Measures for the assessment of stressful life events in the Spanish adult population: A systematic review

Objetivo: Este estudio pretende identificar y analizar los instrumentos de evaluación de los eventos vitales estresantes creados/adaptados para su uso con población española adulta, publicados en la literatura nacional e internacional, con especial atención en sus propiedades psicométricas y en su asociación con medidas de problemas de salud. Métodos: Se llevó a cabo una revisión sistemática de la literatura de todos los instrumentos publicados a través de los buscadores MEDLINE; ProQuest Health y Medical Complete ProQuest Psychology Journals PsycARTICLES PsycINFO Psicodoc OpenSIGLE desde la fecha de inicio hasta el 31 de enero de 2016. Dos investigadores independientes evaluaron la elegibilidad de todos los artículos, extrajeron los datos y evaluaron sus propiedades psicométricas. Resultados: Se seleccionaron 12 instrumentos que cumplían los criterios de inclusión en el estudio. Las medidas presentaron una gran heterogeneidad. La mayoría no incluían información sobre sus propiedades psicométricas o necesitaban aportar más datos, ya que eran pocas los que evaluaban su estabilidad test-retest y/o su estructura interna. Los cuestionarios creados o adaptados por González de Rivera y Morena (1983), Sandín y Chorot (1987), Fernández y Mielgo (1992), Gracia y Herrero (2004) y Motrico et al. (2013) mostraron asociaciones significativas con variables de problemas de salud. Discusión: Se requieren más estudios sobre la asociación de los instrumentos con variables de problemas de salud mental y física, lo que facilitaría su aplicación clínica. Estos resultados tienen una gran utilidad a la hora de seleccionar un instrumento de evaluación de eventos vitales estresantes en el ámbito clínico y de investigación en España

Epigenetic and post-transcriptional regulation of somatostatin receptor subtype 5 (SST5) in pituitary and pancreatic neuroendocrine tumors

Somatostatin receptor subtype 5 (SST5) is an emerging biomarker and actionable target in pituitary (PitNETs) and pancreatic (PanNETs) neuroendocrine tumors. Transcriptional and epigenetic regulation of SSTR5 gene expression and mRNA biogenesis is poorly understood. Recently, an overlapping natural antisense transcript, SSTR5-AS1, potentially regulating SSTR5 expression, was identified. We aimed to elucidate whether epigenetic processes contribute to the regulation of SSTR5 expression in PitNETs (somatotropinomas) and PanNETs. We analyzed the SSTR5/SSTR5-AS1 human locus in silico to identify CpG islands. SSTR5 and SSTR5-AS1 expression was assessed by quantitative real-time PCR (qPCR) in 27 somatotropinomas, 11 normal pituitaries (NPs), and 15 PanNETs/paired adjacent (control) samples. We evaluated methylation grade in four CpG islands in the SSTR5/SSTR5-AS1 genes. Results revealed that SSTR5 and SSTR5-AS1 were directly correlated in NP, somatotropinoma, and PanNET samples. Interestingly, selected CpG islands were differentially methylated in somatotropinomas compared with NPs. In PanNETs cell lines, SSTR5-AS1 silencing downregulated SSTR5 expression, altered aggressiveness features, and influenced pasireotide response. These results provide evidence that SSTR5 expression in PitNETs and PanNETs can be epigenetically regulated by the SSTR5-AS1 antisense transcript and, indirectly, by DNA methylation, which may thereby impact tumor behavior and treatment response.Junta de AndalucíaMinisterio de EconomíaMinisterio de Ciencia e Innovació

Unwrap Them First: Operando Potential- induced Activation Is Required when Using PVP-Capped Ag Nanocubes as Catalysts of CO2 Electroreduction

Metallic nanoparticles of different shape can be used as efficient electrocatalysts for many technologically and environmentally relevant processes, like the electroreduction of CO2. Intense research is thus targeted at finding the morphology of nanosized features that best suits catalytic needs. In order to control the shape and size distribution of the designed nanoobjects, and to prevent their aggregation, synthesis routes often rely on the use of organic capping agents (surfactants). It is known, however, that these agents tend to remain adsorbed on the surface of the synthesized nanoparticles and may significantly impair their catalytic performance, both in terms of overall yield and of product selectivity. It thus became a standard procedure to apply certain methods (e.g. involving UV-ozone or plasma treatments) for the removal of capping agents from the surface of nanoparticles, before they are used as catalysts. Proper design of the operating procedure of the electrocatalysis process may, however, render such cleaning steps unnecessary. In this paper we use poly-vinylpyrrolidone (PVP) capped Ag nanocubes to demonstrate a mere electrochemical, operando activation method. The proposed method is based on an observed hysteresis of the catalytic yield of CO (the desired product of CO2 electroreduction) as a function of the applied potential. When as-synthesized nanocubes were directly used for CO2 electroreduction, the CO yield was rather low at moderate overpotentials. However, following a potential excursion to more negative potentials, most of the (blocking) PVP was irreversibly removed from the catalyst surface, allowing a significantly higher catalytic yield even under less harsh operating conditions. The described hysteresis of the product distribution is shown to be of transient nature, and following operando activation by a single 'break-in' cycle, a truly efficient catalyst was obtained that retained its stability during long hours of operation

