Salud y Cambio Climático. Es hoy. ¿Estamos preparados?

En el siglo XXI, nos encontramos en un momento crucial donde la salud y el bienestar de las personas están intrínsecamente ligados a la preservación del medio ambiente y a la sostenibilidad de nuestro planeta. Cada vez más, comprendemos que no podemos separar el cuidado de nuestra salud de la salud del ecosistema en el que vivimos. Surge así la necesidad imperante de abordar la interrelación entre la salud humana, el cambio climático y la conservación de la biodiversidad. Este enfoque holístico nos exige replantear nuestros conceptos y prácticas en el ámbito de la salud pública, reconociendo que la promoción del bienestar individual y colectivo está estrechamente vinculada con la protección y preservación del entorno natural que nos rodea. Es necesario adoptar una perspectiva integradora y multidimensional en el ámbito de la salud, que abarque desde las dimensiones individuales hasta las colectivas, desde lo biológico hasta lo ambiental, y desde lo local hasta lo global. Cada persona y comunidad tiene una concepción propia de lo que entiende por salud y esta concepción rige el modo en que cada comunidad se organiza para su cuidado. El concepto de salud, por lo tanto, es dinámico y está influido por aspectos socio-históricos propios de cada contexto. Tan es así, que desde las primeras definiciones donde la salud se concebía como la ausencia de enfermedad, el concepto ha evolucionado incorporando cada vez más dimensiones yendo de lo individual a lo colectivo, de lo biológico a lo emocional e interacción con el ambiente[i] y desde una concepción objetiva a la de salud sentida. Hoy, más que nunca, esto cobra cabal importancia, puesto que los desastres naturales y situaciones sanitarias de los últimos años nos han obligado a reconocer la interdependencia del clima, los ecosistemas, la biodiversidad y las sociedades humanas, al punto tal que la Organización de las Naciones Unidas promueve desde 2021 el concepto de “Una salud” (2021) para este enfoque integrador y como aspecto fundamental para alcanzar los objetivos del desarrollo sostenible[ii].  El VI informe del Panel Internacional para el cambio climático[iii] ha mostrado cómo el cambio climático está afectando la salud y el bienestar humano en todo el mundo. La evidencia señala un aumento de las inequidades en salud, mayor frecuencia de enfermedades infecciosas y emergentes, así como el aumento en la intensidad y distribución de enfermedades transmisibles y no transmisibles.  En todas las regiones, los sistemas y comunidades más vulnerables son los más afectados por los impactos del cambio climático. Esas comunidades son también las con mayor carga de enfermedad, incluso por causas prevenibles, y por tanto las más desafiadas en su capacidad adaptativa.  A los determinantes sociales de la enfermedad se les suman los ambientales y climáticos que exacerban las inequidades. El cambio climático ha provocado ya pérdidas irreversibles en ecosistemas marinos, costeros y terrestres y son mayores a los que se esperaban. El deterioro de los ecosistemas, su resiliencia y capacidad adaptativa, así como cambios en el patrón climático estacional, han tenido importantes consecuencias socioeconómicas. El incremento en frecuencia e intensidad en eventos extremos ha provocado disminución en la biodiversidad y afectado negativamente los sistemas hídricos y productivos de alimentos. La acidificación y calentamiento de los océanos ha ocasionado pérdidas importantes en la acuicultura. Todo ello ha puesto en riesgo la seguridad alimentaria e hídrica principalmente en latitudes medianas y bajas e islas pequeñas. Las pérdidas bruscas en producción y acceso a alimentos han afectado la diversidad de la alimentación, aumentando la malnutrición principalmente en pueblos originarios, hogares de bajos recursos, niños y ancianos y ha provocado migraciones poblacionales a zonas más favorables.  En este contexto, los desafíos son múltiples y esta nueva realidad nos convoca a trabajar de manera conjunta e integrada, para anticiparnos en las habilidades para prevenir, mitigar, adaptarnos y mejorar la capacidad de resiliencia a los efectos del cambio climático.  Es tal la inminencia de estas necesidades que los principales organismos internacionales vienen trabajando al respecto desde hace varios años para incluir estos aspectos en la agenda de los países, como lo testimonian el acuerdo de París[iv] o los objetivos del desarrollo sostenible[v].  