Immune-checkpoint-inhibitor therapy directed against PD-L1 is tolerated in the heart without manifestation of cardiac inflammation in a preclinical reversible melanoma mouse model.

Immune-checkpoint-inhibitors (ICI) target key regulators of the immune system expressed by cancer cells that mask those from recognition by the immune system. They have improved the outcome for patients with various cancer types, such as melanoma. ICI-based therapy is frequently accompanied by immune-related adverse side effects (IRAEs).

is a novel allele of the gene ( ) in .

Genetic screens in have long been used to identify genes found in a variety of developmental, cellular, and behavioral processes. Here we describe the characterization and mapping of a mutation identified in a conditional screen for genetic regulators of cell growth and cell division. Within a Flp/FRT system, mutant results in a reduction of mutant tissue and a rough eye phenotype.

Heart-brain axis: Pushing the boundaries of cardiovascular molecular imaging.

Despite decades of research, the heart-brain axis continues to challenge investigators seeking to unravel its complex pathobiology. Strong epidemiologic evidence supports a link by which insult or injury to one of the organs increases the risk of pathology in the other. The putative pathways have important differences between sexes and include alterations in autonomic function, metabolism, inflammation, and neurohormonal mechanisms that participate in crosstalk between the heart and brain and contribute to vascular changes, the development of shared risk factors, and oxidative stress.

Revisiting mandibular symphyseal shape in juvenile early hominins and modern humans using a deformation-based approach.

The juvenile mandible is important in the investigation of ontogenetic and evolutionary changes among early hominins. We revisit the mandibular symphysis in juvenile specimens of Australopithecus africanus and Paranthropus robustus with two main contributions. First, we employ, for the first time, methods of computational anatomy to model complex symphyseal shape differences.

Toward Quantitative Multisite Preclinical Imaging Studies in Acute Myocardial Infarction: Evaluation of the Immune-Fibrosis Axis.

The immune-fibrosis axis plays a critical role in cardiac remodeling after acute myocardial infarction. Imaging approaches to monitor temporal inflammation and fibroblast activation in mice have seen wide application in recent years. However, the repeatability of quantitative measurements remains challenging, particularly across multiple imaging centers.

Intimate Partner Violence: Role of the Pediatrician.

The American Academy of Pediatrics and its members recognize the importance of improving the physician's ability to recognize intimate partner violence (IPV) and understand its effects on child health and development and its role in the continuum of family violence. Pediatricians are in a unique position to identify IPV survivors in pediatric settings, to evaluate and treat children exposed to IPV, and to connect families with available local and national resources. Children exposed to IPV are at increased risk of being abused and neglected and are more likely to develop adverse health, behavioral, psychological, and social disorders later in life.

Molecular Imaging of Myocardial Fibroblast Activation in Patients with Advanced Aortic Stenosis Before Transcatheter Aortic Valve Replacement: A Pilot Study.

Using multimodal imaging, we investigated the extent and functional correlates of myocardial fibroblast activation in patients with aortic stenosis (AS) scheduled for transcatheter aortic valve replacement (TAVR). AS may cause myocardial fibrosis, which is associated with disease progression and may limit response to TAVR. Novel radiopharmaceuticals identify upregulation of fibroblast activation protein (FAP) as a cellular substrate of cardiac profibrotic activity.

Hominin fossils from Kromdraai and Drimolen inform craniofacial ontogeny.

Ontogeny provides critical information about the evolutionary history of early hominin adult morphology. We describe fossils from the southern African sites of Kromdraai and Drimolen that provide insights into early craniofacial development in the Pleistocene robust australopith . We show that while most distinctive robust craniofacial features appear relatively late in ontogeny, a few do not.

Timely Recognition of Abusive Injuries (TRAIN): Results from a Statewide Quality Improvement Collaborative.

Unlabelled: Early recognition of physical abuse is critical as children often experience recurrent abuse if their environment remains unchanged. The Timely Recognition of Abusive Injuries (TRAIN) Collaborative was a quality improvement network of 6 Ohio children's hospitals created in 2015 to improve the management of injuries concerning for abuse in infants. TRAIN's first phase sought to reduce recurrent abuse by recognizing and responding to injured infants.

Child physical abuse screening in a pediatric ED; Does TRAIN(ing) Help?

Background: Child maltreatment is distressingly prevalent yet remains under-recognized by healthcare providers. In 2015 the Ohio Children's Hospital Association developed the Timely Recognition of Abusive INjuries (TRAIN) collaborative in an effort to promote child physical abuse (CPA) screening. Our institution implemented the TRAIN initiative in 2019.

C1q and Tumor Necrosis Factor Related Protein 9 Protects from Diabetic Cardiomyopathy by Alleviating Cardiac Insulin Resistance and Inflammation.

