Paradigm shift: outcomes from a physician-scientist undergraduate pathway program.

Background: Physician-scientists are uniquely positioned to translate research findings into innovations that improve clinical medicine and health outcomes. However, structural inequities stymie the entry of trainees from backgrounds underrepresented in medicine (URiM) into the physician-scientist pathway.

Methods: The Preparation for Graduate and Medical Education (PARAdiGM) program was designed to provide students from underrepresented and disadvantaged backgrounds early exposure to physician-scientist training in the context of ample mentorship and programmatic support.

Human breast milk-derived exosomes attenuate lipopolysaccharide-induced activation in microglia.

Microglia mediate the immune response in the central nervous system to many insults, including lipopolysaccharide (LPS), a bacterial endotoxin that initiates neuroinflammation in the neonatal population, especially preterm infants. The synthesis of the proinflammatory proteins CD40 and NLRP3 depends on the canonical NF-κB cascade as the genes encoding CD40 and NLRP3 are transcribed by the phosphorylated NF-κB p50/p65 heterodimer in LPS-induced microglia. Exosomes, which are nanosized vesicles (40-150 nm) involved in intercellular communication, are implicated in many pathophysiological processes.

Paradigm Shift: Outcomes from a Physician-Scientist Undergraduate Pipeline Program.

Diverse medical and research teams are essential to culturally-responsive care and robust progress of biomedical research. However, structural inequities stymie the entry of trainees from underrepresented in medicine (URiM) backgrounds into the physician-scientist pipeline. The Preparation for Graduate and Medical Education (PARAdiGM) program was designed to provide students from underrepresented backgrounds early exposure to physician-scientist training in the context of ample mentorship and programmatic support.

The relationship between perceived family support and subclinical positive symptoms of psychosis among Black college students.

Aim: Black individuals in the Unites States endure compounded and unique experiences of discrimination and structural racism that may not be as overtly evident in other countries. These distinctive forms of discrimination and racism can impact the mental health of Black individuals in the Unites States, in this case, their risk for psychosis. Adolescence and early adulthood are vulnerable periods in life where mental illness typically begins to manifest.

Human adenovirus type 3 restores pharmacologically inhibited exosomal cargo in lung carcinoma cells.

Drug repurposing is fast growing and becoming an attractive approach for identifying novel targets, such as exosomes for cancer and antiviral therapy. Exosomes are a specialized class of extracellular vesicles that serve as functional mediators in intercellular communication and signaling that are important in normal physiological functions. A continuously growing body of evidence has established a correlation between the abnormal release of exosomes with various viral disease pathologies including cancer.

Selective pharmacological inhibition alters human carcinoma lung cell-derived extracellular vesicle formation.

Unlabelled: Exosomes also termed small extracellular vesicles (sEVs) are important mediators of intercellular communication in many physiological and pathological processes such as protein clearance, immunity, infections, signaling, and cancer. Elevated circulating levels of exosomes have been linked to some viral infections, aggressive cancer, and neurodegenerative diseases. Some pharmacological compounds have been demonstrated to effectively inhibit exosome production pathways.

Human Adenovirus Serotype 3 Infection Modulates the Biogenesis and Composition of Lung Cell-Derived Extracellular Vesicles.

Adenovirus (Ad) is a major causal agent of acute respiratory infections. However, they are a powerful delivery system for gene therapy and vaccines. Some Ad serotypes antagonize the immune system leading to meningitis, conjunctivitis, gastroenteritis, and/or acute hemorrhagic cystitis.

Lipopolysaccharide Administration Alters Extracellular Vesicles in Cell Lines and Mice.

Extracellular vesicles (EVs) play a fundamental role in cell and infection biology and have the potential to act as biomarkers for novel diagnostic tools. In this study, we explored the in vitro impact of bacterial lipopolysaccharide administration on cell lines that represents a target for bacterial infection in the host. Administration of lipopolysaccharide at varying concentrations to A549 and BV-2 cell lines caused only modest changes in cell death, but EV numbers were significantly changed.

Cocaine-Specific Effects on Exosome Biogenesis in Microglial Cells.

Cocaine is a highly addictive stimulant and a well-known drug, with multiple effects on physiology. Cocaine can have direct effects on all cell types in the brain, including microglia. Microglia can be activated by other conditions, such as infection, inflammation, or injury.

Effects of Cocaine on Human Glial-Derived Extracellular Vesicles.

Background: Microglia are important myeloid cells present in the brain parenchyma that serve a surveillance function in the central nervous system. Microglial cell activation results in neuroinflammation that, when prolonged, can disrupt immune homeostasis and neurogenesis. Activated microglia-derived extracellular vesicles (EVs) may be involved in the propagation of inflammatory responses and modulation of cell-to-cell communication.

Effects of on Microglial-Derived Extracellular Vesicle Biogenesis and Composition.