Neurocognitive Function in Acromegaly after Surgical Resection of GH-Secreting Adenoma versus Naïve Acromegaly

Patients with active untreated acromegaly show mild to moderate neurocognitive disorders that are associated to chronic exposure to growth hormone (GH) and insulin-like growth factor (IGF-I) hypersecretion. However, it is unknown whether these disorders improve after controlling GH/IGF-I hypersecretion. The aim of this study was to compare neurocognitive functions of patients who successfully underwent GH-secreting adenoma transsphenoidal surgery (cured patients) with patients with naive acromegaly. In addition, we wanted to determine the impact of different clinical and biochemical variables on neurocognitive status in patients with active disease and after long-term cure. A battery of six standardized neuropsychological tests assessed attention, memory and executive functioning. In addition, a quantitative electroencephalography with Low-Resolution Electromagnetic Tomography (LORETA) solution was performed to obtain information about the neurophysiological state of the patients. Neurocognitive data was compared to that of a healthy control group. Multiple linear regression analysis was also conducted using clinical and hormonal parameters to obtain a set of independent predictors of neurocognitive state before and after cure. Both groups of patients scored significantly poorer than the healthy controls on memory tests, especially those assessing visual and verbal recall. Patients with cured acromegaly did not obtain better cognitive measures than naïve patients. Furthermore memory deficits were associated with decreased beta activity in left medial temporal cortex in both groups of patients. Regression analysis showed longer duration of untreated acromegaly was associated with more severe neurocognitive complications, regardless of the diagnostic group, whereas GH levels at the time of assessment was related to neurocognitive outcome only in naïve patients. Longer duration of post-operative biochemical remission of acromegaly was associated with better neurocognitive state. Overall, this data suggests that the effects of chronic exposure to GH/IGF-I hypersecretion could have long-term effects on brain functions. © 2013 Martín-Rodríguez et al.Funding for this project was provided by an R&D grant from Novartis Oncology and the Plan Andaluz de Investigación (CTS-444). DAC was supported by the “Ramón y Cajal” program (RYC-2006-001071) of the Spanish Ministry of Science and Innovation.Peer Reviewe

Monográfico especial: Diversidad e industria audiovisual, 2015–2020. Análisis del funcionamiento y la regulación del mercado europeo de servicios audiovisuales

Esta publicación se ha elaborado en el marco del proyecto ‘Diversidad audiovisual y plataformas en línea: el caso Netflix’ (ref. CSO2017-83539-R), ejecutado gracias al apoyo de la Agencia Estatal de Investigación (AEI), en el marco del Programa Estatal de I+D+i Orientada a los Retos de la Sociedad del Ministerio de Ciencia, Innovación y Universidades de España, y del Fondo Europeo de Desarrollo Regional (FEDER) de la Unión Europea.El presente boletín monográfico, titulado Diversidad e industria audiovisual, 2015–2020. Análisis del funcionamiento y la regulación del mercado europeo de servicios audiovisuales, pone a disposición de investigadores, profesionales de la comunicación y cualquier lector interesado, una recopilación de recursos centrada en la producción intelectual publicada durante los últimos años en torno a la noción de ‘diversidad’ aplicada al funcionamiento de los servicios audiovisuales.Ministerio de Ciencia, Innovación y Universidades (MICINN) CSO2017-83539-

Instrumentos de evaluación de los eventos vitales estresantes en población española adulta: Una revisión sistemática.

