Prognostic importance of DNA from human papillomavirus in patients with oral squamous cell carcinoma

Survival of patients with oral squamous cell carcinoma (OSCC) is generally low, with the likelihood of locoregional recurrence or disease progression (LR/DP). Knowledge of prognostic factors for survival is key to achieving an understanding and increased survival. The present study aimed to identify prognostic factors for patients with OSCC, especially the presence of DNA from human papillomavirus (HPV). Retrospective cohort study including 119 patients with OSCC treated at the National Cancer Institute in Mexico City (2009-2013). Clinical information was obtained from patient records including LR/DP. Formalin-fixed, paraffin-embedded tissues were obtained and used for detecting DNA from different types of HPV. Potential prognostic factors for Overall Survival (OS) were analyzed using the Cox proportional hazards model. After model adjustment, factors associated with longer OS were a pre-treatment platelet count above 400,000/mm3 (HR=0.09, p=0.026) and response to primary treatment (HR=0.26, p=0.001). HPV DNA was present in 23 (19.3%) of the patients and importantly, type 16 found in 19 of them. Although survival of HPV-positive patients was longer, difference was not significant. However, among patients with LR/DP, HPV positivity was significantly associated with increased survival (HR=0.23, p=0.034). Importantly, survival was significantly different for HPV-positive patients with LR/DP > 6 months (HR=0.20, p=0.002), had higher absolute lymphocyte count at start of treatment (HR=0.50, p=0.028) or had local rescue treatment (HR=0.24, p=0.019). Although HPV positivity was not associated with a longer OS of OSCC patients, a better prognosis was significantly associated with HPV positivity and recurring or progressing disease, particularly with HPV type 16

Compositional mapping by Z-contrast imaging

This research was sponsored by the Office of Basic Energy Sciences, Materials Sciences and Engineering Division, U.S. Department of Energy (SJP, MV), by the Spanish MCI (projects CONSOLIDER INGENIO 2010 CSD2009-00013 andTEC2008-06756-C03-02/TEC,) and the Junta de Andalucía (PAI research’s groups TEP-120 and TIC-145; project P08-TEP-03516).Peer Reviewe

Reversal of SARS-CoV2-Induced Hypoxia by Nebulized Sodium Ibuprofenate in a Compassionate Use Program

