Lady With the Blue Hair: An Atypical Cause of Myasthenic Crisis.

A myasthenic crisis denotes a severe exacerbation of myasthenia gravis, leading a patient to enter a life-threatening state due to progressing muscle weakness that ultimately results in respiratory failure. A crisis can require intubation, mechanical ventilation, and additional critical care to prevent further decompensation and potentially death. Numerous well-documented precipitating factors exist, such as infections, surgery, stress, and various medications. We present the case of a 43-year-old woman recently diagnosed with myasthenia gravis who has experienced two myasthenic crises since diagnosis without evident triggers such as surgery, changes in medication, or infection. Following an unremarkable initial diagnostic test and continued treatment for the crisis, we sought additional information from the patient's family member at the bedside. We were informed that two weeks prior to both times of crisis with intubation, the patient had dyed her hair blue. The common chemical component in the two different hair dyes used was methylisothiazolinone, which is suspected to have contributed to the exacerbation of the patient's myasthenia gravis. As more evidence for new precipitating factors of myasthenic crises develops, it is crucial for physicians to quickly identify signs and symptoms of a crisis so appropriate intervention can occur in a time-sensitive manner. In addition, myasthenia gravis patients should be made aware to be cautious of precipitating factors of a crisis, including but not limited to new beauty products.

Remotely sensing potential climate change tipping points across scales.

Potential climate tipping points pose a growing risk for societies, and policy is calling for improved anticipation of them. Satellite remote sensing can play a unique role in identifying and anticipating tipping phenomena across scales. Where satellite records are too short for temporal early warning of tipping points, complementary spatial indicators can leverage the exceptional spatial-temporal coverage of remotely sensed data to detect changing resilience of vulnerable systems. Combining Earth observation with Earth system models can improve process-based understanding of tipping points, their interactions, and potential tipping cascades. Such fine-resolution sensing can support climate tipping point risk management across scales.

Recommendations for assessing appearance concerns related to plexiform and cutaneous neurofibromas in neurofibromatosis 1 clinical trials.

BACKGROUND/AIMS: Individuals with neurofibromatosis 1 may experience changes in their appearance due to physical manifestations of the disorders and/or treatment sequelae. Appearance concerns related to these physical changes can lead to psychological distress and poorer quality of life. While many neurofibromatosis 1 clinical trials focus on assessing changes in tumor volume, evaluating patients' perspectives on corresponding changes in symptoms such as physical appearance can be key secondary outcomes. We aimed to determine whether any existing patient-reported outcome measures are appropriate for evaluating changes in appearance concerns within neurofibromatosis 1 clinical trials. METHODS: After updating our previously published systematic review process, we used it to identify and rate existing patient-reported outcome measures related to disfigurement and appearance. Using a systematic literature search and initial triage process, we focused on identifying patient-reported outcome measures that could be used to evaluate changes in appearance concerns in plexiform or cutaneous neurofibroma clinical trials in neurofibromatosis 1. Our revised Patient-Reported Outcome Rating and Acceptance Tool for Endpoints then was used to evaluate each published patient-reported outcome measures in five domains, including (1) respondent characteristics, (2) content validity, (3) scoring format and interpretability, (4) psychometric data, and (5) feasibility. The highest-rated patient-reported outcome measures were then re-reviewed in a side-by-side comparison to generate a final consensus recommendation. RESULTS: Eleven measures assessing appearance concerns were reviewed and rated; no measures were explicitly designed to assess appearance concerns related to neurofibromatosis 1. The FACE-Q Craniofacial Module-Appearance Distress scale was the top-rated measure for potential use in neurofibromatosis 1 clinical trials. Strengths of the measure included that it was rigorously developed, included individuals with neurofibromatosis 1 in the validation sample, was applicable to children and adults, covered item topics deemed important by neurofibromatosis 1 patient representatives, exhibited good psychometric properties, and was feasible for use in neurofibromatosis 1 trials. Limitations included a lack of validation in older adults, no published information regarding sensitivity to change in clinical trials, and limited availability in languages other than English. CONCLUSION: The Response Evaluation in Neurofibromatosis and Schwannomatosis patient-reported outcome working group currently recommends the FACE-Q Craniofacial Module Appearance Distress scale to evaluate patient-reported changes in appearance concerns in clinical trials for neurofibromatosis 1-related plexiform or cutaneous neurofibromas. Additional research is needed to validate this measure in people with neurofibromatosis 1, including older adults and those with tumors in various body locations, and explore the effects of nontumor manifestations on appearance concerns in people with neurofibromatosis 1 and schwannomatosis.

