Glutaminase inhibitors are currently being explored as potential treatments for cancer. This study aimed to elucidate the molecular mechanisms underlying the effects of CB-839 on lung tumor cell lines compared to non-tumor cell lines. Viability assays based on NADPH-dependent dehydrogenases activity, ATP energy production, or mitochondrial reductase activity were used to determine that CB-839 caused significant tumor cell specific inhibition of cellular functions.
View Article and Find Full Text PDFAtrial fibrillation (AF) has a high economic burden on the healthcare system with rehospitalizations as the most significant contributing factor necessitating an understanding of aspects related to hospitalizations to minimize economic costs and improve patient outcomes. Our study aims to assess whether all-cause 30-day hospital readmission following AF-specific hospitalization is associated with health-related social needs (HRSN) using the Nationwide Readmissions Database (NRD). All hospitalization data were abstracted from the 2015-2019 NRD, including hospitalizations for patients at least 18 years of age with a primary discharge diagnosis of AF.
View Article and Find Full Text PDFIntroduction: Catecholamine vasopressors such as norepinephrine are the standard drugs used to maintain mean arterial pressure during liver transplantation. At high doses, catecholamines may impair organ perfusion. Angiotensin II is a peptide vasoconstrictor that may improve renal perfusion pressure and glomerular filtration rate, a haemodynamic profile that could reduce acute kidney injury.
View Article and Find Full Text PDFTuricella otitidis belongs to the Corynebacteriaceae family and is a normal inhabitant of the ear and exists in a commensal relationship with its host. In children, T. otitidis is frequently associated with otitis media.
View Article and Find Full Text PDFSleep problems are common among veterans with post-traumatic stress disorder and closely associated with hyperarousal symptoms. Transcutaneous vagus nerve stimulation (tVNS) may have potential to improve sleep quality in veterans with PTSD through effects on brain systems relevant to hyperarousal and sleep-wake regulation. The current pilot study examines the effect of 1 h of tVNS administered at "lights out" on sleep architecture, microstructure, and autonomic activity.
View Article and Find Full Text PDFCoronary artery aneurysms (CAA) are defined as a dilation of a coronary vessel greater than 1.5 times the diameter of a local reference vessel. While CAAs tend to be incidental findings on imaging, they result in complications, such as thrombosis, embolization, ischemia, arrhythmias, and heart failure.
View Article and Find Full Text PDFThe academic half-day (AHD) curriculum is an alternative to the noon conference (NC) approach. To date, there is little literature evaluating the transition from NC to AHD in internal medicine residency programs. We investigated the effectiveness of AHD by comparing in-training exam (ITE) and American Board of Internal Medicine (ABIM) certifying exam scores of residents before and after implementation of AHD.
View Article and Find Full Text PDFBackground: Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) caused by an immunological reaction to repeated inhalational exposure to antigens. The etiology and exact immunopathology are poorly understood. Autoimmunity overlapping with HP has been described but the role of concomitant autoimmunity in the clinical course and outcome of the HP is not clearly established.
View Article and Find Full Text PDFThe prevalence of different cancers after heart transplant (HT) is unclear due to small and conflicting prior studies. Herein, we report a systematic review and meta-analysis to highlight the prevalence and pattern of malignancies post-HT. We conducted an extensive literature search on PubMed, Scopus, Cochrane databases for prospective or retrospective studies reporting malignancies after HT.
View Article and Find Full Text PDFDespite the advancements in the management of heart failure, acute heart failure is one of the most common causes of mortality and morbidity. In light of the financial burden imposed by heart failure hospitalizations on the health care system, this area remains the focus of research, clinical advances, and policy changes aimed at improving the quality of care and outcomes. Despite practice guidelines, high-quality trial data, and consensus statements, barriers to therapy remain.
View Article and Find Full Text PDFOxytocin is a neuropeptide that can produce anxiolytic effects and promote social approach. However, emerging evidence shows that under some conditions, oxytocin can instead induce anxiety-related behaviors. These diverse effects of oxytocin appear to be mediated by circuit-specific actions.
View Article and Find Full Text PDFResearch investigating milk-derived proteins has brought to light the potential for their use as novel anticancer agents. This paper aims to systematically review studies examining the effectiveness of milk-derived proteins in the treatment of head and neck cancer. A systematic literature search of Medline, Evidence-Based Medicine, and Web of Science databases including papers published from all dates was completed.
View Article and Find Full Text PDFFibrosis-driven solid organ failure is an enormous burden on global health. Spiny mice () are terrestrial mammals that can regenerate severe skin wounds without scars to avoid predation. Whether spiny mice also regenerate internal organ injuries is unknown.
