Psychosocial predictors of early postpartum depressive and anxious symptoms in primiparous women and their partners.

BACKGROUND: While the majority of research on postpartum depressive and anxious symptoms has focused on mothers, a growing body of research suggests a need to understand the role of the partner's health and relationship quality as predictors of postpartum maternal depression, while also better understanding correlates of partner or paternal depression in the postpartum period. The purpose of the current study is to evaluate mother and partner stress, anxiety, mood, infant care support, and relationship quality as predictors of perinatal depressive and anxious symptoms in first time mothers and partners during the postpartum hospital stay. METHODS: First time parent couples (n = 116) completed a survey during the two-day postpartum stay in a Midwest hospital. Depressive (EPDS) and anxiety symptoms (DASS-21-Anxiety) were assessed in both mothers and partners. Hierarchical linear regression was used to evaluate relationship satisfaction, partner infant care support, stress, and co-parent mood as predictors of mood in mothers and partners separately. RESULTS: Stress was a predictor of anxiety and depression symptoms in both mothers and partners. Additionally, co-parent anxiety significantly predicted anxiety in both mothers and partners. Maternal relationship satisfaction was a predictor of the partner's depressive symptoms, and maternal perceptions of partner infant support predicted maternal depressive symptoms. CONCLUSIONS: Together, these results suggest that stress, relationship satisfaction, and co-parent mood are related to depressive and anxious symptoms in mothers and partner, underscoring the need to continue exploring mother and partner mental health in a dyadic framework.

Wnt/ß-catenin and sonic hedgehog pathways interact in the regulation of the development of the dorsal mesenchymal protrusion.

BACKGROUND: The dorsal mesenchymal protrusion (DMP) is a second heart field (SHF) derived tissue involved in cardiac septation. Molecular mechanisms controlling SHF/DMP development include the Bone Morphogenetic Protein and Wnt/ß-catenin signaling pathways. Reduced expression of components in these pathways leads to inhibition of proliferation of the SHF/DMP precursor population and failure of the DMP to develop. While the Sonic Hedgehog (Shh) pathway has also been demonstrated to be critically important for SHF/DMP development and atrioventricular septation, its role in the regulation of SHF proliferation is contentious. RESULTS: Tissue-specific deletion of the Shh receptor Smoothened from the SHF resulted in compromised DMP formation and atrioventricular septal defects (AVSDs). Immunohistochemical analysis at critical stages of DMP development showed significant proliferation defect as well as reduction in levels of the Wnt/ß-catenin pathway-intermediates ß-catenin, Lef1, and Axin2. To determine whether the defects seen in the conditional Smoothened knock-out mouse could be attributed to reduced Wnt/ß-catenin signaling, LiCl, a pharmacological activator of this Wnt/ß-catenin pathway, was administered. This resulted in restoration of proliferation and partial rescue of the AVSD phenotype. CONCLUSIONS: The data presented suggest that the Wnt/ß-catenin pathway interact with the Shh pathway in the regulation of SHF/DMP-precursor proliferation and, hence, the development of the DMP.

Alk3 mediated Bmp signaling controls the contribution of epicardially derived cells to the tissues of the atrioventricular junction.

Recent studies using mouse models for cell fate tracing of epicardial derived cells (EPDCs) have demonstrated that at the atrioventricular (AV) junction EPDCs contribute to the mesenchyme of the AV sulcus, the annulus fibrosus, and the parietal leaflets of the AV valves. There is little insight, however, into the mechanisms that govern the contribution of EPDCs to these tissues. While it has been demonstrated that bone morphogenetic protein (Bmp) signaling is required for AV cushion formation, its role in regulating EPDC contribution to the AV junction remains unexplored. To determine the role of Bmp signaling in the contribution of EPDCs to the AV junction, the Bmp receptor activin-like kinase 3 (Alk3; or Bmpr1a) was conditionally deleted in the epicardium and EPDCs using the mWt1/IRES/GFP-Cre (Wt1(Cre)) mouse. Embryonic Wt1(Cre);Alk3(fl/fl) specimens showed a significantly smaller AV sulcus and a severely underdeveloped annulus fibrosus. Electrophysiological analysis of adult Wt1(Cre);Alk3(fl/fl) mice showed, unexpectedly, no ventricular pre-excitation. Cell fate tracing revealed a significant decrease in the number of EPDCs within the parietal leaflets of the AV valves. Postnatal Wt1(Cre);Alk3(fl/fl) specimens showed myxomatous changes in the leaflets of the mitral valve. Together these observations indicate that Alk3 mediated Bmp signaling is important in the cascade of events that regulate the contribution of EPDCs to the AV sulcus, annulus fibrosus, and the parietal leaflets of the AV valves. Furthermore, this study shows that EPDCs do not only play a critical role in early developmental events at the AV junction, but that they also are important in the normal maturation of the AV valves.

