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Functional structure of local connections and differentiation of cerebral cortex areas in the neonate
(Elsevier B.V., 2024-08-08) Falcón Falcón, Carles Maria; Pujol Nuez, Jesús; Blanco Hinojo, Laura; Persavento, Cecilia; Martínez Vilavella, Gerard; Gascón, Mireia; Rivas, Ioar; Vilanova, Marc; Deus Yela, Juan; Gispert, Juan Domingo; Gómez Roig, Ma. Dolores; Llurba Olivé, Elisa; Dadvand, Payam; Sunyer, Jordi
Neuroimaging research on functional connectivity can provide valuable information on the developmental differentiation of the infant cerebral cortex into its functional areas. We examined healthy neonates to comprehensively map brain functional connectivity using a combination of local measures that uniquely capture the rich spatial structure of cerebral cortex functional connections. Optimal functional MRI scans were obtained in 61 neonates. Local functional connectivity maps were based on Iso-Distance Average Correlation (IDAC) measures. Single distance maps and maps combining three distinct IDAC measures were used to assess different levels of cortical area functional differentiation. A set of brain areas showed higher connectivity than the rest of the brain parenchyma in each local distance map. These areas were consistent with those supporting basic aspects of the neonatal repertoire of adaptive behaviors and included the sensorimotor, auditory and visual cortices, the frontal operculum/anterior insula (relevant for sucking, swallowing and the sense of taste), paracentral lobule (processing anal and urethral sphincter activity), default mode network (relevant for self-awareness), and limbicemotional structures such as the anterior cingulate cortex, amygdala and hippocampus. However, the results also indicate that brain areas presumed to be actively developing may not necessarily be mature. In fact, combined distance, second-level maps confirmed that the functional differentiation of the cerebral cortex into functional areas in neonates is far from complete. Our results provide a more comprehensive understanding of the developing brain systems, while also highlighting the substantial developmental journey that the neonatal brain must undergo to reach adulthood.
Prenatal exposure to synthetic phenols assessed in multiple urine samples and dysregulation of steroid hormone homeostasis in two European cohorts
(National Institute of Environmental Health Science, 2025-05-22) Jedynak, Paulina; Bustamante Pineda, Mariona; Rolland, Matthieu; Mustieles, Vicente; Thomsen, Cathrine; Sakhi, Amrit K.; Sabaredzovic, Azemira; Foraster, Maria; Gascón, Mireia; Gómez Roig, Ma. Dolores; Llurba Olivé, Elisa; Rivas, Ioar; Ouellet-Morin, Isabelle; Bayat, Sam; Lyon-Caen, Sarah; Pozo, Oscar J.; Vrijheid, Martine; Sunyer, Jordi; Slama, Rémy; Dadvand, Payam; Philippat, Claire
Background: Some synthetic phenols alter hormonal pathways involved in successful pregnancy and fetal development. Despite high within-subject temporal variability of phenols, previous studies mostly utilized spot urine samples to assess pregnancy exposure. Herein, we investigated associations between pregnancy exposure to eight phenols assessed in multiple pooled urine samples and steroid hormones assessed in maternal hair reflecting cumulative hormone levels over the previous weeks to months.Methods: We assessed phenol-hormone associations in 928 pregnant women from two pooled cohorts recruited in Spain [Barcelona Life Study Cohort (BiSC), 2018-2021] and France [Assessment of Air Pollution exposure during Pregnancy and Effect on Health (SEPAGES), 2014-2017] using pools of up to 21 samples each, collected in early pregnancy (median gestational age: 18.0 wk), as well as hair collected in late pregnancy (BiSC) or at birth (SEPAGES). We measured two bisphenols, four parabens, benzophenone-3, and triclosan along with metabolites of three adrenal(∑cortisol∑cortisol, ∑cortisone∑cortisone, and 11-dehydrocorticosterone) and two reproductive (progesterone and testosterone) hormones. We ran adjusted linear regressions for each exposure biomarker-outcome pair and Bayesian kernel machine regression for phenols mixture.Results: Bisphenol S was associated with higher cortisol and 11-dehydrocorticosterone concentrations. Propylparaben was associated with lower levels of cortisol, cortisone, and 11-dehydrocorticosterone, while methylparaben was linked to a reduction in cortisol levels. Interestingly, associations identified for parabens were stronger for women carrying female fetuses. No associations for phenol mixture were detected.Conclusions: Our study suggests that pregnancy exposure to bisphenol S and some parabens (propyl- and methylparaben) may affect production of maternal corticosteroid hormones that are important for a successful pregnancy and fetal development.
