Exploring the Potential of the Web-Based Virtual World of Second Life to Improve Substance Abuse Treatment Outcomes

Provides an overview of Second Life, an Internet-based virtual world, and summarizes discussions among addiction recovery experts about integrating virtual reality into behavioral treatment as a way to teach patients new responses to real environments

Quantitative Assessment of Experimental Ocular Inflammatory Disease

Ocular inflammation imposes a high medical burden on patients and substantial costs on the health-care systems that mange these often chronic and debilitating diseases. Many clinical phenotypes are recognized and classifying the severity of inflammation in an eye with uveitis is an ongoing challenge. With the widespread application of optical coherence tomography in the clinic has come the impetus for more robust methods to compare disease between different patients and different treatment centers. Models can recapitulate many of the features seen in the clinic, but until recently the quality of imaging available has lagged that applied in humans. In the model experimental autoimmune uveitis (EAU), we highlight three linked clinical states that produce retinal vulnerability to inflammation, all different from healthy tissue, but distinct from each other. Deploying longitudinal, multimodal imaging approaches can be coupled to analysis in the tissue of changes in architecture, cell content and function. This can enrich our understanding of pathology, increase the sensitivity with which the impacts of therapeutic interventions are assessed and address questions of tissue regeneration and repair. Modern image processing, including the application of artificial intelligence, in the context of such models of disease can lay a foundation for new approaches to monitoring tissue health

Datos del subsuelo y su conocimiento para las Ciudades del Mañana: lecciones aprendidas de Glasgow y su aplicabilidad en otros lugares

El conocimiento del subsuelo es de vital importancia en la planificación y ejecución exitosa de proyectos de construcción y regeneración urbanas. Para abordar en el área de Glasgow éste y otros temas del subsuelo urbano (por ejemplo, la planificación, las inundaciones, la contaminación), el proyecto Clyde-Urban Super-Project (CUSP) del Servicio Geológico Británico (BGS, por sus siglas en inglés) ha desarrollado modelos 3D y 4D del subsuelo. Asimismo, se han producido otros conjuntos de datos de geociencias (geoquímica, agua subterránea, geología de ingeniería). Los modelos basados en información obtenida de decenas de miles de perforaciones y otras fuentes, proporcionan nuevos conocimientos sobre: la geología compleja de Glasgow, los impactos de su legado industrial, y las oportunidades para aprovechar el calor de las explotaciones mineras abandonadas. Para que los modelos y datos del proyecto CUSP fueran más accesibles, el BGS y el Ayuntamiento de Glasgow, socio clave, han establecido una red para acceder al conocimiento del subsuelo (ASK, por sus siglas en inglés). Esta red permite el intercambio de datos y conocimientos, implicando a socios de los sectores público y privado. ASK promueve el libre flujo digital de datos del subsuelo y el conocimiento entre sus socios. Las lecciones aprendidas en Glasgow se comparten a través de la Acción Europea COST (Sub-Urban), centrada en el uso sostenible del subsuelo urbano, y en la transformación de las relaciones entre los que desarrollan el conocimiento del subsuelo urbano y los que pueden beneficiarse más de él, los planificadores y promotores de las ciudades del futuro

Risk of Ocular Complications in Patients with Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis

PurposeNoninfectious uveitis results in vision loss and ocular complications without adequate treatment. We compared the risk of developing ocular complications between patients with noninfectious intermediate uveitis, posterior uveitis, or panuveitis (NIIPPU) and matched controls.DesignRetrospective analysis of insurance claims data (OptumHealth, Eden Prairie, MN; January 1, 1998–March 31, 2012).ParticipantsCases 18 to 64 years of age with 2 or more NIIPPU diagnoses (International Classification of Diseases, 9th Revision, Clinical Modification codes) were matched 1:1 by sex, age, region, company, employment status, and index date with controls without uveitis. Patients with an ocular complication during baseline were excluded.MethodsContinuous eligibility for 6 months or more before the first NIIPPU diagnosis date was required. Risks of ocular complications developing during patients' continuous eligibility in the study period were compared using unadjusted Kaplan-Meier survival analysis to estimate risk of and time to complications and adjusted Cox regression analysis to estimate hazard ratios (HRs).Main Outcome MeasuresPercentages of cases and controls who demonstrate ocular complications and 1-, 5-, and 10-year risks and HRs for each complication.ResultsMean age of the 1769 cases and matched controls was 47 years and 47% were men; 302 cases had persistent NIIPPU. During the study period, NIIPPU cases had a higher risk of any ocular complication (P < 0.001); the 5-year risk of any ocular complication was 66% for patients versus 24% for controls. Specifically, NIIPPU patients had greater 5-year risks of glaucoma (20% vs. 9%), cataract (35% vs. 13%), visual disturbance (29% vs. 9%), blindness or low vision (5% vs. 0.5%), retinal detachment (11% vs. 0.8%), and retinal disorder (28% vs. 2%) compared with controls. Hazard ratios indicated greater risks of ocular complications in cases versus controls during the overall observation period (HR, 5.2 for any ocular complication; HR, 4.8 for visual disturbance; HR, 3.2 for cataract; and HR, 2.7 for glaucoma; all P < 0.001). Hazard ratios for persistent cases indicated even greater risks.ConclusionsNoninfectious intermediate uveitis, posterior uveitis, or panuveitis, particularly persistent disease, is associated with a substantial risk of ocular complications. Optimal treatment initiatives remain imperative to reduce the ocular complication–related burden of NIIPPU

Treatment of diabetic retinopathy through neuropeptide Y-mediated enhancement of neurovascular microenvironment

