Impaired CAMK4 Activity Limits Atherosclerosis and Reprograms Myelopoiesis.

Background: Chronic inflammation is a major driver of atherosclerotic cardiovascular disease, and therapeutics that target inflammation reduce cardiac events beyond levels seen with strategies targeting cholesterol alone. RNA sequencing revealed increased expression of CaMK4 (calcium/calmodulin-dependent protein kinase IV) in advanced/unstable human carotid artery plaque. We validated this finding in mouse and human atherosclerotic lesions, demonstrating increased CaMK4 in plaque macrophages.

The transcription factor ZNF469 regulates collagen production in liver fibrosis.

Metabolic dysfunction-associated steatotic liver disease (MASLD) - characterized by excess accumulation of fat in the liver - now affects one-third of the world's population. As MASLD progresses, extracellular matrix components including collagen accumulate in the liver, causing tissue fibrosis, a major determinant of disease severity and mortality. To identify transcriptional regulators of fibrosis, we computationally inferred the activity of transcription factors (TFs) relevant to fibrosis by profiling the matched transcriptomes and epigenomes of 108 human liver biopsies from a deeply characterized cohort of patients spanning the full histopathologic spectrum of MASLD.

Bone Marrow Niche in Cardiometabolic Disease: Mechanisms and Therapeutic Potential.

Cardiovascular and cardiometabolic diseases are leading causes of morbidity and mortality worldwide, driven in part by chronic inflammation. Emerging research suggests that the bone marrow microenvironment, or marrow niche, plays a critical role in both immune system regulation and disease progression. The bone marrow niche is essential for maintaining hematopoietic stem cells (HSCs) and orchestrating hematopoiesis.

Nanoscale imaging of DNA-RNA identifies transcriptional plasticity at heterochromatin.

The three-dimensional structure of DNA is a biophysical determinant of transcription. The density of chromatin condensation is one determinant of transcriptional output. Chromatin condensation is generally viewed as enforcing transcriptional suppression, and therefore, transcriptional output should be inversely proportional to DNA compaction.

Transcriptional synergy in human aortic endothelial cells is vulnerable to combination p300/CBP and BET bromodomain inhibition.

Combinatorial signaling by proinflammatory cytokines synergizes to exacerbate toxicity to cells and tissue injury during acute infections. To explore synergism at the gene-regulatory level, we investigated the dynamics of transcription and chromatin signaling in response to dual cytokines by integrating nascent RNA imaging mass spectrometry, RNA sequencing, amplification-independent mRNA quantification, assay for transposase-accessible chromatin using sequencing (ATAC-seq), and transcription factor profiling. Costimulation with interferon-gamma (IFNγ) and tumor necrosis factor alpha (TNFα) synergistically induced a small subset of genes, including the chemokines , -, and -.

The transcription factor ZNF469 regulates collagen production in liver fibrosis.

Non-alcoholic fatty liver disease (NAFLD) - characterized by excess accumulation of fat in the liver - now affects one third of the world's population. As NAFLD progresses, extracellular matrix components including collagen accumulate in the liver causing tissue fibrosis, a major determinant of disease severity and mortality. To identify transcriptional regulators of fibrosis, we computationally inferred the activity of transcription factors (TFs) relevant to fibrosis by profiling the matched transcriptomes and epigenomes of 108 human liver biopsies from a deeply-characterized cohort of patients spanning the full histopathologic spectrum of NAFLD.

The consumption of animal products is associated with plasma levels of alpha-aminoadipic acid (2-AAA).

Background And Aims: The cardiometabolic disease-associated metabolite, alpha-aminoadipic acid (2-AAA) is formed from the breakdown of the essential dietary amino acid lysine. However, it was not known whether elevated plasma levels of 2-AAA are related to dietary nutrient intake. We aimed to determine whether diet is a determinant of circulating 2-AAA in healthy individuals, and whether 2-AAA is altered in response to dietary modification.

Association of alpha-aminoadipic acid with cardiometabolic risk factors in healthy and high-risk individuals.

Introduction: Plasma levels of the metabolite alpha-aminoadipic acid (2-AAA) have been associated with risk of type 2 diabetes (T2D) and atherosclerosis. However, little is known about the relationship of 2-AAA to other cardiometabolic risk markers in pre-disease states, or in the setting of comorbid disease.