El sistema sanitario en particular, enfrenta retos significativos en muy diversos órdenes, particularmente en la atención a poblaciones eco-refugiadas o migrantes, así como en la integración de registros y sistemas de salud. Las migraciones obligan a pensar en la articulación y acceso a su historial de salud en los lugares de destino dondequiera que estos sean o evaluar las implicancias del desarraigo cultural y las posibilidades de un accionar intersectorial e interjurisdiccional. El accionar con decisiones oportunas y adecuadas a cada contexto, no es un detalle menor a la hora de evaluar la disponibilidad y calidad de la información en sistemas con coexistencia de registros digitales y en papel, o vacíos de información y sistemas de salud desarticulados. El cuidado del ambiente, la preservación de la biodiversidad para la mitigación de los efectos del clima, implica también el desarrollo de nuevas estrategias por parte de los sistemas productivos de bienes y servicios.  Se requiere mejorar la articulación entre el sector público y privado (gobiernos y sociedad civil y empresas), estimulando la competitividad de aquellos emprendimientos de prácticas más ecológicas y sostenibles, y la promoción de patrones de consumo amigables con el ambiente.  Las nuevas y cambiantes condiciones eco-ambientales demandan la adquisición de nuevas competencias en los profesionales de la salud. En este sentido, numerosos organismos educativos se están nucleando en consorcios internacionales[vi] para trabajar en la adecuación de la currícula de las Universidades a las nuevas problemáticas sanitarias, convencidos de la capacidad de los profesionales de la salud para influir en las políticas ambientales y defender los derechos de las comunidades más vulnerables y su capacidad de resiliencia.  Sin embargo, la acción en salud pública no puede limitarse únicamente a las ciencias de la salud, sino que requiere la colaboración de profesionales de diferentes áreas, sociedad civil y responsables de la toma de decisiones. Las instituciones educativas tienen la responsabilidad de generar conciencia y proporcionar una formación integral y transversalmente a todas las disciplinas para enfrentar los desafíos del cambio global, pero también es necesario un profundo ejercicio de responsabilidad individual y colectiva. A medida que enfrentamos los desafíos sin precedentes del cambio climático y la preservación de la salud, también encontramos una gran oportunidad para generar un cambio positivo y construir un futuro más sostenible y saludable. Aprendemos de las lecciones del pasado y nos damos cuenta de que nuestras acciones individuales y colectivas pueden marcar la diferencia. Al adoptar un enfoque integrador, trabajando en colaboración entre sectores, comunidades y países, podemos fortalecer la resiliencia de nuestras sociedades y proteger la salud de las generaciones presentes y futuras. La educación, la conciencia y la responsabilidad son pilares fundamentales en este camino, y cada uno de nosotros tiene un papel relevante que desempeñar. A través de la innovación, la investigación y la implementación de prácticas sostenibles, podemos lograr un equilibrio entre el cuidado de nuestra salud, el respeto por el medio ambiente y la promoción de una sociedad más justa e inclusiva. Con determinación y acción conjunta, podemos forjar un futuro en el que la salud y el bienestar de todos estén en armonía con la salud de nuestro preciado planeta. Construyamos juntos un mundo más saludable y sostenible para todos.   [i] Guerrero L, León A. Aproximación al concepto de salud. Revisión histórica. Fermentum. Revista Venezolana de Sociología y Antropología 2008, 18(53) [ii]FAO. Una Salud.  https://www.fao.org/one-health/es [iii] IPCC (2022) Intergovernmental Panel on Climate Change. Climate Change 2022: Impacts, Adaptation and Vulnerability. Available in: https://report.ipcc.ch/ar6/wg2/IPCC_AR6_WGII_FullReport.pdf  [iv] Acuerdo de Paris. https://unfccc.int/es/acerca-de-las-ndc/el-acuerdo-de-paris [v] Objetivos del Desarrollo sostenible. https://www.un.org/sustainabledevelopment/es/objetivos-de-desarrollo-sostenible/ [vi] Global Consortium on Climate and Health Education. https://www.google.com/url?q=https://www.publichealth.columbia.edu/research/centers/global-consortium-climate-health-education&sa=D&source=docs&ust=1686083471773003&usg=AOvVaw3ibnHkSCuNbCFf5_4CDoeq

