Derechos fundamentales y gestación por sustitución: vuelve el debate jurídico acerca de su regulación a raíz de la STS 277/2022, de 31 de marzo

In the wake of the recent STS (Civil Chamber) no. 277/2022, of 31 March, the discussion about the possibility of regulating surrogacy in our country has re-emerged with force in the public debate. In order to provide a new approach to the legal response which, within the framework established by the Spanish Constitution, should be given to the legal problems involved in this practice, this article attempts to verify the existence and scope of the impact on the rights and interests of those involved in what we could call the «GS triangle» — the clients, the gestational carrier and the minor. In such a way that, after the corresponding balancing exercise, an assessment can be made of the incompatibility of a possible regulation of the growing figure of surrogacy with the Spanish constitutional framework.A raíz de la reciente STS (Sala de lo Civil) núm. 277/2022, de 31 de marzo, ha vuelto a resurgir con fuerza en el debate público la discusión acerca de la posibilidad de regular la gestación por sustitución en nuestro país. A fin de aportar un nuevo enfoque respecto a la respuesta jurídica que dentro del marco establecido por la Constitución Española debe darse a la problemática jurídica que supone esta práctica, en el presente artículo se trata de comprobar la existencia y el alcance de la afectación de los derechos e intereses de los involucrados en lo que podríamos denominar el «triángulo de la GS» —comitentes, gestante y menor—. De tal manera que, tras el correspondiente ejercicio de ponderación, se puede alcanzar una valoración acerca de la incompatibilidad de una posible regulación de la creciente figura de la gestación por sustitución con el marco constitucional español

Et renovabis faciem terrae. The oratories of the congregations of San Quirico di Valleriana. A vehicle for the town’s rebirth

San Quirico di Valleriana is a walled settlement of ancient Lucchesia (the territory surrounding Lucca, Italy) dating to the early Middle Ages, set in the valleys behind Pescia at about 540 metres above sea level. The residents have gradually deserted this settlement after the end of the Second World War, as well as many other “minor” settlements on the Tuscan-Emilian Apennines, to find better job opportunities and living standards elsewhere. Despite the progressive abandonment, San Quirico and the other nine Castella of the Valleriana valley form an unquestioned interesting system for reasons rooting in its culture, art and landscape. From this particular point of view, the mountainous territory around Pescia, the Pesciatina, indeed nurses the economic potential to attract “slow tourists”: those travellers who prefer visiting territories rich in history and traditions, both secular and religious, and that are still able to bring the consolidated image of medieval Tuscany back to life. Prior to the early decades of the XIX century, in this eastern outpost of the Diocese of Lucca, time was marked by the rules and customs instilled by the religious influence, which have survived thanks to the uninterrupted work of numerous congregations. The most important of them had their own oratory, near the ancient parish church, distinguishing the area where the main public events, from the rest of the urban network. Via a historical, typological and architectural assessment of the castle’s oratories and congregations, the relations between religious architecture and the settlement’s community were analysed with the explicit intention to understand what can trigger the complex process of requalification and enhancement for the village’s future. Analysis and project involved San Quirico as a whole but special care was paid to the oratories, which could once again accomplish some key functions in the dynamics of the castle; mostly because of their peculiar characteristics and for the role they have already played during the centuries in the community’s life. Memory, Measure and Material are the three incipits that have guided the entire project: the analysis of the material and immaterial history of the village has led to understand the logic behind the construction of the main religious buildings, which can renew their exterior façade without having to hide their origins, thanks to a sensible use of materials, and therefore playing an active role in every-day life. The design proposal focuses on the introduction of spaces to properly welcome visitors or to host cultural happenings; a new cultural centre that can become a reference point for the residents of the nearby villages as well as for the tourists visiting the valley

Gestión por resultados y desempeño laboral de los servidores en una UGEL de la ciudad de Lima, 2022

