Lung Transplant Improves Survival and Quality of Life Regardless of Telomere Dysfunction

Trasplante de pulmón; Fibrosis pulmonar; Trastornos de los telómerosTrasplantament pulmonar; Fibrosi pulmonar; Trastorns dels telòmersLung transplantation; Pulmonary fibrosis; Telomere disordersIntroduction: Fibrotic interstitial lung diseases (ILDs) are the first indication for lung transplantation (LT). Telomere dysfunction has been associated with poor post-transplant outcomes. The aim of the study was to evaluate the morbi-mortality and quality of life in fibrotic ILDs after lung transplant depending on telomere biology. Methods: Fibrotic ILD patients that underwent lung transplant were allocated to two arms; with or without telomere dysfunction at diagnosis based on the telomere length and telomerase related gene mutations revealed by whole-exome sequencing. Post-transplant evaluation included: (1) short and long-term mortality and complications and (2) quality of life. Results: Fifty-five percent of patients that underwent LT carried rare coding mutations in telomerase-related genes. Patients with telomere shortening more frequently needed extracorporeal circulation and presented a higher rate of early post-transplant hematological complications, longer stay in the intensive care unit (ICU), and a higher number of long-term hospital admissions. However, post-transplant 1-year survival was higher than 80% regardless of telomere dysfunction, with improvement in the quality of life and oxygen therapy withdrawal. Conclusions: Post-transplant morbidity is higher in patients with telomere dysfunction and differs according to elapsed time from transplantation. However, lung transplant improves survival and quality of life and the associated complications are manageable.This study was funded by Instituto de Salud Carlos III through project PI18/00367 (Co-funded by European Regional Development Fund, ERDF, a way to build Europe), Spanish Society of Respiratory (SEPAR), Barcelona Respiratory Network (BRN), and Fundació Ramón Pla Armengol. RP laboratory was funded by grants PI20-00335 (Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain supported by FEDER funds). MM-M was funded by grants PI18/00367 (Fondo de Investigaciones Sanitarias, ISCIII, Spain, supported by FEDER funds), AC19/00006 (Projects of International Programs, ISCIII, Spain, supported by FEDER funds), Cohorte FPI CIBERES-ISCIII, Barcelona Respiratory Network-Fundation Ramon Pla Armengol, Spanish Society of Respiratory (SEPAR), and Catalan Society of Respiratory (SOCAP-FUCAP). CF was funded by Ministerio de Ciencia e Innovación (grant RTC-2017-6471-1; AEI/FEDER, UE), and by Cabildo Insular de Tenerife (CGIEU0000219140)

Valorization of wastewater from table olives: NMR identification of antioxidant phenolic fraction and microwave single-phase reaction of sugary fraction

The table olive industry is producing a huge amount of wastewater, which is a post-processing cost and an environmental concern. The present study aims to valorize this processing by-product to obtain a value-added product, thereby enhancing resource efficiency and contributing to achieving sustainable development goals (SDGs). In this sense, a chemical reaction-based platform was developed to obtain valuable components, such as levulinic acid (LA) and 5-hydromethylfurfural (HMF). The products were then analyzed using NMR identification of the antioxidant phenolic fraction and microwave single-phase reaction of the sugary fraction. According to the results, the highest concentration of phenolic compounds does not correspond to the sample directly obtained from NaOH treatment (S1), indicating that water washing steps (S2-S5) are fundamental to recover phenolic substances. Moreover, glucose was presented in the sugary fraction that can be transformed into levulinic acid by a single-phase reaction under microwave irradiation. The information provided in this manuscript suggests that the wastewater from the olive processing industry can be valorized to obtain valuable products

Lung Transplant Improves Survival and Quality of Life Regardless of Telomere Dysfunction

Introduction: Fibrotic interstitial lung diseases (ILDs) are the first indication for lung transplantation (LT). Telomere dysfunction has been associated with poor post-transplant outcomes. The aim of the study was to evaluate the morbi-mortality and quality of life in fibrotic ILDs after lung transplant depending on telomere biology. Methods: Fibrotic ILD patients that underwent lung transplant were allocated to two arms; with or without telomere dysfunction at diagnosis based on the telomere length and telomerase related gene mutations revealed by whole-exome sequencing. Post-transplant evaluation included: (1) short and long-term mortality and complications and (2) quality of life. Results: Fifty-five percent of patients that underwent LT carried rare coding mutations in telomerase-related genes. Patients with telomere shortening more frequently needed extracorporeal circulation and presented a higher rate of early post-transplant hematological complications, longer stay in the intensive care unit (ICU), and a higher number of long-term hospital admissions. However, post-transplant 1-year survival was higher than 80% regardless of telomere dysfunction, with improvement in the quality of life and oxygen therapy withdrawal. Conclusions: Post-transplant morbidity is higher in patients with telomere dysfunction and differs according to elapsed time from transplantation. However, lung transplant improves survival and quality of life and the associated complications are manageable

