Physical exercise, detraining and lipid profile in obese children: a systematic review

Introducción. El desentrenamiento es la pérdida de las mejoras obtenidas por el ejercicio físico/entrenamiento tras su cese, aspecto poco estudiado en población infantil obesa. Así, el propósito del presente estudio fue evaluar los efectos del desentrenamiento sobre el perfil lipídico (HDL, LDL, colesterol total y triglicéridos) en niños obesos. Población y métodos. Los estudios fueron recuperados mediante la búsqueda en siete bases de datos. Dicha búsqueda se limitó a programas de ejercicio físico de, al menos, ocho semanas de duración y su desentrenamiento, y se evaluó el perfil lipídico de niños obesos. Se calculó el tamaño del efecto (TE), sus intervalos de confianza del 95% y la heterogeneidad de los estudios a través de la Q de Cochrane (modelo de efectos aleatorios). Resultados. Cinco estudios cumplieron los criterios de inclusión y fueron seleccionados para su revisión (n= 330). En general, los resultados intragrupo (postest vs. desentrenamiento) mostraron que, tras el desentrenamiento, el nivel en sangre del colesterol HDL (TE= 0,12) y el colesterol total aumentaron (TE= 1,41). Del mismo modo, los resultados intergrupo (grupo experimental vs. grupo control) confirmaron el aumento del colesterol HDL tras el desentrenamiento (TE= 0,49). Conclusiones. Los resultados de esta revisión sistemática sugieren que el desentrenamiento tras un programa de ejercicio físico no genera una pérdida significativa de los beneficios obtenidos sobre el perfil lipídico de los niños obesos. No obstante, debido al número de estudios analizados y a la heterogeneidad observada en los análisis y en el tiempo considerado como desentrenamiento (de 12 a 48 semanas), se requiere un mayor número de estudios de calidad para obtener resultados más concluyentes.Introduction. Detraining is the loss of improvements obtained through the participation in physical exercise/training after training cessation, an aspect that has been poorly studied in obese child population. Therefore, the purpose of this study was to assess the effects of detraining on the lipid profile (HDL, LDL, total cholesterol and triglycerides) of obese children. Population and Methods. Studies were collected through a search across seven databases. The search was limited to physical exercise programs that lasted, at least, eight weeks and the corresponding detraining, with an assessment of obese children lipid profile. Effect size (ES), 95% confidence intervals and study heterogeneity were estimated using Cochran’s Q test (random effects model). Results. Five studies complied with the inclusion criteria and were selected for review (n= 330). In general, intra-group results (posttest versus detraining) indicated that, following detraining, blood levels of HDL cholesterol (ES= 0.12) and total cholesterol (ES= 1.41) were increased. Likewise, inter-group results (experimental group versus control group) confirmed the increase of HDL cholesterol following detraining (ES= 0.49). Conclusions. The results of this systematic review suggest that detraining after a physical exercise program does not lead to a significant loss of the benefits gained in relation to the lipid profile of obese children. However, given the number of analyzed studies and the heterogeneity observed in the analyses and the period defined as detraining (12 to 48 weeks), a higher number of well designed studies is required to obtain more conclusive results

Physical exercise, detraining and lipid profile in obese children: a systematic review