Urinary bladder retention secondary to intranasal administration of oxymetazoline "Afrin" for intra-arterial chemotherapy.

Selective ophthalmic artery infusion of chemotherapy (SOAIC) has emerged as the standard of care for retinoblastoma (RB). Intranasal oxymetazoline (INO), Afrin, is often intraoperatively administered adjunctively to optimize flow to the orbit. There has been one report to date that suggests the adjunctive use of INO has led to systemic side effects. To our knowledge, this is the first documented case of INO causing urinary retention in a patient undergoing SOAIC, and the recommended treatment.

Reliability of vegetation resilience estimates depends on biomass density.

Concerns have been raised that the resilience of vegetated ecosystems may be negatively impacted by ongoing anthropogenic climate and land-use change at the global scale. Several recent studies present global vegetation resilience trends based on satellite data using diverse methodological set-ups. Here, upon a systematic comparison of data sets, spatial and temporal pre-processing, and resilience estimation methods, we propose a methodology that avoids different biases present in previous results. Nevertheless, we find that resilience estimation using optical satellite vegetation data is broadly problematic in dense tropical and high-latitude boreal forests, regardless of the vegetation index chosen. However, for wide parts of the mid-latitudes-especially with low biomass density-resilience can be reliably estimated using several optical vegetation indices. We infer a spatially consistent global pattern of resilience gain and loss across vegetation indices, with more regions facing declining resilience, especially in Africa, Australia and central Asia.

The Vascular Quality Initiative assessment of the Bard Lifestent for the treatment of popliteal artery occlusive disease.

OBJECTIVE: The Bard LifeStent self-expanding stent is approved for the treatment of occlusive disease involving the superficial femoral artery and proximal popliteal artery. We conducted a post-market trial of treatment of the popliteal artery above and below the knee (P1, P2, and P3 segments) within the Society for Vascular Surgery Vascular Quality Initiative (VQI) Peripheral Vascular Intervention registry. METHODS: A single-arm, prospective trial was conducted at 29 VQI sites in the United States, enrolling 74 patients from November 2016 to May 2019. The primary safety outcome was freedom from major adverse events including device-/procedure-related mortality and major amputation at 1 year. The primary efficacy outcomes were freedom from target vessel revascularization and freedom from target lesion revascularization at 1 year. Secondary outcomes included lesion success; procedural success; primary, primary-assisted, and secondary patency; and sustained clinical (improvement in Rutherford class) and hemodynamic success (increase in ankle brachial index >0.10). Outcomes were assessed by Kaplan-Meier analysis. Arteriogram of patients undergoing target lesion revascularization were assessed for stent fracture by a core laboratory. RESULTS: The mean age was 71 years, with 63.5% male and 55% with diabetes. The indication was claudication 28% and chronic limb-threatening ischemia in 72%. The superficial femoral artery-popliteal artery was stented in 38% and the popliteal artery alone in 62%. The majority of stents were placed in the P1 + P2 (39%) or P1 + P2 + P3 (37%) segments of the popliteal artery. The composite primary endpoint of freedom from major adverse events was 82% and 74% at 1 and 2 years, respectively. Freedom from mortality was 100% and 97%, and freedom from major amputation was 100% and 90% at 1 and 12 months, with all deaths and major amputations occurring in patients with chronic limb-threatening ischemia. freedom from target lesion revascularization was 86%, and freedom from target vessel revascularization was 84% at 12 months. At discharge, lesion treatment success was 99%, and procedural success was 82%. Primary patency was 80% and 72%, primary-assisted patency was 80% and 72%, and secondary patency was 89% and 82% at 12 and 24 months. Sustained clinical success was 98% and 95%, and sustained hemodynamic success was 100% and 79% at 12 and 24 months. CONCLUSIONS: In this multi-center, registry-based, single-arm prospective study the Bard LifeStent self-expanding stent demonstrated favorable performance in the challenging anatomy of the P2 and P3 popliteal segment. Post-market studies for label expansion of peripheral vascular intervention devices can be successfully conducted within the Society for Vascular Surgery VQI registry.