Introduction: Sodium ibuprofenate in hypertonic saline (NaIHS) administered directly to the lungs by nebulization and inhalation has antibacterial and anti-inflammatory effects, with the potential to deliver these benefits to hypoxic patients. We describe a compassionate use program that offered this therapy to hospitalized COVID-19 patients. Methods: NaIHS (50 mg ibuprofen, tid) was provided in addition to standard of care (SOC) to hospitalized COVID-19 patients until oxygen saturation levels of > 94% were achieved on ambient air. Patients wore a containment hood to diminish aerosolization. Outcome data from participating patients treated at multiple hospitals in Argentina between April 4 and October 31, 2020, are summarized. Results were compared with a retrospective contemporaneous control (CC) group of hospitalized COVID-19 patients with SOC alone during the same time frame from a subset of participating hospitals from Córdoba and Buenos Aires. Results: The evolution of 383 patients treated with SOC + NaIHS [56 on mechanical ventilation (MV) at baseline] and 195 CC (21 on MV at baseline) are summarized. At baseline, NaIHS-treated patients had basal oxygen saturation of 90.7 ± 0.2% (74.3% were on supplemental oxygen at baseline) and a basal respiratory rate of 22.7 ± 0.3 breath/min. In the CC group, basal oxygen saturation was 92.6 ± 0.4% (52.1% were on oxygen supplementation at baseline) and respiratory rate was 19.3 ± 0.3 breath/min. Despite greater pulmonary compromise at baseline in the NaIHS-treated group, the length of treatment (LOT) was 9.1 ± 0.2 gs with an average length of stay (ALOS) of 11.5 ± 0.3 days, in comparison with an ALOS of 13.3 ± 0.9 days in the CC group. In patients on MV who received NaIHS, the ALOS was lower than in the CC group. In both NaIHS-treated groups, a rapid reversal of deterioration in oxygenation and NEWS2 scores was observed acutely after initiation of NaIHS therapy. No serious adverse events were considered related to ibuprofen therapy. Mortality was lower in both NaIHS groups compared with CC groups. Conclusions: Treatment of COVID-19 pneumonitis with inhalational nebulized NaIHS was associated with rapid improvement in hypoxia and vital signs, with no serious adverse events attributed to therapy. Nebulized NaIHS s worthy of further study in randomized, placebo-controlled trials (ClinicalTrials.gov: NCT04382768).Fil: Salva, Oscar. Clínica Independencia; ArgentinaFil: Doreski, Pablo A.. Fundación Respirar; ArgentinaFil: Giler, Celia S.. Clínica Independencia; ArgentinaFil: Quinodoz, Dario C.. Sanatorio de la Cañada; ArgentinaFil: Guzmán, Lucia G.. Sanatorio de la Cañada; ArgentinaFil: Muñoz, Sonia Edith. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Carrillo, Mariana Norma del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Porta, Daniela Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Ambasch, Germán. Sanatorio Privado Mayo; ArgentinaFil: Coscia, Esteban. Sanatorio Privado Mayo; ArgentinaFil: Tambini Diaz, Jorge L.. Sanatorio Privado Mayo; ArgentinaFil: Bueno, Germán D.. Sanatorio Privado Mayo; ArgentinaFil: Fandi, Jorge O.. Clínica Independencia; ArgentinaFil: Maldonado, Miriam A.. Sanatorio San Roque; ArgentinaFil: Peña Chiappero, Leandro E.. Sanatori San Roque; ArgentinaFil: Fournier, Fernando. Clínica Francesa; ArgentinaFil: Pérez, Hernán A.. Sanatorio Alive; Argentina. University of Maryland; Estados UnidosFil: Quiroga, Mauro A.. Instituto Modelo de Cardiología; ArgentinaFil: Sala Mercado, Javier Agustin. Instituto Modelo de Cardiología; ArgentinaFil: Martínez Picco, Carlos. Clínica del Sol; ArgentinaFil: Beltrán, Marcelo Alejandro. Hospital Dr. Alberto Duhau; ArgentinaFil: Castillo Argañarás, Luis Fernando. Hospital Dr. Alberto Duhau; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ríos, Nicolás Martínez. Quimica Luar Srl; ArgentinaFil: Kalayan, Galia I.. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; ArgentinaFil: Beltramo, Dante Miguel. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Garcia, Nestor Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; Argentin

The prevalence of bronchiectasis in patients with alpha-1 antitrypsin deficiency: initial report of EARCO

Background: Although bronchiectasis has been recognised as a feature of some patients with Alpha1-Antitrypsin deficiency the prevalence and characteristics are not widely known. We wished to determine the prevalence of bronchiectasis and patient characteristics. The first cohort of patients recruited to the EARCO (European Alpha1 Research Collaboration) International Registry data base by the end of 2021 was analysed for radiological evidence of both emphysema and bronchiectasis as well as baseline demographic features. Results: Of the first 505 patients with the PiZZ genotype entered into the data base 418 (82.8%) had a reported CT scan. There were 77 (18.4%) with a normal scan and 38 (9.1%) with bronchiectasis alone. These 2 groups were predominantly female never smokers and had lung function in the normal range. The remaining 303 (72.5%) ZZ patients all had emphysema on the scan and 113 (27%) had additional evidence of bronchiectasis. Conclusions: The data indicates the bronchiectasis alone is a feature of 9.1% of patients with the PiZZ genotype of Alpha1-antitrypsin deficiency but although emphysema is the dominant lung pathology bronchiectasis is also present in 27% of emphysema cases and may require a different treatment strategy