Introducción. El desentrenamiento es la pérdida de las mejoras obtenidas por el ejercicio físico/entrenamiento tras su cese, aspecto poco estudiado en población infantil obesa. Así, el propósito del presente estudio fue evaluar los efectos del desentrenamiento sobre el perfil lipídico (HDL, LDL, colesterol total y triglicéridos) en niños obesos. Población y métodos. Los estudios fueron recuperados mediante la búsqueda en siete bases de datos. Dicha búsqueda se limitó a programas de ejercicio físico de, al menos, ocho semanas de duración y su desentrenamiento, y se evaluó el perfil lipídico de niños obesos. Se calculó el tamaño del efecto (TE), sus intervalos de confianza del 95% y la heterogeneidad de los estudios a través de la Q de Cochrane (modelo de efectos aleatorios). Resultados. Cinco estudios cumplieron los criterios de inclusión y fueron seleccionados para su revisión (n= 330). En general, los resultados intragrupo (postest vs. desentrenamiento) mostraron que, tras el desentrenamiento, el nivel en sangre del colesterol HDL (TE= 0,12) y el colesterol total aumentaron (TE= 1,41). Del mismo modo, los resultados intergrupo (grupo experimental vs. grupo control) confirmaron el aumento del colesterol HDL tras el desentrenamiento (TE= 0,49). Conclusiones. Los resultados de esta revisión sistemática sugieren que el desentrenamiento tras un programa de ejercicio físico no genera una pérdida significativa de los beneficios obtenidos sobre el perfil lipídico de los niños obesos. No obstante, debido al número de estudios analizados y a la heterogeneidad observada en los análisis y en el tiempo considerado como desentrenamiento (de 12 a 48 semanas), se requiere un mayor número de estudios de calidad para obtener resultados más concluyentes.Introduction. Detraining is the loss of improvements obtained through the participation in physical exercise/training after training cessation, an aspect that has been poorly studied in obese child population. Therefore, the purpose of this study was to assess the effects of detraining on the lipid profile (HDL, LDL, total cholesterol and triglycerides) of obese children. Population and Methods. Studies were collected through a search across seven databases. The search was limited to physical exercise programs that lasted, at least, eight weeks and the corresponding detraining, with an assessment of obese children lipid profile. Effect size (ES), 95% confidence intervals and study heterogeneity were estimated using Cochran’s Q test (random effects model). Results. Five studies complied with the inclusion criteria and were selected for review (n= 330). In general, intra-group results (posttest versus detraining) indicated that, following detraining, blood levels of HDL cholesterol (ES= 0.12) and total cholesterol (ES= 1.41) were increased. Likewise, inter-group results (experimental group versus control group) confirmed the increase of HDL cholesterol following detraining (ES= 0.49). Conclusions. The results of this systematic review suggest that detraining after a physical exercise program does not lead to a significant loss of the benefits gained in relation to the lipid profile of obese children. However, given the number of analyzed studies and the heterogeneity observed in the analyses and the period defined as detraining (12 to 48 weeks), a higher number of well designed studies is required to obtain more conclusive results

Acute oxidant damage promoted on cancer cells by amitriptyline in comparison with some common chemotherapeutic drugs

Oxidative therapy is a relatively new anticancer strategy based on the induction of high levels of oxidative stress, achieved by increasing intracellular reactive oxygen species (ROS) and/or by depleting the protective antioxidant machinery of tumor cells. We focused our investigations on the antitumoral potential of amitriptyline in three human tumor cell lines: H460 (lung cancer), HeLa (cervical cancer), and HepG2 (hepatoma); comparing the cytotoxic effect of amitriptyline with three commonly used chemotherapeutic drugs: camptothecin, doxorubicin, and methotrexate. We evaluated apoptosis, ROS production, mitochondrial mass and activity, and antioxidant defenses of tumor cells. Our results show that amitriptyline produces the highest cellular damage, inducing high levels of ROS followed by irreversible serious mitochondrial damage. Interestingly, an unexpected decrease in antioxidant machinery was observed only for amitriptyline. In conclusion, based on the capacity of generating ROS and inhibiting antioxidants in tumor cells, amitriptyline emerges as a promising new drug to be tested for anticancer therapy

Disponibilidad y promoción de alcohol según la tipología de los locales y las condiciones socioeconómicas del área