Prenatal exposure to per- and polyfluoroalkyl substances, fetoplacental hemodynamics, and fetal growth
(Elsevier Ltd., 2024-11-06) Cserbik, Dora; Knox, Bethany; Güil-Oumrait, Nuria; Basagaña, Xavier; Dadvand, Payam; Foraster, Maria; Galmes, Toni; Gascón, Mireia; Gómez Roig, Ma. Dolores; Gómez-Herrera, Laura; Småstuen Haug, Line; Llurba Olivé, Elisa; Márquez, Sandra; Rivas, Ioar; Sunyer, Jordi; Thomsen, Cathrine; Zanini, Maria Julia; Bustamante Pineda, Mariona; Vrijheid, Martine
Introduction: The impact of legacy per- and polyfluoroalkyl substances (PFAS) on fetal growth has been well studied, but assessments of next-generation PFAS and PFAS mixtures are sparse and the potential role of fetoplacental hemodynamics has not been studied. We aimed to evaluate associations between prenatal PFAS exposure and fetal growth and fetoplacental hemodynamics. Methods: We included 747 pregnant women from the BiSC birth cohort (Barcelona, Spain (2018-2021)). Twenty-three PFAS were measured at 32 weeks of pregnancy in maternal plasma, of which 13 were present above detectable levels. Fetal growth was measured by ultrasound, as estimated fetal weight at 32 and 37 weeks of gestation, and weight at birth. Doppler ultrasound measurements for uterine (UtA), umbilical (UmA), and middle cerebral artery (MCA) pulsatility indices (PI), as well as the cerebroplacental ratio (CPR - ratio MCA to UmA), were obtained at 32 weeks to assess fetoplacental hemodynamics. We applied linear mixed effects models to assess the association between singular PFAS and longitudinal fetal growth and PI, and Bayesian Weighted Quantile Sum models to evaluate associations between the PFAS mixture and the aforementioned outcomes, controlled for the relevant covariates. Results: Single PFAS and the mixture tended to be associated with reduced fetal growth and CPR PI, but few associations reached statistical significance. Legacy PFAS PFOS, PFHpA, and PFDoDa were associated with statistically significant decreases in fetal weight z-score of 0.13 (95%CI (-0.22, -0.04), 0.06 (-0.10, 0.01), and 0.05 (-0.10, 0.00), respectively, per doubling of concentration. The PFAS mixture was associated with a non-statistically significant 0.09 decrease in birth weight z-score (95%CI -0.22, 0.04) per quartile increase. Conclusion: This study suggests that legacy PFAS may be associated with reduced fetal growth, but associations for next generation PFAS and for the PFAS mixture were less conclusive. Associations between PFAS and fetoplacental hemodynamics warrant further investigation.
Seroepidemiology of maternal and childhood pathogen exposure in three European mother-child cohorts
(Elsevier BV, 2025-07-21) Karachaliou, Marianna; Vidal, Marta; Pembrey, Lucy; Bustamante Pineda, Mariona; Espinosa, Ana; Mason, Dan; Bañuls Tornero, Marc; Casabonne, Delphine; Roumeliotaki, Theano; Bempi, Vicky; Marín, Natalia; Delgado Saborit, Juana Maria; Rodríguez Loreto, Santa Marina; Ibarluzea, Jesús; Vrijheid, Martine; Aguilar, Ruth; Dobaño, Carlota, 1969-; Kogevinas, Manolis
Objectives: To describe the epidemiology of common pathogens and risk factors among pregnant women and their children. Methods: In three European population-based birth cohorts, we examined 2213 mother-child pairs, contributing 5036 blood samples from pregnancy to 12 years of age. We measured serum immunoglobulin G levels against polyomaviruses (BKPyV, JCPyV, KIPyV, WUPyV, MCPyV), herpesviruses (Epstein-Barr virus [EBV], cytomegalovirus [CMV], varicella-zoster virus), adenovirus 36, Helicobacter pylori , and Toxoplasma gondii with multiplex serology. Results: Among pregnant women, seroprevalence ranged from 18.7% ( H. pylori ) to 95.7% (EBV); among 4-6-year-old children, seroprevalence ranged from 3.6% ( H. pylori ) to 88.4% (BKPyV). Although most primary infections occurred in the first 4 years of life, some children had primary infections at later ages. Seropositive mothers were more likely to have seropositive children, but an intergenerational decrease in seroprevalence was evident for herpesviruses and H. pylori . There were sizeable differences between countries for H. pylori and T. gondii. Non-western ethnicity mothers and their children were more likely to be infected. Female sex (WUPyV, MCPyV, CMV), breastfeeding (CMV), early daycare attendance (CMV, H. pylori ), and obesity (JCPyV, EBV, Adv-36) were associated with child's seroprevalence. Conclusions: European children acquire common pathogens but often experience first exposure beyond early childhood. Differences are expected between and within countries and across generations. (c) 2025 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
The use of saliva and blood progesterone to profile the menstrual cycles of youth professional football players.
(Frontiers Media, 2024-08-21) Ferrer Vidal-Barraquer, Eva; Rodas Font, Gil; Casals Mercadal, Gregori; Trilla García, Antoni; Balagué-Dobón, Laura; González Ruiz, Juan Ramón; Ridley, Katherine; White, Richard; Burden, Richard J.
Background: Understanding individual ovarian hormone cycles and their relationship with health, performance and injuries is highly important to practitioners supporting female athletes. Venous blood sampling is the current gold standard for measuring the ovarian hormones, but the invasive nature of this method presents a major barrier in sport environments. Saliva analysis may offer an alternative method as it is non-invasive, allowing the sample to be collected “in situ”, with relative ease, necessary in applied sport environments. Objective: The aims of this study were: (i) To compare the concentration of progesterone between capillary blood and saliva, (ii) To assess the efficacy of weekly measurements of progesterone for determining if ovulation has occurred in elite eumenorrheic football players, and (iii) To establish a saliva criteria cut-off for establishing ovulation and assessing the sensitivity, specificity and accuracy values of the method. Methodology: Twenty-one professional and semi-professional, Spanish league female football players (18.6 ± 1.5 years, 58.1 ± 6.0 kg, 164.0 ± 4.8 cm) with natural menstrual cycles, completed the study. Capillary blood and saliva samples were collected from each participant on twelve occasions each separated by at least 7 days. All samples were collected in the morning, following an overnight fast. Results: According to luteal phase serum progesterone concentrations, 11 out of 21 (52%) players presented with menstrual irregularities (oligomenorrheic n = 6, anovulatory n = 4, amenorrhoeic n = 1). A significant correlation was observed between plasma and saliva progesterone in the estimated eumenorrheic group (r = 0.80, p = <0.001, 95% CI 0.72–0.86). The association between serum and saliva progesterone was weaker in the oligomenorrheic group (r = 0.47, p = <0.001, 95% CI 0.27–0.64) and was not present in the anovulatory or amenorrhoeic groups. Conclusions: Salivary measurements of progesterone are well correlated with capillary blood when taken during eumenorrheic menstrual cycles and presents a viable, non-invasive method of establishing characteristic progesterone fluctuations in applied sport settings. The strength of the association appears to be concentration dependent. A luteal phase saliva progesterone (P4) >50 pg/ml and >1.5× follicular baseline has good sensitivity, specificity, and accuracy to indicate ovulation compared to established criteria for serum progesterone.
