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Clinical factors and biomarkers during pregnancy and risk of cardiovascular disease
No full textIMPORTANCE: Cardiovascular disease (CVD) is the leading cause of death among women worldwide. Pregnancy serves as a natural cardiovascular stress test and universal clinical encounter, yet few approaches leverage its insights to inform long-term cardiovascular risk.
OBJECTIVE: To determine whether clinical measures and biomarkers obtained during pregnancy may identify women at risk of long-term CVD.
DESIGN, SETTING, AND PARTICIPANTS: This was a registry-linked, population-based cohort study of all pregnancies reaching at least 22 weeks between June 2010 and October 2013 in Southern Denmark. Primary analyses were performed in a nested prospective subcohort of Odense Child Cohort participants with available pregnancy biomarker data. Women with preexisting CVD were excluded (n = 114). Follow-up was done through December 31, 2023. Among 38 455 eligible women, 2056 had biomarker data at week 12 or week 29. Analytic subsets with complete data were used for prognostic modeling at week 12 (n = 1379) and week 29 (n = 1389).
EXPOSURES: Clinical characteristics, obstetric outcomes, and pregnancy biomarkers including soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor, high-sensitivity cardiac troponin I (hs-cTnI), and N-terminal pro-B-type natriuretic peptide.
MAIN OUTCOMES AND MEASURES: Incident maternal CVD, evaluated using Cox proportional hazards models.
RESULTS: In the biomarker cohort (median [IQR] age, 30.4 [27.4-33.8] years), 28 women (1.4%) developed CVD during a median (IQR) follow-up of 11.9 (11.2-12.5) years. Maternal age, hypertensive disorders of pregnancy (HDPs), and third-trimester concentrations of hs-cTnI and sFlt-1 were each independently associated with higher long-term CVD risk. A combined model including age and sFlt-1 measured at week 29 improved discrimination for CVD compared with a base model of age alone (ΔAUC, 0.16; 95% CI, 0.02-0.30), whereas a clinical model consisting of age, systolic blood pressure, and non-high-density lipoprotein cholesterol did not. Results were consistent in women without prior hypertension or HDPs and in nulliparous women. CVD incidence and the predictive value of the base model were comparable between the biomarker and the contemporaneous background cohorts (n = 36 274).
CONCLUSIONS AND RELEVANCE: These findings support pregnancy as an opportunistic window for sex-specific cardiovascular risk assessment and prevention throughout a woman's life course. Further studies are warranted to validate these findings
Microvascular remodeling and endothelial dysfunction across Post-COVID-19 and ME/CFS: insights from the All Eyes on PCS Study
Full text linkBACKGROUND: Post-viral diseases, including post-COVID-19 syndrome (PCS) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), cause substantial long-term morbidity. Persistent cardiovascular (CV) risk after acute infection highlights the need for accessible tools to quantify microvascular health. METHODS: All Eyes on PCS is a prospective, observational study investigating the retinal microcirculation using retinal vessel analysis (RVA). We compared RVA parameters in 102 PCS patients with 204 age- and sex-matched healthy controls (HC, matched from n = 303). Secondary matched analyses included never infected controls (NI, n = 96), recovered individuals (n = 102), PCS patients, and ME/CFS patients (n = 62). Laboratory variables, circulating markers of endothelial dysfunction (ED) and inflammation were compared between cohorts and their associations with RVA parameters were examined. RESULTS: Compared with HC, PCS patients showed reduced venular flicker-induced dilation (3.7 ± 2.2% vs. 4.5 ± 2.7%, p = 0.005), narrow retinal arterioles (CRAE, 178.3 ± 15.5 µm vs. 183.3 ± 15.9 µm, p = 0.009), and lower arteriolar-to-venular ratio (0.83 ± 0.06 vs. 0.86 ± 0.07, p = 0.004). Findings persisted after adjustment for CV factors and remained evident in an extended secondary matched analysis across NI, recovered, and PCS patients. ME/CFS patients showed the most pronounced alterations. PCS severity correlated with lower AVR (r = -0.21, p = 0.037) and reduced arteriolar FID (r = -0.21, p = 0.039), particularly for neurocognitive symptoms. IL-6, ICAM-1 and VCAM1 were elevated in PCS and ME/CFS and lower AVR correlated with inflammatory and iron-related markers (all adjusted p < 0.01). A combined model discriminated ME/CFS patients with good accuracy (AUC = 0.80). CONCLUSIONS: PCS is associated with persistent ED, most pronounced in ME/CFS patients and linked to symptom severity and ongoing inflammation. RVA may provide a noninvasive, readout of ED in post-viral syndromes