Biological evaluation of novel gemcitabine analog in patient-derived xenograft models of pancreatic cancer.

Gemcitabine (Gem) has been a standard first-line drug for pancreatic cancer (PCa) treatment; however, Gem's rapid metabolism and systemic instability (short half-life) limit its clinical outcome. The objective of this study was to modify Gem into a more stable form called 4-(N)-stearoyl-gemcitabine (4NSG) and evaluate its therapeutic efficacy in patient-derived xenograft (PDX) models from PCa of Black and White patients.Methods 4NSG was synthesized and characterized using nuclear magnetic resonance (NMR), elemental analysis, and high-performance liquid chromatography (HPLC). 4NSG-loaded solid lipid nanoparticles (4NSG-SLN) were developed using the cold homogenization technique and characterized. Patient-derived pancreatic cancer cell lines labeled Black (PPCL-192, PPCL-135) and White (PPCL-46, PPCL-68) were used to assess the in vitro anticancer activity of 4NSG-SLN. Pharmacokinetics (PK) and tumor efficacy studies were conducted using PDX mouse models bearing tumors from Black and White PCa patients.Results 4NSG was significantly stable in liver microsomal solution. The effective mean particle size (hydrodynamic diameter) of 4NSG-SLN was 82 ± 6.7 nm, and the half maximal inhibitory concentration (IC50) values of 4NSG-SLN treated PPCL-192 cells (9 ± 1.1 µM); PPCL-135 (11 ± 1.3 µM); PPCL-46 (12 ± 2.1) and PPCL-68 equaled to 22 ± 2.6 were found to be significantly lower compared to Gem treated PPCL-192 (57 ± 1.5 µM); PPCL-135 (56 ± 1.5 µM); PPCL-46 (56 ± 1.8 µM) and PPCL-68 (57 ± 2.4 µM) cells. The area under the curve (AUC), half-life, and pharmacokinetic clearance parameters for 4NSG-SLN were 3-fourfold higher than that of GemHCl. For in-vivo studies, 4NSG-SLN exhibited a two-fold decrease in tumor growth compared with GemHCl in PDX mice bearing Black and White PCa tumors.Conclusion 4NSG-SLN significantly improved the Gem's pharmacokinetic profile, enhanced Gem's systemic stability increased its antitumor efficacy in PCa PDX mice bearing Black and White patient tumors.

Examining Safety Behavior Subtypes Across Distinct Social Contexts in Social Anxiety Disorder and Major Depression.

People with social anxiety disorder (SAD) use different types of safety behaviors that have been classified as avoidance vs. impression management. The current study investigated differences in safety behavior subtype use in 132 individuals with principal diagnoses of social anxiety disorder (SAD, n = 69), major depressive disorder (MDD, n = 30), and nonpatient controls (n = 33) across two social contexts: an interpersonal relationship-building task (social affiliation) and a speech task (social performance). We examined whether diagnostic groups differed in safety behavior subtype use and whether group differences varied by social context. We also explored relationships between avoidance and impression management safety behaviors, respectively, and positive and negative valence affective and behavioral outcomes within the social affiliation and social performance contexts. Safety behavior use varied by diagnosis (SAD > MDD > nonpatient controls). The effect of diagnosis on impression management safety behavior use depended on social context: use was comparable for the principal SAD and MDD groups in the social performance context, whereas the SAD group used more impression management safety behaviors than the MDD group in the social affiliation context. Greater use of avoidance safety behaviors related to higher negative affect and anxious behaviors, and lower positive affect and approach behaviors across contexts. Impression management safety behaviors were most strongly associated with higher positive affect and approach behaviors within the social performance context. These findings underscore the potential value of assessing safety behavior subtypes across different contexts and within major depression, in addition to SAD.

