Quantitative and qualitative methods of evaluating response to biologics in severe asthma patients: Results from a real-world study

[EN] Asthma is a complex major noncommunicable disease affecting around 333 million people worldwide, both children and adults.New biological therapies for treating severe asthma have remarkably improved disease management. Notwith-standing, one remaining crucial problem is evaluating the response to these treatments. Therefore, adequate measurement of the response to biologics in a holistic manner that integrates clinical variables of interest and quality of life is needed, particularly in identifying super-responder patients (SR). Menzies-Gow et al went more profound in the concept and proposed a consensus to evaluate remission.Instituto de Salud Carlos III (ISCIII); European Union -Next Generation EU; Junta de Castilla y Leó

Beyond T2-asthma biomarkers: risk stratification for NSAID-Exacerbated Respiratory Disease

[EN]Type 2 (T2)-asthma is often associated with chronic rhinosinusitis with nasal polyposis (CRSwNP). Additionally, non-steroidal anti-inflammatory drug intolerance leads to NSAID-exacerbated respiratory disease (N-ERD). Previous transcriptomic data in non-CRSwNP T2-asthma patients showed differentially expressed genes (DEGs). Of them, we focused on ALOX15, CLC, CYSLTR2, HRH4, and SMPD3 to investigate their role in T2-asthma patients. The study included 100 healthy controls (HCs) and 103 T2-asthma patients, divided into asthmatics (54), asthmatics with CRSwNP (30), and N-ERD (19). Quantitative PCR analysis was performed on blood-derived RNA samples first to validate the five DEGs. The data were further analyzed to find potential associations and biomarkers. Patients, regardless of stratification, exhibited significantly higher gene expressions than HCs. The patterns of association revealed that ALOX15 was exclusively present in the non-comorbidity group, SMPD3 and CLC in the comorbidity groups, and HRH4 in all patient groups. ALOX15, CYSLTR2, and SMPD3 expression showed potential as biomarkers to confirm the diagnosis of T2-asthma using peripheral blood eosinophils (PBE) as the initial criterion. PBE combined with gene expressions, especially SMPD3, may improve the diagnosis. CLC and CYSLTR2 expressions play a specific role in discriminating N-ERD. We validated the transcriptomic data of five DEGs in T2-asthma. Different patterns of association were identified in patient stratification, suggesting different molecular mechanisms underlying the spectrum of T2-asthma. Potential biomarkers were also found and used to design an algorithm with practical diagnostic utility for T2-asthma, including risk stratification for N-ERD.Ministerio de Ciencia e Innovación; Junta de Castilla y León; Instituto de Salud Carlos II

PTGDR2 expression in peripheral blood as a potential biomarker in adult patients with asthma

[EN]Background: Precision medicine is a promising strategy to identify biomarkers, stratify asthmatic patients according to different endotypes, and match them with the appropriate therapy. This proof-of-concept study aimed to investigate whether gene expression in peripheral blood could provide a valuable noninvasive approach for the molecular phenotyping of asthma. Methods: We performed whole-transcriptome RNA sequencing on peripheral blood of 30 non-atopic non-asthmatic controls and 30 asthmatic patients. A quantitative PCR (qPCR) validation study of PTGDR2 that encodes for CRTH2 receptor, expressed in cells involved in T2 inflammation, was developed in a cohort of 361 independent subjects: 94 non-asthmatic non-atopic controls, 187 asthmatic patients [including 82 with chronic rhinosinusitis with nasal polyposis (CRSwNP) and 24 with aspirin-exacerbated respiratory disease (AERD)], 52 with allergic rhinitis, and 28 with CRSwNP without asthma. Results: PTGDR2 was one of the most differentially overexpressed genes in asthmatic patients' peripheral blood (p-value 2.64 × 106). These results were confirmed by qPCR in the validation study, where PTGDR2 transcripts were significantly upregulated in asthmatic patients (p < 0.001). This upregulation was mainly detected in some subgroups such as allergic asthma, asthma with CRSwNP, AERD, eosinophilic asthma, and severe persistent asthma. PTGDR2 expression was detected in different blood cell types, and its correlation with eosinophil counts showed differences in some groups of asthmatic patients. Conclusions: We found that PTGDR2 expression levels could identify asthma patients, introduce a minimally invasive biomarker for adult asthma molecular phenotyping, and add additional information to blood eosinophils. Although further studies are required, analyzing PTGDR2 expression levels in peripheral blood of asthmatics might assist in selecting patients for treatment with specific antagonists. Keywords: PTGDR2; aspirin exacerbated respiratory disease (AERD); asthma; biomarker; chronic rhinosinusitis with nasal polyps (CRSwNP); gene expression.Instituto de Salud Carlos III; Juan Rodés contract; Junta de Castilla y Leó