Veränderungen der mentalen Gesundheit während der COVID-19-Pandemie-eine Analyse von Daten der NAKO Gesundheitsstudie von 2014-2022
No full textHINTERGRUND: Die COVID-19-Pandemie und ihre Begleiterscheinungen haben weltweit Besorgnis erregt hinsichtlich ihrer Folgen für die mentale Gesundheit. Die NAKO Gesundheitsstudie bietet die Möglichkeit, die Trends der Veränderungen der mentalen Gesundheit während der Pandemie bei Erwachsenen in Deutschland zu untersuchen. METHODS: Wir haben Daten von 79 239 Teilnehmenden der NAKO Gesundheitsstudie analysiert, die an Erhebungen zu depressiven und Angstsymptomen, Stress und selbst wahrgenommener Gesundheit zu drei Zeitpunkten teilgenommen haben: Baseline (2014–2019), in der frühen (2020) und in der späten Phase der Pandemie (2022). Die Veränderungen der mentalen Gesundheit über die drei Zeitpunkte wurden anhand deskriptiver Statistiken, Sankey-Diagrammen und einer post-hoc multinomialen logistischen Regression analysiert. ERGEBNISSE: Wir beobachteten eine anfängliche Verbesserung der selbst wahrgenommenen Gesundheit von der Baseline bis 2020, später (2020–2022) jedoch eine Verschlechterung. Die mentale Gesundheit der meisten Teilnehmenden blieb über die Zeit gleich. Von Baseline bis 2022 stieg der Anteil der Personen, die depressive Symptome berichteten, von 5,9 % auf 9,7 %, bei moderaten bis schweren Angstsymptomen von 3,9 % auf 6,2 % und bei moderatem bis schwerem Stress von 4,1 % auf 10,2 %. Darüber hinaus erlebten mehr jüngere Erwachsene und Frauen eher Verschlechterungen als Verbesserungen der selbst wahrgenommenen Gesundheit. SCHLUSSFOLGERUNG: Unsere Ergebnisse deuten auf eine Zunahme an mentaler Symptombelastung bei Erwachsenen in Deutschland während der Pandemie hin. Diese Ergebnisse unterstreichen die Notwendigkeit eines kontinuierlichen Monitorings und gezielter Strategien zur Verbesserung der öffentlichen mentalen Gesundheit
From cigarettes to symptoms: the association between smoking and depression in the German National Cohort (NAKO)
Full text linkBACKGROUND: Although the association between smoking and depression is well-established, the underlying mechanisms and contextual factors remain insufficiently understood. We examined the association between smoking and depression, including detailed dose-response and timing-related relationships, using baseline data from a large population-based cohort, the German National Cohort (NAKO). METHODS: The analysis comprised 173,890 participants (19-72 years, 50.21% female). Lifetime and current depression were assessed via self-reported physician’s diagnosis, the Major Depressive Disorder module of the MINI International Neuropsychiatric Interview (MINI), and the depression scale of the Patient Health Questionnaire (PHQ-9). Smoking behavior was assessed using self-reported smoking status, age at initiation, cigarettes per day, and time since smoking cessation. Associations between smoking and depression measures were analyzed using regression models adjusted for sex, age, age², education, Body Mass Index, and alcohol consumption. RESULTS: Lifetime depression was more prevalent among individuals who currently or formerly smoked compared to those who never smoked. Currently smoking individuals also reported most current depressive symptoms, followed by formerly smoking individuals and those who never smoked. A dose-response relationship was observed, with more cigarettes per day being associated with more current depressive symptoms. Later age at smoking initiation was associated with later depression onset. Time since smoking cessation was positively associated with time since last depressive episode and negatively with current depressive symptoms. CONCLUSIONS: Our findings support an association between smoking and depression. Robust dose-response relationships were found, with higher cigarette consumption associated with more severe depressive symptoms, and longer time since cessation linked to lower depression levels. These results highlight smoking as a meaningful and modifiable contributor to current and lifetime depression, suggesting that quitting smoking or reducing cigarette consumption may benefit mental health. Early prevention of smoking initiation, along with integrated approaches that combine smoking cessation support with mental health care, may help reduce both smoking rates and depression burden
