The Relationship between Telomere Length and Gestational Weight Gain: Findings from the Mamma & Bambino Cohort

Inadequate gestational weight gain (GWG) affects a growing number of pregnancies, influencing intrauterine environment and long-term health. Uncovering molecular mechanisms associated with GWG could be helpful to develop public health strategies for tackling this issue. Here, our study aimed to understand the relationship of DNA telomere length with weigh gain during pregnancy, using data and samples from the ongoing prospective “Mamma & Bambino” study (Catania, Italy). GWG was calculated according to the Institute of Medicine (IOM) guidelines. Relative telomere length was assessed by real-time quantitative polymerase chain reaction in 252 samples of maternal leucocyte DNA (mlDNA) and 150 samples of cell-free DNA (cfDNA) from amniotic fluid. We observed that relative telomere length of mlDNA seemed to weakly increase with GWG. In contrast, telomere length of cfDNA exhibited a U-shaped relationship with GWG. Women with adequate GWG showed longer telomere length than those who gained weight inadequately. Accordingly, the logistic regression model confirmed the association between telomere length of cfDNA and adequate GWG, after adjusting for potential confounders. Our findings suggest an early effect of GWG on telomere length of cfDNA, which could represent a molecular mechanism underpinning the effects of maternal behaviours on foetal well-being.

657 Right ventricle systolic function and RV-PA coupling in patients with severe aortic stenosis and the early impact of TAVI

Aims Few data are available on the prevalence of right ventricle (RV) systolic dysfunction, assessed including RV strain, and RV to pulmonary artery (PA) coupling in patients with aortic stenosis (AS) submitted to TAVI and the early effect of the procedure. Methods We performed standard and speckle tracking echocardiography in 80 patients with severe AS the day before TAVI and within 48 h after TAVI. In all patients we measured TAPSE/PASP (cut-off for RV-PA uncoupling 0.31) and in 60/80 we were able to analyse RV global longitudinal strain (RV-GLS) and RV free wall strain (RV-FWS). Results RV-FAC and TAPSE were impaired in 8.3% while RV-GLS and RV-FWS in 45% and 33% before TAVI. TAPSE/PASP<0.31 was documented in 7/80 patients (8.7%) before TAVI. These subjects differed from patients with TAPSE/PASP>0.31 for: enlarged left ventricular (LV) end-diastolic and end-systolic volumes (P<0.001), worst LVEF (P<0.001) and RVFAC (P<0.001), worst RV-GLS and RW-FWS (P=0.01 and P=0.03) and bigger right atrium (RA) area (P<0.001). After TAVI, RV systolic function did not improve while PASP significantly decreased (P=0.005) driving the improvement of TAPSE/PASP (P=0.01). Patients with TAPSE/PASP improvement (51%) differed from the others for worst pre-TAVI diastolic function (E/e’ P=0.045), RV-FAC (P=0.042), RV-GLS (P=0.049) and RA area (P=0.02). Conclusions RV-GLS unveils RV systolic dysfunction in as much as 45% of patients with AS vs. only 8.3% revealed by conventional echocardiography. RV systolic function does not significantly improve early after TAVI while RV-PA coupling does. Patients with lower TAPSE/PASP at baseline have worst LV and RV systolic function as well as larger RA. Patients who improve TAPSE/PASP after TAVI are those with worst diastolic function, RV systolic function and larger RA at baseline.

1145Obesity-related changes in metabolomic profiles in youth

Background Obesity during childhood and adolescence is linked to subclinical atherosclerosis, metabolic dysfunction and later cardiovascular disease. Adults with obesity have metabolomic profiles that predict cardiovascular disease and mortality. Analogous data from children with obesity are sparse. Here, we aimed to investigate i) the relationship between the severity of obesity (determined by the percentage above the 95th BMI-centile (%>95th BMI-centile)) and metabolomic profiles, ii) the effect of changes in the severity of obesity on the metabolomic profile and iii) the relationship between obesity-related metabolites and subclinical atherosclerosis outcomes. Methods Participants from the Childhood Overweight Biorepository of Australia (COBRA) cohort had %>95th BMI-centile and NMR metabolomic profile (Nightingale, Finland) from fasted blood analysed at two time-points (mean interval of 5.5 years). At the follow-up visit, subclinical atherosclerosis phenotypes (carotid elasticity, carotid intima-media thickness, and pulse-wave velocity) were assessed. Results There were 98 participants who attended both visit 1 (mean %>95th BMI-centile 134.6±19.0) and visit 2 (mean %>95th BMI-centile 130.7±26.2). Higher absolute, and increasing severity, of obesity between visits were associated with increased phenylalanine, tyrosine, GlycA (a marker of chronic inflammation), and pyruvate, in both sexes (estimated increases of 0.14-0.18 standard deviations per 10% BMI-centile at visit 2, and 0.15-0.25 per 10% increase in BMI-centile between visits). There was modest evidence for a relationship between lower alanine and higher carotid elasticity. Conclusions In children with obesity, the overall severity of obesity and changes in obesity severity were associated with a metabolomic pattern that in adults is predictive of cardiovascular disease. In children, these metabolites were not related subclinical atherosclerosis; these relationships may become manifest with increasing age. Key messages There is evidence for an early effect of severe obesity on metabolomic profiles in childhood and adolescence.