Incidence and prevalence of hypertension in 18-40-year-old patients referred for palpitations with normal cardiac monitor findings.

Sixteen percent of patients referred for cardiology evaluation are found to have no cause for palpitations. Studies show that hypertension intricately influences "heart rate" and "contractility,?" the key components of "palpitation." While the prevalence of hypertension is 22.4% in 18-39-year-olds, the relationship between palpitations and hypertension remains unknown in this age group. In our study, we assessed the incidence and prevalence of hypertension over 5 years in 18-40-year-olds referred for palpitations who had no known arrhythmic cause for palpitations between January 1, 206 and December 31, 2017. We found that over a period of 2.2 (0.7-4.1) years, an additional 56% patients were diagnosed with stage 1 (65/130) and stage 2 (28/130) hypertension, increasing the prevalence from 16% at the start of the study period to 72% at the end of the study period (p < .0001). Hypertensive patients were obese (BMI: 29 [24-36] kg/m2 vs. 25 [22-31] kg/m2; p = .03), used nonsteroidal anti-inflammatory drugs (NSAIDs) (62 vs. 35%; p = .04), had a stronger family history of hypertension (55 vs. 4%; p < .0001) and exhibited higher systolic (124[120-130] mmHg vs. 112[108-115] mmHg; p < .0001) and diastolic (80[76-83] mmHg vs. 72[69-75] mmHg; p < .0001) blood pressures. Hypertension is commonly diagnosed in 18-40-year-old predominantly white female patients referred for palpitations without a known arrhythmic cause. The possibility of untreated hypertension causing palpitations in this cohort needs further evaluation.

Epicardially derived fibroblasts preferentially contribute to the parietal leaflets of the atrioventricular valves in the murine heart.

The importance of the epicardium for myocardial and valvuloseptal development has been well established; perturbation of epicardial development results in cardiac abnormalities, including thinning of the ventricular myocardial wall and malformations of the atrioventricular valvuloseptal complex. To determine the spatiotemporal contribution of epicardially derived cells to the developing fibroblast population in the heart, we have used a mWt1/IRES/GFP-Cre mouse to trace the fate of EPDCs from embryonic day (ED)10 until birth. EPDCs begin to populate the compact ventricular myocardium around ED12. The migration of epicardially derived fibroblasts toward the interface between compact and trabecular myocardium is completed around ED14. Remarkably, epicardially derived fibroblasts do not migrate into the trabecular myocardium until after ED17. Migration of EPDCs into the atrioventricular cushion mesenchyme commences around ED12. As development progresses, the number of EPDCs increases significantly, specifically in the leaflets which derive from the lateral atrioventricular cushions. In these developing leaflets the epicardially derived fibroblasts eventually largely replace the endocardially derived cells. Importantly, the contribution of EPDCs to the leaflets derived from the major AV cushions is very limited. The differential contribution of EPDCs to the various leaflets of the atrioventricular valves provides a new paradigm in valve development and could lead to new insights into the pathogenesis of abnormalities that preferentially affect individual components of this region of the heart. The notion that there is a significant difference in the contribution of epicardially and endocardially derived cells to the individual leaflets of the atrioventricular valves has also important pragmatic consequences for the use of endocardial and epicardial cre-mouse models in studies of heart development.

Prediction of Rapid Early Progression and Survival Risk with Pre-Radiation MRI in WHO Grade 4 Glioma Patients.

Recent clinical research describes a subset of glioblastoma patients that exhibit REP prior to the start of radiation therapy. Current literature has thus far described this population using clinicopathologic features. To our knowledge, this study is the first to investigate the potential of conventional radiomics, sophisticated multi-resolution fractal texture features, and different molecular features (MGMT, IDH mutations) as a diagnostic and prognostic tool for prediction of REP from non-REP cases using computational and statistical modeling methods. The radiation-planning T1 post-contrast (T1C) MRI sequences of 70 patients are analyzed. An ensemble method with 5-fold cross-validation over 1000 iterations offers an AUC of 0.793 ± 0.082 for REP versus non-REP classification. In addition, copula-based modeling under dependent censoring (where a subset of the patients may not be followed up with until death) identifies significant features (p-value < 0.05) for survival probability and prognostic grouping of patient cases. The prediction of survival for the patients' cohort produces a precision of 0.881 ± 0.056. The prognostic index (PI) calculated using the fused features shows that 84.62% of REP cases fall under the bad prognostic group, suggesting the potential of fused features for predicting a higher percentage of REP cases. The experimental results further show that multi-resolution fractal texture features perform better than conventional radiomics features for prediction of REP and survival outcomes.