El presente trabajo de investigación tuvo como objetivo, determinar la relación que existe entre la gestión por resultados y el desempeño laboral de los servidores en una UGEL de la ciudad de Lima, 2022. El tipo de investigación fue básica, de enfoque cuantitativo, de diseño no experimental, de corte transversal y nivel correlacional, la población estuvo compuesta por 290 servidores con una muestra de 166 servidores de una Unidad de Gestión Educativa Local de la ciudad de Lima, la técnica para recolección de datos fue la encuesta, utilizándose la escala de Likert. Los resultados evidenciaron que el 55,4% percibieron que la gestión por resultados fue regular, mientras que el 40,4% percibieron que fue eficiente y sólo el 4,2% la percibió como deficiente; asimismo, respecto al desempeño laboral, el nivel regular predomina con un 56,6%, el nivel eficiente con un 42,2% y el nivel deficiente con un 1,2%. Se concluyó que existe relación directa moderada entre ambas variables (Rho=0,418**; p valor= 0,000 < 0,05). El cual significa que, al mejorar los procesos en la gestión por resultados mejora el desempeño laboral

Alzheimer's disease and neuroinflammation: will new drugs in clinical trials pave the way to a multi-target therapy?

: Despite extensive research, no disease-modifying therapeutic option, able to prevent, cure or halt the progression of Alzheimer's disease [AD], is currently available. AD, a devastating neurodegenerative pathology leading to dementia and death, is characterized by two pathological hallmarks, the extracellular deposits of amyloid beta (Aβ) and the intraneuronal deposits of neurofibrillary tangles (NFTs) consisting of altered hyperphosphorylated tau protein. Both have been widely studied and pharmacologically targeted for many years, without significant therapeutic results. In 2022, positive data on two monoclonal antibodies targeting Aβ, donanemab and lecanemab, followed by the 2023 FDA accelerated approval of lecanemab and the publication of the final results of the phase III Clarity AD study, have strengthened the hypothesis of a causal role of Aβ in the pathogenesis of AD. However, the magnitude of the clinical effect elicited by the two drugs is limited, suggesting that additional pathological mechanisms may contribute to the disease. Cumulative studies have shown inflammation as one of the main contributors to the pathogenesis of AD, leading to the recognition of a specific role of neuroinflammation synergic with the Aβ and NFTs cascades. The present review provides an overview of the investigational drugs targeting neuroinflammation that are currently in clinical trials. Moreover, their mechanisms of action, their positioning in the pathological cascade of events that occur in the brain throughout AD disease and their potential benefit/limitation in the therapeutic strategy in AD are discussed and highlighted as well. In addition, the latest patent requests for inflammation-targeting therapeutics to be developed in AD will also be discussed

Historia del municipio de Chichigalpa, Departamento de Chinandega a partir de la segunda mitad del siglo XIX a la actualidad

La presente investigacion monográfica titulada “ Historia local del municipio de Chichigalpa, Departamento de Chinandega a partir de la segunda mitad del siglo XIX a la actualidad” se ubica en la línea de investigación de Historia Regional y Local, que permite plantear, descubrir, identificar y comparar los cambios, en el contexto sociocultural y en materia económica, ante el desarrollo del municipio. El municipio de Chichigalpa se vio inmerso en el factor dinamizador de la economía que influyó en el crecimiento agrícola a partir de la llegada de la caña de azúcar y la edificación de vías ferroviarias que permitieron la influencia del medio de transporte y cambios en el municipio, incidió consigo en el involucramiento de los habitantes de esta municipalidad trascendiendo en el entorno sociocultural y económico de una comunidad meramente agrícola, convirtiendose en uno de los lugares mas productivos de la región de Occidente. Para comprender el desarrollo historico del municipio,se aplicó y la metodología de análisis y síntesis de fuentes documentales, primarias y secundarias, la técnica a utilizar fue el fichaje de fuentes históricas para su respectivo análisis e interpretación, se utilizó el método deductivo e inductivo. El perfil de esta temática obedece al enfoque cualitativo para su plena asimilación y entendimiento, de manera comparativa se investigó el antes, y después de la introducción de la caña de azúcar para ir conociendo esos cambios que han tenido las actividades realizadas en esta localidad logrando aportar una nueva fuente de información que permita la iniciativa de nuevos estudios académico

SIRT1 Mediates Melatonin’s Effects on Microglial Activation in Hypoxia: In Vitro and In Vivo Evidence