Global vegetation resilience linked to water availability and variability.

Quantifying the resilience of vegetated ecosystems is key to constraining both present-day and future global impacts of anthropogenic climate change. Here we apply both empirical and theoretical resilience metrics to remotely-sensed vegetation data in order to examine the role of water availability and variability in controlling vegetation resilience at the global scale. We find a concise global relationship where vegetation resilience is greater in regions with higher water availability. We also reveal that resilience is lower in regions with more pronounced inter-annual precipitation variability, but find less concise relationships between vegetation resilience and intra-annual precipitation variability. Our results thus imply that the resilience of vegetation responds differently to water deficits at varying time scales. In view of projected increases in precipitation variability, our findings highlight the risk of ecosystem degradation under ongoing climate change.

Prediction of Mortality and Major Adverse Kidney Events in Critically Ill Patients With Acute Kidney Injury.

RATIONALE & OBJECTIVE: Risk prediction tools for assisting acute kidney injury (AKI) management have focused on AKI onset but have infrequently addressed kidney recovery. We developed clinical models for risk stratification of mortality and major adverse kidney events (MAKE) in critically ill patients with incident AKI. STUDY DESIGN: Multicenter cohort study. SETTING & PARTICIPANTS: 9,587 adult patients admitted to heterogeneous intensive care units (ICUs; March 2009 to February 2017) who experienced AKI within the first 3 days of their ICU stays. PREDICTORS: Multimodal clinical data consisting of 71 features collected in the first 3 days of ICU stay. OUTCOMES: (1) Hospital mortality and (2) MAKE, defined as the composite of death during hospitalization or within 120 days of discharge, receipt of kidney replacement therapy in the last 48 hours of hospital stay, initiation of maintenance kidney replacement therapy within 120 days, or a ≥50% decrease in estimated glomerular filtration rate from baseline to 120 days from hospital discharge. ANALYTICAL APPROACH: Four machine-learning algorithms (logistic regression, random forest, support vector machine, and extreme gradient boosting) and the SHAP (Shapley Additive Explanations) framework were used for feature selection and interpretation. Model performance was evaluated by 10-fold cross-validation and external validation. RESULTS: One developed model including 15 features outperformed the SOFA (Sequential Organ Failure Assessment) score for the prediction of hospital mortality, with areas under the curve of 0.79 (95% CI, 0.79-0.80) and 0.71 (95% CI, 0.71-0.71) in the development cohort and 0.74 (95% CI, 0.73-0.74) and 0.71 (95% CI, 0.71-0.71) in the validation cohort (P < 0.001 for both). A second developed model including 14 features outperformed KDIGO (Kidney Disease: Improving Global Outcomes) AKI severity staging for the prediction of MAKE: 0.78 (95% CI, 0.78-0.78) versus 0.66 (95% CI, 0.66-0.66) in the development cohort and 0.73 (95% CI, 0.72-0.74) versus 0.67 (95% CI, 0.67-0.67) in the validation cohort (P < 0.001 for both). LIMITATIONS: The models are applicable only to critically ill adult patients with incident AKI within the first 3 days of an ICU stay. CONCLUSIONS: The reported clinical models exhibited better performance for mortality and kidney recovery prediction than standard scoring tools commonly used in critically ill patients with AKI in the ICU. Additional validation is needed to support the utility and implementation of these models. PLAIN-LANGUAGE SUMMARY: Acute kidney injury (AKI) occurs commonly in critically ill patients admitted to the intensive care unit (ICU) and is associated with high morbidity and mortality rates. Prediction of mortality and recovery after an episode of AKI may assist bedside decision making. In this report, we describe the development and validation of a clinical model using data from the first 3 days of an ICU stay to predict hospital mortality and major adverse kidney events occurring as long as 120 days after hospital discharge among critically ill adult patients who experienced AKI within the first 3 days of an ICU stay. The proposed clinical models exhibited good performance for outcome prediction and, if further validated, could enable risk stratification for timely interventions that promote kidney recovery.

