Sleep-wake behaviors associated with cognitive performance in middle-aged participants of the Hispanic Community Health Study/Study of Latinos.

OBJECTIVES: Many sleep-wake behaviors have been associated with cognition. We examined a panel of sleep-wake/activity characteristics to determine which are most robustly related to having low cognitive performance in midlife. Secondarily, we evaluate the predictive utility of sleep-wake measures to screen for low cognitive performance. METHODS: The outcome was low cognitive performance defined as being >1 standard deviation below average age/sex/education internally normalized composite cognitive performance levels assessed in the Hispanic Community Health Study/Study of Latinos. Analyses included 1006 individuals who had sufficient sleep-wake measurements about 2years later (mean age=54.9, standard deviation= 5.1; 68.82% female). We evaluated associations of 31 sleep-wake variables with low cognitive performance using separate logistic regressions. RESULTS: In individual models, the strongest sleep-wake correlates of low cognitive performance were measures of weaker and unstable 24-hour rhythms; greater 24-hour fragmentation; longer time-in-bed; and lower rhythm amplitude. One standard deviation worse on these sleep-wake factors was associated with ∼20%-30% greater odds of having low cognitive performance. In an internally cross-validated prediction model, the independent correlates of low cognitive performance were: lower Sleep Regularity Index scores; lower pseudo-F statistics (modellability of 24-hour rhythms); lower activity rhythm amplitude; and greater time in bed. Area under the curve was low/moderate (64%) indicating poor predictive utility. CONCLUSION: The strongest sleep-wake behavioral correlates of low cognitive performance were measures of longer time-in-bed and irregular/weak rhythms. These sleep-wake assessments were not useful to identify previous low cognitive performance. Given their potential modifiability, experimental trials could test if targeting midlife time-in-bed and/or irregular rhythms influences cognition.

Appropriateness of Ophthalmology Recommendations From an Online Chat-Based Artificial Intelligence Model.

Objective: To determine the appropriateness of ophthalmology recommendations from an online chat-based artificial intelligence model to ophthalmology questions. Patients and Methods: Cross-sectional qualitative study from April 1, 2023, to April 30, 2023. A total of 192 questions were generated spanning all ophthalmic subspecialties. Each question was posed to a large language model (LLM) 3 times. The responses were graded by appropriate subspecialists as appropriate, inappropriate, or unreliable in 2 grading contexts. The first grading context was if the information was presented on a patient information site. The second was an LLM-generated draft response to patient queries sent by the electronic medical record (EMR). Appropriate was defined as accurate and specific enough to serve as a surrogate for physician-approved information. Main outcome measure was percentage of appropriate responses per subspecialty. Results: For patient information site-related questions, the LLM provided an overall average of 79% appropriate responses. Variable rates of average appropriateness were observed across ophthalmic subspecialties for patient information site information ranging from 56% to 100%: cataract or refractive (92%), cornea (56%), glaucoma (72%), neuro-ophthalmology (67%), oculoplastic or orbital surgery (80%), ocular oncology (100%), pediatrics (89%), vitreoretinal diseases (86%), and uveitis (65%). For draft responses to patient questions via EMR, the LLM provided an overall average of 74% appropriate responses and varied by subspecialty: cataract or refractive (85%), cornea (54%), glaucoma (77%), neuro-ophthalmology (63%), oculoplastic or orbital surgery (62%), ocular oncology (90%), pediatrics (94%), vitreoretinal diseases (88%), and uveitis (55%). Stratifying grades across health information categories (disease and condition, risk and prevention, surgery-related, and treatment and management) showed notable but insignificant variations, with disease and condition often rated highest (72% and 69%) for appropriateness and surgery-related (55% and 51%) lowest, in both contexts. Conclusion: This LLM reported mostly appropriate responses across multiple ophthalmology subspecialties in the context of both patient information sites and EMR-related responses to patient questions. Current LLM offerings require optimization and improvement before widespread clinical use.