Cytokinin Determines Thiol-Mediated Arsenic Tolerance and Accumulation

The presence of arsenic in soil and water is a constant threat to plant growth in many regions of the world. Phytohormones act in the integration of growth control and stress response, but their role in plant responses to arsenic remains to be elucidated. Here, we show that arsenate [As(V)], the most prevalent arsenic chemical species in nature, causes severe depletion of endogenous cytokinins (CKs) in the model plant Arabidopsis (Arabidopsis thaliana). We found that CK signaling mutants and transgenic plants with reduced endogenous CK levels showed an As(V)-tolerant phenotype. Our data indicate that in CK-depleted plants exposed to As(V), transcript levels of As(V)/phosphate-transporters were similar or even higher than in wild-type plants. In contrast, CK depletion provoked the coordinated activation of As(V) tolerance mechanisms, leading to the accumulation of thiol compounds such as phytochelatins and glutathione, which are essential for arsenic sequestration. Transgenic CK-deficient Arabidopsis and tobacco lines show a marked increase in arsenic accumulation. Our findings indicate that CK is an important regulatory factor in plant adaptation to arsenic stress

Ibuprofen, a traditional drug that may impact the course of COVID-19 new effective formulation in nebulizable solution

The traditional formulation of ibuprofen is poorly soluble in water, so the administered dose must be 10 times higher than the dose required for a therapeutic effect. The development of a hydrosoluble form of ibuprofen can be a strategy to reach a high concentration in the lungs by using modern inhalation devices. Therefore, the development of an inhalable formulation with high bioavailability in the lungs was the leitmotiv of our investigation. The hypertonic ibuprofen solution to be nebulized (NIH) presents great relevant characteristics: bactericidal, virucidal, mucolytic and has a known anti-inflammatory property. Bactericidal and virucidal effects are related to the physico-chemical properties of Na-ibuprofenate as an amphipathic molecule. It has the capability to insert into the bilayer membranes destabilizing the structure, altering its biological properties and avoiding the duplication or infection. Our preliminary results indicate that the presence of this high ionic strength solution reduces 10 times the amount of ibuprofen necessary to kill bacteria, but also the time to kill 1x106 bacteria, from 4 h (in its absence) to only three minutes (in its presence). That was observed using Pseudomona aeruginosa, methicillin-resistant Staphylococcus aureus and Burkholderia cepacia. Also, ?in vitro´´ ibuprofen demonstrated virucidal activity against the so-called enveloped virus, a family that includes coronavirus strain (2019-nCoV). We observed too, the markedly reduced local inflammation in the airways after administering NIH lays on its ability to inhibit the enzyme cyclooxygenase and to markedly diminish reactive oxygen species (ROS). Other investigators also showed the importance of actin in the rapid spread of virus infection. Furthermore, reorganization of the actin filaments is a key step in lung inflammation induced by systemic inflammatory responses caused by SARS-CoV-2. These findings suggest that the interaction between actin proteins and S1 is involved in the 2019-nCoV infection and pathogenesis.Consequently, the possibility of interfering in this interaction could represent a valid hypothesis for the development of promising therapeutic and prevention strategies. In conclusion, we consider that treating people with COVID-19 with NIH may be beneficial and an opportunity to contribute for the current global health emergency.publishedVersionFil: García Canclini, Néstor. Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina. Instituto de Investigaciones en Ciencias de la Salud; Argentina.Fil: García Canclini, Néstor. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; Argentina.Fil: Porta, Daniela Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina. Instituto de Investigaciones en Ciencias de la Salud; Argentina.Fil: Porta, Daniela Josefina. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; Argentina.Fil: Muñoz, Sonia Edith. Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina. Instituto de Investigaciones en Ciencias de la Salud; Argentina; Argentina.Fil: Muñoz, Sonia Edith. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; Argentina.Fil: Alasino, Roxana Valeria. Ministerio de Ciencia y Tecnología de Córdoba. Centro de Excelencia en Productos y Procesos de Córdoba; Argentina.Fil: Beltramo, Dante MiguelIcon. Ministerio de Ciencia y Tecnología de Córdoba. Centro de Excelencia en Productos y Procesos de Córdoba; Argentina

Cytoadhesion to gC1qR through Plasmodium falciparum Erythrocyte Membrane Protein 1 in Severe Malaria