Correction for Systematic Bias in Radiomics Measurements Due to Variation in Imaging Protocols.

RATIONALE AND OBJECTIVES: The accuracy of measured radiomics features is affected by CT imaging protocols. This study aims to ascertain if applying bias corrections can improve the classification performance of the radiomics features. MATERIALS AND METHODS: A cohort of 144 Non-Small Cell Lung Cancer patient CT images was used to calculate radiomics features for use in predictive models of patient pathological stage. Simulation models of the tumors, matched to patient lesion qualities of size, contrast, and degree of spiculation, were used to both create and assess protocol-specific correction factors. The usefulness of correction was first assessed by applying the corrections to simulated lesion phantoms with known properties using a corrected paired Student's t-test. The sensitivity of radiomics features to correction factors was assessed by applying a library of possible theoretical correction factors to the uncorrected radiomics from the patient data. The data were then used to assess the effect of the correction on prediction performance (AUC) from a logistic regression radiomics model across the patient cases. RESULTS: The correction factors were shown to reduce the bias of radiomics features, caused by protocols, provided that the correction factors were derived from lesion models with similar properties. The sensitivity of the radiomics features to changes due to protocol effects was on average 89% among all features. The corrections applied to patient data resulted in a small increase of 0.0074 in AUC that was not statistically significant (p=0.60). CONCLUSION: Protocol-specific correction factors can be applied to radiomics studies to control for biases introduced by different imaging protocols. The correction factors should ideally be lesion-specific, derived using lesion models that echo patient lesion characteristics in terms of size, contrast, and degree of spiculation. Small corrections in the 10% range offers only a small improvement in the predictability of radiomics.

Multi-disciplinary Approach for Drug and Gene Delivery Systems to the Brain.

Drug delivery into the brain has for long been a huge challenge as the blood-brain barrier (BBB) offers great resistance to entry of foreign substances (with drugs inclusive) into the brain. This barrier in healthy individuals is protective to the brain, disallowing noxious substances present in the blood to get to the brain while allowing for the exchange of small molecules into the brain by diffusion. However, BBB is disrupted under certain disease conditions, such as cerebrovascular diseases including acute ischemic stroke and intracerebral hemorrhage, and neurodegenerative disorders including multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD), and cancers. This review aims to provide a broad overview of present-day strategies for brain drug delivery, emphasizing novel delivery systems. Hopefully, this review would inspire scientists and researchers in the field of drug delivery across BBB to uncover new techniques and strategies to optimize drug delivery to the brain. Considering the anatomy, physiology, and pathophysiological functioning of the BBB in health and disease conditions, this review is focused on the controversies drawn from conclusions of recently published studies on issues such as the penetrability of nanoparticles into the brain, and whether active targeted drug delivery into the brain could be achieved with the use of nanoparticles. We also extended the review to cover novel non-nanoparticle strategies such as using viral and peptide vectors and other non-invasive techniques to enhance brain uptake of drugs.

Spinal Epidural Lipomatosis: A Comprehensive Review.