Truncating FLNC Mutations Are Associated With High-Risk Dilated and Arrhythmogenic Cardiomyopathies

BACKGROUND: Filamin C (encoded by the FLNC gene) is essential for sarcomere attachment to the plasmatic membrane. FLNC mutations have been associated with myofibrillar myopathies, and cardiac involvement has been reported in some carriers. Accordingly, since 2012, the authors have included FLNC in the genetic screening of patients with inherited cardiomyopathies and sudden death. OBJECTIVES: The aim of this study was to demonstrate the association between truncating mutations in FLNC and the development of high-risk dilated and arrhythmogenic cardiomyopathies. METHODS: FLNC was studied using next-generation sequencing in 2,877 patients with inherited cardiovascular diseases. A characteristic phenotype was identified in probands with truncating mutations in FLNC. Clinical and genetic evaluation of 28 affected families was performed. Localization of filamin C in cardiac tissue was analyzed in patients with truncating FLNC mutations using immunohistochemistry. RESULTS: Twenty-three truncating mutations were identified in 28 probands previously diagnosed with dilated, arrhythmogenic, or restrictive cardiomyopathies. Truncating FLNC mutations were absent in patients with other phenotypes, including 1,078 patients with hypertrophic cardiomyopathy. Fifty-four mutation carriers were identified among 121 screened relatives. The phenotype consisted of left ventricular dilation (68%), systolic dysfunction (46%), and myocardial fibrosis (67%); inferolateral negative T waves and low QRS voltages on electrocardiography (33%); ventricular arrhythmias (82%); and frequent sudden cardiac death (40 cases in 21 of 28 families). Clinical skeletal myopathy was not observed. Penetrance was >97% in carriers older than 40 years. Truncating mutations in FLNC cosegregated with this phenotype with a dominant inheritance pattern (combined logarithm of the odds score: 9.5). Immunohistochemical staining of myocardial tissue showed no abnormal filamin C aggregates in patients with truncating FLNC mutations. CONCLUSIONS: Truncating mutations in FLNC caused an overlapping phenotype of dilated and left-dominant arrhythmogenic cardiomyopathies complicated by frequent premature sudden death. Prompt implantation of a cardiac defibrillator should be considered in affected patients harboring truncating mutations in FLNC.Instituto de Salud Carlos III [PI11/0699, PI14/0967, PI14/01477, RD012/0042/0029, RD012/0042/0049, RD012/0042/0066, RD12/0042/0069]; Spanish Ministry of Economy and Competitiveness [SAF2015-71863-REDT]; Plan Nacional de I+D+I; Plan Estatalde I+D+I, European Regional Development Fund; Health in Code SLS

Services provided by birds (high-mobile link species) in farmland and forest mosaics: forest regeneration and plague regulation

