AIP and MEN1 mutations and AIP immunohistochemistry in pituitary adenomas in a tertiary referral center.

Background: Pituitary adenomas have a high disease burden due to tumor growth/ invasion and disordered hormonal secretion. Germline mutations in genes such as MEN1 and AIP are associated with early onset of aggressive pituitary adenomas that can be resistant to medical therapy. Aims: We performed a retrospective screening study using published risk criteria to assess the frequency of AIP and MEN1 mutations in pituitary adenoma patients in a tertiary referral center. Methods: Pituitary adenoma patients with pediatric/adolescent onset, macroadenomas occurring ≤30 years of age, familial isolated pituitary adenoma (FIPA) kindreds and acromegaly or prolactinoma cases that were uncontrolled by medical therapy were studied genetically. We also assessed whether immunohistochemical staining for AIP (AIP-IHC) in somatotropinomas was associated with somatostatin analogs (SSA) response. Results: Fifty-five patients met the study criteria and underwent genetic screening for AIP/MEN1 mutations. No mutations were identified and large deletions/duplications were ruled out using MLPA. In a cohort of sporadic somatotropinomas, low AIP-IHC tumors were significantly larger (P = 0.002) and were more frequently sparsely granulated (P = 0.046) than high AIP-IHC tumors. No significant relationship between AIP-IHC and SSA responses was seen. Conclusions: Germline mutations in AIP/MEN1 in pituitary adenoma patients are rare and the use of general risk criteria did not identify cases in a large tertiary-referral setting. In acromegaly, low AIP-IHC was related to larger tumor size and more frequent sparsely granulated subtype but no relationship with SSA responsiveness was seen. The genetics of pituitary adenomas remains largely unexplained and AIP screening criteria could be significantly refined to focus on large, aggressive tumors in young patients

Loss of pancreas upon activated Wnt signaling is concomitant with emergence of gastrointestinal identity

Organ formation is achieved through the complex interplay between signaling pathways and transcriptional cascades. The canonical Wnt signaling pathway plays multiple roles during embryonic development including patterning, proliferation and differentiation in distinct tissues. Previous studies have established the importance of this pathway at multiple stages of pancreas formation as well as in postnatal organ function and homeostasis. In mice, gain-of-function experiments have demonstrated that activation of the canonical Wnt pathway results in pancreatic hypoplasia, a phenomenon whose underlying mechanisms remains to be elucidated. Here, we show that ectopic activation of epithelial canonical Wnt signaling causes aberrant induction of gastric and intestinal markers both in the pancreatic epithelium and mesenchyme, leading to the development of gut-like features. Furthermore, we provide evidence that β -catenin-induced impairment of pancreas formation depends on Hedgehog signaling. Together, our data emphasize the developmental plasticity of pancreatic progenitors and further underscore the key role of precise regulation of signaling pathways to maintain appropriate organ boundaries

True power consumption labeling and mapping of the health system of the Castilla y León region in Spain by clustering techniques

[EN] The latest revisions in April 2018 of the 2010/31/UE and 2012/27/UE Directives on Energy Efficiency and Energy Savings respectively, point out the need of the development of smart energy indexes for buildings with the aim to (i) supervise the energy consumption on the building sector -that currently represents up to one third of the total final energy consumption- and (ii) lead the appropriate actions to transform the current buildings stock to nearly Zero Energy Buildings and Positive Energy Buildings. From public managed buildings, the Health System is the first energy consumer with great difference with other government administration sectors, such as Education or General Administration. Moreover, the energy bill has great impact on the sustainability of the public health care system. However, very few real data were available to characterize the energy demand on public buildings, which are usually the most intensive energy consumers, and efficiency indexes were usually obtained from simulation results. Nevertheless, thanks to the deployment of Smart Metering systems in the last years, it is possible to access to the true energy demand profiles of hundreds of these buildings. In this paper, with three years historical monthly electrical energy consumption data from the health system of the region of Castilla y León in Spain -including hospitals, outpatient facilities, clinics and other medical institutions- and the application of data mining techniques, an end-use electrical energy analysis was conducted to cluster the building housing according to the energy consumption into several energy use intensity clusters and, then, an average value and a Reference Building Energy Index for each cluster is proposed. Thus, a true energy labeling of these buildings based on their distance to the Reference Building Energy Index is done and presented in georeferenced maps.S

Data Envelopment Analysis Applications on Primary Health Care Using Exogenous Variables and Health Outcomes