Metabolomic Plasma Profile of Chronic Obstructive Pulmonary Disease Patients
(MDPI, 2025-05-09) Casadevall, Carme; Agranovich, Bella; Enríquez Rodríguez, Cesar Jesse; Faner, Rosa; Pascual-Guardia, Sergi; Castro Acosta, Ady Angélica; Camps Ubach, Ramon; García Aymerich, Judith; Barreiro, Esther; Monsó, Eduard; Seijo Maceiras, Luis Miguel; Soler Cataluña, Juan José; Santos Pérez, Salud; Peces Barba, Germán; López Campos, José Luis; Casanova, Ciro; Agustí García-Navarro, Àlvar; García Cosío, Borja; Abramovich, Ifat; Gea Guiral, Joaquim; EARLY COPD group; BIOMEPOC group
The analysis of blood metabolites may help identify individuals at risk of having COPD and offer insights into its underlying pathophysiology. This study aimed to identify COPD-related metabolic alterations and generate a biological signature potentially useful for screening purposes. Plasma metabolomic profiles from 91 COPD patients and 91 controls were obtained using complementary semi-targeted and untargeted LC-MS approaches. Univariate analysis identified metabolites with significant differences between groups, and enrichment analysis highlighted the most affected metabolic pathways. Multivariate analysis, including ROC curve assessment and machine learning algorithms, was applied to assess the discriminatory capacity of selected metabolites. After adjustment for major potential confounders, 56 metabolites showed significant differences between COPD patients and controls. The enrichment analysis revealed that COPD-associated metabolic alterations primarily involved lipid metabolism (especially fatty acids and acylcarnitines), followed by amino acid pathways and xenobiotics. A panel of 10 metabolites, mostly related to lipid metabolism, demonstrated high discriminatory performance for COPD (ROC-AUC: 0.916; 90.1% sensitivity and 89% specificity). These findings may contribute to improving screening strategies and a better understanding of COPD-related metabolic changes. However, our findings remain exploratory and should be interpreted with caution, needing further validation and mechanistic studies.
Perceptions and future perspectives of medical students on the use of artificial intelligence based chatbots : an exploratory analysis
(Frontiers Media, 2025-01-22) Gualda Gea, Juan José; Barón Miras, Lourdes Estefanía; Bertran, Maria Jesús; Vilella i Morató, Anna; Torà Rocamora, Isabel; Prat, Andrés
Background: Artificial Intelligence (AI) has made a strong entrance into different fields such as healthcare, but currently, medical degree curricula are not adapted to the changes that adopting these types of tools entitles. It is important to understand the future needs of students to provide the most comprehensive education possible. Objective: The aim of this teaching improvement project is to describe the knowledge, attitudes, and perspectives of medical students regarding the application of AI and chatbots with patients, also considering their ethical perceptions. Methods: Descriptive cross-sectional analysis in which the participants were students enrolled in the subject "Preventive Medicine, Public Health and Applied Statistics" during the second semester of the 2023/24 academic year, corresponding to the fifth year of the Degree in Medicine at the University of Barcelona. The students were invited to complete a specific questionnaire anonymously and voluntarily, which they could respond to using their mobile devices by scanning a QR code projected on the classroom screen, we used Microsoft Forms to perform the survey. Results: Out of the 61 students enrolled in the subject, 34 (56%) attended the seminar, of whom 29 (85%) completed the questionnaire correctly. Of those completing the questionnaire, 20 (69%) had never used chatbots for medical information, 19 (66%) expressed a strong interest in the practical applications of AI in medicine, 14 (48%) indicated elevated concern about the ethical aspects, 17 (59%) acknowledged potential biases in these tools, and 17 (59%) expressed at least moderate confidence in chatbot-provided information. Notably, 24 (83%) agreed that acquiring AI-related knowledge will be essential to effectively perform their future professional roles. Conclusion: Surveyed medical students demonstrated limited exposure to AI-based tools and showed a mid-level of awareness about ethical concerns, but they recognized the importance of AI knowledge for their careers, emphasizing the need for AI integration in medical education.