Smoking and substance use during pregnancy are major preventable causes of mortality and morbidity, having a bidirectional and deleterious relationship with the mental health of the mother and child. As part of the WOMAP (Woman Mental Health and Addictions on Pregnancy) initiative, our study aimed to describe the prevalence of co-occurring mental illness and substance use problems, diagnoses and severity of those considered at risk and rates of treatment.A screening of 2,014 pregnant women was done using the AC-OK scale and they were asked about their smoking habits and services use for mental health/substance abuse. Of these, 170 women were considered at risk of co-occurring mental illness and substance use problems (≥ 2 positive responses to the AC-OK-Mental Health subscale, ≥ 1 positive response to the AC-OK-Substance Abuse subscale and/or smoking more than once a month and no use of specialized services) and were assessed with a more extensive battery of measures (Patient Health Questionnaire [PHQ-9], General Anxiety Disorder [GAD-7], Posttraumatic stress disorder [PTSD] Checklist for DSM-5 [PCL-5], Alcohol Use Disorders Identification Test [AUDIT], Drug Abuse Screening Test [DAST] and Fagerström).In the last year, 614 women (30.5%) smoked tobacco (42.5% daily) and 9.8% were positive for both substance use and mental illness per the AC-OK. Only 11.1% of them received specific treatment in the previous three months while another 13.6% were scheduled to attend services in the following month. From the subsample assessed in depth, 62(36.5%) endorsed at least moderate depression, 35(20.6%) endorsed at least moderate anxiety, 32(18.8%) endorsed PTSD on the PCL, and 37 out of 88 alcohol users scored above the threshold in AUDIT (≥ 3).In conclusion, high prevalence and low treatment rates suggest that effective detection mechanisms should be integrated into usual care, allowing for early interventions. ------------------------------------------------------------------ El tabaquismo y el consumo de sustancias durante el embarazo son importantes causas prevenibles de morbimortalidad, teniendo una relación bidireccional y deletérea con la salud mental de la madre y el niño. Como parte de la iniciativa WOMAP (Woman Mental Health and Addictions on Pregnancy), se estudiaron 2014 embarazadas buscando describir la prevalencia de trastornos mentales y por uso de sustancias concurrentes, las tasas de tratamiento y los diagnósticos y la gravedad. Las participantes fueron evaluadas con la escala AC-OK y se les preguntó sobre sus hábitos tabáquicos y uso de servicios de salud mental/sustancias. De las participantes, 170 mujeres resultaron positivas para un trastorno mental y por uso de sustancias concurrentes (≥ 2 positivos a la subescala AC-OK-Salud Mental, ≥ 1 positivos a la subescala AC-OK-Sustancias y/o fumar más de una vez al mes y no estar en tratamiento) y fueron evaluadas en profundidad mediante una batería de escalas (Patient Health Questionnaire [PHQ-9], General Anxiety Disorder [GAD-7], Post-traumatic stress disorder Checklist [PCL-5], Alcohol Use Disorders Identification Test [AUDIT], Drug Abuse Screening Test [DAST] y Fagerström). En el último año, 614 mujeres (30,5 %) fumaron tabaco (42,5 % diariamente) y el 9,8 % fueron positivas para problemas por uso de sustancias y salud mental según la AC-OK. Solo el 11,1 % había recibido tratamiento en los tres meses previos y solo un 13,6 % tenía una cita en el siguiente mes. De las 170 pacientes evaluadas secundariamente, 62(36,5 %) presentaron al menos depresión moderada, 35(20,6 %) al menos ansiedad moderada, 32(18,8 %) fueron positivas a la PCL-5, y 37 de las 88 que reconocieron uso de alcohol puntuaron por encima del umbral en AUDIT (≥ 3). En conclusión, la combinación de una prevalencia significativa junto con bajas tasas de tratamiento, remarcan la necesidad de mecanismos de detección efectivos en la atención habitual, permitiendo una intervención temprana.2020-2

Inmunohistochemical Profile of Solid Cell Nest of Thyroid Gland

It is widely held that solid cell nests (SCN) of the thyroid are ultimobranchial body remnants. SCNs are composed of main cells and C cells. It has been suggested that main cells might be pluripotent cells contributing to the histogenesis of C cells and follicular cells, as well as to the formation of certain thyroid tumors. The present study sought to analyze the immunohistochemical profile of SCN and to investigate the potential stem cell role of SCN main cells. Tissue sections from ten cases of nodular hyperplasia (non-tumor goiter) with SCNs were retrieved from the files of the Hospital Infanta Luisa (Seville, Spain). Parathormone (PTH), calcitonin (CT), thyroglobulin (TG), thyroid transcription factor (TTF-1), galectin 3 (GAL3), cytokeratin 19 (CK 19), p63, bcl-2, OCT4, and SALL4 expression were evaluated by immunohistochemistry. Patient clinical data were collected, and tissue sections were stained with hematoxylin–eosin for histological examination. Most cells stained negative for PTH, CT, TG, and TTF-1. Some cells staining positive for TTF-1 and CT required discussion. However, bcl-2, p63, GAL3, and CK 19 protein expression was detected in main cells. OCT4 protein expression was detected in only two cases, and SALL4 expression in none. Positive staining for bcl-2 and p63, and negative staining for PTH, CT, and TG in SCN main cells are both consistent with the widely accepted minimalist definition of stem cells, thus supporting the hypothesis that they may play a stem cell role in the thyroid gland, although further research will be required into stem cell markers. Furthermore, p63 and GAL-3 staining provides a much more sensitive means of detecting SCNs than staining for carcinoembryonic antigen, calcitonin, or other markers; this may help to distinguish SCNs from their mimics