Where Have All the FLOWERS Gone? A Multicenter Investigation of Frequent Users of Midwest Emergency Department Services During the COVID-19 Stay-at-home Orders.

INTRODUCTION: In this study we aimed to determine the impact of the mandatory coronavirus disease 2019 (COVID-19) pandemic stay-at-home order on the proportional makeup of emergency department (ED) visits by frequent users and super users. METHODS: We conducted a secondary analysis of existing data using a multisite review of the medical records of 280,053 patients to measure the impact of the COVID-19 pandemic stay-at-home order on ED visits. The primary outcomes included analysis before and during the lockdown in determining ED use and unique characteristics of non-frequent, frequent, and super users of emergency services. RESULTS: During the mandatory COVID-19 stay-at-home order (lockdown), the percentage of frequent users increased from 7.8% (pre-lockdown) to 21.8%. Super users increased from 0.7% to 4.7%, while non-frequent users dropped from 91.5% to 73.4%. Frequent users comprised 23.7% of all visits (4% increase), while super user encounters (4.7%) increased by 53%. Patients who used Medicaid and Medicare increased by 39.3% and 4.6%, respectively, while those who were uninsured increased ED use by 190.3% during the lockdown. CONCLUSION: When barriers to accessing healthcare are implemented as part of a broader measure to reduce the spread of an infectious agent, individuals reliant on these services are more likely to seek out the ED for their medical needs. Policymakers considering future pandemic planning should consider this finding to ensure that vital healthcare resources are allocated appropriately.

Outcomes from a tertiary care center using a catheter thrombectomy system for managing acute iliofemoral deep vein thrombosis.

OBJECTIVE: The aim of the present study was to report a large, single-center experience using the ClotTriever thrombectomy system (Inari Medical, Irvine, CA) for the management of acute iliofemoral (IF) deep vein thrombosis (DVT). One limitation of all endovascular devices for the treatment of acute IF-DVT has been the inability to completely remove all acute thrombus and the need for adjunctive thrombolysis with its attendant risk of bleeding complications. METHODS: A single-center retrospective review of consecutive patients with acute IF-DVT treated with the ClotTriever thrombectomy system (Inari Medical) is reported. Procedural efficacy was evaluated by an independent core imaging laboratory (Syntactx, New York, NY). Both procedural and in-hospital safety were assessed during the index hospitalization. The treated vein patency was assessed using duplex ultrasound at 30 days after the procedure. RESULTS: A total of 96 patients were included in the present retrospective review, 40 of whom (40%) had contraindications to thrombolytic therapy. In terms of efficacy, 93 patients (97%) had ≥75% thrombus removal. During the index hospitalization, two patients (2%) had experienced a symptomatic pulmonary embolus. However, no mortality, major bleeding, or device-related complications had occurred in the study population. Of the 96 patients, 64 had undergone duplex ultrasound at 30 days after the procedure. Of the 64 patients, 62 had normal flow (97%), 53 (83%) had normal compressibility, and 11 (17%) had partial compressibility. CONCLUSIONS: The ClotTriever thrombectomy catheter was both safe and effective in our cohort of patients with acute IF-DVT outside a randomized clinical trial.

Extracellular matrix and heart development.

The extracellular matrix (ECM) of the developing heart contains numerous molecules that form a dynamic environment that plays an active and crucial role in the regulation of cellular events. ECM molecules found in the heart include hyaluronan, fibronectin, fibrillin, proteoglycans, and collagens. Tight regulation of the spatiotemporal expression, and the proteolytic processing of ECM components by proteases including members of the ADAMTS family, is essential for normal cardiac development. Perturbation of the expression of genes involved in matrix composition and remodeling can interfere with a myriad of events involved in the formation of the four-chambered heart and result in prenatal lethality or cardiac malformations as seen in humans with congenital heart disease. In this review, we summarize what is known about the specific importance of some of the components of the ECM in relation to the cardiovascular development.

Role of the Epicardium in the Development of the Atrioventricular Valves and Its Relevance to the Pathogenesis of Myxomatous Valve Disease.

This paper is dedicated to the memory of Dr. Adriana "Adri" Gittenberger-de Groot and in appreciation of her work in the field of developmental cardiovascular biology and the legacy that she has left behind. During her impressive career, Dr. Gittenberger-de Groot studied many aspects of heart development, including aspects of cardiac valve formation and disease and the role of the epicardium in the formation of the heart. In this contribution, we review some of the work on the role of epicardially-derived cells (EPDCs) in the development of the atrioventricular valves and their potential involvement in the pathogenesis of myxomatous valve disease (MVD). We provide an overview of critical events in the development of the atrioventricular junction, discuss the role of the epicardium in these events, and illustrate how interfering with molecular mechanisms that are involved in the epicardial-dependent formation of the atrioventricular junction leads to a number of abnormalities. These abnormalities include defects of the AV valves that resemble those observed in humans that suffer from MVD. The studies demonstrate the importance of the epicardium for the proper formation and maturation of the AV valves and show that the possibility of epicardial-associated developmental defects should be taken into consideration when determining the genetic origin and pathogenesis of MVD.