[EN] A data envelopment analysis was used to evaluate the efficiency of 18 primary healthcare centres in a health district of the Valencian Community, Spain. Factor analysis was used as a first step in order to identify the most explanatory variables to be incorporated in the models. Included as variable inputs were the ratios of general practitioners, nurses, and costs; as output variables, those included were consultations, emergencies, avoidable hospitalisations, and prescription efficiency; as exogenous variables, those included were the percentage of population over 65 and a multimorbidity index. Confidence intervals were calculated using bootstrapping to correct possible biases. Efficient organisations within the set were identified, although the results depend on the models used and the introduction of exogenous variables. Pharmaceutical expenditure showed the greatest slack and room for improvement in its management. Data envelopment analysis allows an evaluation of efficiency that is focussed on achieving better results and a proper distribution and use of healthcare resources, although it needs the desired goals of the healthcare managers to be clearly identified, as the perspective of the analysis influences the results, as does including variables that measure the achievements and outcomes of the healthcare services.This research was funded by "Conselleria de Hacienda y Modelo Economico de la Comunitat Valenciana (Spain)", file number HIECPU/2019/1, in the context of the Project "Desarrollo de un Modelo para el analisis de la eficiencia en las Unidades Basicas de Salud de atencion primaria en un departamento de Salud perteneciente al mapa sanitario de la Comunidad Valenciana".González-De Julián, S.; Barrachina Martínez, I.; Vivas-Consuelo, D.; Bonet-Pla, Á.; Usó-Talamantes, R. (2021). Data Envelopment Analysis Applications on Primary Health Care Using Exogenous Variables and Health Outcomes. Sustainability. 13(3):1-18. https://doi.org/10.3390/su1303133711813

Wind energy planning for a sustainable transition to a decarbonized generation scenario based on the opportunity cost of the wind energy: Spanish Iberian Peninsula as case study

[EN] Most countries in Europe are going under a significant transformation process from carbonized power energy sources to renewable and sustainable ones to feed their increasing demands. European Union targets on its energy roadmap states that by 2030, a reduction of 40% of CO2 emissions regarding the 1990 levels must be done and full transition must be completed by 2050. Thus, EU member countries, such Spain, are carrying out lots of investments to transform their power generation structure by promoting the installation of renewable energy power plants, with a significant visual and environmental impact. In the case of Spain, it is planned that, by 2030, 27% of final power consumption must be renewable, with approximately 31 GW of installed wind energy (8 GW must be installed in the next 10 years). Wind energy is supposed to be one of the generation leaders in this transformation context due to its high performance, high availability and fast decreasing costs. Nevertheless, wind farms have been installed on-shore with great success since the decade of the 90s covering the locations with the best wind resource. Thus, many of the installed wind turbines have overcome the half part of their expected lifespan and their payback periods, but the learning curve of the wind energy technology has improved exponentially since then. This paper is focused on the true valorization of an existing wind farm and the efficacy of the exploitation of the site’s wind resource. A novel repowering decision support model based on the opportunity cost analysis between repowering the current wind farm with the latter technologies and full depletion of the wind farm is proposed and applied to the Spanish Iberian Peninsula case study. Results show that the repowering option is significantly attractive in most cases and its proper application could have, not only a positive environmental effect, but also an economic impact on the sustainability of this source of energy.S

Electrical Consumption Profile Clusterization: Spanish Castilla y León Regional Health Services Building Stock as a Case Study

[EN] Health Services building stock is usually the top energy consumer in the Administrative sector, by a considerable margin. Therefore, energy consumption supervision, prediction, and improvement should be carried out for this group in a preferential manner. Most prior studies in this field have characterized the energy consumption of buildings based on complex simulations, which tend to be limited by modelisation restrictions and assumptions. In this paper, an improved method for the clusterization of buildings based on their electrical energy consumption is proposed and, then, reference profiles are determined by examining the variation of energy consumption over the typical yearly consumption period. The temporary variation has been analyzed by evaluating the temporary evolution of the area consumption index through data mining and statistical clusterization techniques. The proposed methodology has been applied to building stock of the Health Services in the Castilla y León region in Spain, based on three years of historical monthly electrical energy consumption data for over 250 buildings. This building stock consists of hospitals, health centers (with and without emergency services) and a miscellaneous set of administrative and residential buildings. Results reveal five distinct electrical consumption profiles that have been associated with five reference buildings, permitting significant improvement in the demand estimation as compared to merely using the classical energy consumption indicators.SIEREN (Ente Regional de la Energía de Castilla y León)Laboratorio de Inspección Técnica de Minas (LITEM