Population-based multicase-control study in common tumors in Spain (MCC-Spain): rationale and study design

Introduction: We present the protocol of a large population-based case-control study of 5 common tumors in Spain (MCC-Spain) that evaluates environmental exposures and genetic factors. Methods: Between 2008-2013, 10,183 persons aged 20-85 years were enrolled in 23 hospitals and primary care centres in 12 Spanish provinces including 1,115 cases of a new diagnosis of prostate cancer, 1,750 of breast cancer, 2,171 of colorectal cancer, 492 of gastro-oesophageal cancer, 554 cases of chronic lymphocytic leukaemia (CLL) and 4,101 population-based controls matched by frequency to cases by age, sex and region of residence. Participation rates ranged from 57% (stomach cancer) to 87% (CLL cases) and from 30% to 77% in controls. Participants completed a face-to-face computerized interview on sociodemographic factors, environmental exposures, occupation, medication, lifestyle, and personal and family medical history. In addition, participants completed a self-administered food-frequency questionnaire and telephone interviews. Blood samples were collected from 76% of participants while saliva samples were collected in CLL cases and participants refusing blood extractions. Clinical information was recorded for cases and paraffin blocks and/or fresh tumor samples are available in most collaborating hospitals. Genotyping was done through an exome array enriched with genetic markers in specific pathways. Multiple analyses are planned to assess the association of environmental, personal and genetic risk factors for each tumor and to identify pleiotropic effects. Discussion: This study, conducted within the Spanish Consortium for Biomedical Research in Epidemiology & Public Health (CIBERESP), is a unique initiative to evaluate etiological factors for common cancers and will promote cancer research and prevention in Spain.The study was partially funded by the “Accion Transversal del Cancer”, approved on the Spanish Ministry Council on the 11th October 2007, by the Instituto de Salud Carlos III-FEDER (PI08/1770, PI08/0533, PI08/1359, PS09/00773, PS09/01286, PS09/01903, PS09/02078, PS09/01662, PI11/01403, PI11/01889, PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150), by the Fundación Marqués de Valdecilla (API 10/09), by the ICGC International Cancer Genome Consortium CLL, by the Junta de Castilla y León (LE22A10-2), by the Consejería de Salud of the Junta de Andalucía (PI-0571), by the Conselleria de Sanitat of the Generalitat Valenciana (AP 061/10), by the Recercaixa (2010ACUP 00310), by the Regional Government of the Basque Country by European Commission grants FOOD-CT- 2006-036224-HIWATE, by the Spanish Association Against Cancer (AECC) Scientific Foundation, by the The Catalan Government DURSI grant 2009SGR1489

Estudio molecular del cáncer de tiroides experimental

Tesis descargada en Fondos DigitalesLa tiroides es una glándula endocrina de origen ectodérmico que se desarrolla precozmente en la porción cefálica del tubo digestivo. Su función consiste en sintetizar las hormonas tiroxina (T4) y triiodotironina (T3), que controlan la tasa metabólica de l organismo. Se hallan en la región cervical, anterior a la laringe, y está constituida por dos lóbulos unidos por un istmo.Esta glándula está integrada por miles de folículos tiroideos, que son pequeñas esferas que miden en el hombre de 0,2 a 0,9 mm de diámetro. Los folículos están formados por epitelio simple y su cavidad contiene una sustancia gelatinosa llamada coloide. Las células de los folículos varían de aplanadas a columnares y los folículos muestran diámetros muy variables. El aspecto de los folículos tiroideos varía en función de la región de la glándula y de su actividad funcional. En una misma glándula hallamos folículos grandes, llenos de coloide y formados por epitelio cúbico o pavimentoso, al lado de folículos más pequeños con epitelio columnar. A pesar de esta variabilidad, cuando la altura media del epitelio es baja la glándula se considera hipoactiva. En cambio, cuando hay mucha hormona tirotrópica circulante aumenta muy notablemente la altura del epitelio folicular y la glándula está hiperactiva. Esta alteración se acompaña de un descenso de la cantidad de coloide y del diámetro de los folículos. La glándula está recubierta por una cápsula de tejido conjuntivo laxo de la que salen tabiques hacia el parénquima, los cuales se hacen gradualmente más delgados hasta llegar a los folículos, que están separados entre sí principalmente por las fibras reticulares. La glándula tiroidea es un órgano sumamente vascularizado por una extensa red de capilares sanguíneos y de vasos linfáticos que rodea a los folículos. Las células endoteliales de estos vasos capilares están fenestradas, como es frecuente también en otras glándulas endocrinas. Esta configuración facilita el transporte de sustancias entre las células endocrinas y la sangre.En este trabajo se pretende caracterizar molecularmente los tumores tiroideos que se desarrollan en ratas tratadas con perclorato potásico y determinar si este tratamiento aporta tumores aptos como modelo experimental de alguna variedad de cáncer tiroideo. Para la caracterización molecular se estudiarán varios genes involucrados en la ruta MAPK, concretamente, ret/PTC, N-ras, B-raf y PI3K