Trametes versicolor Laccase-Based Magnetic Inorganic-Protein Hybrid Nanobiocatalyst for Efficient Decolorization of Dyes in the Presence of Inhibitors.

In the present investigation, an ecofriendly magnetic inorganic-protein hybrid system-based enzyme immobilization was developed using partially purified laccase from Trametes versicolor (TvLac), Fe3O4 nanoparticles, and manganese (Mn), and was successfully applied for synthetic dye decolorization in the presence of enzyme inhibitors. After the partial purification of crude TvLac, the specific enzyme activity reached 212 U∙mg total protein-1. The synthesized Fe3O4/Mn3(PO4)2-laccase (Fe3O4/Mn-TvLac) and Mn3(PO4)2-laccase (Mn-TvLac) nanoflowers (NFs) exhibited encapsulation yields of 85.5% and 90.3%, respectively, with relative activities of 245% and 260%, respectively, compared with those of free TvLac. One-pot synthesized Fe3O4/Mn-TvLac exhibited significant improvements in catalytic properties and stability compared to those of the free enzyme. Fe3O4/Mn-TvLac retained a significantly higher residual activity of 96.8% over that of Mn-TvLac (47.1%) after 10 reuse cycles. The NFs showed potential for the efficient decolorization of synthetic dyes in the presence of enzyme inhibitors. For up to five reuse cycles, Fe3O4/Mn-TvLac retained a decolorization potential of 81.1% and 86.3% for Coomassie Brilliant Blue R-250 and xylene cyanol, respectively. The synthesized Fe3O4/Mn-TvLac showed a lower acute toxicity towards Vibrio fischeri than pure Fe3O4 nanoparticles did. This is the first report of the one-pot synthesis of biofriendly magnetic protein-inorganic hybrids using partially purified TvLac and Mn.

Neonatal Bacillus cereus: an unusual case of congenital pneumonia requiring ECMO.

A term neonate presented with cyanosis from birth, with refractory hypoxaemia despite intubation, administration of 100% oxygen and inhaled nitric oxide. Structural congenital heart disease was excluded. He developed profuse pulmonary haemorrhage at 6 hours of life with worsening hypoxia and was transferred to a paediatric intensive care unit (PICU) for initiation of veno-venous extracorporeal membrane oxygenation (vvECMO). Endotracheal aspirates from both the birth hospital and the PICU were positive for Bacillus cereus, with all other investigations finding no alternative cause for his presentation. Of note, mother was a practising veterinarian raising another potential source of exposure to this pathogen. A full recovery occurred after a total of 5 days of vvECMO, 13 days of ventilation and 20 days of PICU stay.

Ten-Year Stability of an Insomnia Sleeper Phenotype and Its Association With Chronic Conditions.

OBJECTIVE: To identify distinct sleep health phenotypes in adults, examine transitions in sleep health phenotypes over time, and subsequently relate these to the risk of chronic conditions. METHODS: A national sample of adults from the Midlife in the United States study ( N = 3683) provided longitudinal data with two time points (T1: 2004-2006, T2: 2013-2017). Participants self-reported on sleep health (regularity, satisfaction, alertness, efficiency, duration) and the number and type of chronic conditions. Covariates included age, sex, race, education, education, partnered status, number of children, work status, smoking, alcohol, and physical activity. RESULTS: Latent transition analysis identified four sleep health phenotypes across both time points: good sleepers, insomnia sleepers, weekend catch-up sleepers, and nappers. Between T1 and T2, the majority (77%) maintained their phenotype, with the nappers and insomnia sleepers being the most stable. In fully adjusted models with good sleepers at both time points as the reference, being an insomnia sleeper at either time point was related to having an increased number of total chronic conditions by 28%-81% at T2, adjusting for T1 conditions. Insomnia sleepers at both time points were at 72%-188% higher risk for cardiovascular disease, diabetes, depression, and frailty. Being a napper at any time point related to increased risks for diabetes, cancer, and frailty. Being a weekend catch-up sleeper was not associated with chronic conditions. Those with lower education and unemployed were more likely to be insomnia sleepers; older adults and retirees were more likely to be nappers. CONCLUSION: Findings indicate a heightened risk of chronic conditions involved in suboptimal sleep health phenotypes, mainly insomnia sleepers.

