticulum (ER) homeostasis was assessed using thapsigargin, electron microscopy and intracellular calcium measurements. [Results]: PAX4 overexpression blunted EAD, whereas the diabetes-linked mutant variant PAX4R129W did not convey protection. PAX4-expressing islets exhibited reduced insulitis and decreased beta cell apoptosis, correlating with diminished DNA damage and increased islet cell proliferation. Microarray profiling revealed that PAX4 but not PAX4R129W targeted expression of genes implicated in cell cycle and ER homeostasis. Consistent with the latter, islets overexpressing PAX4 were protected against thapsigargin-mediated ER-stress-related apoptosis. Luminal swelling associated with ER stress induced by thapsigargin was rescued in PAX4-overexpressing beta cells, correlating with preserved cytosolic calcium oscillations in response to glucose. In contrast, RNA interference mediated repression of PAX4-sensitised MIN6 cells to thapsigargin cell death. [Conclusions/interpretation]: The coordinated regulation of distinct cellular pathways particularly related to ER homeostasis by PAX4 not achieved by the mutant variant PAX4R129W alleviates beta cell degeneration and protects against diabetes mellitus. The raw data for the RNA microarray described herein are accessible in the Gene Expression Omnibus database under accession number GSE62846

Long-Term Treatment and Effect of Discontinuation of Calcifediol in Postmenopausal Women with Vitamin D Deficiency: A Randomized Trial

Vitamin D plays a major role in bone health and probably also in multiple extraskeletal acute and chronic diseases. Although supplementation with calcifediol, a vitamin D metabolite, has demonstrated efficacy and safety in short-term clinical trials, its effects after long-term monthly administration have been studied less extensively. This report describes the results of a 1-year, phase III-IV, double-blind, randomized, controlled, parallel, multicenter superiority clinical trial to assess the efficacy and safety of monthly calcifediol 0.266 mg versus cholecalciferol 25,000 IU (0.625 mg) in postmenopausal women with vitamin D deficiency (25(OH)D < 20 ng/mL). A total of 303 women were randomized and 298 evaluated. Patients were randomized 1:1:1 to calcifediol 0.266 mg/month for 12 months (Group A1), calcifediol 0.266 mg/month for 4 months followed by placebo for 8 months (Group A2), and cholecalciferol 25,000 IU/month (0.625 mg/month) for 12 months (Group B). By month 4, stable 25(OH)D levels were documented with both calcifediol and cholecalciferol (intention-to-treat population): 26.8 ± 8.5 ng/mL (Group A1) and 23.1 ± 5.4 ng/mL (Group B). By month 12, 25(OH)D levels were 23.9 ± 8.0 ng/mL (Group A1) and 22.4 ± 5.5 ng/mL (Group B). When calcifediol treatment was withdrawn in Group A2, 25(OH)D levels decreased to baseline levels (28.5 ± 8.7 ng/mL at month 4 versus 14.4 ± 6.0 ng/mL at month 12). No relevant treatment-related safety issues were reported in any of the groups. The results confirm that long-term treatment with monthly calcifediol in vitamin D-deficient patients is effective and safe. The withdrawal of treatment leads to a pronounced decrease of 25(OH)D levels. Calcifediol presented a faster onset of action compared to monthly cholecalciferol. Long-term treatment produces stable and sustained 25(OH)D concentrations with no associated safety concerns.This study was funded by Faes Farma, S.A. and Bruno Farmaceutici S.p.A. The authors wish to thank the study participants, research staff, the secondary investigators of the Osteoferol study group, the home nursing staff (Emibet), and Faes Farma clinical research team: Paula Arranz Gutiérrez, Lorena Elgezabal González, Mariana Frau Usoz, and Iñigo Saez Riesco. Medical writing support was provided by Francisco López de Saro (Trialance SCCL), funded by Faes Farma, S.A

Production yields at the distal fall-off of the β+ emitters 11C and 13N for in-vivo range verification in proton therapy

In proton therapy, Positron Emission Tomography (PET) range verification relies on the comparison of the measured and estimated activity distributions from β+ emitters produced by the proton beam in the patient. The accuracy of the estimated activity distributions is basically that of the underlying reaction cross section data. In this context, we have developed a new method for measuring β+ production yields combining the multi-foil technique with a clinical PET scanner, resulting in energy differential cross sections from a single irradiation. The method has been applied to the production of (t1/2 = 20.36 min) and (t1/2 = 9.97 min), the main candidates for off-line PET range verification, in carbon, nitrogen and oxygen, the main elements of the human body. The energy range studied with the 18 MeV CNA cyclotron corresponds to the distal fall-off of the activity curve, i.e. near the Bragg peak.Ministerio de Economía y Competitividad RYC-2014-15271, FPA2016- 77689-C2-1-R, RTI2018-098117-B-C2