(1) Background: Diabetic cardiomyopathy is a major health problem worldwide. CTRP9, a secreted glycoprotein, is mainly expressed in cardiac endothelial cells and becomes downregulated in mouse models of diabetes mellitus; (2) Methods: In this study, we investigated the impact of CTRP9 on early stages of diabetic cardiomyopathy induced by 12 weeks of high-fat diet; (3) Results: While the lack of CTRP9 in knock-out mice aggravated insulin resistance and triggered diastolic left ventricular dysfunction, AAV9-mediated cardiac CTRP9 overexpression ameliorated cardiomyopathy under these conditions. At this early disease state upon high-fat diet, no fibrosis, no oxidative damage and no lipid deposition were identified in the myocardium of any of the experimental groups.

Nuclear Methods for Immune Cell Imaging: Bridging Molecular Imaging and Individualized Medicine.

Inflammation is a key mechanistic contributor to the progression of cardiovascular disease, from atherosclerosis through ischemic injury and overt heart failure. Recent evidence has identified specific roles of immune cell subpopulations in cardiac pathogenesis that diverges between individual patients. Nuclear imaging approaches facilitate noninvasive and serial quantification of inflammation severity, offering the opportunity to predict eventual outcome, stratify patient risk, and guide novel targeted molecular therapies against specific leukocyte subpopulations.

Molecular imaging of the brain-heart axis provides insights into cardiac dysfunction after cerebral ischemia.

Ischemic stroke imparts elevated risk of heart failure though the underlying mechanisms remain poorly described. We aimed to characterize the influence of cerebral ischemic injury on cardiac function using multimodality molecular imaging to investigate brain and cardiac morphology and tissue inflammation in two mouse models of variable stroke severity. Transient middle cerebral artery occlusion (MCAo) generated extensive stroke damage (56.

Student Attitudes Contribute to the Effectiveness of a Genomics CURE.

The Genomics Education Partnership (GEP) engages students in a course-based undergraduate research experience (CURE). To better understand the student attributes that support success in this CURE, we asked students about their attitudes using previously published scales that measure epistemic beliefs about work and science, interest in science, and grit. We found, in general, that the attitudes students bring with them into the classroom contribute to two outcome measures, namely, learning as assessed by a pre- and postquiz and perceived self-reported benefits.

Identification of Initial and Subsequent Injury in Young Infants: Opportunities for Quality Improvement in the Evaluation of Child Abuse.

Methods: Six children's hospitals identified infants with an initial injury and recurrent injury over a 1-year period using 2 methods: (1) diagnostic code method - infants 6 months or younger presenting with at least 1 diagnostic code for injury were tracked for 12 months to determine the frequency of recurrent injury, and (2) consult method - all available medical records of children 18 months or younger seen for an inpatient consultation for suspected child abuse were reviewed to identify history of a first injury at 6 months or younger.

Results: Using the diagnostic code method, 682 unique infants were identified with initial injuries, most commonly fractures (37.0%), bruising/ecchymosis (35.

Characterizing the transition from immune response to tissue repair after myocardial infarction by multiparametric imaging.

Persistent inflammation following myocardial infarction (MI) precipitates adverse outcome including acute ventricular rupture and chronic heart failure. Molecular imaging allows longitudinal assessment of immune cell activity in the infarct territory and predicts severity of remodeling. We utilized a multiparametric imaging platform to assess the immune response and cardiac healing following MI in mice.

Cardiac Fibroblast Activation in Patients Early After Acute Myocardial Infarction: Integration with MR Tissue Characterization and Subsequent Functional Outcome.

After acute myocardial infarction (AMI), fibroblast activation protein (FAP) upregulation exceeds the infarct region. We sought further insights into the physiologic relevance by correlating FAP-targeted PET with tissue characteristics from cardiac MRI (CMR) and functional outcome. Thirty-five patients underwent CMR, perfusion SPECT, and Ga-FAP inhibitor (FAPI)-46 PET/CT within 11 d after AMI.

Can Sensory- and Attachment-Informed Approaches Modify the Perception of Pain? An Experimental Study.

Accumulating evidence linking pain with both attachment and sensory processing variables introduces the possibility that attachment- and sensory-informed strategies may modify pain experiences. The aim of this study was to investigate this proposition using an experimentally induced pain procedure. Pain perceptions of individuals using either a sensory-informed (weighted modality) or an attachment-informed (secure base priming) coping strategy were compared with those of individuals using no designated coping strategy.

A mutation phenocopies oblique alleles altered vesicle trafficking.

The Drosophila extracellular matrix protein Dumpy (Dpy) is one of the largest proteins encoded by any animal. One class of mutations produces a characteristic shortening of the wing blade known as oblique ( ), due to altered tension in the developing wing. We describe here the characterization of , a gene originally named because of an allele producing a truncated wing.