Sodium-Glucose Cotransporter-2 Inhibitors in Patients with Hereditary Podocytopathies, Alport Syndrome, and FSGS: A Case Series to Better Plan a Large-Scale Study

Hereditary diseases of the glomerular filtration barrier are characterized by a more vulnerable glomerular basement membrane and dysfunctional podocytes. Recent clinical trials have demonstrated the nephroprotective effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in chronic kidney disease (CKD). SGLT2-mediated afferent arteriole vasoconstriction is hypothesized to correct the hemodynamic overload of the glomerular filtration barrier in hereditary podocytopathies. To test this hypothesis, we report data in a case series of patients with Alport syndrome and focal segmental glomerulosclerosis (FSGS) with respect of the early effect of SGLT2i on the kidney function. Mean duration of treatment was 4.5 (±2.9) months. Mean serum creatinine before and after SGLT-2i initiation was 1.46 (±0.42) and 1.58 (±0.55) mg/dL, respectively, with a median estimated glomerular filtration rate of 64 (±27) before and 64 (±32) mL/min/1.73 m2 after initiation of SGLT2i. Mean urinary albumin-creatinine ratio in mg/g creatinine before SGLT-2i initiation was 1827 (±1560) and decreased by almost 40% to 1127 (±854) after SGLT2i initiation. To our knowledge, this is the first case series on the effect and safety of SGLT2i in patients with hereditary podocytopathies. Specific large-scale trials in podocytopathies are needed to confirm our findings in this population with a tremendous unmet medical need for more effective, early on, and safe nephroprotective therapies.

High coverage COVID-19 mRNA vaccination rapidly controls SARS-CoV-2 transmission in long-term care facilities

Background Residents of Long-Term Care Facilities (LTCFs) represent a major share of COVID-19 deaths worldwide. Measuring the vaccine effectiveness among the most vulnerable in these settings is essential to monitor and improve mitigation strategies. Methods We evaluate the early effect of the administration of BNT162b2-mRNA vaccine to individuals older than 64 years residing in LTCFs in Catalonia, Spain. We monitor all the SARS-CoV-2 documented infections and deaths among LTCFs residents once more than 70% of them were fully vaccinated (February–March 2021). We develop a modeling framework based on the relationship between community and LTCFs transmission during the pre-vaccination period (July–December 2020). We compute the total reduction in SARS-CoV-2 documented infections and deaths among residents of LTCFs over time, as well as the reduction in the detected transmission for all the LTCFs. We compare the true observations with the counterfactual predictions. Results We estimate that once more than 70% of the LTCFs population are fully vaccinated, 74% (58–81%, 90% CI) of COVID-19 deaths and 75% (36–86%, 90% CI) of all expected documented infections among LTCFs residents are prevented. Further, detectable transmission among LTCFs residents is reduced up to 90% (76–93%, 90% CI) relative to that expected given transmission in the community. Conclusions Our findings provide evidence that high-coverage vaccination is the most effective intervention to prevent SARS-CoV-2 transmission and death among LTCFs residents. Widespread vaccination could be a feasible avenue to control the COVID-19 pandemic conditional on key factors such as vaccine escape, roll out and coverage.

Assessment of Potential Health Risks of Portuguese Wildland Firefighters’ Occupational Exposure: Biomonitoring Approach

Introduction:Worldwide, forest fires are among the most common forms of natural disasters. In the closing years of the last century there was an increase of the burned area in some parts of the globe, including in Europe. Portugal has been particularly affected by large forest fires and megafires, which have been occurred mainly in the central and northern regions. The proximity of firefighters to fire exposes them to high levels of toxic compounds making this occupation one of the most dangerous and leading International Agency for Research on Cancer to classified occupational firefighting activity as possibly carcinogenic to humans. Up to date, the existing studies are mainly focused on environmental monitoring, existing limited information regarding biomonitoring assessments during real scenarios of wildland fires combat. This study aims to evaluate the impact of firefighting occupational exposure at molecular and cellular levels, considering personal exposure levels. Early-effect biomarkers (e.g., micronucleus, DNA strand breaks and oxidative DNA damage) will be analyzed in order to understand the mechanisms of action through which woodsmoke may impact firefighters’ health, including the risk of cancer. Methodology:This ongoing prospective longitudinal study will comprise three different stages, specifically pre-exposure, exposure, and post-exposure to fire season. Around 200 wildland northern Portuguese firefighters will be involved in this study. Characterization of the study population will be conducted via questionnaires. Firefighters’ personal exposurelevels will be assessed by means of metabolites in exhaled breath, using an artificial olfactory system (e-nose technology). Buccal and urine samples will be used to measure genomic instability through micronucleus test in buccal epithelial cells and urothelial cells. DNA damage and oxidative DNA damage will be evaluated in peripheral blood lymphocytes using the comet assay. Statistical analysis will be performed to determine the relationship between personal exposure levels to toxic compounds and the early-effect biomarkers over the three different phases of the study. Expected results: The obtained results will support a more accurate and comprehensive assessment of occupational risks among wildland firefighters, crucial to prevent/reduce the associated health impacts. This work will contribute tothe establishment of recommendations/good practices to improve firefighters’ working conditions, allowing better definitions of policies and prevention strategies highly needed in this sector.