Influence of Impaired Diffusing Capacity and Sleep-disordered Breathing on Nocturnal Hypoxemia and Health Outcomes in Men with and without HIV.

RATIONALE: Nocturnal hypoxemia is common in sleep-disordered breathing (SDB) and is associated with increased morbidity and mortality. Although impaired diffusing capacity of the lungs for carbon monoxide (DLCO) is associated with daytime hypoxemia, its influence on SDB-related nocturnal hypoxemia is not known. OBJECTIVE: To characterize the effects of DLCO impairment on SDB-related nocturnal hypoxemia and associated health outcomes. METHODS: Data from a multi-center cohort of men with and without HIV, with concomitant measures of DLCO and home-based polysomnography (N=544), were analyzed. Multivariable quantile regression models characterized associations between DLCO and several measures of SDB-related hypoxemia (e.g., total sleep time with oxygen saturation [SpO2]<90% [T90]). Structural equation models assessed associations between impaired DLCO and SDB-related hypoxemia measures with prevalent hypertension and type 2 diabetes. RESULTS: DLCO impairment (<80% predicted) was associated with sleep-related hypoxemia. Participants with severe SDB (apnea-hypopnea index≥30 events/hr) and impaired DLCO had a higher T90 (median difference: 15.0%; [95% CI: 10.3,19.7]) and average SDB-related desaturation (median difference: 1.0; [0.5, 1.5]), and lower nadir SpO2 (median difference: -8.2%; [-11.4, -4.9]) and average SpO2 during sleep (median difference: -1.1%; [-2.1, -0.01]), than those with severe SDB and preserved DLCO. A higher T90 was associated with higher adjusted odds of prevalent hypertension (OR 1.39; [1.14,1.70]) and type 2 diabetes (OR 1.25; [1.07,1.46]). CONCLUSIONS: DLCO impairment in severe SDB was associated with sleep-related hypoxemia, prevalent hypertension and type 2 diabetes. Assessment of SDB should be considered in those with impaired DLCO to guide testing and risk-stratification strategies.

Sequential Co-Immobilization of Enzymes on Magnetic Nanoparticles for Efficient l-Xylulose Production.

Multi-enzymatic strategies have shown improvement in bioconversion during cofactor regeneration. In this study, purified l-arabinitol 4-dehydrogenase (LAD) and nicotinamide adenine dinucleotide oxidase (Nox) were immobilized via individual, mixed, and sequential co-immobilization approaches on magnetic nanoparticles, and were evaluated to enhance the conversion of l-arabinitol to l-xylulose. Initially, the immobilization of LAD or Nox on the nanoparticles resulted in a maximum immobilization yield and relative activity of 91.4% and 98.8%, respectively. The immobilized enzymes showed better pH and temperature profiles than the corresponding free enzymes. Furthermore, co-immobilization of these enzymes via mixed and sequential methods resulted in high loadings of 114 and 122 mg/g of support, respectively. Sequential co-immobilization of these enzymes proved more beneficial for higher conversion than mixed co-immobilization because of better retaining Nox residual activity. Sequentially co-immobilized enzymes showed a high relative conversion yield with broader pH, temperature, and storage stability profiles than the controls, along with high reusability. To the best of our knowledge, this is the first report on the mixed or sequential co-immobilization of LAD and Nox on magnetic nanoparticles for l-xylulose production. This finding suggests that selecting a sequential co-immobilization strategy is more beneficial than using individual or mixed co-immobilized enzymes on magnetic nanoparticles for enhancing conversion applications.