A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio

Tendencias de la investigación en Ingeniería Ambiental

Esta obra incluye las memorias del Simposio “Tendencias de la Investigación en Ingeniería Ambiental”, organizado por el Grupo de Investigaciones y Mediciones Ambientales (GEMA), realizado en la Universidad de Medellín en agosto de 2007. El texto está conformado por 14 capítulos agrupados en cuatro partes. En la primera se agrupan los trabajos relacionados con la calidad y alternativas de tratamiento del agua e hidráulica ambiental (capítulos 1 al 4). La segunda trata temas relacionados con la contaminación atmosférica y calidad del aire (capítulos 5 al 6). La tercera está relacionada con las tecnologías ambientales para la recuperación y conservación de suelos (capítulos 7 al 10) y la cuarta y última comprende las temáticas asociadas con la sostenibilidad ambiental del territorio (capítulos 11 al 14). En este sentido, estamos convencidos del valioso aporte que el libro dará a la comunidad científica, por ser este un documento de divulgación de resultados de investigación en ingeniería ambiental.PRÓLOGO............13 PRESENTACIÓN.............15 PRIMERA PARTE CALIDAD Y ALTERNATIVAS DE TRATAMIENTO DEL AGUA HIDRÁULICA AMBIENTAL Capítulo 1 PRETRATAMIENTO DE AGUAS RESIDUALES INDUSTRIALES MEDIANTE FOTO-FENTON SOLAR A ESCALA INDUSTRIAL ACOPLADO A BIOTRATAMIENTO CON FANGOS ACTIVOS INMOVILIZADOS Manuel Ignacio Maldonado, Isabel Oller, Wolfgang Gernjak, Sixto Malato 1.1 INTRODUCCIÓN............19 1.2 MATERIALES Y MÉTODOS.............21 1.2.1 Reactivos............21 1.2.2 Determinaciones analíticas.............22 1.2.3 Dispositivo experimental.............23 1.3 R ESULTADOS Y DISCUSIÓN............ 27 1.3.1 Tratamiento foto-Fenton solar............27 1.3.2 Biotratamiento mediante fangos activos inmovilizados.............33 1.3.3 Sistema combinado foto-Fenton solar-biológico aeróbico............35 1.4 CONCLUSIONES............. 42 Capítulo 2 DEGRADACIÓN DE LA ATRAZINA EN SOLUCIÓN ACUOSA USANDO RADIACIÓN UV Y PROCESOS DE OXIDACIÓN AVANZADA Margarita Hincapié, Gustavo Peñuela, Manuel I. Maldonado, Sixto Malato 2.1 INTRODUCCIÓN..............47 2.2 SECCIÓN EXPERIMENTAL..............53 2.2.1 Materiales.............53 2.2.2 Metodología...............53 2.2.3 Determinación analítica..............55 2.2.4 Determinación de la toxicidad...............55 2.3 R ESULTADOS Y DISCUSIÓN...............56 2.3.1 Hidrólisis..............56 2.3.2 Fotólisis y fotocatálisis con TiO2 Degussa P25.............56 2.3.3 Efecto de los agentes oxidantes peróxido de hidrógeno y persulfato de sodio en la fotocatálisis..............59 2.3.4 Proceso foto Fenton..............63 2.3.5 Evaluación de los aniones inorgánicos durante los dos tratamientos.............66 2.3.6 Cuantificación e identificación de los productos de degradación...............68 2.3.7 Evaluación de la toxicidad...............71 2.4 CONCLUSIONES...............74 Capítulo 3 HUMEDALES ARTIFICIALES PARA EL TRATAMIENTO DE AGUAS RESIDUALES Nazly E. Sánchez P., Gustavo A. Peñuela M., Juan C. Casas Z. 3.1 INTRODUCCIÓN...............81 3.2 MARCO TEÓRICO...............83 3.2.1 Humedales construidos para el tratamiento de aguas residuales..............84 3.2.2 Clasificación de los humedales.............85 3.2.3 Ventajas y desventajas de los humedales subsuperficiales..............87 3.2.4 Aspectos a considerar en los humedales subsuperficiales..............88 3.3 MATERIALES Y MÉTODOS.................89 3.3.1 Diseño y construcción de los humedales a escala piloto..............89 3.3.2 Componentes del agua residual sintética................90 3.3.3 Siembra y aclimatación de plantas............... 