COVID-19: A Comprehensive Analysis of the Pandemic’s Effect on an Emergency Department

Objective: COVID-19 (caused by SARS-CoV-2) is a historic pandemic severely impacting health care. This study examines its early effect on a busy academic emergency department. Methods: A retrospective analysis of patients from an academic tertiary care Level I trauma, cardiac and stroke center’s emergency department seeing an average of 54,000 adults and 21,000 pediatric patients per year. Total visits, reasons for patient visits, demographics, disposition, and length of stay were analyzed from January through July 2020 and compared to the same time period in the previous two years. Results: From March through July 2020 there were statistically significant decreases in the total number of patient visits (−47%) especially among pediatric (−73%) and elderly (−43%) patients and those with cardiovascular (−39%), neurological (−63%) complaints, headaches (−60%), back pain (−64%), abdominal pain (−51%), and minor trauma (−71%). There was however a significant increase in pulmonary complaints (+54%), as well as admissions (+32%), and length of stay (+40%). Conclusions: There was a significant drop in overall patients and select groups early in the pandemic, while admissions and emergency department length of stay both increased. This has implications for future pandemic planning.

Conflict Detection In Affective Language Content: Affective Incongruency In Semantically Correct Sentences Describing Social Interactions Activates The Anterior Cingulate Cortex

Neurocognitive studies on the emotion-language relation report a significant influence of affective content on the level of single words. However, it is rather difficult to investigate such influence on the sentence level – partly due to a missing theoretical approach to integrate multiple affective meanings. In a previous EEG study, we used impression formation equations based on Affect Control Theory to calculate affective congruency of sentences describing social interactions to successfully predict ERP effects. The current study was crucially motivated by the assumption that the reported early effect of affective incongruency was related to automatic conflict detection associated with activation in anterior cingulate cortex (ACC). To test this hypothesis, we replicated the study as an event-related fMRI design: we visually presented the same sentences to 23 participants (12 f, 11 m) in a silent reading reading task while measuring differences in the hemodynamic response in two conditions of affective congruency. The ROI analysis results showed expected enhancement of neural activity for affectively incongruent sentences in left ACC, supporting the assumption that affective language content influences meaning making already at basic semantic processing stages. The reported results represent a replication of neuroscientific evidence for ACT's mathematical model of impression formation.

The Experience, Prerequisites, and the Barriers in Organizing a Specialized Rehabilitation Program for Patients with Pulmonary Hypertension

<b><i>Background:</i></b> Pulmonary hypertension (PH) is a severe progressive disease, associated with reduced exercise capacity and poor quality of life. Although scientific evidence supports the incorporation of specialized training in the treatment of PH, it is only available in a few countries. <b><i>Objectives and Methods:</i></b> This article aims to share the experience of implementing a PH rehabilitation program, to summarize the barriers and prerequisites for launching this service, and to assess its early effect. We retrospectively analyzed our pathway in organizing this program, by singling out essential steps. <b><i>Results:</i></b> The preparation phase took about 14 months. Establishing and running of a PH rehabilitation program required dedicated rehabilitation specialists to join the multidisciplinary PH expert team. Team members needed to gain special knowledge on exercise training in severely compromised patients; thus, supervision and education by experienced consultants was crucial. The main eligibility criteria for patients were stable status, optimal medical treatment, and motivation to undergo the training. The first results evaluating the effect of a specialized PH training program in 9 patients are promising. Seven of them improved their functional capacity over the period of 15 weeks. <b><i>Conclusions:</i></b> Despite a number of challenges and barriers, the implementation of a specialized rehabilitation program should be encouraged in a few dedicated PH expert centers per country, who are capable to fulfill all prerequisites and organizational aspects. Local PH experts, supervision by an experienced center, in-patient rehabilitation facilities, dedicated personnel, equipment, and patient motivation are essential.