SARS-CoV-2 transmission in teenagers and young adults in Fútbol Club Barcelona's Multidisciplinary Sports Training Academy
(Springer Verlag, 2023-03-14) Hernández García, María; Bassat Orellana, Quique; Fumadó, Victoria; Rodas Font, Gil; Pi, Ramon; Miranda García, Maite; Girona Alarcón, Mònica; Català, Martí; Alonso, Sergio; Alvarez Lacalle, Enrique; López, Daniel; Melé Casas, Maria; Pons Tomàs, Gemma; Fernández de Sevilla Estrach, Mariona; Bonet Carné, Elisenda; Fortuny Guasch, Claudia; Garcia Miquel, Aleix; Jou, Cristina; Adroher, Cristina; Claverol, Joana; Cubells, Marta; Codina, Anna; Cuadras, Daniel; Gratacós Solsona, Eduard; Brotons, Pedro; Muñoz Almagro, Carmen; Prats, Clara; García García, Juan José; Jordán García, Iolanda
Most studies, aimed at determining the incidence and transmission of SARS-CoV-2 in children and teenagers, have been developed in school settings. Our study conducted surveillance and inferred attack rates focusing on the practice of sports. Prospective and observational study of those attending the sports facilities of Fútbol Club Barcelona (FCB), in Barcelona, Spain, throughout the 2020-2021 season. Participants were young players (from five different sports) and adult workers, who belonged to stable teams (shared routines and were involved in same quarantine rules). Biweekly health questionnaires and SARS-CoV-2 screening were conducted. From the 234 participants included, 70 (30%) both lived and trained in the FCB facilities (Recruitment Pathway 1;RP1) and 164 (70%) lived at their own household and just came to the facilities to train (RP2). During the study, 38 positive cases were identified; none had severe symptoms or needed hospitalization. The overall weekly incidence in the cohorts did not differ compared to the one expected in the community, except for 2 weeks when an outbreak occurred. The attack rate (AR) was three times higher for the participants from RP1, in comparison to those from RP2 (p < 0.01). A Basketball team showed a significant higher AR. Conclusion: Physical activities in stable teams are not related to an increased risk of transmission of SARS-CoV-2, since there were the same observed cases than expected in the community. The risk is higher in indoor sports (Basketball vs. Football), and in closed cohort living settings (RP1 vs. RP2). The fulfilment of preventive measures is essential. What is Known: Despite the low numerical impact caused in paediatric hospitalizations during COVID-19 pandemic, the social impact has been maximum. The transmission potential in children and teenagers is limited, and it had been widely demonstrated in school settings. What is New: Group physical activities in children and teenagers are not also related to an increased risk of transmission of SARS-CoV-2, when preventive measures, such as washing hands, and screening protocols are applied. Routine and semi-professional sports activities seem safe environments to promote during this pandemic.
Long-Term Reassurance with Negative High-Risk Human Papillomavirus (HR-HPV) and Clear Margins After Large Loop Excision of the Transformation Zone (LLETZ)
(MDPI, 2025-02-01) Heydari, Fatima; Sanjosé Llongueras, Silvia de; Peñafiel, Judith; Fernández Montolí, Ma. Eulalia
Background/objective: Women treated with large loop excision of the transformation zone (LLETZ) for cervical intraepithelial neoplasia grade 2-3 (CIN2-3) remain at risk of CIN2-3 and cervical cancer for many years. We assessed the roles of high-risk human papillomavirus (HR-HPV) post-LLETZ, surgical margins, and LLETZ characteristics on the long-term risk of CIN2-3. Methods: A retrospective observational study was performed using data for 432 women with a histological diagnosis of CIN2-3 treated by LLETZ between 1996 and 2020 and followed-up until October 2021 at Hospital Bellvitge in Barcelona, Spain. Age, surgical margins, 6-month HR-HPV status, excision type, and cone volume/dimensions were analyzed in association with the risk of persistent/recurrent CIN2-3. The cumulative probability of persistent/recurrent CIN2-3 was calculated using the Kaplan-Meier and Cox models. Results: Persistent/recurrent CIN2-3 was detected in 7.4%, with over 90% found within 5 years post-LLETZ. Predictors of persistent/recurrent CIN2-3 were HR-HPV (HR = 7.36, 95% CI = 3.55-15.26), involved margins (HR = 3.94, 95% CI = 1.68-9.25), uncertain margins (HR = 4.42, 95% CI = 1.55-12.55), and age ≥ 35 years (HR = 2.92, 95% CI = 1.19-7.13). Type 3 excision (p = 0.035) and cone length (p = 0.010) correlated with clear margins. The negative predictive value (NPV) of both negative HR-HPV and clear margins post-LLETZ was 98.7%. Conclusions: The combination of negative HR-HPV and clear margins post-LLETZ provides stronger reassurance against the risk of persistent/recurrent CIN2-3 than do LLETZ characteristics. However, larger excisions in older women likely reduce the risk of involved margins. Close surveillance, including repeat HR-HPV testing in the first 5 years post-LLETZ, is crucial.
Exposure to residential air pollution and the development of functional connectivity of brain networks throughout adolescence
(Elsevier BV, 2025-02-01) Kusters, Michelle S.W.; Granés, Laura; Petricola, Sami; Tiemeier, Henning; Muetzel, Ryan L.; Guxens, Mònica
Background: A few studies linked air pollution to differences in functional connectivity of resting-state brain networks in children, but how air pollution exposure affects the development of brain networks remains poorly understood. Therefore, we studied the association of air pollution exposure from birth to 3 years and one year before the first imaging assessment with the development of functional connectivity across adolescence. Methods: We utilized data from 3,626 children of the Generation R Study (The Netherlands). We estimated residential exposure to PM10, PM2.5, PM 2.5 absorbance, NOX, and NO2 with land-use regression models. Between- and within-network functional connectivity was calculated for 13 cortical networks, and the amygdala, hippo- campus, and caudate nucleus at two assessments (8.6-12.0 and 12.6-17.1 years), resulting in 4,628 scans (2,511 for assessment 1 and 2,117 for assessment 2) from 3,626 individuals. We investigated the association between air pollution and functional connectivity with linear mixed models adjusted for life-style and socioeconomic variables, and corrected for multiple testing. Results: Higher exposure to PM 2.5 from birth to 3 years was associated with persistently lower functional connectivity over time between the amygdala and the ventral attention, somatomotor hand, and auditory networks throughout adolescence (e.g.-0.027 functional connectivity [95 % CI-0.040;-0.013] amygdala - ventral attention network per 5 mu g/m3 higher PM2.5). Higher exposure to PM10 one year before the first imaging assessment was associated with persistently lower functional connectivity between the salience and medial- parietal networks throughout adolescence. Air pollution was not associated with a faster or slower change in functional connectivity with age. Conclusions: Air pollution exposure early in life was associated with persistent alterations in connectivity between the amygdala and cortical networks involved in attention, somatomotor, and auditory function. Concurrent exposure was associated with persistent connectivity alterations between networks related to higher cognitive functions (i.e. the salience and medial-parietal networks).