Melatonin exerts direct neuroprotection against cerebral hypoxic damage, but the mechanisms of its action on microglia have been less characterized. Using both in vitro and in vivo models of hypoxia, we here focused on the role played by silent mating type information regulation 2 homolog 1 (SIRT1) in melatonin’s effects on microglia. Viability of rat primary microglia or microglial BV2 cells and SH-SY5Y neurons was significantly reduced after chemical hypoxia with CoCl2 (250 µM for 24 h). Melatonin (1 µM) significantly attenuated CoCl2 toxicity on microglia, an effect prevented by selective SIRT1 inhibitor EX527 (5 µM) and AMP-activated protein kinase (AMPK) inhibitor BML-275 (2 µM). CoCl2 did not modify SIRT1 expression, but prevented nuclear localization, while melatonin appeared to restore it. CoCl2 induced nuclear localization of hypoxia-inducible factor-1α (HIF-1α) and nuclear factor-kappa B (NF-kB), an effect contrasted by melatonin in an EX527-dependent fashion. Treatment of microglia with melatonin attenuated potentiation of neurotoxicity. Common carotid occlusion was performed in p7 rats, followed by intraperitoneal injection of melatonin (10 mg/kg). After 24 h, the number of Iba1+ microglia in the hippocampus of hypoxic rats was significantly increased, an effect not prevented by melatonin. At this time, SIRT1 was only detectable in the amoeboid, Iba1+ microglial population selectively localized in the corpus callosum. In these cells, nuclear localization of SIRT1 was significantly lower in hypoxic animals, an effect prevented by melatonin. NF-kB showed an opposite expression pattern, where nuclear localization in Iba1+ cells was significantly higher in hypoxic, but not in melatonin-treated animals. Our findings provide new evidence for a direct effect of melatonin on hypoxic microglia through SIRT1, which appears as a potential pharmacological target against hypoxic-derived neuronal damage.Fil: Merlo, Sara. Universidad de Catania; ItaliaFil: Luaces, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Spampinato, Simona Federica. Universidad de Catania; ItaliaFil: Toro Urrego, Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Caruso, Grazia Ilaria. Universidad de Catania; ItaliaFil: D´Amico, Fabio. Universidad de Catania; ItaliaFil: Capani, Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Sortino, Maria Angela. Universidad de Catania; Itali

Gonadotropin Releasing Hormone Agonists Have an Anti-apoptotic Effect on Cumulus Cells

Background: Ovaries are sensitive to chemotherapy, which may lead to early depletion of primordial follicle reserve. One strategy for gonadal function preservation is temporary ovarian suppression with Gonadotropin Releasing Hormone agonists (GnRHa) during chemotherapy. To date, GnRHa protective mechanism of action remains not fully elucidated. Methods: We collected 260 immature cumulus cell-oocyte complexes (COC) from 111 women &lt; 38 years old, with a normal ovarian reserve. The COC were randomly assigned to the following groups: (a) control; culture with the addition of (b) GnRHa; (c) cyclophosphamide; (d) cyclophosphamide plus GnRHa. After in vitro treatments, RNA and proteins were extracted from oocytes and cumulus cells (CC), separately. Potential effects of drugs were evaluated on GnRH receptors, apoptosis pathways, ceramide pathway, and glutathione synthesis by quantitative PCR and, whenever possible, by Western blot. Results: Cyclophosphamide triggered activation of the extrinsic pathway of apoptosis mediated by BAX in CC. The co-administration of GnRHa inhibited the apoptosis pathway in CC. According to our model, the GnRHa does not directly act on oocytes, which do not express GnRH receptors. Moreover, glutathione synthesis was decreased after GnRHa treatment both in CC and oocytes. Conclusion: Our data suggest that the protective mechanisms induced by GnRHa is mediated by an anti-apoptotic effect on CC

Velusetrag rescues GI dysfunction, gut inflammation and dysbiosis in a mouse model of Parkinson's disease