Pérdida auditiva y consumo de alcohol en mujeres entre 20 y 40 años de edad, en la comuna de Temuco, Chile

Objective: To analyze the relationship between alcohol consumption and loss hearing in women between 20 and 40 years of age in Temuco city. Methodology: Cutting study. We evaluated 30 consuming and non alcoholic women divided into 3 groups (G): G1 abstemies, G2 consumers of 40-59 and G3 consumers of> 60 grams alcohol daily (15, 6 and 9 respectively), intentional sampling contacted in shopping centers. Auditory tests were performed: Audiometry, Discrimination of the Word and Auditory Evoked Potentials of the Brain Stem. Results: In the right ear, there were significant differences in medium frequencies and word discrimination between groups 1 versus 2 (p = 0.045 and 0.010, respectively). In left ear, there were significant differences in the high frequencies between groups 1 versus 3, interpeak latencies of iii-v waves (time elapsed between iii and v waves in millisecond after the stimulus)between groups 1 versus 2 (p = 0.003) and groups 2 versus 3 (p = 0.005) to 80 dB; in interpeak latencies i-iii and iii-vbetween groups 1 versus 2 (p = 0.039) at 60 dB and in word discrimination between groups 1 versus 2 (p = 0.009) and 1 versus 3 (p = 0.013). Conclusion: In the group studied there is hearing loss related to a daily consumption from the 40 grams of alcohol being the most affected ear the left in the medium and high frequencies and affecting to the cochlea and also brainstem.  Objetivo: O objetivo foi analisar a relação entre consumo de álcool e perda auditiva em mulheres entre 20 e 40 anos. Metodologia: Foi realizado um estudo transversal não experimental  em que 30 consumidoras femininas e não o álcool foram divididas em 3 grupos: abstêmios G1, consumidores G2 de 40-59 gramas e consumidores G3> 60 gramas de álcool por dia. Testes auditivos foram realizados: audiometria, discriminação de palavras e potencial evocado auditivo de tronco encefálico. O teste não paramétrico de Mann-Whitney U foi utilizado para a análise estatística. Resultados: Na orelha direita, há diferenças significativas nas frequências médias e discriminação de palavras entre os grupos 1 e 2 (p = 0,045 e 0,010, respectivamente). Na orelha esquerda, há diferenças significativas nas freqüências agudas entre os grupos 1 versus 3, nas latências interpicos das ondas iii-v entre os grupos 1 versus 2 (p = 0,003) e os grupos 2 versus 3 (p = 0,005) a 80 dB; nas latências interpicos i-iii e iii-v entre os grupos 1 versus 2 (p = 0,039) a 60 dB e na discriminação de palavras entre os grupos 1 versus 2 (p = 0,009) e 1 versus 3 (p = 0,013). Conclusões: Há uma perda auditiva relacionada ao consumo diário de 40 gramas de álcool, sendo que a orelha mais afetou a esquerda nas freqüências média e aguda, afetando a cóclea e o tronco cerebral.Objetivo: Analizar la diferencia en la pérdida auditiva según el consumo de alcohol, en mujeres de entre 20 y 40 años de edad, en la comuna de Temuco, Chile. Metodología: Estudio de corte, donde se evaluaron 30 mujeres consumidoras y no consumidoras de alcohol, divididas en 3 grupos (G): G1 abstemias, G2 consumidoras de 40-59 y G3 consumidoras de más de 60 g de alcohol diarios (15, 6 y 9 respectivamente), con un muestreo intencional, contactadas en centros comerciales. Se realizaron pruebas auditivas: audiometría, discriminación de la palabra y potenciales evocados auditivos de tronco cerebral. Resultados: El oído derecho presentó diferencias significativas en las frecuencias medias y discriminación de la palabra en G1 vs. G2 (p = 0,045 y 0,010, respectivamente). El oído izquierdo mostró diferencias significativas en las frecuencias agudas en G1 vs. G3, en las latencias interpeakde las ondas iii-v (tiempo en milisegundo transcurrido entre la onda iii y v posterior al estímulo) en G1 vs. G2 (p = 0,003) y G2 vs. G3 (p = 0,005) a 80 dB; en las latencias interpeak i-iiiy iii-v en G1 vs. G2 (p = 0,039) a 60 dB y en la discriminación de la palabra en G1 vs. G2 (p = 0,009) y G1 vs. G3 (p =0,013). Conclusiones: En el grupo estudiado existe pérdida auditiva relacionada con un consumo diario a partir de los 40 g de alcohol, siendo el oído más afectado el izquierdo, en las frecuencias medias y agudas, en la cóclea y el tronco cerebral.