Linee guida ESC 2025 per il trattamento delle miocarditi e pericarditi - [2025 ESC Guidelines for the management of myocarditis and pericarditis]
No full textThe IBEX knowledge-base a community resource enabling adoption and development of immunofluorescence imaging methods
Full text linkThe iterative bleaching extends multiplexity (IBEX) Knowledge- Base is a central portal for researchers adopting IBEX and related 2D and 3D immunofluorescence imaging methods. The design of the Knowledge- Base is modeled after efforts in the open- source software community and includes three facets: a development platform (GitHub), static website, and service for data archiving. The Knowledge- Base facilitates the practice of open science throughout the research life cycle by providing validation data for recommended and non- recommended reagents, such as primary and secondary antibodies. In addition to reporting negative data, the Knowledge- Base empowers method adoption and evolution by providing a venue for sharing protocols, videos, datasets, software, and publications. A dedicated discussion forum fosters a sense of community among researchers while addressing questions not covered in published manuscripts. Together, scientists from around the world are advancing scientific discovery at a faster pace, reducing wasted time and effort, and instilling greater confidence in the resulting data
Population-scale sequencing resolves determinants of persistent EBV DNA
Full text linkEpstein–Barr virus (EBV) is an endemic herpesvirus implicated in autoimmunity, cancer and neurological disorders. Although primary infection is often subclinical, persistent EBV infection can drive immune dysregulation and long-term complications. Despite the ubiquity of infection, the determinants of EBV persistence following primary exposure remain poorly understood, although human genetic variation partially contributes to this phenotypic spectrum. Here we demonstrate that existing whole genome sequencing (WGS) data of human populations can be used to quantify persistent EBV DNA. Using WGS and health record data from the UK Biobank (n = 490,560) and All of Us (n = 245,394), we uncover reproducible associations between blood-derived EBV DNA quantifications and respiratory, autoimmune, neurological and cardiovascular diseases. We evaluate genetic determinants of persistent EBV DNA via genome association studies, revealing heritability enrichment in immune-associated regulatory regions and protein-altering variants in 148 genes. Single-cell and pathway level analyses of these loci implicate variable antigen processing as a primary determinant of EBV DNA persistence. Further, relevant gene programs were enriched in B cells and antigen-presenting cells, consistent with their roles in viral reservoir and clearance. Human leukocyte antigen genotyping and predicted viral epitope presentation affinities implicate major histocompatibility complex class II variation as a key modulator of EBV persistence. Together, our analyses demonstrate how re-analysis of human population-scale WGS data can elucidate the genetic architecture of viral DNA persistence, a framework generalizable to the broader human virome
TENM4 is an essential transduction component for touch
Full text linkGentle touch is conveyed to the brain by fast-conducting sensory fibers. Mechanosensitive ion channels at the terminals of these neurons are thought to be gated by extracellular tethers that transmit force from the surrounding matrix to the channel complex, but the molecular identity of such tethers has remained unknown. Here, we identify Teneurin-4 (TENM4) as an essential extracellular linker protein for mechanotransduction in mechanoreceptors. Sensory neuron-specific deletion of Tenm4 in mice caused profound touch insensitivity, while acute and reversible proteolytic disassembly of TENM4 at sensory endings confirmed its direct role in force transduction. Ultrastructural analyses revealed TENM4 localization to filamentous structures at the neurite-laminin interface, defining it as a structural component of the mechanosensory tether. These findings identify TENM4 as a core element of fast somatic sensation and provide molecular insight into how extracellular forces are coupled to ion channel activation
