Galactosylated hydroxyl-polyamidoamine dendrimer targets hepatocytes and improves therapeutic outcomes in a severe model of acetaminophen poisoning-induced liver failure.

Toxicity to hepatocytes caused by various insults including drugs is a common cause of chronic liver failure requiring transplantation. Targeting therapeutics specifically to hepatocytes is often a challenge since they are relatively nonendocytosing unlike the highly phagocytic Kupffer cells in the liver. Approaches that enable targeted intracellular delivery of therapeutics to hepatocytes have significant promise in addressing liver disorders.

Nanofiber-based glaucoma drainage implant improves surgical outcomes by modulating fibroblast behavior.

Biomaterials are implanted in millions of individuals worldwide each year. Both naturally derived and synthetic biomaterials induce a foreign body reaction that often culminates in fibrotic encapsulation and reduced functional lifespan. In ophthalmology, glaucoma drainage implants (GDIs) are implanted in the eye to reduce intraocular pressure (IOP) in order to prevent glaucoma progression and vision loss.

Function and form of the shoulder in congenital and untreated growth hormone deficiency.

Objectives: The shoulder is the most mobile joint in the entire human body. During arm elevation, it requires the integrity of a set of muscles, bones, and tendons. Individuals with short stature often need to raise their arms above the shoulder girdle and may have functional restriction or shoulder injuries.

Rural age-friendly ecosystems for older adults: An international scoping review with recommendations to support age-friendly communities.

Background And Aims: The population of older adults in rural areas is rising, and they experience higher rates of poverty and chronic illness, have poorer health behaviors, and experience different challenges than those in urban areas. This scoping review seeks to (1) map the state of the science of age-friendly systems in rural areas regarding structural characteristics, processes for delivering age-friendly practices, and outcomes of age-friendly systems, (2) analyze strengths, weakness, opportunities, and threats of age-friendly system implementation, and (3) make person, practice, and policy-level recommendations to support active aging and development of age-friendly communities.

Methods: An international scoping review was conducted of articles that used age-friendly framing, had a sample age of 45 years of age or older, self-identified as rural, and reported empiric data.

The remarkable journey of one female individual with ornithine transcarbamylase deficiency diagnosed post-mortem.

Urea cycle disorders (UCDs) comprise a group of inborn errors of metabolism with impaired ammonia clearance and an incidence of ~1:35 000 individuals. First described in the 1970s, the diagnosis and management of these disorders has evolved dramatically. We report on a 59-year-old woman with a UCD who contributed to advances in the understanding and treatment of this group of disorders.

Tobacco use in Crohn's disease patients and association with disease outcomes in the United States Medicaid population, 2010-2019.

Background And Aim: To identify demographic factors associated with tobacco use in Crohn's disease (CD) patients in the US Medicaid population and examine how tobacco use affects disease outcomes.

Methods: We included Medicaid-eligible patients who had ≥1 ICD code for CD, and 1 year of eligibility before and after the initial encounter. We used ICD codes to identify tobacco use with respect to the time of diagnosis and used logistic regression to identify the association between age, sex, and race with tobacco use at any point before diagnosis and after diagnosis, and determine the association of tobacco use before and after diagnosis on disease outcomes.

Contemporary Homozygous Familial Hypercholesterolemia in the United States: Insights From the CASCADE FH Registry.

Background Homozygous familial hypercholesterolemia (HoFH) is a rare, treatment-resistant disorder characterized by early-onset atherosclerotic and aortic valvular cardiovascular disease if left untreated. Contemporary information on HoFH in the United States is lacking, and the extent of underdiagnosis and undertreatment is uncertain. Methods and Results Data were analyzed from 67 children and adults with clinically diagnosed HoFH from the CASCADE (Cascade Screening for Awareness and Detection) FH Registry.

Factors related to wellness and burnout in academic otolaryngology: A pre- and Post-COVID-19 analysis.

Objectives: Describe demographic and professional factors predictive of burnout in academic otolaryngology before and during the COVID-19 pandemic.

Methods: In 2018 and 2020, cross-sectional surveys on physician wellness and burnout were distributed to faculty members of a single academic institution's otolaryngology department. Faculty were dichotomized into low and high burnout groups for 2018 ( = 8 high burnout, 19%) and 2020 ( = 11 high burnout, 37%).

Stakeholder-engaged co-design and implementation of web-based tools to enhance the dissemination and implementation of AHRQ EPC reports.

Introduction: A mission-critical aspect of learning health systems (LHSs) is the provision of evidence-based practice. One source of such evidence is provided by the Agency for Healthcare Research and Quality (AHRQ) through rigorous systematic reviews, termed evidence reports that synthesize available evidence on nominated topics of interest. However, the AHRQ Evidence-based Practice Center (EPC) program recognizes that the production of high-quality evidence reviews does not guarantee or promote their use and usability in practice.

Intraoperative ventricular septal rupture: A case report.

Ventricular septal rupture (VSR) is a rare complication of myocardial infarction that requires surgical repair. Herein, we describe a case of intraoperative VSR requiring patch repair and postoperative extracorporeal membrane oxygenation (ECMO) support. This case highlights the risk factors, patient presentation, and management recommendations for this potentially lethal pathology.

Trends in Timing and Provision of Pediatric Cochlear Implant Care During COVID-19.

Objectives: To identify trends in timing of pediatric cochlear implant (CI) care during COVID-19.

Study Design: Retrospective cohort.

Setting: Tertiary care center.