Este trabajo ha sido financiado con fondos de los proyectos CICYT Ministerio de Educación y Ciencia (CGL2007−60533/BOS, CGL2010−18312/BOS) y del Ministerio de Economía y Competitividad (CGL2014−53308−P), de la red REMEDINAL (S−0505/AMB/ 0335, S2009 AMB−1783, S2013/MAE−2719 y TE-CM S2018/EMT- 4338), de la Universidad de Alcalá (CCG2014/BIO−002) y del MAGRAMA y la Fundación Biodiversidad a través de la Fundación Internacional para la Restauración de Ecosistemas. GGS fue financiado con una beca FPU (AP2006−00891) y SMH por una beca FPI (BES−2008−006630), ambas del Ministerio de Educación y Ciencia. LMB fue financiada por una beca FPI (BES-2015-075276) del Ministerio de Ciencia y Tecnología. NM fue financiada por una beca de la Universidad de Alcalá. ABL agradece ayudas postdoctorales Juan de la Cierva (FJCI-2015-23687) y de la Fundación Alexander von Humboldt. Agradecemos la colaboración de la Dirección Xeral de Conservación da Natureza de la Xunta de Galicia por las facilidades para desarrollar las investigaciones realizadas en esta Comunidad y de las bodegas de Abadía Retuerta y Martín Berdugo y de Haciendas Bio. Finalmente, agradecemos la contribución de un revisor anónimo que mejoró la versión original de este artículo.Los elementos que soportan las funciones y servicios de los ecosistemas son insuficientemente conocidos, mermando nuestra capacidad para planificar la conservación, restauración y manejo de los ecosistemas. Entre dichos elementos, el papel de la avifauna es especialmente relevante al ser especies de gran movilidad (high mobile link species) que conectan distintas unidades del paisaje. Este trabajo analiza servicios ecosistémicos importantes dependientes de interacciones biológicas mediadas por la avifauna en mosaicos agroforestales. Abordamos tres objetivos específicos: el papel de (1) los córvidos en la dispersión y reclutamiento de quercíneas, (2) la avifauna insectívora en la regulación de plagas en cultivos leñosos y (3) las aves rapaces en la regulación de avifauna-plaga en viñedos. Nuestros resultados evidencian que la avifauna realiza funciones y servicios claves para la regeneración forestal y la regulación de plagas en mosaicos agroforestales. Identificamos especies que se desconocía que realizaban una función relevante, en particular la urraca (Pica pica), cuya actividad resulta en una dispersión efectiva de nueces y bellotas, y el abejero europeo (Pernis apivorus), con un elevado consumo de avispa asiática (Vespa velutina). La instalación de cajas-nido en cultivos leñosos aumenta las poblaciones de aves insectívoras que regulan plagas; sin embargo, la capacidad de regulación de las plagas es moderada y depende del contexto ambiental o estudio de caso. Las rapaces diurnas existentes en los paisajes estudiados contribuyen al control de plagas agrícolas como la del estornino negro (Sturnus unicolor). Proponemos integrar los servicios que proporcionan las aves en la ordenación del territorio para alcanzar modelos de desarrollo más sostenibles.The elements that support functions and ecosystem services are not well known yet, and this gap reduces our capacity to plan the conservation, restoration, and management of ecosystems. Among these elements, the role of avifauna is especially relevant as birds are high-mobile link species that connect different landscape units. This article analyzes important ecosystem services driven by biological interactions that are mediated by birds in farmland and forest mosaics. We propose three specific goals: to assess the role of (1) corvids in the dispersal and recruitment of oak species, (2) insectivorous birds in pest regulation of woody crops, and (3) raptors in regulation of plague birds in vineyards. Our results show that the avifauna performs key functions and services for forest regeneration and pest regulation in agroforestry mosaics. We identified species that were not known to perform relevant functions, particularly the magpie (Pica pica) and its effective dispersion of nuts and acorns, and the honey buzzard (Pernis apivorus) and its high consumption of Asian black hornet (Vespa velutina). The installation of nest-boxes in woody crops increases the populations of insectivorous birds that regulate pests; however, the capacity of pest control is moderate and depends on the environmental context or case study. The diurnal raptors thriving in the studied landscapes contribute to the control of agricultural pests such as the spotless starling (Sturnus unicolor). We propose to integrate the services provided by birds in landscape planning to achieve more sustainable development systems.Financiado con fondos de los proyectos CICYT Ministerio de Educación y Ciencia (CGL2007−60533/BOS, CGL2010−18312/BOS) y del Ministerio de Economía y Competitividad (CGL2014−53308−P), de la red REMEDINAL (S−0505/AMB/ 0335, S2009 AMB−1783, S2013/MAE−2719 y TE-CM S2018/EMT- 4338), de la Universidad de Alcalá (CCG2014/BIO−002) y del MAGRAMA y la Fundación Biodiversidad a través de la Fundación Internacional para la Restauración de Ecosistemas. GGS fue financiado con una beca FPU (AP2006−00891) y SMH por una beca FPI (BES−2008−006630), ambas del Ministerio de Educación y Ciencia. LMB fue financiada por una beca FPI (BES-2015-075276) del Ministerio de Ciencia y Tecnología. NM fue financiada por una beca de la Universidad de Alcalá. ABL agradece ayudas postdoctorales Juan de la Cierva (FJCI-2015-23687) y de la Fundación Alexander von Humbold