Accurate Determination of the Average Rate Constant of Pyrene Excimer Formation for Pyrene-Labeled Macromolecules from the Analysis of Individual Fluorescence Decays with Sums of Exponentials.

The average rate constant (⟨k⟩) for pyrene excimer formation (PEF) between an excited and a ground-state pyrenyl label covalently attached to a pyrene-labeled macromolecule (PyLM) has been found to be an ideal parameter to probe macromolecular conformations due to its proportionality to the local concentration ([Py]loc) of pyrenyl labels in PyLM. To date, ⟨k⟩ has only been determined with the model-free analysis (MFA) involving the global analysis of the pyrene monomer and excimer fluorescence decays of PyLM. Unfortunately, the MFA is computationally demanding which prevents its widespread use. To circumvent this complication, a methodology is introduced that involves the analysis of individual fluorescence decays with sums of exponentials (SoE), which are commonly used in the analysis packages of commercial time-resolved fluorometers. The individual fluorescence decays of the pyrene monomer acquired with 286 PyLM were analyzed with a SoE to yield ⟨kSoE-M⟩. The strong correlation between ⟨kSoE-M⟩ and ⟨kMF⟩ obtained from the global MFA indicated that ⟨kSoE-M⟩ was a good representation of ⟨k⟩. Furthermore, the AE-/AE+ ratio, equal to the ratio of the sum of the negative pre-exponential factors over the sum of the positive pre-exponential factors, was determined by fitting the individual pyrene excimer fluorescence decays of the 286 PyLM with a SoE. AE-/AE+ was found to take a value between -1.0 and -0.8, indicating that the pyrenyl labels were not aggregated. This result indicated that [Py]loc was well described by ⟨kSoE-M⟩, so that ⟨kSoE-M⟩ could be used to describe the conformation of macromolecules in the same manner as ⟨kMF⟩. Consequently, the methodology based on the analysis of individual fluorescence decays with sums of exponentials to determine ⟨kSoE-M⟩ and AE-/AE+ provides a robust alternative to the use of the MFA for the study of PyLM to many scientists interested in the characterization of macromolecular conformations.

Production of hydrogen-rich fuel gas from waste plastics using continuous plasma pyrolysis reactor.

There is a serious concern about the large amount of accumulated plastic waste all around the world. Synthetic polymers such as polyethylene terephthalate (PET), polypropylene (PP), and polyethylene (HDPE, LDPE) are substantially present in the plastic waste generated. There are various methods reported to minimise such plastics waste with certain limitations. To overcome such limitations the present study have been carried out in which thermal decomposition of plastic waste of PET, PP, HDPE, and LDPE studied using a novel plasma pyrolysis reactor. The major objective of this work is to investigate the viability of the continuous plasma pyrolysis process for the treatment of various plastic wastes with respect to waste volume reduction and production of combustible hydrogen-rich fuel gas. The effect of temperature and feed flow rate on product gas yield, product gas efficiency, solid residue yield, and H2/CO ratio has been evaluated. The experiments have been carried out at different temperatures within the range of 700-1000 °C. Plasma pyrolysis system exhibited combustible hydrogen-rich gas as a product and solid residue. Liquid products have not been observed during plasma pyrolysis, unlike conventional pyrolysis. The reaction mechanism of plastic cracking has been discussed based on literature and products obtained in the present work. The effects of feed flow rate and temperature on exergy efficiency were studied using the response surface method. The mass, energy, and exergy analyses have also been carried out for all the experiments, which are in the range of 0.95-0.99, 0.48 to 0.77, and 0.30 to 0.69, respectively.

Subcutaneous panniculitic-like T-cell lymphoma localized to a site of peginterferon alfa-2a administration.