Temperature Exposure and Psychiatric Symptoms in Adolescents From 2 European Birth Cohorts
(American Medical Association (AMA), 2025-01-28) Essers, Esmée; Kusters, Michelle; Granés, Laura; Ballester, Joan; Petricola, Sami; Lertxundi, Nerea; Arregi, Ane; Ballester, Ferran; Vrijheid, Martine; El Marroun, Hanan; Iñiguez, Carmen; Tiemeier, Henning; Guxens, Mònica
Importance Climate change can adversely affect mental health, but the association of ambient temperature with psychiatric symptoms remains poorly understood. Objective To assess the association of ambient temperature exposure with internalizing, externalizing, and attention problems in adolescents from 2 population-based birth cohorts in Europe. Design, Setting, and Participants This cohort study analyzed data from the Dutch Generation R Study and the Spanish INMA (Infancia y Medio Ambiente) Project. Generation R recruited 9898 women during pregnancy or shortly after birth, with children born between 2002 and 2006. INMA recruited 2270 pregnant women from Gipuzkoa, Sabadell, and Valencia, Spain, with children born between 2003 and 2008. Individuals born from live singleton births with available outcome and exposure data were included in the study. Data were analyzed between October 2023 and November 2024. Exposure Daily ambient temperature 2 weeks, 1 month, and 2 months preceding outcome assessment was calculated between December 2015 and November 2022 at the residence at 100 x 100 m resolution utilizing the UrbClim model. Main Outcomes and Measures The primary outcomes were internalizing, externalizing, and attention problems, measured with the maternal-reported Child Behavioral Checklist for ages 6 to 18 years; raw scores were square-root transformed, with higher scores indicating more problems. Distributed lag nonlinear models evaluated the associations of temperature exposure with problem scores in each country and region. For Spain, results from the 3 INMA regions were combined using random-effects meta-analysis. Results show the accumulated temperature association over each exposure period. Results A total of 3934 participants from Generation R (mean [SD] age at assessment, 13.6 [0.4] years; 1971 female [50%]) and 885 from INMA (mean [SD] age at assessment, 14.9 [1.0] years; 458 female [52%]) were included. Most parents in both cohorts were native to the respective countries of each cohort and had relatively high socioeconomic status. Daily temperatures ranged from -5.2 degrees C to 32.6 degrees C in the Netherlands and 3.3 degrees C to 33.9 degrees C in Spain. In Generation R, the mean (SD) square-root transformed scores were 2.0 (1.2) for internalizing problems, 1.6 (1.3) for externalizing problems, and 1.5 (1.0) for attention problems, while in INMA these were 2.4 (1.2), 2.1 (1.3), and 1.5 (1.1), respectively. In the Netherlands, cumulative exposure to cold was associated with more internalizing problems (eg, 0.76 [95% CI, 0.20-1.32] higher square-root points at 5.5 degrees C exposure over a 2-month exposure). In Spain, cumulative exposure to heat was associated with more attention problems (eg, 1.52 [95% CI, 0.39-2.66] higher square-root points at 21.7 degrees C exposure over a 2-month exposure). Conclusions and Relevance In this cohort study, exposure to cold in the Netherlands and heat in Spain were associated with more psychiatric symptoms, highlighting distinct temperature exposure and mental health associations among adolescents. Future studies should explore this across diverse climates to further quantify the intricate and multifactorial association of climate change with mental health.
Problems undermining the health-related quality of life of people living with HIV in Spain: a qualitative study to inform the development of a novel clinic screening tool
(BioMed Central, 2022-05-25) Safreed-Harmon, Kelly; Fuster Ruizdeapodaca, Maria J.; Pastor de la Cal, Marta; Lazarus, Jeffrey V.
Background: In settings with high antiretroviral therapy coverage, numerous health-related issues continue to undermine the health and health-related quality of life (HRQoL) of people living with HIV (PLHIV). As part of a larger study to develop and validate a new patient-reported outcome measure for use in HIV clinical care in Spain, we sought to identify the most burdensome health-related issues experienced by PLHIV in order to determine which issues should be addressed in the new instrument. Methods: We conducted a literature review and a qualitative study based on four focus group discussions (FGDs) with key informants in Spain. Participants were selected via purposive sampling. Two FGDs convened 16 expert HIV service providers, and two convened 15 PLHIV with diverse epidemiological profiles. FGDs followed semi-structured interview scripts and incorporated an exercise to prioritise the most critical health-related issues among those named in the discussions. Content analysis was conducted using MAXQDA 12. Results: The analysis of FGD data identified several broad categories of issues that were perceived to negatively affect PLHIV. The most frequently named issues fell within the categories of social problems; physical symptoms; psychological problems; and sexuality-related problems. Regarding social problems, stigma/discrimination was by far the issue raised the most frequently. In the prioritisation exercise, stigma/discrimination was also ranked as the most burdensome issue by both service providers and PLHIV. Within the physical symptoms category, the issues named most frequently were sleep-related problems, fatigue, physical pain and body fat changes. Regarding psychological problems, FGD participants most commonly spoke of emotional distress in general terms, and also called attention to depression and anxiety. In the prioritisation exercise, both service providers and PLHIV ranked psychological well-being as the second-most important issue following stigma. Sexuality-related problems that were reported included sexually transmitted infections, hormonal problems, lack of libido, and general sexual dissatisfaction. Conclusions: PLHIV are negatively affected by a wide range of health-related issues. HIV-related stigma and psychological well-being remain major challenges. Identifying and addressing these and other issues in routine clinical care supports healthy aging and may ultimately contribute to better health and HRQoL outcomes in this population.