90 3.3.4 Muestreos............91 3.4 R ESULTADOS Y DISCUSIÓN..............91 3.4.1 pH..............91 3.4.2 Demanda bioquímica de oxígeno (DBO5)..............92 3.4.3 Carbono orgánico total (COT)................94 3.5 CONCLUSIONES................95 Capítulo 4 DESCRIPCIÓN DE LA DINÁMICA OCEANOGRÁFICA DEL GOLFO DE URABÁ UTILIZANDO MEDICIONES DE CAMPO Luis Javier Montoya Jaramillo, Francisco Mauricio Toro Botero 4.1 INTRODUCCIÓN...............103 4.2 DATOS Y MÉTODOS................107 4.3 DISCUSIÓN..............118 4.4 CONCLUSIONES............. 120 SEGUNDA PARTE CONTAMINACIÓN ATMOSFÉRICA Y CALIDAD DEL AIRE Capítulo 5 IMPACTO DE LAS MOTOCICLETAS EN LA CALIDAD DEL AIRE. ESTUDIO DE CASO: MONTERÍA Carlos Alberto Echeverri Londoño 5.1 INTRODUCCIÓN.................127 5.2 MATERIALES Y MÉTODOS...............131 5.2.1 S elección de los sitios de medición...............131 5.2.2 Período de medición................131 5.2.3 Parámetros seleccionados...............132 5.2.4 Equipos y materiales utilizados..............132 5.2.5 Índices de calidad del aire..............133 5.2.6 Legislación.............. 138 5.2.7 Inventario de emisiones..............141 5.3 RESULTADOS...............142 5.3.1 Calidad del aire y calidad acústica................142 5.3.2 Emisiones vehiculares.............150 5.3.3 Inventario de emisiones.............155 5.4 CONCLUSIONES.............. 158 5.5 RECOMENDACIONES............. 160 Capítulo 6 ROMPIMIENTO DE LA INVERSIÓN TÉRMICA EN EL VALLE DE ABURRÁ Ángela M. Rendón, José F. Jiménez, Carlos Palacio 6.1 INTRODUCCIÓN...............163 6.2 MEDICIÓN DE VARIABLES ATMOSFÉRICAS..............164 6.3 CAMPAÑAS DE MEDICIÓN.............165 6.4 RESULTADOS..............166 6.5 CONCLUSIONES................170 TERCERA PARTE TECNOLOGÍAS AMBIENTALES PARA LA RECUPERACIÓN Y CONSERVACIÓN DE SUELOS Capítulo 7 ESTRUCTURA MODELO DE LA PARTÍCULA FUNDAMENTAL DEL COMPOST Carlos E. Arroyave M., Carlos A. Peláez J. 7.1 INTRODUCCIÓN..............177 7.2 MATERIALES Y EQUIPOS.............178 7.2.1 Materias primas y planta de compostaje............178 7.2.2 Obtención de fracciones............. 182 7.2.3 Análisis estadístico.............184 7.3 RESULTADOS Y DISCUSIÓN.............184 7.3.1 Caracterización fisicoquímica del material de RSUsf...........184 7.3.2 Tamaño de partícula.............185 7.3.3 Análisis instrumental................187 7.3.4 Modelo de partícula..............194 7.4 CONCLUSIONES..............195 Capítulo 8 DEGRADACIÓN DE HEXACLOROCICLOHEXANO (HCH) CON HONGOS DE PODREDUMBRE DE LA MADERA Juan Carlos Quintero Díaz, Gumersindo Feijoo, Juan Manuel Lema 8.1 INTRODUCCIÓN..............199 8.2 MATERIALES Y MÉTODOS..............204 8.2.1 Microorganismos.............204 8.2.2 Ensayos de selección de los hongos de podredumbre de la madera.............204 8.2.3 Ensayos de degradación de HCH en medio líquido.............205 8.2.4 Ensayos de degradación de HCH en sobre suelo contaminado.............205 8.2.5 Extracción y análisis de los isómeros de HCH.............208 8.3 RESULTADOS Y DISCUSIÓN..............209 8.3.1 Selección de los microorganismos.............209 8.3.2 Degradación de HCH en medio líquido.............210 8.3.3 Degradación de HCH en fase sólida.............212 8.4 CONCLUSIONES.............. 