Methods: We measured circulating 2-AAA using two methods in 1) a sample of 261 healthy individuals (2-AAA Study), and 2) in a sample of 134 persons comprising 110 individuals with treated HIV, with or without T2D, a population at high risk of metabolic disease and cardiovascular events despite suppression of circulating virus, and 24 individuals with T2D without HIV (HATIM Study).

Association of alpha-aminoadipic acid (2-AAA) with cardiometabolic risk factors in healthy and high-risk individuals.

Plasma levels of the metabolite alpha-aminoadipic acid (2-AAA) have been associated with risk of type 2 diabetes (T2D) and atherosclerosis. However, little is known about the relationship of 2-AAA to other cardiometabolic risk markers in pre-disease states, or in the setting of comorbid disease. We measured circulating 2-AAA using two methods in 1) a sample of 261 healthy individuals (2-AAA Study), and 2) in a sample of 134 persons comprising 110 individuals with treated HIV, with or without T2D, a population at high risk of metabolic disease and cardiovascular events despite suppression of circulating virus, and 24 individuals with T2D without HIV (HATIM Study).

Impacts of the Certified Community Behavioral Health Clinic Demonstration on Emergency Department Visits and Hospitalizations.

Objective: The Certified Community Behavioral Health Clinic (CCBHC) demonstration is designed to increase access to comprehensive ambulatory care and crisis services, which may reduce emergency department (ED) visits and hospitalizations. This study examined whether the demonstration had an impact on ED visits and hospitalizations in Missouri, Oklahoma, and Pennsylvania.

Methods: This difference-in-differences analysis used Medicaid claims data from 2015 to 2019 to examine service use during a 12-month baseline period and the first 24 months of the demonstration for beneficiaries who received care from CCBHCs and beneficiaries who received care from other behavioral health clinics in the same state, representing care as usual.

Comparative effects of weight loss and incretin-based therapies on vascular endothelial function, fibrinolysis and inflammation in individuals with obesity and prediabetes: A randomized controlled trial.

Aim: To test the hypothesis that glucagon-like peptide-1 receptor (GLP-1R) agonists have beneficial effects on vascular endothelial function, fibrinolysis and inflammation through weight loss-independent mechanisms.

Materials And Methods: Individuals with obesity and prediabetes were randomized to 14 weeks of the GLP-1R agonist liraglutide, hypocaloric diet or the dipeptidyl peptidase-4 inhibitor sitagliptin in a 2:1:1 ratio. Treatment with drug was double blind and placebo-controlled.

Differences in Services Offered by Certified Community Behavioral Health Clinics and Community Mental Health Centers.

Objective: This study examined differences between certified community behavioral health clinics (CCBHCs) and community mental health centers (CMHCs) in the services offered and populations served.

Methods: Data from the 2020 National Mental Health Services Survey were used to quantify the proportion of CCBHCs (N=336) and CMHCs (N=1,953) that offered services and served populations described in the CCBHC certification criteria.

Results: A higher proportion of CCBHCs than CMHCs offered crisis services, peer support, substance use disorder treatment, treatment for co-occurring disorders, antipsychotics, assertive community treatment, general medical health screening, tobacco cessation services, psychiatric rehabilitation services, and other outpatient services.

Factors Associated with the Receipt of Follow-Up Care Among Medicare Beneficiaries Discharged from Inpatient Psychiatric Facilities.

This study examined the extent to which facility characteristics, discharge practices, and the availability of outpatient mental health care are associated with receiving follow-up care within 7 days of discharge from an inpatient psychiatric facility among Medicare beneficiaries. The study merged 2018 National Mental Health Services Survey data with 2018 Inpatient Psychiatric Facility Quality Reporting program data representing 1147 inpatient psychiatric facilities. Results from logistic regression analyses indicated that inpatient facilities operated by private for-profit organizations and public agencies had lower odds of achieving high performance on a measure that assessed if Medicare beneficiaries received follow-up care within 7 days of discharge relative to private nonprofit facilities; follow-up rates were inversely associated with the proportion of involuntarily committed patients at the facility.

Targeting transcription in heart failure via CDK7/12/13 inhibition.