PURPOSE OF REVIEW: This is a comprehensive review regarding the epidemiology, diagnosis, and management of spinal epidural lipomatosis (SEL). RECENT FINDINGS: SEL is a relatively rare condition that has gained scientific relevance over the past few decades. Recent findings include expanding treatment strategies to include minimally invasive surgical techniques. SUMMARY: SEL is caused by an excess of adipose tissue accumulation localized to the thoracic and lumbar regions of the spine. While the exact pathogenesis is not fully elucidated, the etiology of SEL can be broadly classified based on five commonly associated risk factors; exogenous steroid use, obesity, endogenous steroid hormonal disease, spine surgery, and idiopathic disease. Progression of SEL may lead to neurological deficits, myelopathy, radiculopathy, neurogenic claudication, loss of sensation, difficulty voiding, lower extremity weakness, and rarely cauda equina syndrome. Conservative management is largely patient-specific and aimed at mitigating symptoms that arise from shared risk factors. If more advanced treatment measures are necessary, minimally invasive surgery and open surgical techniques, have proven successful.

Development and validation of an automated methodology to assess perceptual in vivo noise texture in liver CT.

Purpose: Developing, validating, and evaluating a method for measuring noise texture directly from patient liver CT images (i.e., in vivo). Approach: The method identifies target regions within patient scans that are least likely to have major contribution of patient anatomy, detrends them locally, and measures noise power spectrum (NPS) there using a previously phantom-validated technique targeting perceptual noise-non-anatomical fluctuations in the image that may interfere with the detection of focal lesions. Method development and validation used scanner-specific CT simulations of computational, anthropomorphic phantom (XCAT phantom, three phases of contrast-enhancement) with known ground truth of the NPS. Simulations were based on a clinical scanner (Definition Flash, Siemens) and clinically relevant settings (tube voltage of 120 kV at three dose levels). Images were reconstructed with filtered backprojection (kernel: B31, B41, and B50) and Sinogram Affirmed Iterative Reconstruction (kernel: I31, I41, and I50) using a manufacturer-specific reconstruction software (ReconCT, Siemens). All NPS measurements were made in the liver. Ground-truth NPS were taken as the sum of (1) a measurement in parenchymal regions of anatomy-subtracted (i.e., noise only) scans, and (2) a measurement in the same region of noise-free (pre-noise-insertion) images. To assess in vivo NPS performance, correlation of NPS average frequency ( f avg ), was reported. Sensitivity of accuracy [root-mean-square-error (RMSE)] to number of pixels included in measurement was conducted via bootstrapped pixel-dropout. Sensitivity of NPS to dose and reconstruction kernel was assessed to confirm that ground truth NPS similarities were maintained in patient-specific measurements. Results: Pearson and Spearman correlation coefficients 0.97 and 0.96 for f avg indicated good correlation. Results suggested accurate NPS measurements (within 5% total RMSE) could be acquired with ∼ 10 6 pixels . Conclusions: Relationships of similar NPS due to reconstruction kernel and dose were preserved between gold standard and observed in vivo estimations. The NPS estimation method was further deployed on clinical cases to demonstrate the feasibility of clinical analysis.

Development, validation, and relevance of in vivo low-contrast task transfer function to estimate detectability in clinical CT images.

