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Introduction and objective: Eosinophilic esophagitis is a chronic, immune-mediated disease described in case series and publications worldwide. Over the past twenty years, the authors of different studies have attempted to evaluate its incidence and prevalence. The objetive of the present study was to estimate the prevalence of eosinophilic esophagitis in a group of children seen at 36 pediatric gastroenterology centers in ten Latin American countries. Materials and methods: A multicenter, observational, and cross-sectional study was conducted that estimated the period prevalence of eosinophilic esophagitis in children seen at outpatient consultation and that underwent diagnostic upper gastrointestinal endoscopy for any indication at 36 centers in 10 Latin American countries, within a 3-month time frame. Results: Between April and June 2016, 108 cases of eosinophilic esophagitis were evaluated. Likewise, an average of 29,253 outpatient consultations and 4,152 diagnostic upper gastrointestinal endoscopies were carried out at the 36 participating centers. The period prevalence of eosinophilic esophagitis in the population studied (n = 29,253) was 3.69 cases × 1,000 (95% CI: 3.04 to 4.44), and among the children that underwent routine upper gastrointestinal endoscopy (n = 4,152), it was 26 x 1,000 (95% CI: 22.6 to 29.4). Conclusions: The general period prevalence of eosinophilic esophagitis in a group of children evaluated at 36 Latin American pediatric gastroenterology centers was 3.69 × 1,000, and in the children that underwent endoscopy, it was 26 × 1,000. There was important prevalence variability between the participating countries and centers. The present analysis is the first study conducted on the prevalence of pediatric eosinophilic esophagitis in Latin America. Resumen: Introducción y objetivo: La esofagitis eosinofílica es una enfermedad crónica, mediada inmunológicamente, descrita en series y publicaciones alrededor del mundo. En los últimos 20 años diversos estudios han intentado evaluar la incidencia y prevalencia de la enfermedad. El objetivo del presente trabajo es estimar la prevalencia de esofagitis eosinofílica en un grupo de niños atendidos en 36 centros de gastroenterología pediátrica de 10 países latinoamericanos. Materiales y métodos: A través de un protocolo multicéntrico, observacional y transversal se estimó la prevalencia de período de esofagitis eosinofílica entre los niños atendidos en consulta externa y sometidos a endoscopia superior diagnóstica por cualquier motivo en 36 centros de 10 países latinoamericanos durante un período de 3 meses. Resultados: Entre abril y junio de 2016 108 casos de esofagitis eosinofílica fueron evaluados. Asimismo, un promedio de 29,253 consultas ambulatorias y 4,152 endoscopias superiores de carácter diagnóstico fueron realizadas en los 36 centros participantes. La tasa de prevalencia de esofagitis eosinofílica en la población estudiada (n = 29,253) fue de 3,69 casos × 1,000 (IC 95%: 3.04 a 4.44) y entre los niños sometidos a endoscopia superior de rutina (n = 4,152) fue de 26 x 1,000 (IC 95%: 22.6 a 29.4). Conclusión: La tasa general de prevalencia de período de esofagitis eosinofílica en un grupo de niños evaluados en 36 centros latinoamericanos de gastroenterología pediátrica resultó de 3,69 × 1,000, y entre aquellos sometidos a endoscopia fue de 26 × 1,000. La prevalencia mostró una importante variabilidad entre los países y centros participantes. Este es el primer estudio de prevalencia de esofagitis eosinofílica pediátrica en Latinoamérica. Keywords: Esophagitis, Eosinophilic, Children, Prevalence, Latin America, Palabras clave: Esofagitis, Eosinofílica, Niños, Prevalencia, Latinoamérica