Viral epidemic preparedness: a perspective from five clinical microbiology laboratories in Europe
(European Society of Clinical Microbiology and Infectious Diseases, 2023-04-28) Martínez Yoldi, Miguel Julián; Cotten, Matthew; Phan, My V.T.; Becker, Karsten; Espasa, Mateu; Leegaard, Truls M.; Lisby, Gorm; Schneider, Uffe Vest; Casals Pascual, Climent
Background: Pandemic preparedness is critical to respond effectively to existing and emerging/new viral pathogens. Important lessons have been learned during the last pandemic at various levels. This revision discusses some of the major challenges and potential ways to address them in the likely event of future pandemics. Objectives: To identify critical points of readiness that may help us accelerate the response to future pandemics from a clinical microbiology laboratory perspective with a focus on viral diagnostics and genomic sequencing. The potential areas of improvement identified are discussed from the sample collection to information reporting. Sources: Microbiologists and researchers from five countries reflect on challenges encountered during the COVID-19 pandemic, review published literature on prior and current pandemics, and suggest potential solutions in preparation for future outbreaks. Content: Major challenges identified in the pre-analytic and post-analytic phases from sample collection to result reporting are discussed. From the perspective of clinical microbiology laboratories, the preparedness for a new pandemic should focus on zoonotic viruses. Laboratory readiness for scalability is critical and should include elements related to material procurement, training personnel, specific funding programmes, and regulatory issues to rapidly implement "in-house" tests. Laboratories across various countries should establish (or re-use) operational networks to communicate to respond effectively, ensuring the presence of agile circuits with full traceability of samples. Implications: Laboratory preparedness is paramount to respond effectively to emerging and re-emerging viral infections and to limit the clinical and societal impact of new potential pandemics. Agile and fully traceable methods for sample collection to report are the cornerstone of a successful response. Expert group communication and early involvement of information technology personnel are critical for preparedness. A specific budget for pandemic preparedness should be ring-fenced and added to the national health budgets.
Agreement Between High-Risk Human Papillomavirus Testing in Paired Self-Collected and Clinician-Collected Samples from Cervical Cancer Screening in Spain
(MDPI, 2024-12-29) Ibáñez, Raquel; Roura Fornells, Esther; Morey, Francisca; Andújar, Miguel; Pavón, Miquel Ángel; Acera, Amelia; Bruni, Laia; De Sanjosé, Silvia
Background: Implementing self-sampling (SS) in cervical cancer screening requires comparable results to clinician-collected samples (CCS). Agreement measures are essential for evaluating HPV test performance. Previous studies on non-paired samples have reported higher viral cycle threshold (Ct) values in SS compared to CCS, affecting sensitivity for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Objectives: We aimed to evaluate the agreement of high-risk (hr)HPV testing results between SS and CCS using paired samples and to explore differences in Ct values. Methods: Women aged 30 to 65 years attending cervical cancer screening in two regions of Spain were invited to participated in this study. For each woman there was: CCS collected during the screening visit using liquid-based cytology and cytobrush, and a SS using a brush at home one month later. A PCR-based assay was used for hrHPV detection. Agreement in hrHPV results among both samples, Ct value differences, and their association with screening outcomes were analyzed. Results: This study included 981 women with paired samples. SS had a higher hrHPV prevalence than CCS (overall ratio of 1.3). Positive agreement for all hrHPV genotypes, HPV16, HPV18, and other hrHPV types were 85%, 91.3%, 66.7%, and 83.3%, respectively. Negative agreement was >95% for all results. Median Ct values was slightly higher in SS than in CSS (32.9 vs. 30.6, p = 0.02). Seven CIN2+ cases HPV positive were detected by both methods. One CIN3 case was missed by SS. Conclusions: This study showed a good agreement between SS and CCS for hrHPV testing in a routine screening in Spain. Despite the slightly higher Ct values for SS, no significant impact on sensitivity could be determined due to the low incidence of CIN2+ cases. Further research on larger paired samples is needed to assess the implications of Ct values on test sensitivity.
Combined COVID-19 vaccination and hepatitis C virus screening intervention in marginalised populations in Spain
(Nature Publishing Group, 2023-05-12) Lazarus, Jeffrey V.; Villota Rivas, Marcela; Ryan Murúa, Pablo; Buti, Maria; Grau López, Lara; Cuevas, Guillermo; Espada, José Luis; Morón, William; Palma Álvarez, R. Felipe; Feld, Jordan J.; Valencia, Jorge
Background: COVID-19 has hindered hepatitis C virus (HCV) and HIV screening, particularly in marginalised groups, who have some of the highest rates of these conditions and lowest rates of COVID-19 vaccination. We assessed the acceptability of combining HCV testing with COVID-19 vaccination in a centre for addiction services (CAS) in Barcelona and a mobile testing unit (MTU) in Madrid, Spain. Methods: From 28/09/2021 to 30/06/2022, 187 adults from marginalised populations were offered HCV antibody (Ab) testing along with COVID-19 vaccination. If HCV Ab+, they were tested for HCV-RNA. MTU participants were also screened for HIV. HCV-RNA+ and HIV+ participants were offered treatment. Data were analysed descriptively. Results: Findings show how of the 86 CAS participants: 80 (93%) had been previously vaccinated for COVID-19, of whom 72 (90%) had the full first round schedule; none had a COVID-19 vaccine booster and all received a COVID-19 vaccine; 54 (62.8%) were tested for HCV Ab, of whom 17 (31.5%) were positive, of whom all were tested for HCV-RNA and none were positive. Of the 101 MTU participants: none had been vaccinated for COVID-19 and all received a COVID-19 vaccine; all were tested for HCV Ab and HIV and 15 (14.9%) and 9 (8.9%) were positive, respectively; of those HCV Ab+, 9 (60%) were HCV-RNA+, of whom 8 (88.9%) have started treatment; 5 (55.6%) of those HIV+ had abandoned antiretroviral therapy, of whom 3 (60%) have re-started it. Conclusions: The intervention was accepted by 54 (62.8%) CAS participants and all MTU participants and can be used in marginalised communities.