Acció dels andrògens en el testicle: un paper per a la meiosi

La funció que duen a terme els andrògens en l'espermatogènesi és, encara en certa mesura, enigmàtica: mentre que llur implicació és absolutament vital en la iniciació i en el manteniment del procés espermatogènic normal, la seva funció específica encara no està definida de manera precisa. Els andrògens, com les altres hormones esteroïdals, actuen a través del seu corresponent receptor anomenat receptor d'andrògens (AR). Fins avui, no hi ha gaire evidència que recolzi l'existència de diverses isoformes de l'AR com en el cas del sistema estrògensreceptor d'estrògens. Per tant, la pregunta de com els andrògens duen a terme la seva acció en l'espermatogènesi s'ha d'abordar definint dos processos: en primer lloc, s'han d'identifi- car amb total certesa els tipus cell. ulars testiculars capaços de respondre directament a l'estimulació androgènica. De manera específica, la qüestió per resoldre és quins són els tipus cellulars que expressen l'AR en el testicle. En segon lloc, sabent també que el complex del lligand unit a l'AR actua com a factor de transcripció, caldrà determinar quins són els gens que estaran activats o reprimits en les cèll. ules que tenen AR en resposta a l'estimulació androgènica. Fins que aquestes dues preguntes no estiguin contestades amb tota certesa, el mecanisme pel qual els andrògens regulen l'espermatogènesi serà, en el millor dels casos, especulatiu. En aquesta revisió presentem evidència que els andrògens actuen únicament a les cèll. ules somàtiques del testicle, com són les cèll. ules de Sertoli, les de Leydig, les mioides peritubulars i les cèll. ules del múscul llis que envolten els vasos sanguinis. A més a més, també discutim la possibilitat que els andrògens siguin indispensables per a l'inici de la meiosi, encara que continua essent desconegut el mecanisme pel qual els andrògens actuen en aquest procés.The role that androgens play in spermatogenesis still remains enigmatic: whereas their involvement is absolutely vital to the initiation and maintenance of the normal spermatogenic process, their specific role is yet to be defined. Androgens, like other steroid hormones, act via their corresponding receptor termed the androgen receptor (AR). To date, there is little evidence to support the notion that there are multiple forms of AR as is the case for the estrogen-estrogen receptor system. Thus, the question of how androgens manifest their action on spermatogenesis becomes one of defining two processes: First, the cell types within the testis that are capable of responding directly to androgen stimulation must be identified with absolute certainty. Specifically, this question can be stated as what cell types in the testis express AR. Second, given that the ligand-bound AR serves as a transcription factor, the question then becomes what are the genes turned on or off in AR positive cells in response to androgen stimulation? Until these two questions are unequivocally answered, the mechanism of how androgens regulate spermatogenesis will remain speculative at best. In this review we present evidence that androgens act solely at the level of the somatic cells of the testis, including Sertoli cells, Leydig cells, peritubular myoid cells and smooth muscle cells surrounding blood vessels. In addition, we discuss the likely possibility that androgens are indispensable for the onset of meiosis, albeit how they accomplish this remains a mystery

Effect of Farnesol in Trichoderma Physiology and in Fungal–Plant Interaction

[EN] Farnesol is an isoprenoid intermediate in the mevalonate (MVA) pathway and is produced by the dephosphorylation of farnesyl diphosphate. Farnesol plays a central role in cell growth and differentiation, controls production of ubiquinone and ergosterol, and participates in the regulation of filamentation and biofilm formation. Despite these important functions, studies of farnesol in filamentous fungi are limited, and information on its effects on antifungal and/or biocontrol activity is scarce. In the present article, we identified the Trichoderma harzianum gene dpp1, encoding a diacylglycerol pyrophosphatase that catalyzes production of farnesol from farnesol diphosphate. We analyzed the function of dpp1 to address the importance of farnesol in Trichoderma physiology and ecology. Overexpression of dpp1 in T. harzianum caused an expected increase in farnesol production as well as a marked change in squalene and ergosterol levels, but overexpression did not affect antifungal activity. In interaction with plants, a dpp1-overexpressing transformant acted as a sensitizing agent in that it up-regulated expression of plant defense salicylate-related genes in the presence of a fungal plant pathogen. In addition, toxicity of farnesol on Trichoderma and plants was examined. Finally, a phylogenetic study of dpp1 was performed to understand its evolutionary history as a primary metabolite gene. This article represents a step forward in the acquisition of knowledge on the role of farnesol in fungal physiology and in fungus-environment interactionsSIThis research was funded by the Spanish I+D+i Grants AGL2012-40041-C02-02, AGL2015-70671-C2-2-R, RTI2018-099600-B-I00 and PID2021-123874OB-I00, financed by the MCIN/ AEI/10.13039/501100011033. GC-H was awarded with a Grant from the Ministry of Education, Culture, and Sport (Spain) (Grant number FPU15/04681). NM-R was awarded with a Grant from the Junta de Castilla y León (Spain) (ORDEN EDU/875/2021, 13 July 2021