PURPOSE: The current state-of-the-art calculation of detectability index (d') is largely phantom-based, with the latest being based on a hybrid phantom noise power spectrum (NPS) combined with patient-specific noise magnitude and high-contrast air-skin interface. The purpose of this study was to develop and assess the use of fully patient-specific measurements of noise and low-contrast resolution, derived entirely from patient images on d'. METHODS: This study developed a d' calculation that is patient- and task-specific, employing newly developed algorithms for estimating patient-specific NPS and low-contrast task transfer function (TTF). The TTF estimation methodology used a trained regression support vector machine (SVM) to estimate a fitted form of the TTF given a variance-normalized estimate of the NPS (referred to as the TTFNPS ). The regression SVM was trained and tested using five-fold cross-validation on 192 scans (4 dose levels x 6 reconstruction kernels x 4 repeats) of a phantom with low-contrast polyethylene insert and reconstructed with filtered backprojection and iterative reconstructions across 12 clinically relevant kernels (FBP: B20f, B31f, B45f; SAFIRE: I26f, I31f, J45f with strengths: 2, 3, 5). To test the low-contrast TTF estimation method, the estimated TTFNPS measurements were compared to (1) TTF measurements from the air-phantom interface (referred to as the TTFair , representing the most patient-specific clinical alternative) and (2) TTF measurements from the edge of the low-contrast polyethylene insert (referred to as the TTFpoly ), which represented the gold standard of low-contrast TTF measurement. Patient-specific NPS, patient-specific noise magnitude, and patient-specific low-contrast TTF were further combined with a reference task function to calculate a d' (according to a non-prewhitening matched filter model) across 1120 lesions previously evaluated in 2AFC human observer detection of liver lesions. The resulting values were compared to the observer results using a generalized linear mixed-effects statistical model. The correlations between the model and observer results were also compared with previously reported values (using a hybrid method with phantom-derived NPS and TTFair ). RESULTS: The TTFNPS more accurately represented resolution across the considered reconstruction settings, compared with the TTFair . The out-of-fold predictions of the TTFNPS had statistically better root-mean-square error concordance (p < 0.05, one-tailed Wilcoxon rank-sum test) to gold standard than the TTFair (the alternative, measured from the air-phantom interface). Detectability indices informed by purely patient-specific NPS and TTF were strongly correlated with 2AFC outcomes (p < 0.05). R2 between human detection accuracy and model-predicted detection accuracy were shown to be greater for those measured with patient-specific d' than for the hybrid d' but failed to rise to the level of statistical significance (p ≥ 0.05, bootstrap resampled corrected paired Student's t-test). CONCLUSIONS: The results suggest that fully patient-specific characterization of image quality based on in vivo NPS and low-contrast TTF offer advantages over hybrid methods. The results in terms of d' favorably relate to observer detection of liver lesions. The method can potentially be integrated into an automated image quality tracking system to assess image quality across a computed tomography clinical operation without needing phantom scans.

Nuclear factor of activated T-cells (NFAT) regulation of IL-1ß-induced retinal vascular inflammation.

Chronic low-grade retinal inflammation is an essential contributor to the pathogenesis of diabetic retinopathy (DR). It is characterized by increased retinal cell expression and secretion of a variety of inflammatory cytokines; among these, IL-1ß has the reputation of being a major driver of cytokine-induced inflammation. IL-1ß and other cytokines drive inflammatory changes that cause damage to retinal cells, leading to the hallmark vascular lesions of DR; these include increased leukocyte adherence, vascular permeability, and capillary cell death. Nuclear factor of activated T-cells (NFAT) is a transcriptional regulator of inflammatory cytokines and adhesion molecules and is expressed in retinal cells. Consequently, it may influence multiple pathogenic steps early in DR. We investigated the NFAT-dependency of IL-1ß-induced inflammation in human Müller cells (hMC) and human retinal microvascular endothelial cells (hRMEC). Our results show that an NFAT inhibitor, Inhibitor of NFAT-Calcineurin Association-6 (INCA-6), decreased IL-1ß-induced expression of IL-1ß and TNFα in hMC, while having no effect on VEGF, CCL2, or CCL5 expression. We also demonstrate that INCA-6 attenuated IL-1ß-induced increases of IL-1ß, TNFα, IL-6, CCL2, and CCL5 (inflammatory cytokines and chemokines), and ICAM-1 and E-selectin (leukocyte adhesion molecules) expression in hRMEC. INCA-6 similarly inhibited IL-1ß-induced increases in leukocyte adhesion in both hRMEC monolayers in vitro and an acute model of retinal inflammation in vivo. Finally, INCA-6 rescued IL-1ß-induced permeability in both hRMEC monolayers in vitro and an acute model of retinal inflammation in vivo. Taken together, these data demonstrate the potential of NFAT inhibition to mitigate retinal inflammation secondary to diabetes.