Utilizing geospatial artificial intelligence to map cancer disparities across health regions.

We have developed an innovative tool, the Intelligent Catchment Analysis Tool (iCAT), designed to identify and address healthcare disparities across specific regions. Powered by Artificial Intelligence and Machine Learning, our tool employs a robust Geographic Information System (GIS) to map healthcare outcomes and disease disparities. iCAT allows users to query publicly available data sources, health system data, and treatment data, offering insights into gaps and disparities in diagnosis and treatment paradigms. This project aims to promote best practices to bridge the gap in healthcare access, resources, education, and economic opportunities. The project aims to engage local and regional stakeholders in data collection and evaluation, including patients, providers, and organizations. Their active involvement helps refine the platform and guides targeted interventions for more effective outcomes. In this paper, we present two sample illustrations demonstrating how iCAT identifies healthcare disparities and analyzes the impact of social and environmental variables on outcomes. Over time, this platform can help communities make decisions to optimize resource allocation.

The energetics of the acetylation switch in p53-mediated transcriptional activation.

Targeted therapeutic intervention in receptor-ligand interactions of p53-mediated tumor suppression can impact progression of disease, aging, and variation in genetic expression. Here, we conducted a number of molecular simulations, based on structures of p53 in complex with its transcriptional coactivating CBP bromodomain, determined by NMR spectroscopy, to investigate the energetics of the binding complex. Building on the observation that acetylation of K382 in p53 serves as the essential triggering switch for a specific interaction with CBP, we assessed the differential effect of acetylation on binding from simulations of an octapeptide derived from p53 with acetylated and nonacetylated K382 (residues 379-386). Cluster analysis of the simulations shows that acetylation of the free peptide does not significantly change the population of the preferred conformation of the peptide in solution for binding to CBP. Conversion of the acetylated K382 to nonacetylated form with free energy perturbation (FEP) simulations of the p53 CBP complex and the free peptide showed that the relative contribution of the acetyl group to binding is 4.8 kcal/mol. An analysis of residue contributions to the binding energy using an MM-GBSA approach agrees with the FEP results and sheds additional light on the origin of selectivity in p53 binding to the CBP bromodomain.

Acute lung injury after thoracic surgery.

In this review, the authors discussed criteria for diagnosing ALI; incidence, etiology, preoperative risk factors, intraoperative management, risk-reduction strategies, treatment, and prognosis. The anesthesiologist needs to maintain an index of suspicion for ALI in the perioperative period of thoracic surgery, particularly after lung resection on the right side. Acute hypoxemia, imaging analysis for diffuse infiltrates, and detecting a noncardiogenic origin for pulmonary edema are important hallmarks of acute lung injury. Conservative intraoperative fluid administration of neutral to slightly negative fluid balance over the postoperative first week can reduce the number of ventilator days. Fluid management may be optimized with the assistance of new imaging techniques, and the anesthesiologist should monitor for transfusion-related lung injuries. Small tidal volumes of 6 mL/kg and low plateau pressures of < or =30 cmH2O may reduce organ and systemic failure. PEEP may improve oxygenation and increases organ failure-free days but has not shown a mortality benefit. The optimal mode of ventilation has not been shown in perioperative studies. Permissive hypercapnia may be needed in order to reduce lung injury from positive-pressure ventilation. NO is not recommended as a treatment. Strategies such as bronchodilation, smoking cessation, steroids, and recruitment maneuvers are unproven to benefit mortality although symptomatically they often have been shown to help ALI patients. Further studies to isolate biomarkers active in the acute setting of lung injury and pharmacologic agents to inhibit inflammatory intermediates may help improve management of this complex disease.

Modern pathology: protein mis-folding and mis-processing in complex disease.

Electrostatic and electrochemical properties of bio-molecules, such as proteins, are governed by energy parameters that are, in part dependent on its folding. Disruption of this process can lead to the development of complex, multisystem diseases whose presentation may be organ-dependent. Examples include cystic fibrosis, alpha-1 antitrypsin deficiency, and Alzheimer disease. In addition to explaining exotic pathologic syndromes, an understanding of protein folding mechanisms may facilitate the understanding of less complex diseases and allow the development of novel therapeutic approaches.

Mycoplasma genomics: tailoring the genome for minimal life requirements through reductive evolution.