A Case Study of Successful Application of the Principles of ME/CFS Care to an Individual with Long COVID.

Persistent fatigue is one of the most common symptoms of post-COVID conditions, also termed long COVID. At the extreme end of the severity spectrum, some individuals with long COVID also meet the criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), raising the possibility that symptom management approaches for ME/CFS may benefit some long COVID patients. We describe the long-term outcomes of a 19-year-old male who developed profound impairment consistent with ME/CFS after a SARS-CoV-2 infection early in the pandemic.

Human Resistin Induces Cardiac Dysfunction in Pulmonary Hypertension.

Background Cardiac failure is the primary cause of death in most patients with pulmonary arterial hypertension (PH). As pleiotropic cytokines, human resistin (Hresistin) and its rodent homolog, resistin-like molecule α, are mechanistically critical to pulmonary vascular remodeling in PH. However, it is still unclear whether activation of these resistin-like molecules can directly cause PH-associated cardiac dysfunction and remodeling.

Vascular stiffening in aging females with a hypertension-induced HIF2A gain-of-function mutation.

Pulmonary arterial hypertension (PAH) is more prevalent in females than males; the causes of this sex difference have not been adequately explored. Gain-of-function (GOF) mutations in hypoxia-inducible factor 2α (HIF2A) lead to PAH and thrombotic consequences in patients and mice. Additionally, multiple emerging studies suggest that elevated systemic arterial stiffening (SAS) occurs in PAH; this could have critical prognostic value.

Development of nintedanib nanosuspension for inhaled treatment of experimental silicosis.

Silicosis is an irreversible and progressive fibrotic lung disease caused by massive inhalation of crystalline silica dust at workplaces, affecting millions of industrial workers worldwide. A tyrosine kinase inhibitor, nintedanib (NTB), has emerged as a potential silicosis treatment due to its inhibitory effects on key signaling pathways that promote silica-induced pulmonary fibrosis. However, chronic and frequent use of the oral NTB formulation clinically approved for treating other fibrotic lung diseases often results in significant side effects.

Protective role of mineralocorticoid receptor signaling in urothelial tumorigenesis.

The expression status of mineralocorticoid receptor (MR) and its biological significance in human urothelial carcinoma remain unknown. The present study aimed to determine the functional role of MR in the development of urothelial cancer. In human normal urothelial SVHUC cells with exposure to a chemical carcinogen 3-methylcholanthrene (MCA), we assessed the effects of a natural MR ligand, aldosterone, and 3 MR antagonists, including spironolactone, eplerenone, and esaxerenone, as well as knockdown of MR via shRNA virus infection, on their neoplastic/malignant transformation.

Antiviral effect and mechanism of Phillyrin and its reformulated FS21 against influenza.

Background: Influenza virus causes significant morbidity and mortality with pandemic threat. is a medicinal herb. This study aimed to investigate antiviral effect of Phillyrin, a purified bioactive compound from this herb, and its reformulated preparation FS21 against influenza and its mechanism.

Transpulmonary amino acid metabolism in the sugen hypoxia model of pulmonary hypertension.

In pulmonary artery hypertension (PAH), emerging evidence suggests that metabolic abnormalities may be contributing to cellular dysfunction in PAH. Metabolic abnormalities such as glycolytic shift have been observed intracellularly in several cell types in PAH, including microvacular endothelial cells (MVECs). Concurrently, metabolomics of human PAH samples has also revealed a variety of metabolic abnormalities; however the relationship between the intracellular metabolic abnormalities and the serum metabolome in PAH remains under investigation.

Efficacy of competing stimulus assessments: A summary of 35 consecutively encountered cases.

Competing stimulus assessments (CSAs) are designed to identify stimuli that reduce challenging behavior through competition with its maintaining reinforcers. Recently, Haddock and Hagopian (2020) found that over 92% of CSAs described in published studies identified at least one high-competition stimulus (i.e.

The Genetic Testing Experience of Individuals with Parkinson's Disease.

Background: The perspective and experiences of individuals with Parkinson's disease (PD) regarding genetic testing is limited.

Objectives: To determine if anticipated benefits and negative consequences of genetic testing noted in prior studies have occurred in a surveyed group of patients with PD and to identify reasons why some individuals with PD have not had testing.

Methods: Individuals were surveyed from 22 support/advocacy groups throughout the US.

Targeted therapy for pancreatic ductal adenocarcinoma: Mechanisms and clinical study.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and lethal malignancy with a high rate of recurrence and a dismal 5-year survival rate. Contributing to the poor prognosis of PDAC is the lack of early detection, a complex network of signaling pathways and molecular mechanisms, a dense and desmoplastic stroma, and an immunosuppressive tumor microenvironment. A recent shift toward a neoadjuvant approach to treating PDAC has been sparked by the numerous benefits neoadjuvant therapy (NAT) has to offer compared with upfront surgery.

Obesity and Overweight: Probing Causes, Consequences, and Novel Therapeutic Approaches Through the American Heart Association's Strategically Focused Research Network.

As the worldwide prevalence of overweight and obesity continues to rise, so too does the urgency to fully understand mediating mechanisms, to discover new targets for safe and effective therapeutic intervention, and to identify biomarkers to track obesity and the success of weight loss interventions. In 2016, the American Heart Association sought applications for a Strategically Focused Research Network (SFRN) on Obesity. In 2017, 4 centers were named, including Johns Hopkins University School of Medicine, New York University Grossman School of Medicine, University of Alabama at Birmingham, and Vanderbilt University Medical Center.