220 Capítulo 9 AVANCES EN LA PROPAGACIÓN ASIMBIÓTICA IN VITRO DE ORQUÍDEAS CON ESPECIAL ÉNFASIS EN EL GÉNERO CATTLEYA Liliana R. Botero, María A. Jaramillo, Óscar O. Ossa R., Tatiana Saldarriaga F., Estefanía Ortiz R. 9.1 INTRODUCCIÓN...............227 9.2 MATERIALES Y MÉTODOS...............231 9.2.1 Evaluación de la metodología de desinfección de cápsulas de orquídeas.............231 9.2.2 Evaluación del efecto de un abono comercial y un suplemento comercial de banano............239 9.3 R ESULTADOS Y DISCUSIÓN..............242 9.3.1 Ensayos de desinfección...............242 9.3.2 Resultados del efecto de un abono comercial y un suplemento de banano comercial....246 9.4 CONCLUSIONES..............254 Capítulo 10 MOVILIDAD DEL BRAVONIL 720 (CLOROTALONILO) A TRAVÉS DE LA ZONA NO SATURADA Y SATURADA DE UN ACUÍFERO LIBRE SIMULADO Idalia Jacqueline López Sánchez, Gustavo Antonio Peñuela Mesa 10.1 INTRODUCCIÓN...............259 10.2 MATERIALES Y MÉTODOS...............261 10.3 RESULTADOS Y DISCUSIÓN..............269 10.4 CONCLUSIONES..............292 CUARTA PARTE SOSTENIBILIDAD AMBIENTAL DEL TERRITORIO Capítulo 11 LA RESPONSABILIDAD SOCIAL EMPRESARIAL COMO COMPONENTE DE SOSTENIBILIDAD AMBIENTAL John Fredy López Pérez 11.1 INTRODUCCIÓN...............299 11.2 UNA LECTURA DE LA SOSTENIBILIDAD AMBIENTAL DESDE UN PUNTO DE VISTA SOCIAL..............300 11.3 EL CONCEPTO DE LA RESPONSABILIDAD SOCIAL EMPRESARIAL...............303 11.4 LA RESPONSABILIDAD SOCIAL COMO ESPACIO PARA L A SOSTENIBILIDAD AMBIENTAL.............309 11.5 ESBOZOS DE UN CASO: EL SECTOR ELÉCTRICO COLOMBIANO..............311 11.6 CONCLUSIONES..............319 Capítulo 12 DETERMINACIÓN ESPACIAL DE ÁREAS DE IMPORTANCIA ESTRATÉGICA El caso de microcuencas abastecedoras de acueductos veredales del municipio de Medellín Joaquín Hincapié, Álvaro Lema 12.1 INTRODUCCIÓN................323 12.2 LA NOCIÓN DE ÁREA DE IMPORTANCIA ESTRATÉGICA...............325 12.3 LA IDEA DE LOS SERV ICIOS AMBIENTALES..............328 12.4 ESTRATEGIA METODOLÓGICA EN LA IDENTIFICACIÓN Y DETERMINACIÓN DE LAS ÁREAS DE IMPORTANCIA ESTRATÉGICA............332 12.5 L OS RESULTADOS DEL MODELO...............359 12.6 CONCLUSIONES............. 361 Capítulo 13 LA EDUCACIÓN AMBIENTAL EN LA TRANSFORMACIÓN DE LA CULTURA Luz Ángela Peña Marín, Alba Miriam Vergara Vargas 13.1 INTRODUCCIÓN..............369 13.2 APROXIMACIÓN CONCEPTUAL...............370 13.2.1 La reflexividad...............372 13.2.2 La construcción del otro...............374 13.2.3 El discurso.............. 372 13.2.4 La autonomía y la participación..............375 13.2.5 La educación ambiental y el desarrollo humano..............378 13.2.6 Base conceptual de la educación ambiental..............380 13.2.7 Contexto sociocultural..............382 13.2.8 Diagnóstico de la educación ambiental y la administración de los recursos naturales..............392 13.2.9 Criterios corporativos de educación ambiental.............394 13.3 CONCLUSIONES...............398 Capítulo 14 ENFOQUE CONCEPTUAL DE UN SISTEMA DE INDICADORES AMBIENTALES PARA LA EVALUACIÓN DE LOS POT: municipios del Valle de San Nicolás Oriente Antioqueño Carolina Arias Muñoz, Diana Elizabeth Valencia Londoño, Boris Puerto López 14.1 INTRODUCCIÓN...............401 14.2 ENFOQUE CONCEPTUAL DEL SISTEMA DE INDICADORES..............406 14.2.1 Primera aproximación: el enfoque de impacto ambiental..............406 14.2.2 Enfoque sistémico: de la sostenibilidad ambiental..............408 14.3 PROPUESTA FINAL DE INDICADORES E ÌNDICE DE SOSTENIBILIDAD AMBIENTAL DEL POT ISAPOT.............424 14.4 R EFLEXIONES FINALES..............42

