In this review, we will discuss the current use of patient-specific induced pluripotent stem cells in identifying populations who are at risk to drug-induced cardiotoxicity and their potential applications in future precision medicine practice. Graphic Abstract A graphic abstract is available for this article.[Figure see text].
  Plaque necrosis is a key feature of defective resolution in atherosclerosis. Recent evidence suggests that necroptosis promotes plaque necrosis; therefore, we sought to determine how necroptotic cells (NCs) impact resolution programs in plaques. Approach and Results To investigate the role(s) of necroptosis in advanced atherosclerosis, we used mice deficient of 
  , an effector of necroptosis. 
  
  mice that were injected with a gain-of-function mutant PCSK9 (AAV8-gof-PCSK9) and fed a Western diet for 16 weeks, showed significantly less plaque necrosis, increased fibrous caps and improved efferocytosis compared with AAV8-gof-PCSK9 injected wt controls.  https://www.selleckchem.com/products/ml385.html  Additionally, hypercholesterolemic 
  
  mice had a significant increase in proresolving mediators including resolvin D1 (RvD1) and a decrease in prostanoids including thromboxane in plaques and in vitro. We found that exuberant thromboxane released by NCs impaired the clearance of both apoptotic cells and NCs through disruption of oxidative phosphorylation in urther suggests RvD1 as a potential therapeutic strategy to limit NCs in tissues. Graphic Abstract A graphic abstract is available for this article.
  COMP (cartilage oligomeric matrix protein) is abundantly expressed in the cardiovascular system, cartilage, and atherosclerotic plaques. We investigated if the total COMP (COMPtotal) and COMP neoepitope (COMPneo) with other cardiovascular markers and clinical parameters could identify symptomatic carotid stenosis. Approach and Results Blood samples were collected from patients with symptomatic carotid stenosis (stenosis, n=50), patients with stroke without carotid stenosis but small plaques (plaque, n=50), and control subjects (n=50). COMPtotal and COMPneo were measured using an ELISA. Ninety-two cardiovascular disease markers were measured by the Olink CVD kit. The presence of native COMP and COMPneo was determined by immunohistochemistry. The concentration of COMPneo was higher and COMPtotal was lower in the stenosis group. When the concentration was compared between the stenosis and control groups, IL-1ra (interleukin-1 receptor antagonist protein), IL6 (interleukin-6), REN (Renin), MMP1 (matrix metallopsclerosis progression and generation of a specific COMP fragment-COMPneo. This may represent a novel biomarker that together with COMPtotal and other risk-markers could be used to identify symptomatic carotid stenosis. Graphic Abstract A graphic abstract is available for this article.
 Degradation of COMP may be associated with atherosclerosis progression and generation of a specific COMP fragment-COMPneo. This may represent a novel biomarker that together with COMPtotal and other risk-markers could be used to identify symptomatic carotid stenosis. Graphic Abstract A graphic abstract is available for this article.
  Right heart catheterization using exercise stress is the reference standard for the diagnosis of heart failure with preserved ejection fraction (HFpEF) but carries the risk of the invasive procedure. We hypothesized that real-time cardiac magnetic resonance (RT-CMR) exercise imaging with pathophysiologic data at excellent temporal and spatial resolution may represent a contemporary noninvasive alternative for diagnosing HFpEF.
 
  The HFpEF-Stress trial (CMR Exercise Stress Testing in HFpEF; URL https//www.clinicaltrials.gov; Unique identifier NCT03260621. URL https//dzhk.de/; Unique identifier DZHK-17) prospectively recruited 75 patients with echocardiographic signs of diastolic dysfunction and dyspnea on exertion (E/e'>8, New York Heart Association class ≥II) to undergo echocardiography, right heart catheterization, and RT-CMR at rest and during exercise stress. HFpEF was defined according to pulmonary capillary wedge pressure (≥15 mm Hg at rest or ≥25 mm Hg during exercise stress). RT-CMR functional ass URL https//dzhk.de/; Unique identifier DZHK-17.
  Mental health among military personnel is an important public health priority. It is known that military personnel experience a high prevalence of child maltreatment and deployment-related traumatic events (DRTEs) and both are related to mental health outcomes. However, few, if any, studies have examined the cumulative and interactive effects of child maltreatment and DRTEs on mental health disorders in a sample of active duty service members and military veterans.
 
  Data were from the Canadian Armed Forces (CAF) Members and Veterans Mental Health Follow-up Survey collected in 2018 (
  = 2,941, response rate = 68.7%), a 16-year follow-up survey of CAF Regular Force members interviewed in 2002. Five types of child maltreatment and 10 types of DTREs were assessed for impact on mental health. Mental disorders included past 12-month generalized anxiety disorder (GAD), panic disorder, social phobia, and major depressive episode (MDE). Past 12-month symptoms of posttraumatic stress disorder (PTSD) were also examiamong active Canadian military and veterans. As well, child maltreatment may increase the likelihood of mental disorders across the life span. This may be especially true for individuals who also experience DRTEs. Understanding these relationships may provide insight into developing effective interventions for military personnel and veteran mental health outcomes.
  Prolonged grief disorder was newly included in ICD-11 and resembles persistent complex bereavement disorder, newly included in DSM-5. Although prolonged grief disorder in adults can be successfully treated by cognitive-behavioral therapy (CBT), there is no evidence yet that CBT interventions can successfully alleviate the disorder in children and adolescents. The goal of this randomized clinical trial was to examine the effects of a CBT program, CBT Grief-Help, for prolonged grief disorder in children and adolescents in comparison with the effects of nondirective supportive counseling.
 
  A total of 134 children and adolescents with prolonged grief disorder (mean age, 13.10 years [SD=2.84], bereaved a mean of 37.79 months [SD=36.23] earlier) were randomly assigned to receive either CBT Grief-Help (N=74) or supportive counseling (N=60). Both treatment conditions encompassed nine individual sessions with children and adolescents paralleled by five counseling sessions with parents or caretakers. Children and adolescents completed measures of prolonged grief disorder, depression, and posttraumatic stress disorder (PTSD), and their parents or caretakers completed measures of their children's problem behavior before treatment, immediately after treatment, and 3, 6, and 12 months after treatment.