T cell dyscrasias that demonstrate a proclivity for the subcutaneous fat include atypical lymphocytic lobular panniculitis, lupus profundus, and primary subcutaneous T cell lymphoma, including subcutaneous panniculitis-like T cell lymphoma (SPTCL). We encountered two patients who developed fever and indurated abdominal erythema at their peginterferon alfa-2a injection sites. Biopsies showed an atypical CD8 positive, granzyme positive, CD5 negative, MXA negative lymphocytic lobular panniculitis, diagnostic of SPTCL. Peginterferon alfa-2a was held in both patients. One patient received chemotherapy with an excellent response, while the other continued to have progressive disease. Peginterferon alfa-2a is known to significantly elevate serum MXA, which may induce high levels of MXA expression at the injection site, creating a microenvironment for the development of lupus profundus, which may eventuate into SPTCL. In summation, a potential risk of peginterferon alfa-2a injections is the development of SPTCL potentially arising in a background of an exogenous interferon triggered lymphocytic panniculitis.

Sleep-wake behavioral characteristics associated with depression symptoms: findings from the Multi-Ethnic Study of Atherosclerosis.

STUDY OBJECTIVES: To help prioritize target/groups for experimental intervention studies, we characterized cross-sectional associations between 24-hour sleep-wake measures and depression symptoms, and evaluated if similar sleep-wake-depression relationships existed in people with and without higher insomnia severity. METHODS: Participants had ≥3 days of actigraphy data (n = 1884; mean age = 68.6/SD = 9.1; 54.1% female). We extracted 18 sleep, activity, timing, rhythmicity, and fragmentation measures from actigraphy. We used individual and multivariable regressions with the outcome of clinically significant depression symptoms (Center for Epidemiologic Studies Depression Scale ≥ 16). We conducted sensitivity analyses in people with higher insomnia severity (top quartile of the Women's Health Initiative Insomnia Rating Scale total score). RESULTS: From separate models in the overall sample, the odds of having depression symptoms were higher with: later timing (e.g. activity onset time odds ratio [OR]/1 SD = 1.32; 95% confidence interval [CI]: 1.16 to 1.50), lower rhythmicity (e.g. pseudo-F OR/1 SD = 0.75; 95% CI: 0.66 to 0.85), less activity (e.g. amplitude OR/1 SD = 0.83; 95% CI: 0.72 to 0.95), and worse insomnia (OR/1 SD = 1.48, 95% CI: 1.31 to 1.68). In multivariable models conducted among people with lower insomnia severity, later timing, lower rhythmicity, and higher insomnia severity were independent correlates of depression. In people with higher insomnia symptom severity, measures of later timing were most strongly associated with depression symptoms. CONCLUSIONS: These correlative observations suggest that experimental studies are warranted to test if: broadly promoting 24-hour sleep-wake functioning reduces depression even in people without severe insomnia, and if advancing timing leads to depression symptom reductions in people with insomnia.

Permanent ocular remodeling in the setting of chronic hypotony after trabeculectomy: A case report.

Purpose: Trabeculectomy surgery is a commonly performed procedure for treatment of glaucoma. While the goal is to lower intraocular pressure, over-filtration may cause hypotony with ocular structural changes and vision loss. Observations: A 53-year-old woman with primary open-angle glaucoma was referred to our service for further evaluation. The patient previously underwent trabeculectomy 9 years prior and was found to have a cataract and hypotony maculopathy in the right eye. Treatment options included cataract surgery alone, bleb revision alone, or combined cataract extraction and bleb revision. Biometry revealed corneal astigmatism in the right eye, and significant disparity in axial length between the two eyes. Since the axial length and corneal astigmatic changes were presumed to be at least partially reversible, measurements from the non-operative left eye influenced the lens selection for the hypotonous right eye. The patient underwent combined phacoemulsification and bleb revision. While IOP increased and hypotony was partly reversed, there was hyperopic and astigmatic refractive surprise after surgery.The patient subsequently underwent intraocular lens exchange using biometric values of the previously hypotonous eye and met the target post-operative refractive goal. Conclusions and importance: This case demonstrates changes to the axial length and ocular structure following longstanding hypotony maculopathy may be permanent, even after restoration of normotensive intraocular pressure.