Clinical Evaluation and Utilization of Multiple Molecular In Vitro Diagnostic Assays for the Detection of SARS-CoV-2.

OBJECTIVES: To evaluate the clinical performance of 3 molecular assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We used 184 nasopharyngeal swab specimens to compare Abbott ID NOW COVID-19 (Abbott ID NOW), DiaSorin Molecular Simplexa COVID-19 Direct (DiaSorin Simplexa), and Roche cobas 6800 SARS-CoV-2 (Roche cobas) assays. In a separate analysis, 3 specimens (nasopharyngeal, oropharyngeal, and nasal) were collected from 182 unique patients presenting to the emergency department with suspicion of coronavirus disease 2019 and were tested utilizing Abbott ID NOW. To further characterize each assay, relative limits of detection were evaluated utilizing positive nasopharyngeal patient samples. RESULTS: The positive percent agreement was 91% (95% confidence interval [CI], 0.76-0.97) for Abbott ID NOW and 100% (95% CI, 0.90-1.00) for DiaSorin Simplexa and Roche cobas. The negative percent agreement was 100% (95% CI, 0.98-1.00) for all 3 assays. All swab types tested with the Abbott assay produced concordant results. Polymerase chain reaction assays had approximately 10 to 100 times lower limits of detection than Abbott ID NOW. CONCLUSIONS: Based on these evaluations, a multiplatform testing approach is proposed, depending on patient population and assay sensitivity, to address testing needs during a public health emergency.

Tissue expression pattern of class II and class V genes found in the Adh complex on mouse chromosome 3.

The alcohol dehydrogenase enzymes in mice and humans are encoded by a linked group of genes in the same transcriptional orientation. The enzymes play important roles in alcohol metabolism and retinoid signaling and homeostasis. The expression patterns at the mRNA level of the mouse Adh4 (class II) gene and the recently identified Adh6a and Adh6b genes (class V) are now reported to complete this analysis for the entire family. Adh4 is expressed at high levels in liver and is detectable in small intestine and testes. Adh6b is expressed in liver but Adh6a is not. Adh6a is expressed at high levels in small intestine while Adh6b is not. Adh6a expression is detectable in the female adrenal and not at all in the male adrenal, but Adh6b is expressed at moderate levels in both sexes. Although Adh6a and Adh6b have expression patterns different from each other, neither expresses like any other gene in the complex, suggesting different control mechanisms and possibly different functions.

The Epicardium and the Development of the Atrioventricular Junction in the Murine Heart.

Insight into the role of the epicardium in cardiac development and regeneration has significantly improved over the past ten years. This is mainly due to the increasing availability of new mouse models for the study of the epicardial lineage. Here we focus on the growing understanding of the significance of the epicardium and epicardially-derived cells in the formation of the atrioventricular (AV) junction. First, through the process of epicardial epithelial-to-mesenchymal transformation (epiEMT), the subepicardial AV mesenchyme is formed. Subsequently, the AV-epicardium and epicardially-derived cells (EPDCs) form the annulus fibrosus, a structure important for the electrical separation of atrial and ventricular myocardium. Finally, the AV-EPDCs preferentially migrate into the parietal AV valve leaflets, largely replacing the endocardially-derived cell population. In this review, we provide an overview of what is currently known about the regulation of the events involved in this process.

Mef2c regulates transcription of the extracellular matrix protein cartilage link protein 1 in the developing murine heart.

Cartilage Link Protein 1 (Crtl1) is an extracellular matrix (ECM) protein that stabilizes the interaction between hyaluronan and versican and is expressed in endocardial and endocardially-derived cells in the developing heart, including cells in the atrioventricular (AV) and outflow tract (OFT) cushions. Previous investigations into the transcriptional regulation of the Crtl1 gene have shown that Sox9 regulates Crtl1 expression in both cartilage and the AV valves. The cardiac transcription factor Mef2c is involved in the regulation of gene expression in cardiac and skeletal muscle cell lineages. In this study we have investigated the potential role of Mef2c in the regulation of ECM production in the endocardial and mesenchymal cell lineages of the developing heart. We demonstrate that the Crtl1 5' flanking region contains two highly conserved Mef2 binding sites and that Mef2c is able to bind to these sites in vivo during cardiovascular development. Additionally, we show that Crtl1 transcription is dependent on Mef2c expression in fetal mitral valve interstitial cells (VICs). Combined, these findings highlight a new role for Mef2c in cardiac development and the regulation of cardiac extracellular matrix protein expression.