: In patients with Parkinson's disease (PD), constipation is common, and it appears in a prodromal stage before the hallmark motor symptoms. The present study aimed to investigate whether Velusetrag, a selective 5‑HT4 receptor agonist, may be a suitable candidate to improve intestinal motility in a mouse model of PD. Five months old PrP human A53T alpha-synuclein transgenic (Tg) mice, which display severe constipation along with decreased colonic cholinergic transmission already at 3 months, were treated daily with the drug for 4 weeks. Velusetrag treatment reduced constipation by significantly stimulating both the longitudinal and circular-driven contractions and improved inflammation by reducing the level of serum and colonic IL1β and TNF-α and by decreasing the number of GFAP-positive glia cells in the colon of treated mice. No significant downregulation of the 5-HT4 receptor was observed but instead Velusetrag seemed to improve axonal degeneration in Tgs as shown by an increase in NF-H and VAChT staining. Ultimately, Velusetrag restored a well-balanced intestinal microbial composition comparable to non-Tg mice. Based on these promising data, we are confident that Velusetrag is potentially eligible for clinical studies to treat constipation in PD patients

BRAF and MLH1 Analysis Algorithm for the Evaluation of Lynch Syndrome Risk in Colorectal Carcinoma Patients: Evidence-Based Data from the Analysis of 100 Consecutive Cases

settingsOrder Article Reprints Open AccessFeature PaperArticle BRAF and MLH1 Analysis Algorithm for the Evaluation of Lynch Syndrome Risk in Colorectal Carcinoma Patients: Evidence-Based Data from the Analysis of 100 Consecutive Cases by Thais Maloberti 1,2,†ORCID,Antonio De Leo 1,2,†ORCID,Viviana Sanza 2,Lidia Merlo 2,Michela Visani 1ORCID,Giorgia Acquaviva 1,Sara Coluccelli 1,2ORCID,Annalisa Altimari 2,3,Elisa Gruppioni 2,3,Stefano Zagnoni 2,3,Daniela Turchetti 4,Sara Miccoli 4,Michelangelo Fiorentino 5,6ORCID,Antonietta D’Errico 3ORCID,Dario de Biase 7,*,‡ORCID andGiovanni Tallini 1,2,‡ORCID 1 Department of Experimental, Diagnostic and Specialty Medicine, Anatomic Pathology Unit-University of Bologna Medical Center, 40138 Bologna, Italy 2 Solid Tumor Molecular Pathology Laboratory, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy 3 Department of Pathology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy 4 Unit of Medical Genetics, IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico), Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy 5 Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40138 Bologna, Italy 6 Pathology Department, Maggiore Hospital, 40133 Bologna, Italy 7 Department of Pharmacy and Biotechnology, University of Bologna, 40126 Bologna, Italy * Author to whom correspondence should be addressed. † These authors contributed equally to this work. ‡ These authors contributed equally to this work. J. Mol. Pathol. 2022, 3(3), 115-124; https://doi.org/10.3390/jmp3030011 Received: 30 March 2022 / Revised: 27 May 2022 / Accepted: 21 June 2022 / Published: 25 June 2022 (This article belongs to the Collection Feature Papers in Journal of Molecular Pathology) Download Browse Figures Versions Notes Abstract Several causes may lead to CRC, either extrinsic (sporadic forms) or genetic (hereditary forms), such as Lynch syndrome (LS). Most sporadic deficient mismatch repair (dMMR) CRC cases are characterized by the methylation of the MLH1 promoter gene and/or BRAF gene mutations. Usually, the first test performed is the mismatch repair deficiency analysis. If a tumor shows a dMMR, BRAF mutations and then the MLH1 promoter methylation status have to be assessed, according to the ACG/ASCO screening algorithm. In this study, 100 consecutive formalin-fixed and paraffin-embedded samples of dMMR CRC were analyzed for both BRAF mutations and MLH1 promoter methylation. A total of 47 (47%) samples were BRAF p.V600E mutated, while MLH1 promoter methylation was found in 77 cases (77.0%). The pipeline “BRAF-followed-by-MLH1-analysis” led to a total of 153 tests, while the sequence “MLH1-followed-by-BRAF-analysis” resulted in a total of 123 tests. This study highlights the importance of performing MLH1 analysis in LS screening of BRAF-WT specimens before addressing patients to genetic counseling. We show that MLH1 analysis performs better as a first-line test in the screening of patients with LS risk than first-line BRAF analysis. Our data indicate that analyzing MLH1 methylation as a first-line test is more cost-effective