Publications by authors named "Lowenstein C"

Background: The purpose of this report is to examine to what extent the COVID-19 pandemic affected pre-existing trends in mental health, with a focus on subgroup differences across age, gender and socioeconomic status.

Methods: Our analysis uses data from two survey periods (HUNT4: 2017-2019 and HUNT-COVID: 2021-2023) from the Trøndelag Health Study in Norway. We estimate overall and stratified (by age, sex and educational attainment) prevalence values for above-threshold (≥8) anxiety and depression scores using the Hospital Anxiety and Depression Scale.

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  • Clonal hematopoiesis (CH) occurs when genetically identical blood cells expand, often influenced by genetic mutations linked to blood cancers; however, many cases happen without known driver mutations.
  • Researchers analyzed 51,399 genomes to study a specific type of CH (CH-LPMneg) without detectable leukemia-related mutations, developing a new method (GEM rate) to estimate mutation burden without paired samples.
  • Through their study, they identified seven genes linked to CH-LPMneg and found that alterations in hematopoietic stem cell (HSC) behavior may drive this mutation burden, while a broader analysis revealed relationships between GEM and the expression of 404 genes.
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GENETIC DETERMINANTS OF THROMBOSIS.

Trans Am Clin Climatol Assoc

August 2024

Venous thromboembolism (VTE) is a major cause of morbidity and mortality in the United States. VTE is caused by genetic and acquired conditions, but the genetic variants that increase the risk of VTE are not fully characterized. Recent genome-wide association studies (GWAS) have discovered novel genetic loci linked to VTE.

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  • Increased risk of venous thromboembolism (VTE) is a critical concern for individuals using oral contraceptives (OCs) or hormone therapy (HT), prompting research into genetic factors that may increase this risk.
  • A gene-by-environment case-only meta-analysis of genome-wide association studies (GWAS) examined genetic predispositions in OC and HT users, identifying potential risk variants associated with VTE events.
  • While primary GWAS results did not find significant genetic variants, the analysis of 138 candidate variants revealed two noteworthy associations: F5 rs6025 (previously noted) and F11 rs2036914 (newly identified), offering insight into genetic risks related to OC and HT use.
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  • * Discovery of 7 new genetic loci associated with FVIII and 1 new locus for VWF, supporting their roles in thrombotic outcomes via Mendelian randomization.
  • * Functional testing revealed that silencing genes like B3GNT2 and CD36 impacted FVIII and VWF release from endothelial cells, indicating their potential regulatory roles.
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Background: COVID-19 has been associated with endothelial injury, resultant microvascular inflammation and thrombosis. Activated endothelial cells release and express P-selectin and von Willebrand factor, both of which are elevated in severe COVID-19 and may be implicated in the disease pathophysiology. We hypothesized that crizanlizumab, a humanized monoclonal antibody to P-selectin, would reduce morbidity and death in patients hospitalized for COVID-19.

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Dyslipidemia is an important risk factor for coronary artery disease and stroke. All persons with dyslipidemia should be advised to focus on lifestyle interventions, including regular aerobic exercise, a healthy diet, maintenance of a healthy weight, and abstinence from smoking. In addition to lifestyle interventions, lipid-lowering therapy should be considered for persons at moderate to high risk for atherosclerotic cardiovascular disease based on validated risk equations.

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Despite the prevalence of pericytes in the microvasculature of the heart, their role during ischemia-induced remodeling remains unclear. We used multiple lineage-tracing mouse models and found that pericytes migrated to the injury site and expressed profibrotic genes, coinciding with increased vessel leakage after myocardial infarction (MI). Single-cell RNA-Seq of cardiac pericytes at various time points after MI revealed the temporally regulated induction of genes related to vascular permeability, extracellular matrix production, basement membrane degradation, and TGF-β signaling.

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Background: Oral contraceptive (OC) use increases venous thromboembolism risk 2-5-fold. Procoagulant changes can be detected in plasma from OC users even without thrombosis, but cellular mechanisms that provoke thrombosis have not been identified. Endothelial cell (EC) dysfunction is thought to initiate venous thromboembolism.

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The present study explores psychosocial needs among university employees and the extent to which these needs influence employee perceptions of how work positively or negatively affects their health. Structural equation modeling (SEM) analyses among Norwegian faculty members ( = 11,533) suggest that needs differ in importance to the two work-related health outcomes. Multi-group analyses suggest gender differences in the level of these needs and in their degree of relationship with positive/negative work-related health.