Heart failure with reduced ejection fraction (HFrEF) is associated with high mortality, highlighting an urgent need for new therapeutic strategies. As stress-activated cardiac signaling cascades converge on the nucleus to drive maladaptive gene programs, interdicting pathological transcription is a conceptually attractive approach for HFrEF therapy. Here, we demonstrate that CDK7/12/13 are critical regulators of transcription activation in the heart that can be pharmacologically inhibited to improve HFrEF.

The FoxOs are in the ApoM house.

The prevalence of metabolic syndrome continues to increase globally and heightens the risk for cardiovascular disease (CVD). Insulin resistance is a core pathophysiologic mechanism that causes abnormal carbohydrate metabolism and atherogenic changes in circulating lipoprotein quantity and function. In particular, dysfunctional HDL is postulated to contribute to CVD risk in part via loss of HDL-associated sphingosine-1-phosphate (S1P).

KLF15 cistromes reveal a hepatocyte pathway governing plasma corticosteroid transport and systemic inflammation.

Circulating corticosteroids orchestrate stress adaptation, including inhibition of inflammation. While pathways governing corticosteroid biosynthesis and intracellular signaling are well understood, less is known about mechanisms controlling plasma corticosteroid transport. Here, we show that hepatocyte KLF15 (Kruppel-like factor 15) controls plasma corticosteroid transport and inflammatory responses through direct transcriptional activation of , which encodes corticosteroid-binding globulin (CBG).

Structural Components of Integrated Behavioral Health Care: A Comparison of National Programs.

Initiatives that support and incentivize the integration of behavioral health and general medical care have become a focus of government strategies to achieve the triple aim of improved health, better patient experience, and reduced costs. The authors describe the components of four large-scale national initiatives aimed at integrating care for a wide range of behavioral health needs. Commonalities across these national initiatives highlight health care and social services needs that must be addressed to improve care for people with co-occurring behavioral health and general medical conditions.

Targeting the locus for liver-directed gene therapy.

Clinical application of somatic genome editing requires therapeutics that are generalizable to a broad range of patients. Targeted insertion of promoterless transgenes can ensure that edits are permanent and broadly applicable while minimizing risks of off-target integration. In the liver, the Albumin () locus is currently the only well-characterized site for promoterless transgene insertion.

Improving Physical Health Among People With Serious Mental Illness: The Role of the Specialty Mental Health Sector.

People with serious mental illness die 10-20 years earlier, compared with the overall population, and the excess mortality is driven by undertreated physical health conditions. In the United States, there is growing interest in models integrating physical health care delivery, management, or coordination into specialty mental health programs, sometimes called "reverse integration." In November 2019, the Johns Hopkins ALACRITY Center for Health and Longevity in Mental Illness convened a forum of 25 experts to discuss the current state of the evidence on integrated care models based in the specialty mental health system and to identify priorities for future research, policy, and practice.

Role of Psychiatric Hospitals in the Equitable Distribution of COVID-19 Vaccines.

Objective: This study examined the feasibility of offering COVID-19 vaccinations to patients in inpatient psychiatric facilities (IPFs).

Methods: Descriptive analyses were conducted to examine relationships among measures of influenza immunization, transmission of transition records, and attainment of follow-up care with data from 1,602 IPFs in 2018 and the COVID-19 Community Vulnerability Index.

Results: One-quarter of IPFs were in counties with high or very high COVID-19 vulnerability.

Application of the Spanish-Language Consultation and Relational Empathy (CARE) Measure to Assess Patient-Centered Care Among Latino Populations.

Introduction: Reliable and valid measures are needed to assess the patient-centeredness of clinical care among Latino populations.

Methods: We translated the Consultation and Relational Empathy (CARE) measure from English to Spanish and assessed its psychometric properties using data from 349 Latino parents/guardians visiting a pediatric clinic. Using confirmatory factor analysis, we examined the psychometric properties of the Spanish CARE measure.

Macrophage SR-BI modulates autophagy via VPS34 complex and PPARα transcription of Tfeb in atherosclerosis.

Autophagy modulates lipid turnover, cell survival, inflammation, and atherogenesis. Scavenger receptor class B type I (SR-BI) plays a crucial role in lysosome function. Here, we demonstrate that SR-BI regulates autophagy in atherosclerosis.