Objetivo: Este estudio pretende identificar y analizar los instrumentos de evaluación de los eventos vitales estresantes creados/adaptados para su uso con población española adulta, publicados en la literatura nacional e internacional, con especial atención en sus propiedades psicométricas y en su asociación con medidas de problemas de salud. Métodos: Se llevó a cabo una revisión sistemática de la literatura de todos los instrumentos publicados a través de los buscadores MEDLINE; ProQuest Health y Medical Complete ProQuest Psychology Journals PsycARTICLES PsycINFO Psicodoc OpenSIGLE desde la fecha de inicio hasta el 31 de enero de 2016. Dos investigadores independientes evaluaron la elegibilidad de todos los artículos, extrajeron los datos y evaluaron sus propiedades psicométricas. Resultados: Se seleccionaron 12 instrumentos que cumplían los criterios de inclusión en el estudio. Las medidas presentaron una gran heterogeneidad. La mayoría no incluían información sobre sus propiedades psicométricas o necesitaban aportar más datos, ya que eran pocas los que evaluaban su estabilidad test-retest y/o su estructura interna. Los cuestionarios creados o adaptados por González de Rivera y Morena (1983), Sandín y Chorot (1987), Fernández y Mielgo (1992), Gracia y Herrero (2004) y Motrico et al. (2013) mostraron asociaciones significativas con variables de problemas de salud. Discusión: Se requieren más estudios sobre la asociación de los instrumentos con variables de problemas de salud mental y física, lo que facilitaría su aplicación clínica. Estos resultados tienen una gran utilidad a la hora de seleccionar un instrumento de evaluación de eventos vitales estresantes en el ámbito clínico y de investigación en España.Objetivo: Este estudio pretende identificar y analizar los instrumentos de evaluación de los eventos vitales estresantes creados/adaptados para su uso con población española adulta, publicados en la literatura nacional e internacional, con especial atención en sus propiedades psicométricas y en su asociación con medidas de problemas de salud. Métodos: Se llevó a cabo una revisión sistemática de la literatura de todos los instrumentos publicados a través de los buscadores MEDLINE; ProQuest Health y Medical Complete ProQuest Psychology Journals PsycARTICLES PsycINFO Psicodoc OpenSIGLE desde la fecha de inicio hasta el 31 de enero de 2016. Dos investigadores independientes evaluaron la elegibilidad de todos los artículos, extrajeron los datos y evaluaron sus propiedades psicométricas. Resultados: Se seleccionaron 12 instrumentos que cumplían los criterios de inclusión en el estudio. Las medidas presentaron una gran heterogeneidad. La mayoría no incluían información sobre sus propiedades psicométricas o necesitaban aportar más datos, ya que eran pocas los que evaluaban su estabilidad test-retest y/o su estructura interna. Los cuestionarios creados o adaptados por González de Rivera y Morena (1983), Sandín y Chorot (1987), Fernández y Mielgo (1992), Gracia y Herrero (2004) y Motrico et al. (2013) mostraron asociaciones significativas con variables de problemas de salud. Discusión: Se requieren más estudios sobre la asociación de los instrumentos con variables de problemas de salud mental y física, lo que facilitaría su aplicación clínica. Estos resultados tienen una gran utilidad a la hora de seleccionar un instrumento de evaluación de eventos vitales estresantes en el ámbito clínico y de investigación en España.Depto. de Sociología: Metodología y TeoríaFac. de Ciencias Políticas y SociologíaTRUEpu

A Somatostatin Receptor Subtype-3 (SST3) Peptide Agonist Shows Antitumor Effects in Experimental Models of Nonfunctioning Pituitary Tumors

[Purpose] Somatostatin analogues (SSA) are efficacious and safe treatments for a variety of neuroendocrine tumors, especially pituitary neuroendocrine tumors (PitNET). Their therapeutic effects are mainly mediated by somatostatin receptors SST2 and SST5. Most SSAs, such as octreotide/lanreotide/pasireotide, are either nonselective or activate mainly SST2. However, nonfunctioning pituitary tumors (NFPTs), the most common PitNET type, mainly express SST3 and finding peptides that activate this particular somatostatin receptor has been very challenging. Therefore, the main objective of this study was to identify SST3-agonists and characterize their effects on experimental NFPT models.[Experimental Design] Binding to SSTs and cAMP level determinations were used to screen a peptide library and identify SST3-agonists. Key functional parameters (cell viability/caspase activity/chromogranin-A secretion/mRNA expression/intracellular signaling pathways) were assessed on NFPT primary cell cultures in response to SST3-agonists. Tumor growth was assessed in a preclinical PitNET mouse model treated with a SST3-agonist. [Results] We successfully identified the first SST3-agonist peptides. SST3-agonists lowered cell viability and chromogranin-A secretion, increased apoptosis in vitro, and reduced tumor growth in a preclinical PitNET model. As expected, inhibition of cell viability in response to SST3-agonists defined two NFPT populations: responsive and unresponsive, wherein responsive NFPTs expressed more SST3 than unresponsive NFPTs and exhibited a profound reduction of MAPK, PI3K-AKT/mTOR, and JAK/STAT signaling pathways upon SST3-agonist treatments. Concurrently, SSTR3 silencing increased cell viability in a subset of NFPTs. [Conclusions] This study demonstrates that SST3-agonists activate signaling mechanisms that reduce NFPT cell viability and inhibit pituitary tumor growth in experimental models that expresses SST3, suggesting that targeting this receptor could be an efficacious treatment for NFPTs.This work has been funded by the following grants: Junta de Andalucía [CTS-1406 (R.M. Luque), BIO-0139 (J.P. Castaño)]; Ministerio de Ciencia, Innovación y Universidades [BFU2016-80360-R (J.P. Castaño)] and Instituto de Salud Carlos III, co-funded by European Union [ERDF/ESF, “Investing in your future”: PI16/00264 (R.M. Luque), CP15/00156 (M.D. Gahete) and CIBERobn]. CIBER is an initiative of Instituto de Salud Carlos III