Pneumococcal nasopharyngeal carriage in children and adults self-confined at home during a COVID-19 national lockdown.
(Public Library of Science (PLoS), 2024-12-05) Brotons, Pedro; Cisneros, María; Pérez Argüello, Amaresh; Henares, Desiree; Lluansí, Aleix; Fernández de Sevilla Estrach, Mariona; Ciruela, Pilar; Blanco Fuertes, Miguel; Launes Montaña, Cristian; Jordán García, Iolanda; Bassat Orellana, Quique; García García, Juan José; Muñoz Almagro, Carmen
Background: Despite growing evidence of reduced invasive and non-invasive pneumococcal disease attributed to public health measures against the COVID-19 pandemic, the effect of these measures on pneumococcal carriage remains unclear. This study aimed to assess pneumococcal nasopharyngeal carriage among children and adults self-confined at home during the COVID-19 national lockdown in Spain while identifying predictors of pneumococcal carriage in children. Methods: Household study conducted across the metropolitan area of Barcelona (Spain) between April-June 2020. Nasopharyngeal samples were collected from young children and adults for real-time PCR pneumococcal lytA and wgz gene detection, quantification, and serotyping, as well as for detection of respiratory viruses. Results: Among 332 children (median age: 3.1 years [IQR: 1.9-4.0 years]; 59% male) and 278 adults (median age: 38.9 years [IQR: 36.1-41.3 years]; 64% female), pneumococcal carriage rates were 28.3% and 2.5%, respectively. Highly invasive serotypes 3, 7F/7A, and 19A were detected in 14.0% of samples from children carriers. Pneumococcal co-infections with respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and influenza virus (IV) were not identified in children. Attendance to kindergarten before the lockdown (aOR: 2.65; IQR: 1.57-4.47; p<0.001) and household crowding (aOR: 1.85; IQR: 1.09-3.15; p = 0.02) were independent risk factors for children's pneumococcal carriage. Conclusions: Pneumococcal carriage rate among quarantined children during a full COVID-19 lockdown was moderate and correlated with limited presence of highly invasive serotypes and absence of pneumococcal co-infections with RSV, hMPV, and IV. Pre-lockdown daycare and household crowding predisposed children to carriage.
Using anal cytology and HPV DNA and E6/E7 mRNA detection to optimize high-resolution anoscopy referrals in men who have sex with men living with HIV
(Oxford University Press (OUP), 2024-12-23) Silva klug, Ana C; Paytubi Casabona, Sònia; Torres, Montserrat; Trenti, Loris; Baixeras, Nuria; Sanchez Llamas, Monica; Pavón, Miquel Ángel; Sanjose, Silvia De; Catala, Isabel; Vidal, August; Poljak, Mario; Alemany, Laia; Podzamczer Palter, Daniel; Videla, Sebastià; Saumoy, Maria
Background This study was conducted to evaluate screening procedures for anal high-grade squamous intraepithelial lesions (HSILs) with anal liquid-based cytology (aLBC) and biomarkers to identify candidates for high-resolution anoscopy (HRA).Methods This cross-sectional study included men who have sex with men with HIV. Participants underwent HRA, aLBC, and biomarker testing. Three screening procedures were compared with aLBC: biomarker alone, cytology and biomarker in all, and cytology and reflex biomarkers (biomarkers applied if aLBC results were atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion). Biomarkers included Linear Array (LA), LA for 14 high-risk human papillomavirus (LA 14 HR-HPV) genotypes, LA HPV-16, Hybrid Capture 2 (HC2), E6/E7 mRNA, and E6/E7 mRNA HPV-16.Results Of 354 participants, 179 (50.6%) had atypical squamous cells of undetermined significance or worse, requiring HRA (sensitivity, 80%; specificity, 57.3%; area under the curve, 0.687; reference, biopsy-proven HSIL). Cytology and reflex biomarkers per E6/E7 mRNA, LA 14 HR-HPV, and HC2 and the biomarker-alone procedure with HC2 showed comparable accuracy (sensitivities: 71.6%, 78.8%, 73.1%, 75.7%; specificities: 73.5%, 67.9%, 76.1%, 65.5%; areas under the curve: 0.726, 0.734, 0.746, 0.706) with fewer HRA referrals (number needed to diagnose: 2.2, 2.1, 2, 2.4).Conclusions Our findings suggest that E6/E7 mRNA, LA 14 HR-HPV, and HC2 in the cytology and reflex biomarkers procedure, as well as HC2 in the biomarker-alone procedure, can improve anal HSIL screening effectiveness.