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Severe coronavirus disease-19 (COVID-19) is characterized by vascular inflammation and thrombosis. We and others have proposed that the inflammatory response to coronavirus infection activates endothelial cells, leading to endothelial release of pro-thrombotic proteins. These mediators can trigger obstruction of the pulmonary microvasculature, leading to worsening oxygenation, acute respiratory distress syndrome, and death.

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As blood transitions from steady laminar flow (S-flow) in healthy arteries to disturbed flow (D-flow) in aneurysmal arteries, platelets are subjected to external forces. Biomechanical platelet activation is incompletely understood and is a potential mechanism behind antiplatelet medication resistance. Although it has been demonstrated that antiplatelet drugs suppress the growth of abdominal aortic aneurysms (AAA) in patients, we found that a certain degree of platelet reactivity persisted in spite of aspirin therapy, urging us to consider additional antiplatelet therapeutic targets.

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Background: Of the nearly 50,000 women in the United States who undergo treatment for ductal carcinoma in situ (DCIS) annually, many may not benefit from treatment. To better understand the impact of a DCIS diagnosis, patients self-identified as having had DCIS were engaged regarding their experience.

Methods: In July 2014, a web-based survey was administered through the Susan Love Army of Women breast cancer listserv.

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COVID-19 is characterized by vascular inflammation and thrombosis, including elevations in P-selectin, a mediator of inflammation released by endothelial cells. We tested the effect of P-selectin inhibition on biomarkers of thrombosis and inflammation in patients with COVID-19. Hospitalized patients with moderate COVID-19 were randomly assigned to receive either placebo or crizanlizumab, a P-selectin inhibitor, in a double-blind fashion.

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  • Inflammation is a vital biological process that supports defense and healing but can cause harm when it becomes chronic, leading to diseases like rheumatoid arthritis and atherosclerosis.
  • Research has shifted the understanding of atherosclerosis from merely a cholesterol build-up to recognizing how inflammatory processes, driven by cytokines and immune cells, play a central role in the progression of the disease.
  • The text also explores how certain biomarkers of inflammation can predict cardiovascular risk and reviews clinical trials examining drugs aimed at reducing inflammation to lower the risk of heart-related events.
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Estrogen therapy is used to treat patients with post-menopausal symptoms, such as hot flashes and dyspareunia. Estrogen therapy also decreases the risk of fractures from osteoporosis in post-menopausal women. However, estrogen increases the risk of venous thromboembolic events, such as pulmonary embolism, but the pathways through which estrogen increase the risk of thromboembolism is unknown.

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Background: Knowledge gaps remain in the epidemiology and clinical implications of myocardial injury in coronavirus disease 2019 (COVID-19). We aimed to determine the prevalence and outcomes of myocardial injury in severe COVID-19 compared with acute respiratory distress syndrome (ARDS) unrelated to COVID-19.

Methods: We included intubated patients with COVID-19 from 5 hospitals between March 15 and June 11, 2020, with troponin levels assessed.

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Objective: To compare several monetary incentive programmes for promoting smoking abstinence among employees who smoke at workplaces in a middle income country.

Design: Parallel group, open label, assessor blinded, cluster randomized controlled trial.

Setting: Large industrial workplaces in metropolitan Bangkok, Thailand.

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While smoking is widely acknowledged to be a social activity, limited evidence exists on the extent to which friends influence each other during worksite-based tobacco cessation interventions. Drawing on data from adult smokers (N = 1823) in a large, cluster randomized controlled trial in worksites in Thailand, this study examines the presence of social spillovers in the decision to abstain from smoking. We leverage a unique aspect of social network structure in these data-the existence of non-overlapping friendship networks-to address the challenge of isolating the effects of peers on smoking behavior from the confounding effects of endogenous friend selection and bidirectional peer influence.

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  • Genetic factors play a role in thrombotic diseases, with studies identifying SLC44A2 as a key gene involved in regulating thrombosis.
  • Research shows that mice lacking the Slc44a2 gene (Slc44a2(KO)) experience increased bleeding and delayed clot formation compared to normal mice (Slc44a2(WT)).
  • The study highlights that Slc44a2 is crucial for choline transport into mitochondria, affecting ATP production and platelet activation, indicating why its absence leads to impaired clotting function.
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