Targeted Systemic Treatment of Neuroendocrine Tumors: Current Options and Future Perspectives

Neuroendocrine tumors (NETs) originate from the neuroendocrine cell system in the bronchial and gastrointestinal tract and can produce hormones leading to distinct clinical syndromes. Systemic treatment of patients with unresectable NETs aims to control symptoms related to hormonal overproduction an

Bariatric surgery and calcifediol treatment, Gordian knot of severe-obesity-related comorbidities treatment

BackgroundObesity (OB) is a chronic metabolic disease with important associated comorbidities and mortality. Vitamin D supplementation is frequently administered after bariatric surgery (BS), so as to reduce OB-related complications, maybe including chronic inflammation.AimThis study aimed to explore relations between vitamin D metabolites and components of the inflammasome machinery in OB before and after BS and their relations with the improvement of metabolic comorbidities.Patients and methodsEpidemiological/clinical/anthropometric/biochemical evaluation was performed in patients with OB at baseline and 6 months after BS. Evaluation of i) vitamin-D metabolites in plasma and ii) components of the inflammasome machinery and inflammatory-associated factors [NOD-like-receptors (NLRs), inflammasome-activation-components, cytokines and inflammation/apoptosis-related components, and cell-cycle and DNA-damage regulators] in peripheral blood mononuclear cells (PBMCs) was performed at baseline and 6 months after BS. Clinical and molecular correlations/associations were analyzed.ResultsSignificant correlations between vitamin D metabolites and inflammasome-machinery components were observed at baseline, and these correlations were significantly reduced 6 months after BS in parallel to a decrease in inflammation markers, fat mass, and body weight. Treatment with calcifediol remarkably increased 25OHD levels, despite 24,25(OH)2D3 remained stable after BS. Several inflammasome-machinery components were associated with improvement in metabolic comorbidities, especially hypertension and dyslipidemia.ConclusionThe beneficial effects of vitamin D on OB-related comorbidities after BS patients are associated with significant changes in the molecular expression of key inflammasome-machinery components. The expression profile of these inflammasome components can be dynamically modulated in PBMCs after BS and vitamin D supplementation, suggesting that this profile could likely serve as a sensor and early predictor of the reversal of OB-related complications after BS

Differences in the immune response elicited by two immunization schedules with an inactivated SARS-CoV-2 vaccine in a randomized phase 3 clinical trial

BACKGROUND: The development of vaccines to control the COVID-19 pandemic progression is a worldwide priority. CoronaVac® is an inactivated SARS-CoV-2 vaccine approved for emergency use with robust efficacy and immunogenicity data reported in trials in China, Brazil, Indonesia, Turkey, and Chile. METHODS: This study is a randomized, multicenter, and controlled phase 3 trial in healthy Chilean adults aged ≥18 years. Volunteers received two doses of CoronaVac® separated by two (0-14 schedule) or four weeks (0-28 schedule). 2,302 volunteers were enrolled, 440 were part of the immunogenicity arm, and blood samples were obtained at different times. Samples from a single center are reported. Humoral immune responses were evaluated by measuring the neutralizing capacities of circulating antibodies. Cellular immune responses were assessed by ELISPOT and flow cytometry. Correlation matrixes were performed to evaluate correlations in the data measured. RESULTS: Both schedules exhibited robust neutralizing capacities with the response induced by the 0-28 schedule being better. No differences were found in the concentration of antibodies against the virus and different variants of concern between schedules. Stimulation of PBMCs with MPs induced the secretion of IFN-g and the expression of activation induced markers for both schedules. Correlation matrixes showed strong correlations between neutralizing antibodies and IFN-g secretion. CONCLUSIONS: Immunization with CoronaVac® in Chilean adults promotes robust cellular and humoral immune responses. The 0-28 schedule induced a stronger humoral immune response than the 0-14 schedule. FUNDING: Ministry of Health, Government of Chile, Confederation of Production and Commerce & Millennium Institute on Immunology and Immunotherapy, Chile. CLINICAL TRIAL NUMBER: NCT04651790