Cytoadhesion of Plasmodium falciparum infected erythrocytes to gC1qR has been associated with severe malaria, but the parasite ligand involved is currently unknown. To assess if binding to gC1qR is mediated through the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family, we analyzed by static binding assays and qPCR the cytoadhesion and var gene transcriptional profile of 86 P. falciparum isolates from Mozambican children with severe and uncomplicated malaria, as well as of a P. falciparum 3D7 line selected for binding to gC1qR (Pf3D7gC1qR). Transcript levels of DC8 correlated positively with cytoadhesion to gC1qR (rho = 0.287, P = 0.007), were higher in isolates from children with severe anemia than with uncomplicated malaria, as well as in isolates from Europeans presenting a first episode of malaria (n = 21) than Mozambican adults (n = 25), and were associated with an increased IgG recognition of infected erythrocytes by flow cytometry. Pf3D7gC1qR overexpressed the DC8 type PFD0020c (5.3-fold transcript levels relative to Seryl-tRNA-synthetase gene) compared to the unselected line (0.001-fold). DBLbeta12 from PFD0020c bound to gC1qR in ELISA-based binding assays and polyclonal antibodies against this domain were able to inhibit binding to gC1qR of Pf3D7gC1qR and four Mozambican P. falciparum isolates by 50%. Our results show that DC8-type PfEMP1s mediate binding to gC1qR through conserved surface epitopes in DBLbeta12 domain which can be inhibited by strain-transcending functional antibodies. This study supports a key role for gC1qR in malaria-associated endovascular pathogenesis and suggests the feasibility of designing interventions against severe malaria targeting this specific interaction

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

Awareness and knowledge of HPV, cervical cancer, and vaccines in young women after first delivery in São Paulo, Brazil : a cross-sectional study

BACKGROUND: The success of HPV vaccination programs will require awareness regarding HPV associated diseases and the benefits of HPV vaccination for the general population. The aim of this study was to assess the level of awareness and knowledge of human papillomavirus (HPV) infection, cervical cancer prevention, vaccines, and factors associated with HPV awareness among young women after birth of the first child. METHODS: This analysis is part of a cross-sectional study carried out at Hospital Maternidade Leonor Mendes de Barros, a large public maternity hospital in Sao Paulo. Primiparous women (15-24 years) who gave birth in that maternity hospital were included. A questionnaire that included questions concerning knowledge of HPV, cervical cancer, and vaccines was applied. To estimate the association of HPV awareness with selected factors, prevalence ratios (PR) were estimated using a generalized linear model (GLM). RESULTS: Three hundred and one primiparous women were included; 37% of them reported that they "had ever heard about HPV", but only 19% and 7%, respectively, knew that HPV is a sexually transmitted infection (STI) and that it can cause cervical cancer. Seventy-four percent of interviewees mentioned the preventive character of vaccines and all participants affirmed that they would accept HPV vaccination after delivery. In the multivariate analysis, only increasing age (P for trend = 0.021) and previous STI (P < 0.001) were factors independently associated with HPV awareness ("had ever heard about HPV"). CONCLUSIONS: This survey indicated that knowledge about the association between HPV and cervical cancer among primiparous young women is low. Therefore, these young low-income primiparous women could benefit greatly from educational interventions to encourage primary and secondary cervical cancer prevention programs.This study was supported by a research grant from Department of Immunization, Vaccines and Biologicals, World Health Organization (ref: V20-181-13). The authors are grateful to Dr M.T. Aguado for helpful discussions. We are also grateful to Dr Corintio Mariani Neto for the unconditional support provided during field work and to nurses from Hospital Maternidade Leonor Mendes de Barros

Nature of viruses and pandemics: Coronaviruses

Coronaviruses (CoVs) have the largest genome among RNA viruses and store large amounts of information without genome integration as they replicate in the cell cytoplasm. The replication of the virus is a continuous process, whereas the transcription of the subgenomic mRNAs is a discontinuous one, involving a template switch, which resembles a high frequency recombination mechanism that may favor virus genome variability. The origin of the three deadly human CoVs SARS-CoV, MERS-CoV and SARS-CoV-2 are zoonotic events. SARS-CoV-2 has incorporated in its spike protein a furine proteolytic site that facilitates the activation of the virus in any tissue, making this CoV strain highly polytropic and pathogenic. Using MERS-CoV as a model, a propagation-deficient RNA replicon was generated by removing E protein gene (essential for viral morphogenesis and involved in virulence), and accessory genes 3, 4a, 4b and 5 (responsible for antagonism of the innate immune response) to attenuate the virus: MERS-CoV-Δ[3,4a,4b,5,E]. This RNA replicon is strongly attenuated and elicits sterilizing protection after a single immunization in transgenic mice with the receptor for MERS-CoV, making it a promising vaccine candidate for this virus and an interesting platform for vector-based vaccine development. A strategy could be developed for the design of RNA replicon vaccines for other human pathogenic coronaviruses.This work was supported by grants from the Government of Spain (PID2019-107001RB-I00 AEI/FEDER, UE; SEV 2017-0712 and PIE_INTRAMURAL_LINEA 1-202020E079), the CSIC (PIE_INTRAMURAL-202020E043), the European Commission (ISOLDA_848166 H2020-SC1-2019-Two-Stage-RTD, RIA; MANCO_101003651 H2020-SC1-PHE-CORONAVIRUS-2020 RIA), and the U.S. National Institutes of Health (NIH_2P01AI060699).Peer reviewe