Common Variation in the PIN1 Locus Increases the Genetic Risk to Suffer from Sertoli Cell-Only Syndrome

Funding Information: Funding: This work was supported by the Plan Andaluz de Investigación, Desarrollo e Innovación (PAIDI 2020) (ref. PY20_00212, P20_00583), and the Spanish Ministry of Economy and Competitiveness through the Spanish National Plan for Scientific and Technical Research and Innovation (ref. SAF2016–78722-R, PID2020–120157RB-I00) and the Proyectos I + D + i del Programa Operativo FEDER 2020 (ref. B-CTS-584-UGR20, B-CTS-260-UGR20). FDC was supported by the “Ramón y Cajal” program (ref. RYC-2014–16458), and LBC was supported by the Spanish Ministry of Economy and Competitiveness through the “Juan de la Cierva Incorporación” program (Grant ref. IJC2018– 038026-I, funded by MCIN/AEI/10.13039/501100011033), all of them including FEDER funds. AGJ was funded by MCIN/AEI/10.13039/501100011033 and FSE “El FSE invierte en tu futuro”(grant ref. FPU20/02926). SGM was funded by a previously mentioned project (ref. PY20_00212). IPATIMUP integrates the i3S Research Unit, which is partially supported by the Portuguese Foundation for Science and Technology (FCT), financed by the European Social Funds (COMPETE-FEDER) and National Funds (projects PEstC/SAU/LA0003/2013 and POCI-01–0145-FEDER-007274). AML is funded by the Portuguese Government through FCT (IF/01262/2014). PIM is supported by the FCT post-doctoral fellowship (SFRH/BPD/120777/2016), financed from the Portuguese State Budget of the Ministry for Science, Technology and High Education and from the European Social Fund, available through the Programa Operacional do Capital Humano. ToxOmics—Centre for Toxicogenomics and Human Health, Genetics, Oncology and Human Toxicology, Nova Medical School, Lisbon, is also partially supported by FCT (Projects: UID/BIM/00009/2013 and UIDB/UIDP/00009/2020). SLarriba received support from Instituto de Salud Carlos III (grant DTS18/00101], co-funded by FEDER funds/European Regional Development Fund (ERDF)—a way to build Europe), and from “Generalitat de Catalunya” (grant 2017SGR191). SLarriba is sponsored by the “Researchers Consolidation Program” from the SNS-Dpt. Salut Generalitat de Catalunya (Exp. CES09/020). This article is related to the Ph.D. Doctoral Thesis of Miriam Cerván-Martín (grant ref. BES-2017–081222 funded by MCIN/AEI/10.13039/501100011033 and FSE “El FSE invierte en tu futuro”). Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.We aimed to analyze the role of the common genetic variants located in the PIN1 locus, a relevant prolyl isomerase required to control the proliferation of spermatogonial stem cells and the integrity of the blood–testis barrier, in the genetic risk of developing male infertility due to a severe spermatogenic failure (SPGF). Genotyping was performed using TaqMan genotyping assays for three PIN1 taggers (rs2287839, rs2233678 and rs62105751). The study cohort included 715 males diagnosed with SPGF and classified as suffering from non-obstructive azoospermia (NOA, n = 505) or severe oligospermia (SO, n = 210), and 1058 controls from the Iberian Peninsula. The allelic frequency differences between cases and controls were analyzed by the means of logistic regression models. A subtype specific genetic association with the subset of NOA patients classified as suffering from the Sertoli cell-only (SCO) syndrome was observed with the minor alleles showing strong risk effects for this subset (ORaddrs2287839 = 1.85 (1.17–2.93), ORaddrs2233678 = 1.62 (1.11–2.36), ORaddrs62105751 = 1.43 (1.06–1.93)). The causal variants were predicted to affect the binding of key transcription factors and to produce an altered PIN1 gene expression and isoform balance. In conclusion, common non-coding single-nucleotide polymorphisms located in PIN1 increase the genetic risk to develop SCO.publishersversionpublishe