A transgenic mouse model for reticulated platelet detection reveals expansion after myocardial ischemia/reperfusion
Full text linkReticulated platelets are newly formed, RNA-rich platelets with heightened reactivity. Although elevated levels are observed after myocardial ischemia/reperfusion injury, their functional contributions to postischemic pathology remains poorly defined. We aimed to determine whether reticulated platelets actively contribute to inflammation and repair following myocardial ischemia and reperfusion, rather than serving solely as biomarkers of platelet turnover. We generated Pf4-Cre:RiboTag mice, in which hemagglutinin-tagged ribosomal proteins are selectively expressed in megakaryocytes and platelets. Using hemagglutinin-based flow cytometry, we identified reticulated platelets without relying on nucleic acid dyes. Surface marker expression and agonist responsiveness were evaluated ex vivo. Bulk RNA sequencing was performed on sorted reticulated and non-reticulated platelets 48 hours after ischemia/reperfusion injury. Hemagglutinin-based detection revealed a time-dependent increase in circulating reticulated platelets after myocardial ischemia/reperfusion, confirmed by conventional dye-based methods. These platelets exhibited higher baseline expression of glycoprotein Ibα and greater agonist-induced activation of glycoprotein IIb/IIIa and P-selectin. Transcriptomic profiling demonstrated enrichment of genes associated with platelet activation, cytoskeletal reorganization, and wound healing. Ligand-receptor analysis suggested interactions between reticulated platelets and cardiac endothelial cells, fibroblasts, and macrophages. In conclusion, reticulated platelets constitute a transcriptionally distinct, hyperreactive platelet subset that may modulate post–ischemia/reperfusion inflammation and tissue remodeling. This genetic model provides a platform for mechanistic studies and may inform therapeutic strategies targeting platelet-mediated responses in cardiovascular disease
Assessing cardiac 2D flow MRI reliability across various physiologic, technical, and observer confounders in healthy traveling volunteers
No full textPURPOSE: To evaluate the repeatability and reproducibility of phase-contrast two-dimensional blood flow cardiac MRI (2D flow) measurements in the presence of physiologic, technical, and observer confounders. MATERIALS AND METHODS: In this prospective observational study from January to June 2022, 20 healthy volunteers underwent 2D flow cardiac MRI at four sites (one 1.5-T and three 3-T scanners). Each participant received two consecutive segmented gradient-echo acquisitions and one real-time sequence with a scan-rescan examination at one site. Intraclass correlation coefficients (ICC) assessed sequence repeatability, scan-rescan reproducibility, sequence-type comparison, field-strength and scanner-configuration effects, and interobserver agreement. Correlations between forward flow volume (FF), peak velocity (PV), heart rate, and blood pressure were calculated using Pearson and Spearman coefficients. Segmented 2D flow cardiac MRI was compared with four-dimensional flow cardiac MRI at the sinotubular junction and aortic valve. RESULTS: Nineteen participants (mean age, 26 years ± 6 [SD]; 11 male participants) were analyzed. FF and PV demonstrated excellent sequence repeatability (ICC, 0.986 and 0.969, respectively) and scan-rescan reproducibility (ICC, 0.976 and 0.903, respectively). Different sequence types and field strengths showed excellent agreement for FF (ICC for sequence type, 0.925; ICC for field strength, 0.918), as did different scanner configurations and interobserver analyses with measurements within equivalence limits, except for PV across sequence types, field strengths, and between sites 2 and 3. Heart rate and FF correlated mildly (r, −0.40) but not systolic or diastolic blood pressure with FF and PV and heart rate with PV (r, −0.02). 2D and four-dimensional flow cardiac MRI correlated and had good to excellent agreement with FF at the sinotubular junction and aortic valve (r, 0.86; ICC, 0.930 and r, 0.89; ICC, 0.939, respectively) and moderate for PV (r, 0.77; ICC, 0.862 and r, 0.66; ICC, 0.767, respectively). CONCLUSION: 2D flow cardiac MRI measurements showed excellent repeatability for FF and moderate agreement for PV across sequences, field strengths, and observers. Physiologic and technical confounders had minimal impact on measurement precision