Transcriptomics reveals new regulatory mechanisms involved in benralizumab response

[EN] Benralizumab, a monoclonal antibody targeting IL5RA, significantly improves asthma symptoms and quality of life in severe asthmatic patients. However, understanding the factors influencing treatment response remains a challenge. In this prospective observational study, we analyzed transcriptomic changes in peripheral whole blood samples from 15 severe asthmatic patients treated with benralizumab for 6 months. The study included patients with two frequent comorbidities: nasal polyposis (CRSwNP) and NSAID-exacerbated respiratory disease (N-ERD)Instituto de Salud Carlos III (ISCIII); European Union -NextGeneration EU; Junta de Castilla y Leó

Un santuario doméstico del siglo VII a. C. de culto a Hathor-Astarté en el Cerro de San Vicente (Salamanca, España)

Se presentan los resultados de las excavaciones de 2022 en el Cerro de San Vicente (Salamanca), que amplían el área exhumada en 2021. Se discute la secuencia diacrónica de dicho espacio y su interpretación funcional y social. Se aborda la religiosidad doméstica a partir de varios edificios de uso cultual y un abundante elenco de objetos litúrgicos: vajilla torneada egipcia o levantina pintada y fenicia de engobe rojo, un aplique de taracea y abalorios de fayenza con iconografía oriental, pebeteros y terracotas y vajilla local con temas orientalizantes, etc. Además, sobresalen los nuevos indicadores de prácticas aristocráticas: instrumentos para artesanías de alta calidad –alfarería y actividades textiles– y atalajes ecuestres –dos camas de bocados óseos–. El cocinado con bandejas y hornillos de atanor, las artesanías especializadas, los rituales domésticos y la edilicia remiten también al ámbito mediterráneo. Todas estas evidencias permiten interpretar el sector excavado como un espacio ceremonial y a la vez doméstico dedicado a una deidad femenina –probable trasunto local de Hathor-Astarté– integrado en el vecindario de patio central de un grupo residencial virilocal multifamiliar. Se reivindica el protagonismo de las mujeres de aquella unidad corporativa amplia y de alto rango en la transmisión y desempeño de todos esos saberes procedimentales y actividades de mantenimiento espiritual y material

Un santuario doméstico del siglo VII a. C. de culto a Hathor-Astarté en el Cerro de San Vicente (Salamanca, España)

This article presents the major outcomes from the excavations undertaken in 2022 at the site of Cerro de San Vicente (Salamanca), enlarging the area unearthed in 2021. The paper discusses the diachronic sequence of this setting and its functional and social interpretation. Household religion is addressed via several cult buildings and a large repertoire of liturgical objects: wheel-thrown painted Egyptian or Levantine and Phoenician red-slip tableware, a faience piece of inlay and faience beads featuring oriental iconography, local terracotta, burners, and tableware with orientalizing motifs, etc. In addition, new indicators of aristocratic practices stand out: instruments for high-quality handicrafts –pottery and textile work– and two equestrian bone items of harnesses. Cooking with ceramic trays and portable tandoor-like stoves, specialized crafts, domestic cults, and buildings refer, as a whole, to the Mediterranean koiné. All these lines of evidence lead to interpret the excavated sector as a domestic sanctuary dedicated to a female deity –likely a local expression of Hathor-Ashtart– integrated into the neighbourhood of a central courtyard compound occupied by a multi-family virilocal residential group. The article reclaims the key role of the women of that broad and high-ranking corporate social unit in the transmission and performance of know-how and practices of spiritual and material maintenance.Se presentan los resultados de las excavaciones de 2022 en el Cerro de San Vicente (Salamanca), que amplían el área exhumada en 2021. Se discute la secuencia diacrónica de dicho espacio y su interpretación funcional y social. Se aborda la religiosidad doméstica a partir de varios edificios de uso cultual y un abundante elenco de objetos litúrgicos: vajilla torneada egipcia o levantina pintada y fenicia de engobe rojo, un aplique de taracea y abalorios de fayenza con iconografía oriental, pebeteros y terracotas y vajilla local con temas orientalizantes, etc. Además, sobresalen los nuevos indicadores de prácticas aristocráticas: instrumentos para artesanías de alta calidad –alfarería y actividades textiles– y atalajes ecuestres –dos camas de bocados óseos–. El cocinado con bandejas y hornillos de atanor, las artesanías especializadas, los rituales domésticos y la edilicia remiten también al ámbito mediterráneo. Todas estas evidencias permiten interpretar el sector excavado como un espacio ceremonial y a la vez doméstico dedicado a una deidad femenina –probable trasunto local de Hathor-Astarté– integrado en el vecindario de patio central de un grupo residencial virilocal multifamiliar. Se reivindica el protagonismo de las mujeres de aquella unidad corporativa amplia y de alto rango en la transmisión y desempeño de todos esos saberes procedimentales y actividades de mantenimiento espiritual y material