Relationship of metabolic syndrome and its components with -844 G/A and HindIII C/G PAI-1 gene polymorphisms in Mexican children

<p>Abstract</p> <p>Background</p> <p>Several association studies have shown that -844 G/A and <it>HindIII </it>C/G <it>PAI-1 </it>polymorphisms are related with increase of PAI-1 levels, obesity, insulin resistance, glucose intolerance, hypertension and dyslipidemia, which are components of metabolic syndrome. The aim of this study was to analyze the allele and genotype frequencies of these polymorphisms in <it>PAI-1 </it>gene and its association with metabolic syndrome and its components in a sample of Mexican mestizo children.</p> <p>Methods</p> <p>This study included 100 children with an age range between 6-11 years divided in two groups: a) 48 children diagnosed with metabolic syndrome and b) 52 children metabolically healthy without any clinical and biochemical alteration. Metabolic syndrome was defined as the presence of three or more of the following criteria: fasting glucose levels ≥ 100 mg/dL, triglycerides ≥ 150 mg/dL, HDL-cholesterol < 40 mg/dL, obesity BMI ≥ 95^thpercentile, systolic blood pressure (SBP) and diastolic blood pressure (DBP) ≥ 95^thpercentile and insulin resistance HOMA-IR ≥ 2.4. The -844 G/A and <it>HindIII </it>C/G <it>PAI-1 </it>polymorphisms were analyzed by PCR-RFLP.</p> <p>Results</p> <p>For the -844 G/A polymorphism, the G/A genotype (OR = 2.79; 95% CI, 1.11-7.08; <it>p </it>= 0.015) and the A allele (OR = 2.2; 95% CI, 1.10-4.43; <it>p </it>= 0.015) were associated with metabolic syndrome. The -844 G/A and A/A genotypes were associated with increase in plasma triglycerides levels (OR = 2.6; 95% CI, 1.16 to 6.04; <it>p </it>= 0.02), decrease in plasma HDL-cholesterol levels (OR = 2.4; 95% CI, 1.06 to 5.42; <it>p </it>= 0.03) and obesity (OR = 2.6; 95% CI, 1.17-5.92; <it>p </it>= 0.01). The C/G and G/G genotypes of the <it>HindIII </it>C/G polymorphism contributed to a significant increase in plasma total cholesterol levels (179 vs. 165 mg/dL; <it>p </it>= 0.02) in comparison with C/C genotype.</p> <p>Conclusions</p> <p>The -844 G/A <it>PAI-1 </it>polymorphism is related with the risk of developing metabolic syndrome, obesity and atherogenic dyslipidemia, and the <it>HindIII </it>C/G <it>PAI-1 </it>polymorphism was associated with the increase of total cholesterol levels in Mexican children.</p

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Estudio de prevalencia de isquemia crónica de miembros inferiores y de aneurisma de aorta abdominal en mayores de 65 años

Introducción. El aumento de la expectativa de vida ha conducido a que patologías vasculares, especialmente prevalentes en el segmento de población con más edad, se hayan constituido en problemas de salud. Objetivo. Determinar la prevalencia de la isquemia crónica (IC) y de los aneurismas de aorta abdominal (AAA) infrarrenal en la población mayor de 65 años del Área Sanitaria V (Gijón) del Servicio de Salud del Principado de Asturias. Pacientes y métodos. Se diseña un estudio descriptivo transversal, incluyendo finalmente 232 pacientes, 114 hombres y 118 mujeres, seleccionados aleatoriamente a partir de los datos de la tarjeta sanitaria. Se les explora, se realiza un eco-Doppler de la aorta abdominal y se calcula el índice tobillo-brazo. Resultados. La prevalencia de la IC es del 9,9% y de un 2,6% para el AAA. Se desagregan los resultados por sexos y dos grupos de edad, de 65-74 años y mayores de 75. La prevalencia de la IC está seis puntos por encima en el grupo de los mayores de 75 años (13,4%) y la del AAA es más de siete veces superior (5,2%). Conclusión. La prevalencia es más elevada en los mayores de 75 años y los varones para la IC y el AAA, con diferencias estadísticamente significativas. Este estudio abre las puertas a un seguimiento de los integrantes de la muestra, que permita determinar la incidencia de las diversas patologías