Contribution of TEX15 genetic variants to the risk of developing severe non-obstructive oligozoospermia

Background: Severe spermatogenic failure (SPGF) represents one of the most relevant causes of male infertility. This pathological condition can lead to extreme abnormalities in the seminal sperm count, such as severe oligozoospermia (SO) or non-obstructive azoospermia (NOA). Most cases of SPGF have an unknown aetiology, and it is known that this idiopathic form of male infertility represents a complex condition. In this study, we aimed to evaluate whether common genetic variation in TEX15, which encodes a key player in spermatogenesis, is involved in the susceptibility to idiopathic SPGF.Materials and Methods: We designed a genetic association study comprising a total of 727 SPGF cases (including 527 NOA and 200 SO) and 1,058 unaffected men from the Iberian Peninsula. Following a tagging strategy, three tag single-nucleotide polymorphisms (SNPs) of TEX15 (rs1362912, rs323342, and rs323346) were selected for genotyping using TaqMan probes. Case-control association tests were then performed by logistic regression models. In silico analyses were also carried out to shed light into the putative functional implications of the studied variants.Results: A significant increase in TEX15-rs1362912 minor allele frequency (MAF) was observed in the group of SO patients (MAF = 0.0842) compared to either the control cohort (MAF = 0.0468, OR = 1.90, p = 7.47E-03) or the NOA group (MAF = 0.0472, OR = 1.83, p = 1.23E-02). The genotype distribution of the SO population was also different from those of both control (p = 1.14E-02) and NOA groups (p = 4.33-02). The analysis of functional annotations of the human genome suggested that the effect of the SO-associated TEX15 variants is likely exerted by alteration of the binding affinity of crucial transcription factors for spermatogenesis.Conclusion: Our results suggest that common variation in TEX15 is involved in the genetic predisposition to SO, thus supporting the notion of idiopathic SPGF as a complex trait