An exceptional case of household archaeology from Early Iron Age Central Iberia: House 1 at Cerro de San Vicente (Salamanca, Spain)

RESUMEN: Se presentan los resultados de las excavaciones (2006, 2017 y 2021) en un sector de la aldea del Hierro I del Cerro de San Vicente (Salamanca). Se ha exhumado un agregado informal de edificios y estructuras adjetivas de adobe cuyo patrón espacial es afín al esquema transcultural patrilocal. El artículo se centra en la casa 1 y sus cenizales. Tal vivienda fue excepcional por su larga e ininterrumpida biografía, su mobiliario de barro –con dos poyos que pudieron acoger hasta 20 personas y un hogar con forma de piel de toro extendida– y su abandono ritualizado –quemada c. 650-575 a.C. y recrecida con adobes de sus paredes–. La excavación reveló una alta concentración de molinos y vajilla fina local pintada, así como instrumental de labores especializadas y altamente cualificadas –alfarería e hilado–. Sobresale un lote de hallazgos inéditos en el interior de la península ibérica: exóticos abalorios y vajilla de fayenza del Mediterráneo oriental, cerámica de engobe rojo fenicia y objetos litúrgicos y coroplástica con paralelos tartésicos y mediterráneos. Todos estos hallazgos indican que la casa 1 acogió una asidua actividad social –banquetes y transacciones con huéspedes– como cabaña de reuniones de un grupo corporativo extenso, donde acabaron tan destacados objetosABSTRACT: The excavations undertaken at the Early Iron Age vil¬lage of Cerro de San Vicente (Salamanca) revealed an infor¬mal aggregate of dwellings and ancillary buildings of adobe which matches the cross cultural spatial pattern for patrilo¬cal practices. The paper focuses on house 1 and its adjoin¬ing middens. This dwelling was exceptional due to its long and stable biography, its clay furniture –with two benches for 20 people and a hearth in the shape of an oxhide– and ritualized abandonment using an intense conflagration dated to 650 575 BC and its filling with adobes. The excavations revealed an unusual concentration of querns and fine local hand made pottery. The excavations recovered implements used for specialized and high quality crafts, such as pottery-making and weaving, as well as a set of finds unprecedented in the interior of Iberia stands out: exotic faience beads and tableware from the eastern Mediterranean, Phoenician red slip ceramics, and liturgical terracotta items with Tartes¬sian and Mediterranean parallels. All these findings suggest that house 1 was the gathering hall of an extended corporate group where intense social activities –hosting banquets and transactions with guests– took place and where such star¬tling artefacts ended up.Trabajo realizado en el marco del proyecto “ARQPARENT - Arqueología del parentesco a través de la vivienda en la Submeseta Norte (1800-400 AC)” (PID2019-104349GA-I00) del Plan Estatal de I+D+i del Ministerio de Ciencia e Innovación y con subvenciones de la Junta de Castilla y León (B2017/006589 y SUBV-21086-SA) y del Ayuntamiento de Salamanca

Un singular ambiente doméstico del Hierro I en el interior de la península ibérica: la casa 1 del Cerro de San Vicente (Salamanca, España)

