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.

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.

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.

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.

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.

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.