View Article and Find Full Text PDFThe pathogen Staphylococcus aureus can readily develop antibiotic resistance and evade the human immune system, which is associated with reduced levels of neutrophil recruitment. Here, we present a class of antibacterial peptides with potential to act both as antibiotics and as neutrophil chemoattractants. The compounds, which we term 'antibiotic-chemoattractants', consist of a formylated peptide (known to act as chemoattractant for neutrophil recruitment) that is covalently linked to the antibiotic vancomycin (known to bind to the bacterial cell wall).
View Article and Find Full Text PDFPosttraumatic stress disorder (PTSD) is prevalent among veterans with a history of traumatic brain injury (TBI); however, the relationship between TBI and PTSD is not well understood. We present the case of a 31-year-old male veteran with PTSD who reported TBI before entering the military. The reported injury appeared to be mild: He was struck on the head by a baseball, losing consciousness for ∼10 seconds.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
October 2020
Oxytocin increases the salience of both positive and negative social contexts and it is thought that these diverse actions on behavior are mediated in part through circuit-specific action. This hypothesis is based primarily on manipulations of oxytocin receptor function, leaving open the question of whether different populations of oxytocin neurons mediate different effects on behavior. Here we inhibited oxytocin synthesis in a stress-sensitive population of oxytocin neurons specifically within the medioventral bed nucleus of the stria terminalis (BNSTmv).
View Article and Find Full Text PDFMethods Enzymol
February 2020
Recent advances have demonstrated the feasibility and robustness of chemical synthesis for the production of homogeneously glycosylated protein forms (glycoforms). By taking advantage of the unmatchable flexibility and precision provided by chemical synthesis, the quantitative effects of glycosylation were obtained using chemical glycobiology approaches. These findings greatly advanced our fundamental knowledge of glycosylation.
View Article and Find Full Text PDFSignificance: Vertically yoked prisms have been used in treatment of binocular vision dysfunction despite minimal supporting evidence. In people with normal binocular vision, the impact on phorias has been assessed but not the impact on accommodation, accommodation vergence interactions, or the horopter. We found that vertically yoked prisms have minor effects during short-term wear in young adults.
View Article and Find Full Text PDFBackground And Objective: Both chronic and aggressive periodontal disease are associated with vitamin D deficiency. The active form of vitamin D, 1,25(OH) D , induces the expression of the antimicrobial peptide LL-37 and innate immune mediators in cultured human gingival epithelial cells (GECs). The aim of this study was to further delineate the mechanism by which vitamin D enhances the innate defense against the development of periodontal disease (PD).
View Article and Find Full Text PDFJ Can Acad Child Adolesc Psychiatry
August 2018
Objective: People with mental illness have high rates of physical illness that are not detected and that shorten their lifespan. Health behaviours are central to physical health, and many children and adolescents with psychiatric illness may be at risk for poor physical health. The purpose for this study was to explore the self-reported health behaviours and well-being of pediatric psychiatric patients and their association with mental health problems.
View Article and Find Full Text PDFMany human proteins have the potential to be developed as therapeutic agents. However, side effects caused by direct administration of natural proteins have significantly slowed expansion of protein therapeutics into the clinic. Post-translational modifications (PTMs) can improve protein properties, but because of significant knowledge gaps, we are considerably limited in our ability to apply PTMs to generate better protein therapeutics.
View Article and Find Full Text PDFDiabetes is a leading cause of death worldwide and results in over 3 million annual deaths. While insulin manages the disease well, many patients fail to comply with injection schedules, and despite significant investment, a more convenient oral formulation of insulin is still unavailable. Studies suggest that glycosylation may stabilize peptides for oral delivery, but the demanding production of homogeneously glycosylated peptides has hampered transition into the clinic.
View Article and Find Full Text PDFProtein O-glycosylation is a diverse, common, and important post-translational modification of both proteins inside the cell and those that are secreted or membrane-bound. Much work has shown that O-glycosylation can alter the structure, function, and physical properties of the proteins to which it is attached. One gap remaining in our understanding of O-glycoproteins is how O-glycans might affect the folding of proteins.
View Article and Find Full Text PDFProtein glycosylation has been shown to have a variety of site-specific and glycan-specific effects, but so far, the molecular logic that leads to such observations has been elusive. Understanding the structural changes that occur and being able to correlate those with the physical properties of the glycopeptide are valuable steps toward being able to predict how specific glycosylation patterns will affect the stability of glycoproteins. By systematically comparing the structural features of the O-glycosylated carbohydrate-binding module of a Trichoderma reesei-derived Family 7 cellobiohydrolase, we were able to develop a better understanding of the influence of O-glycan structure on the molecule's physical stability.
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