The packaging of molecular constituents inside extracellular vesicles (EVs) allows them to participate in intercellular communication and the transfer of biological molecules, however the role of EVs during bacterial infection is poorly understood. The goal of this study was to examine the effects of ( infection on the biogenesis and composition of EVs derived from the mouse microglia cell line, BV-2. BV-2 cells were cultured in exosome-free media and infected with 0, 1.

Alcohol Exposure Impacts the Composition of HeLa-Derived Extracellular Vesicles.

Extracellular vesicles are nanosized vesicles that are under intense investigation for their role in intercellular communication. Extracellular vesicles have begun to be examined for their role in disease protection and their role as disease biomarkers and/or vaccine agents. The goal of this study was to investigate the effects of alcohol exposure on the biogenesis and composition of extracellular vesicles derived from the cervical cancer line, HeLa.

The Role of Lipopolysaccharide-Induced Extracellular Vesicles in Cardiac Cell Death.

Exosomes play a crucial role in the progression of infectious diseases, as exosome release and biogenesis are affected by external factors, such as pathogenic infections. Pyrogens may aide in the progression of diseases by triggering inflammation, endothelial cell injury, and arterial plaque rupture, all of which can lead to acute coronary disease, resulting in cardiac tissue death and the onset of a cardiac event (CE). To better understand the effects of Gram-negative bacterial infections on exosome composition and biogenesis, we examined exosome characteristics after treatment of AC16 human cardiomyocytes with lipopolysaccharide (LPS), which served as a model system for Gram-negative bacterial infection.

The Association of Intraventricular Hemorrhage and Acute Kidney Injury in Premature Infants from the Assessment of the Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) Study.

Background: Acute kidney injury (AKI) and intraventricular hemorrhage (IVH) are common in premature infants. We previously demonstrated that infants with AKI have a higher hazards ratio to develop grade ≥2 IVH when controlling for confounders. However, that single-center study was unable to show an overall association.

Alcohol Modulates the Biogenesis and Composition of Microglia-Derived Exosomes.

Exosomes are small extracellular vesicles that have emerged as an important tool for intercellular communication. In the central nervous system, exosomes can mediate glia and neuronal communication. Once released from the donor cell, exosomes can act as discrete vesicles and travel to distant and proximal recipient cells to alter cellular function.

Exosome Biogenesis and Biological Function in Response to Viral Infections.

Introduction: Exosomes are extracellular vesicles that originate as intraluminal vesicles during the process of multivescular body formation. Exosomes mediate intercellular transfer of functional proteins, lipids, and RNAs. The investigation into the formation and role of exosomes in viral infections is still being elucidated.

Opioid Detoxification in Pregnancy: Systematic Review and Meta-Analysis of Perinatal Outcomes.

Objective: We sought to compare the efficacy and safety of detoxification from opioids compared with opioid replacement therapy (ORT) during pregnancy.

Study Design: We searched PubMed, Embase, Cochrane Library, and ClinicalTrials.gov from inception to June 2017 for English-language randomized-controlled trials or cohort studies that compared detoxification with ORT.

Human breast milk-derived exosomes attenuate cell death in intestinal epithelial cells.

Human breast milk has been shown to reduce the incidence of necrotizing enterocolitis (NEC). Breast milk has many components (immunoglobulins, proteins, fat, and, of recent interest, exosomes), but the specific component that affords protection against NEC is not known. Exosomes are small-nanometer vesicles that are rich in protein, lipid, and microRNA.

Tetraspanin blockage reduces exosome-mediated HIV-1 entry.

HIV-1 is one of the most studied retroviruses. The role of exosomes in HIV-1 entry and pathogenesis are beginning to be appreciated. Exosomes can incorporate host proteins that are also contained in viruses (e.

Role of TIM-4 in exosome-dependent entry of HIV-1 into human immune cells.

Exosomes, 30-200 nm nanostructures secreted from donor cells and internalized by recipient cells, can play an important role in the cellular entry of some viruses. These microvesicles are actively secreted into various body fluids, including blood, urine, saliva, cerebrospinal fluid, and breast milk. We successfully isolated exosomes from human breast milk and plasma.

Differential binding of the HIV-1 envelope to phosphatidylserine receptors.

Prior work has shown that the HIV-1 envelope of the human immunodeficiency virus (HIV) interacts directly with T-cell immunoglobulin mucin (TIM) family proteins. Herein, we demonstrate that HIV-1 envelope glycoproteins from varying HIV-1 clades bind differentially to TIM proteins and functionally similar proteins acting as phosphatidylserine (PtdSer) receptors. Using enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR) technology, we show that lysate containing HIV-1 envelope and recombinant HIV-1 envelope glycoproteins bind TIM-4 and advanced glycosylation end product-specific receptor (AGER).

Erythropoietin-induced cytoprotection in intestinal epithelial cells is linked to system Xc.

Necrotizing enterocolitis is a common but serious complication among premature babies. Currently, there are limited treatment options. These include intensive supportive care and surgical intervention.