Reaction and inelastic processes in the collision O2 (v ≫ 0) + O2 (v = 0)

A reduced dimensionality model is used to study the reaction O2(X3Σg -, v ≫ 0)+O2(3Σg -, v′ = 0) → O3(X1A1)+ O(3P) by means of time-dependent and time-independent quantum-mechanical methods. State-selected probabilities and rate constants are obtained for the reactive process as well as for the inelastic collision in which the vibrationally excited oxygen loses one or more quanta. It is found that the experimentally observed jump in depletion rates above a critical value of v could be partially explained by the vibrational relaxation rather than reaction. Reaction only becomes important for relatively high translational energies and therefore the calculated rates are too small at the temperatures of interest. It is concluded, however, that the reaction saddle point region in the potential energy surface plays a crucial role in the enhancement of vibrational relaxation. © EDP Sciences Springer-Verlag 1998.This work has been partially supported by the DGICYT, (Spain) grant number PB95-0071 and CONACYT (Mexico) grant number 3111P-E9607. RH-L and JC-M wish to thank CSIC (Spain) and CONACYT (Mexico) for the financial support (grant E130.2128) that made possible this collaboration. JE, MIH and JC-M had partial support from European Union grant CI1*-CT94-0128.Peer Reviewe

Women's neuroplasticity during gestation, childbirth and postpartum.

Pregnancy is a unique neuroplastic period in adult life. This longitudinal study tracked brain cortical changes during the peripartum period and explored how the type of childbirth affects these changes. We collected neuroanatomic, obstetric and neuropsychological data from 110 first-time mothers during late pregnancy and early postpartum, as well as from 34 nulliparous women evaluated at similar time points. During late pregnancy, mothers showed lower cortical volume than controls across all functional networks. These cortical differences attenuated in the early postpartum session. Default mode and frontoparietal networks showed below-expected volume increases during peripartum, suggesting that their reductions may persist longer. Results also pointed to different cortical trajectories in mothers who delivered by scheduled C-section. The main findings were replicated in an independent sample of 29 mothers and 24 nulliparous women. These data suggest a dynamic trajectory of cortical decreases during pregnancy that attenuates in the postpartum period, at a different rate depending on the brain network and childbirth type.The project leading to these results has received funding from the Instituto de Salud Carlos III (project PI22/01365), Ministerio de Ciencia, Innovación y Universidades (project RTI2018-093952-B-100), ‘la Caixa’ Foundation under project code LCF/PR/HR19/52160001, the European Research Council under the ‘European Union’s Horizon 2020’ research and innovation programme (grant agreement no. 883069) and the Centro Nacional de Investigaciones Cardiovasculares (CNIC), and was co-funded by the European Regional Development Fund (ERDF), ‘A way of making Europe.’ M.M.-G. was funded by Ministerio de Ciencia, Innovación y Universidades, Instituto de Salud Carlos III, Predoctorales de Formación en Investigación en Salud (PFIS) contract (FI18/00255) and a predoctoral Fulbright grant; S.C. was funded by a Miguel Servet Type II research contract (CPII21/00016). M.M.-G. and S.C. were co-funded by the European Social Fund ‘Investing in your future’.S