Adjunctive rosiglitazone treatment for severe pediatric malaria: A randomized placebo-controlled trial in Mozambican children
(Elsevier B.V., 2024-02-01) Varo, Rosauro; Crowley, Valerie M.; Mucasse, Humberto; Sitoe, Antonio; Bramugy, Justina; Serghides, Lena; Weckman, Andrea M.; Erice, Clara; Bila, Rubao; Vitorino, Pio; Mucasse, Campos; Valente, Marta; Ajanovic, Sara; Balanza Lombardia, Núria; Zhong, Kathleen; Derpsch, Yiovanna; Gladstone, Melissa; Mayor Aparicio, Alfredo Gabriel; Bassat Orellana, Quique; Kain, Kevin C.
Objectives: We tested the hypothesis that adjunctive rosiglitazone treatment would reduce levels of circulating angiopoietin-2 (Angpt-2) and improve outcomes of Mozambican children with severe malaria. Methods: A randomized, double-blind, placebo-controlled trial of rosiglitazone vs placebo as adjunctive treatment to artesunate in children with severe malaria was conducted. A 0.045 mg/kg/dose of rosiglitazone or matching placebo were administered, in addition to standard of malaria care, twice a day for 4 days. The primary endpoint was the rate of decline of Angpt-2 over 96 hours. Secondary outcomes included the longitudinal dynamics of angiopoietin-1 (Angpt-1) and the Angpt-2/Angpt-1 ratio over 96 hours, parasite clearance kinetics, clinical outcomes, and safety metrics. Results: Overall, 180 children were enrolled; 91 were assigned to rosiglitazone and 89 to placebo. Children who received rosiglitazone had a steeper rate of decline of Angpt-2 over the first 96 hours of hospitalization compared to children who received placebo; however, the trend was not significant (P = 0.28). A similar non-significant trend was observed for Angpt-1 (P = 0.65) and the Angpt-2/Angpt-1 ratio (P = 0.34). All other secondary and safety outcomes were similar between groups (P >0.05). Conclusion: Adjunctive rosiglitazone at this dosage was safe and well tolerated but did not significantly affect the longitudinal kinetics of circulating Angpt-2.
Management of cytomegalovirus in adult solid organ transplant patients: GESITRA-IC-SEIMC, CIBERINFEC, and SET recommendations update
(Elsevier BV, 2024-12-01) Ruiz Arabi, Elisa; Torre Cisneros, Julian; Aguilera, Victoria; Alonso, Rodrigo; Berenguer, Marina; Bestard Matamoros, Oriol; Bodro, Marta; Cantisán, Sara; Carratalà, Jordi; Castón, Juan José; Cordero, Elisa; Facundo, Carme; Fariñas, María Carmen; Fernández Alonso, Mirian; Fernández Ruiz, Mario; Fortún, Jesús; García Cosío, María Dolores; Herrera, Sabina; Iturbe Fernández, David; Len, Oscar; López Medrano, Francisco; López Oliva, María Ovidia; Los-Arcos, Ibai; Marcos, María Ángeles; Martín Dávila, Pilar; Monforte, Víctor; Muñoz, Patricia; Navarro, David; Páez Vega, Aurora; Pérez, Ana Belén; Redondo, Natalia; Álvarez, R. Rodríguez; Rodríguez Benot, Alberto; Rodríguez Goncer, Isabel; San Juan, Rafael; Sánchez Céspedes, Javier; Valerio, Maricela; Vaquero, José Manuel; Viasus, Diego; Vidal, Elisa; Aguado, José María
Cytomegalovirus (CMV) infection remains a significant challenge in solid organ transplantation (SOT). The last international consensus guidelines on the management of CMV in SOT were published in 2018, highlighting the need for revision to incorporate recent advances, notably in cell-mediated immunity monitoring, which could alter the current standard of care. A working group including members from the Group for the Study of Infection in Transplantation and the Immunocompromised Host (GESITRA-IC) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and the Spanish Society of Transplantation (SET), developed consensus-based recommendations for managing CMV infection in SOT recipients. Recommendations were classified based on evidence strength and quality using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The final recommendations were endorsed through a consensus meeting and approved by the expert panel.
Drug use and access to drug dependency services for vulnerable migrants who use drugs in the European Union: Consensus statements and recommendations from civil society experts in Europe
(Elsevier, 2023-06-10) van Selm, Lena; White, Trenton M.; Picchio, Camila A.; Requena Méndez, Ana; Busz, Machteld; Bakker, Ingrid; Romero, Diana; Perez Gayo, Roberto; Pouille, Aline; Vanderplasschen, Wouter; Lazarus, Jeffrey V.
Background: The number of migrants in the European Union (EU) has been growing, including migrants at risk of using drugs. Little information is available on the actual drug use among first-generation migrants who use drugs in the EU, nor on their access to drug dependency services. This study aims to reach consensus among experts in the EU on the current situation regarding vulnerable migrants who use drugs in the EU and to develop a set of actionable recommendations. Methods: Between April and September 2022, a panel of 57 experts on migration and/or drug use, working in 24 countries, participated in a three-stage Delphi study to develop statements and recommendations about drug use and access to healthcare services for migrants who use drugs in the EU. Results: High levels of agreement were reached on the 20 statements (mean=98.0%) and 15 recommendations (mean=99.7%). The recommendations focus on four main topics; 1) increasing data availability and quality, to inform guidelines; 2) increasing the availability of drug dependency services for migrants, including screening for mental health issues and involving migrants who use drugs in the development of services; 3) eliminating country and service level barriers for accessing these services, as well as providing migrants who use drugs with suitable information, and combating stigma and discrimination; 4) the need for increased collaboration among and within EU countries regarding healthcare for migrants who use drugs, at the policy level as well as the service level, including civil society organisations, peer navigation and multilingual cultural mediators. Conclusion: Policy action and increased collaboration are required by the EU as a whole and by individual EU member states, in addition to collaboration among healthcare providers and social welfare services, to increase access to healthcare services for migrants who use drugs.

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