Diabetic retinopathy (DR) is one of the most severe clinical manifestations of diabetes mellitus and a major cause of blindness. DR is principally a microvascular disease, although the pathogenesis also involves metabolic reactive intermediates which induce neuronal and glial activation resulting in disruption of the neurovascular unit and regulation of the microvasculature. However, the impact of neural/glial activation in DR remains controversial, notwithstanding our understanding as to when neural/glial activation occurs in the course of disease. The objective of this study was to determine a potential protective role of neuropeptide Y (NPY) using an established model of DR permissive to N‐methyl‐D‐aspartate (NMDA)‐induced excitotoxic apoptosis of retinal ganglion cells (RGC) and vascular endothelial growth factor (VEGF)‐induced vascular leakage. In vitro evaluation using primary retinal endothelial cells demonstrates that NPY promotes vascular integrity, demonstrated by maintained tight junction protein expression and reduced permeability in response to VEGF treatment. Furthermore, ex vivo assessment of retinal tissue explants shows that NPY can protect RGC from excitotoxic‐induced apoptosis. In vivo clinical imaging and ex vivo tissue analysis in the diabetic model permitted assessment of NPY treatment in relation to neural and endothelial changes. The neuroprotective effects of NPY were confirmed by attenuating NMDA‐induced retinal neural apoptosis and able to maintain inner retinal vascular integrity. These findings could have important clinical implications and offer novel therapeutic approaches for the treatment in the early stages of DR

Reproducibility of hospital rankings based on centers for Medicare & Medicaid Services Hospital Compare measures as a function of measure reliability

Importance: Unreliable performance measures can mask poor-quality care and distort financial incentives in value-based purchasing. Objective: To examine the association between test-retest reliability and the reproducibility of hospital rankings. Design, Setting, and Participants: In a cross-sectional design, Centers for Medicare & Medicaid Services Hospital Compare data were analyzed for the 2017 (based on 2014-2017 data) and 2018 (based on 2015-2018 data) reporting periods. The study was conducted from December 13, 2020, to September 30, 2021. This analysis was based on 28 measures, including mortality (acute myocardial infarction, congestive heart failure, pneumonia, and coronary artery bypass grafting), readmissions (acute myocardial infarction, congestive heart failure, pneumonia, and coronary artery bypass grafting), and surgical complications (postoperative acute kidney failure, postoperative respiratory failure, postoperative sepsis, and failure to rescue). Exposures: Measure reliability based on test-retest reliability testing. Main Outcomes and Measures: The reproducibility of hospital rankings was quantified by calculating the reclassification rate across the 2017 and 2018 reporting periods after categorizing the hospitals into terciles, quartiles, deciles, and statistical outliers. Linear regression analysis was used to examine the association between the reclassification rate and the intraclass correlation coefficient for each of the classification systems. Results: The analytic cohort consisted of 28 measures from 4452 hospitals with a median of 2927 (IQR, 2378-3160) hospitals contributing data for each measure. The hospitals participating in the Inpatient Prospective Payment System (n = 3195) had a median bed size of 141 (IQR, 69-261), average daily census of 70 (IQR, 24-155) patients, and a median disproportionate share hospital percentage of 38.2% (IQR, 18.7%-36.6%). The median intraclass correlation coefficient was 0.78 (IQR, 0.72-0.81), ranging between 0.50 and 0.85. The median reclassification rate was 70% (IQR, 62%-71%) when hospitals were ranked by deciles, 43% (IQR, 39%-45%) when ranked by quartiles, 34% (IQR, 31%-36%) when ranked by terciles, and 3.8% (IQR, 2.0%-6.2%) when ranked by outlier status. Increases in measure reliability were not associated with decreases in the reclassification rate. Each 0.1-point increase in the intraclass correlation coefficient was associated with a 6.80 (95% CI, 2.28-11.30; P = .005) percentage-point increase in the reclassification rate when hospitals were ranked into performance deciles, 4.15 (95% CI, 1.16-7.14; P = .008) when ranked into performance quartiles, 1.47 (95% CI, 1.84, 4.77; P = .37) when ranked into performance terciles, and 3.70 (95% CI, 1.30-6.09; P = .004) when ranked by outlier status. Conclusions and Relevance: In this study, more reliable measures were not associated with lower rates of reclassifying hospitals using test-retest reliability testing. These findings suggest that measure reliability should not be assessed with test-retest reliability testing

Impairing autophagy in retinal pigment epithelium leads to inflammasome activation and enhanced macrophage-mediated angiogenesis

Age-related decreases in autophagy contribute to the progression of age-related macular degeneration (AMD). We have now studied the interaction between autophagy impaired in retinal pigment epithelium (RPE) and the responses of macrophages. We find that dying RPE cells can activate the macrophage inflammasome and promote angiogenesis. In vitro, inhibiting rotenone-induced autophagy in RPE cells elicits caspase-3 mediated cell death. Co-culture of damaged RPE with macrophages leads to the secretion of IL-1β, IL-6 and nitrite oxide. Exogenous IL-6 protects the dysfunctional RPE but IL-1β causes enhanced cell death. Furthermore, IL-1β toxicity is more pronounced in dysfunctional RPE cells showing reduced IRAK3 gene expression. Co-culture of macrophages with damaged RPE also elicits elevated levels of pro-angiogenic proteins that promote ex vivo choroidal vessel sprouting. In vivo, impaired autophagy in the eye promotes photoreceptor and RPE degeneration and recruitment of inflammasome-activated macrophages. The degenerative tissue environment drives an enhanced pro-angiogenic response, demonstrated by increased size of laser-induced choroidal neovascularization (CNV) lesions. The contribution of macrophages was confirmed by depletion of CCR2 + monocytes, which attenuates CNV in the presence of RPE degeneration. Our results suggest that the interplay between perturbed RPE homeostasis and activated macrophages influences key features of AMD development