Prokaryotic organisms of the genus Mycoplasma are characterized by their small body and genome size containing a 0.6-1.35 M bp genome. The genome is noted for its low G+C frequency ranging from 8-40 mol%. The Mycoplasma genus stems from the class Mollicutes (for soft skin), which lacks the cell walls and external motility appendages often present in other bacteria. To date, there are more than 100 known species of Mycoplasma. 34 species have been partially or completely sequenced. Widely known pathogenic species of Mycoplasma include: M. pneumoniae, causing pneumonia and other respiratory disorders, and M. genitalium, which are involved in pelvic inflammatory disease. Because of their small genome size, Mycoplasmas provide researchers a unique model of the minimal genomic requirements to maintain life. As the number of complete Mycoplasma genomes increase, these organisms become more established, thus laying the foundation for mapping evolutionary development. This manuscript provides an overview and update on Mycoplasma research, with particular focus on current genomics.

Farm animal genomics and informatics: an update.

Farm animal genomics is of interest to a wide audience of researchers because of the utility derived from understanding how genomics and proteomics function in various organisms. Applications such as xenotransplantation, increased livestock productivity, bioengineering new materials, products and even fabrics are several reasons for thriving farm animal genome activity. Currently mined in rapidly growing data warehouses, completed genomes of chicken, fish and cows are available but are largely stored in decentralized data repositories. In this paper, we provide an informatics primer on farm animal bioinformatics and genome project resources which drive attention to the most recent advances in the field. We hope to provide individuals in biotechnology and in the farming industry with information on resources and updates concerning farm animal genome projects.

Minimally invasive method for murine brain fixation.

Complete brain fixation can be achieved with transthoracic cardiac infusion without thoracotomy. Light and electron microscopy tissue sections reveal preservation of cytoplasmic and nuclear structure at all magnification levels. Punched samples were obtained from the fixed tissue specimens in precisely localized areas for study using electron microscopy. This perfusion fixation technique provides both faster tissue harvesting capability and higher quality tissue preservation, without the artifacts of brain swelling and ventricular dilation observed in direct cardiac perfusion. Acute, discrete change in brain tissue can be studied.

Perioperative management of combined carotid and coronary artery bypass grafting procedures.

The objective of this review is to provide a high level overview on current thinking for treatment of patients with combined carotid and coronary artery disease given that these patients are at higher risk of adverse cardiac events, stroke, and death. This review discusses (1) the current literature addressing perioperative stroke risk in the setting of coronary artery bypass graft, (2) the literature regarding different surgical approaches when both carotid and coronary revascularization are being considered, and (3) the data available to guide optimal management of this complex patient population to minimize complications regardless of the surgical approach taken.

A zebrafish retinal graded photochemical stress model.

INTRODUCTION: In order to develop a model for investigating the genes that contribute to retinal degeneration, we examined the early graded photochemical stress response in the adult zebrafish (Danio rerio) retina and investigated the role of an NMDA inhibitor, thiokynurenate. METHODS: Following intravitreal injection of rose bengal (6 or 12 mg/mL), light (37x10(3) or 83x10(3) lx) was directed onto the central retina with and without 400 nM thiokynurenate. Histologic and electron microscopic analysis was performed at 2 and 4 h and gene expression analysis was carried out at 2, 4 and 6 h. RESULTS: Light and electron microscopy demonstrated a graded photochemical response in photoreceptor, nuclear, and ganglion cell layer thickness. Increased vacuolation of the inner plexiform layer was also observed. The inhibitor produced a distinct lesion pattern. Cellular stress genes were elevated in low and high lesions, while some homeobox gene expression was reduced with thiokynurenate. DISCUSSION: The phenotypic and genetic changes observed from this model can serve as a basis for understanding the pathology of retinal oxidative and cellular stress. These changes may aid our understanding of aging and macular degeneration.

Toxic epidermal necrolysis induced by sulfonamide eyedrops.

PURPOSE: To describe a case of toxic epidermal necrolysis (TEN) triggered by sulfonamide eyedrops. METHODS: A 9-year-old white boy with type I diabetes developed fever, constitutional symptoms, and a widespread blistering rash within hours of beginning a course of sulfonamide eyedrops for conjunctivitis. The patient was intubated and treated with broad-spectrum antibiotics and systemic and topical corticosteroids. RESULTS: The patient survived and has bilateral acuities of 20/30 at 12 months of follow-up. Pathological examination of a skin biopsy sample confirmed the diagnosis of TEN. CONCLUSIONS: TEN is a rare but life-threatening side effect of topical sulfonamide eyedrops.

Comparing dynamic contour tonometry to Goldmann and hand-held tonometry in normal, ocular hypertension, and glaucoma populations.

We prospectively compared dynamic contour tonometry (DCT) to Goldmann (GAT) and hand-held tonometry (HHT) in normal, ocular hypertension, and glaucoma populations. Both measurements were made on each patient within a 5-minute period during routine office exams over 4 months. While DCT is in good overall agreement with GAT and HTT, there is some systematic deviation at different pressure ranges in normal, ocular hypertension, and glaucoma populations.