The excavations undertaken at the Early Iron Age village of Cerro de San Vicente (Salamanca) revealed an informal aggregate of dwellings and ancillary buildings of adobe which matches the cross‑cultural spatial pattern for patrilocal practices. The paper focuses on house 1 and its adjoining middens. This dwelling was exceptional due to its long and stable biography, its clay furniture –with two benches for 20 people and a hearth in the shape of an oxhide– and ritualized abandonment using an intense conflagration dated to 650‑575 BC and its filling with adobes. The excavations revealed an unusual concentration of querns and fine local hand‑made pottery. The excavations recovered implements used for specialized and high‑quality crafts, such as potterymaking and weaving, as well as a set of finds unprecedented in the interior of Iberia stands out: exotic faience beads and tableware from the eastern Mediterranean, Phoenician red slip ceramics, and liturgical terracotta items with Tartessian and Mediterranean parallels. All these findings suggest that house 1 was the gathering hall of an extended corporate group where intense social activities –hosting banquets and transactions with guests– took place and where such startling artefacts ended up.Se presentan los resultados de las excavaciones (2006, 2017 y 2021) en un sector de la aldea del Hierro I del Cerro de San Vicente (Salamanca). Se ha exhumado un agregado informal de edificios y estructuras adjetivas de adobe cuyo patrón espacial es afín al esquema transcultural patrilocal. El artículo se centra en la casa 1 y sus cenizales. Tal vivienda fue excepcional por su larga e ininterrumpida biografía, su mobiliario de barro –con dos poyos que pudieron acoger hasta 20 personas y un hogar con forma de piel de toro extendida– y su abandono ritualizado –quemada c. 650-575 a.C. y recrecida con adobes de sus paredes–. La excavación reveló una alta concentración de molinos y vajilla fina local pintada, así como instrumental de labores especializadas y altamente cualificadas –alfarería e hilado–. Sobresale un lote de hallazgos inéditos en el interior de la península ibérica: exóticos abalorios y vajilla de fayenza del Mediterráneo oriental, cerámica de engobe rojo fenicia y objetos litúrgicos y coroplástica con paralelos tartésicos y mediterráneos. Todos estos hallazgos indican que la casa 1 acogió una asidua actividad social –banquetes y transacciones con huéspedes– como cabaña de reuniones de un grupo corporativo extenso, donde acabaron tan destacados objetos

Certificación de un material de referencia de carne en base a un estudio de colaboración = Certification of a meat reference material based on a collaborative study

Mediante un proyecto de colaboración, se llevaron a cabo estudios de comparación para mejorar la capacidad de mediciónde los laboratorios participantes, apoyándolos en la producción, caracterización y distribución de materiales de referencia delsector agroalimentario. El proyecto fue planteado en cuatro etapas anuales (leche, agua, carne y granos). La tercera etapa enespecífico tuvo el objetivo de cuantificar y certificar el contenido de los parámetros nutrimentales (nitrógeno, grasa, sodio ypotasio) de un lote candidato a Material de Referencia Certificado (MRC) de carne bovina enlatada. Dicho estudio fue realizadoen colaboración entre varios Institutos Nacionales de Metrología (INM) y/o laboratorios colaboradores, los cuales, una vez queidentificaron las posibles causas de variabilidad o de sesgo en las mediciones, así como las oportunidades de mejora, lograronla certificación del material de carne bovina. El MRC fue distribuido entre los participantes para cubrir las necesidades de laindustria alimentaria de productos cárnicos y laboratorios de prueba de sus respectivos países

Modulation of the endocannabinoids N-Arachidonoylethanolamine (AEA) and 2-Arachidonoylglycerol (2-AG) on Executive Functions in Humans

Animal studies point to an implication of the endocannabinoid system on executive functions. In humans, several studies have suggested an association between acute or chronic use of exogenous cannabinoids (Δ9-tetrahydrocannabinol) and executive impairments. However, to date, no published reports establish the relationship between endocannabinoids, as biomarkers of the cannabinoid neurotransmission system, and executive functioning in humans. The aim of the present study was to explore the association between circulating levels of plasma endocannabinoids N-arachidonoylethanolamine (AEA) and 2-Arachidonoylglycerol (2-AG) and executive functions (decision making, response inhibition and cognitive flexibility) in healthy subjects. One hundred and fifty seven subjects were included and assessed with the Wisconsin Card Sorting Test; Stroop Color and Word Test; and Iowa Gambling Task. All participants were female, aged between 18 and 60 years and spoke Spanish as their first language. Results showed a negative correlation between 2-AG and cognitive flexibility performance (r = −.37; p<.05). A positive correlation was found between AEA concentrations and both cognitive flexibility (r = .59; p<.05) and decision making performance (r = .23; P<.05). There was no significant correlation between either 2-AG (r = −.17) or AEA (r = −.08) concentrations and inhibition response. These results show, in humans, a relevant modulation of the endocannabinoid system on prefrontal-dependent cognitive functioning. The present study might have significant implications for the underlying executive alterations described in some psychiatric disorders currently associated with endocannabinoids deregulation (namely drug abuse/dependence, depression, obesity and eating disorders). Understanding the neurobiology of their dysexecutive profile might certainly contribute to the development of new treatments and pharmacological approaches