Manipulating Microbial Cell Morphology for the Sustainable Production of Biopolymers.

The total rate of plastic production is anticipated to surpass 1.1 billion tons per year by 2050. Plastic waste is non-biodegradable and accumulates in natural ecosystems. In 2020, the total amount of plastic waste was estimated to be 367 million metric tons, leading to unmanageable waste disposal and environmental pollution issues. Plastics are produced from petroleum and natural gases. Given the limited fossil fuel reserves and the need to circumvent pollution problems, the focus has shifted to biodegradable biopolymers, such as polyhydroxyalkanoates (PHAs), polylactic acid, and polycaprolactone. PHAs are gaining importance because diverse bacteria can produce them as intracellular inclusion bodies using biowastes as feed. A critical component in PHA production is the downstream processing procedures of recovery and purification. In this review, different bioengineering approaches targeted at modifying the cell morphology and synchronizing cell lysis with the biosynthetic cycle are presented for product separation and extraction. Complementing genetic engineering strategies with conventional downstream processes, these approaches are expected to produce PHA sustainably.

Shorter total sleep time is associated with lower CD4+/CD8+ T cell ratios in virally suppressed men with HIV.

Study Objectives: Although poor sleep quality is associated with lower CD4+ T cell counts among people living with HIV (PLWH), the association between objective sleep metrics and T lymphocyte subset counts is unknown. We evaluated the association between polysomnography (PSG) derived sleep metrics and T lymphocyte subpopulations in a cohort of men living with HIV. Methods: Virally suppressed men living with HIV participating in the Multicenter AIDS Cohort Study underwent home overnight PSG. We assessed the association of PSG parameters with CD4+ and CD8+ T cell counts and the CD4+/CD8+ T cell ratio. Results: Overall, 289 men with mean (±SD) age 55.3 ±â€…11.3 years and mean CD4+ T cell count 730 ±â€…308 cells/mm3 were evaluated. Total sleep time (TST) was significantly associated with CD8+ but not CD4+ T cell counts. After adjusting for age, race, depressive symptoms, antidepressant use, and non-nucleoside reverse transcriptase inhibitors use, every hour of shorter TST was associated with an additional 33 circulating CD8+ T cells/mm3 (p = 0.05) and a 5.6% (p = 0.0007) decline in CD4+/CD8+ T cell ratio. In adjusted models, every hour of shorter rapid eye movement (REM) sleep was associated with an additional 113 CD8+ T cells/mm3 (p = 0.02) and a 15.1% lower CD4+/CD8+ T cell ratio (p = 0.006). In contrast, measures of sleep efficiency and sleep-disordered breathing were not associated with differences in T lymphocyte subpopulations. Conclusions: Our findings suggest that shorter TST and REM sleep durations are associated with differences in T lymphocyte subpopulations among men living with HIV. Addressing sleep may reflect a novel opportunity to improve immune function in PLWH.

Colchicine in atherosclerotic cardiovascular disease.

Inflammation has a direct role in the development of atherosclerotic vascular disease, and oral colchicine displays broad anti-inflammatory properties. Several large, randomised controlled trials (RCTs) have evaluated colchicine's impact on cardiovascular outcomes. Results from a meta-analysis of these trials demonstrate that colchicine reduces the risk of recurrent major adverse cardiovascular events (MACEs) by 25%, leading to its recent approval by the Food and Drug Administration for the treatment and prevention of cardiovascular disease. Despite this, colchicine has not been shown to confer any survival benefit in these trials. The non-significant reduction in cardiovascular death of 18% (95% CI: 45% decrease to 23% increase) is outweighed by a more prominent, borderline non-significant increase in the risk of non-cardiovascular death by 38% (95% CI: 1% decrease to 92% increase). Key populations including those with heart failure, those undergoing surgical revascularisation, women, elderly individuals and non-Caucasians are under-represented in completed trials, which limits generalisability. C reactive protein has been proposed as a biomarker for colchicine response and shows promise for identifying a high-risk population where the benefit on MACE reduction and specifically reduced cardiovascular death might outweigh any real increased risk of non-cardiovascular death; however, this approach is still to be validated in ongoing RCTs. In conclusion, while colchicine shows promise in reducing MACE, its net risk-benefit profile requires further elucidation before its widespread adoption into clinical practice for the secondary prevention of atherosclerotic cardiovascular disease. Much more large-scale, long-term trial data are still needed in this space.