Breast cancer phenotypic variability is affected by the biological age

Resumen del póster presentado al XXXIX Congreso de la Sociedad Española de Bioquímica y Biología Molecular, celebrado en Salamanca del 5 al 8 de septiembre de 2016.Breast cancer incidence rates considerably increase with age and young age at diagnosis correlates with worse prognosis due to a more aggressive breast cancer behaviour. Biological age estimates the functional status of individuals comparing to other individuals of the same chronological age. We defined the biological age integrating phenotypes of oxidative stress, and calculated Δ biological age as the difference between chronological and predicted (biological) age. Mice with predicted ages older than chronological age, were considered biologically older; and mice with predicted ages younger than chronological age, were considered biologically younger. Our main goals were (i) define biological age using processes that are common to cancer and ageing, such as the oxidative stress, and (ii) analyze breast cancer phenotypic variability according to the biological age. We generated a cohort of mice with different susceptibility and evolution to ERBB2-induced breast cancer, using a backcross strategy, and dissected the disease into different pathophenotypes. We also measured intermediate phenotypes of oxidative stress. Linkage analysis was carried out to identify quantitative trait loci (QTL) associated with these phenotypes, and used multivariate models to define biological age. We identified that biologically older mice developed more aggressive disease than biologically younger mice. We also identified QTL simultaneously associated with Δ biological age and tumor pathophenotypes. We identified several genetic and molecular markers that define biological age and observed that ERBB2 breast cancer phenotypic variability is affected by the biological age.Peer reviewe

Assessing the impact of COVID-19 on liver cancer management (CERO-19).

BACKGROUND & AIMS: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems and it may have heavily impacted patients with liver cancer (LC). Herein, we evaluated whether the schedule of LC screening or procedures has been interrupted or delayed because of the COVID-19 pandemic. METHODS: An international survey evaluated the impact of the COVID-19 pandemic on clinical practice and clinical trials from March 2020 to June 2020, as the first phase of a multicentre, international, and observational project. The focus was on patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma, cared for around the world during the first COVID-19 pandemic wave. RESULTS: Ninety-one centres expressed interest to participate and 76 were included in the analysis, from Europe, South America, North America, Asia, and Africa (73.7%, 17.1%, 5.3%, 2.6%, and 1.3% per continent, respectively). Eighty-seven percent of the centres modified their clinical practice: 40.8% the diagnostic procedures, 80.9% the screening programme, 50% cancelled curative and/or palliative treatments for LC, and 41.7% modified the liver transplantation programme. Forty-five out of 69 (65.2%) centres in which clinical trials were running modified their treatments in that setting, but 58.1% were able to recruit new patients. The phone call service was modified in 51.4% of centres which had this service before the COVID-19 pandemic (n = 19/37). CONCLUSIONS: The first wave of the COVID-19 pandemic had a tremendous impact on the routine care of patients with liver cancer. Modifications in screening, diagnostic, and treatment algorithms may have significantly impaired the outcome of patients. Ongoing data collection and future analyses will report the benefits and disadvantages of the strategies implemented, aiding future decision-making. LAY SUMMARY: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems globally. Herein, we assessed the impact of the first wave pandemic on patients with liver cancer and found that routine care for these patients has been majorly disrupted, which could have a significant impact on outcomes

Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks : The GR@ACE project

Introduction: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. Methods: Genome Research at Fundacio ACE (GR@ACE) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta-analyzed with additional genome-wide association study data sets. Results: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444. Discussion: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series