Production, optimization, scale up and characterization of polyhydoxyalkanoates copolymers utilizing dairy processing waste.

The microbial biotransformation using low-cost feedstock to produce biopolymers (degradable), an alternative to petrochemical-based synthesis plastics (non-degradable), can be a beneficial approach towards sustainable development. In this study, the dairy industry processes waste (whey) is used in polyhydroxyalkanoate (PHA) copolymer production. Initial screening suggested that Ralstonia eutropha produced higher PHA as compared to Bacillus megaterium. A central composite rotatable design-based optimization using two process variables (amino acid and tween-80) concentration remarkably influenced PHA co-polymer production under physiological conditions of pH (7), temperature (37 °C), and agitation rate of 150 rpm. High polyhydroxybutyrate (PHB) mass fraction yield of 69.3% was observed as compared to predicted yield of 62.8% from deproteinized whey as feed. The combination of tryptophan (50 mg L-1) and tween-80 (3 mL-1) enhanced R. eutropha mass gain to 6.80 g L-1 with PHB contents of 4.71 g L-1. Further, characterization of PHA and its copolymers was done by ESI-MS, FTIR, and TEM. On upscaling up to 3.0 L, the PHA contents and yields were noted as quite similar by R. eutropha. This study demonstrates that dairy waste processing waste can be potentially utilized as inexpensive feed for producing high content of biopolymers to develop a sustainable system of waste management.

Wilms' tumor 1 (WT1) antigen is overexpressed in Kaposi Sarcoma and is regulated by KSHV vFLIP.

In people living with HIV, Kaposi Sarcoma (KS), a vascular neoplasm caused by KS herpesvirus (KSHV/HHV-8), remains one of the most common malignancies worldwide. Individuals living with HIV, receiving otherwise effective antiretroviral therapy, may present with extensive disease requiring chemotherapy. Hence, new therapeutic approaches are needed. The Wilms' tumor 1 (WT1) protein is overexpressed and associated with poor prognosis in several hematologic and solid malignancies and has shown promise as an immunotherapeutic target. We found that WT1 was overexpressed in >90% of a total 333 KS biopsies, as determined by immunohistochemistry and image analysis. Our largest cohort from ACTG, consisting of 294 cases was further analyzed demonstrating higher WT1 expression was associated with more advanced histopathologic subtypes. There was a positive correlation between the proportion of infected cells within KS tissues, assessed by expression of the KSHV-encoded latency-associated nuclear antigen (LANA), and WT1 positivity. Areas with high WT1 expression showed sparse T-cell infiltrates, consistent with an immune evasive tumor microenvironment. We show that major oncogenic isoforms of WT1 are overexpressed in primary KS tissue and observed WT1 upregulation upon de novo infection of endothelial cells with KSHV. KSHV latent viral FLICE-inhibitory protein (vFLIP) upregulated total and major isoforms of WT1, but upregulation was not seen after expression of mutant vFLIP that is unable to bind IKKÆ´ and induce NFκB. siRNA targeting of WT1 in latent KSHV infection resulted in decreased total cell number and pAKT, BCL2 and LANA protein expression. Finally, we show that ESK-1, a T cell receptor-like monoclonal antibody that recognizes WT1 peptides presented on MHC HLA-A0201, demonstrates increased binding to endothelial cells after KSHV infection or induction of vFLIP expression. We propose that oncogenic isoforms of WT1 are upregulated by KSHV to promote tumorigenesis and immunotherapy directed against WT1 may be an approach for KS treatment.