Resumen: Introducción y objetivo: La esofagitis eosinofílica es una enfermedad crónica, mediada inmunológicamente, descrita en series y publicaciones alrededor del mundo. En los últimos 20 años diversos estudios han intentado evaluar la incidencia y prevalencia de la enfermedad. El objetivo del presente trabajo es estimar la prevalencia de esofagitis eosinofílica en un grupo de niños atendidos en 36 centros de gastroenterología pediátrica de 10 países latinoamericanos. Materiales y métodos: A través de un protocolo multicéntrico, observacional y transversal se estimó la prevalencia de período de esofagitis eosinofílica entre los niños atendidos en consulta externa y sometidos a endoscopia superior diagnóstica por cualquier motivo en 36 centros de 10 países latinoamericanos durante un período de 3 meses. Resultados: Entre abril y junio de 2016 108 casos de esofagitis eosinofílica fueron evaluados. Asimismo, un promedio de 29,253 consultas ambulatorias y 4,152 endoscopias superiores de carácter diagnóstico fueron realizadas en los 36 centros participantes. La tasa de prevalencia de esofagitis eosinofílica en la población estudiada (n = 29,253) fue de 3,69 casos × 1,000 (IC 95%: 3.04 a 4.44) y entre los niños sometidos a endoscopia superior de rutina (n = 4,152) fue de 26 x 1,000 (IC 95%: 22.6 a 29.4). Conclusión: La tasa general de prevalencia de período de esofagitis eosinofílica en un grupo de niños evaluados en 36 centros latinoamericanos de gastroenterología pediátrica resultó de 3,69 × 1,000, y entre aquellos sometidos a endoscopia fue de 26 × 1,000. La prevalencia mostró una importante variabilidad entre los países y centros participantes. Este es el primer estudio de prevalencia de esofagitis eosinofílica pediátrica en Latinoamérica. Abstract: Introduction and objective: Eosinophilic esophagitis is a chronic, immune-mediated disease described in case series and publications worldwide. Over the past twenty years, the authors of different studies have attempted to evaluate its incidence and prevalence. The objetive of the present study was to estimate the prevalence of eosinophilic esophagitis in a group of children seen at 36 pediatric gastroenterology centers in ten Latin American countries. Materials and methods: A multicenter, observational, and cross-sectional study was conducted that estimated the period prevalence of eosinophilic esophagitis in children seen at outpatient consultation and that underwent diagnostic upper gastrointestinal endoscopy for any indication at 36 centers in 10 Latin American countries, within a 3-month time frame. Results: Between April and June 2016, 108 cases of eosinophilic esophagitis were evaluated. Likewise, an average of 29,253 outpatient consultations and 4,152 diagnostic upper gastrointestinal endoscopies were carried out at the 36 participating centers. The period prevalence of eosinophilic esophagitis in the population studied (n = 29,253) was 3.69 cases × 1,000 (95% CI: 3.04 to 4.44), and among the children that underwent routine upper gastrointestinal endoscopy (n = 4,152), it was 26 x 1,000 (95% CI: 22.6 to 29.4). Conclusions: The general period prevalence of eosinophilic esophagitis in a group of children evaluated at 36 Latin American pediatric gastroenterology centers was 3.69 × 1,000, and in the children that underwent endoscopy, it was 26 × 1,000. There was important prevalence variability between the participating countries and centers. The present analysis is the first study conducted on the prevalence of pediatric eosinophilic esophagitis in Latin America. Palabras clave: Esofagitis, Eosinofílica, Niños, Prevalencia, Latinoamérica, Keywords: Esophagitis, Eosinophilic, Children, Prevalence, Latin America

The specification and formal verification of distributed systems is usually a complex task. It requires extensive knowledge of algorithm theory and modeling of distributed or concurrent systems. In this context, we present LeGESD which is a framework oriented to support the specification and formal validation of concurrent and distributed systems. LeGESD has a graphical formal language for the specification and analysis of distributed systems which is used to describe functional and of communication requirements. The semantics of LeGESD is based on the process algebra. This semantics is also described in this paper and it is called Analysis and Design of Distributed Systems (ADSD). ADSD is an algebraic specification with operational semantics defined to be used with LeGESD. ADSD provides graphical-algebraic equivalence relations which can be used to generate formal specifications of distributed systems. Lastly, this paper presents an example which shows the usefulness and potential of the language and its semantics.

Objective: Interictal epileptiform discharges (IEDs) alter brain connectivity in children with epilepsy; this connectivity change may be a mechanism by which epilepsy induces cognitive deficits. Here, we test whether repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulation technique, modulates connectivity and reduces IEDs in children with epilepsy., Methods: Nineteen children with self-limited epilepsy with centrotemporal spikes (SeLECTS) participated in a cross-over study comparing the impact of active vs. sham rTMS on IEDs and brain connectivity. SeLECTS is an epilepsy syndrome affecting the motor cortex, and prior studies show that motor cortices become pathologically hyper-connected to frontal and temporal language cortices. Using a crossover design, we compared the effect of single doses of active versus sham motor cortex rTMS. Connectivity, which was quantified by the weighted phase lag index (wPLI), was measured before and after rTMS using single pulses of TMS combined with EEG (spTMS-EEG). Analyses focused on six regions: bilateral motor cortices and bilateral inferior frontal and superior temporal regions. IEDs were counted in the five minutes before and after rTMS., Results: Active, but not sham, rTMS significantly and globally decreased wPLI connectivity between multiple regions, with the greatest reductions seen in the superior temporal region connections in the stimulated hemisphere. Additionally, there was a trend suggesting that rTMS decreases IED frequency., Interpretation: These findings underscore the potential of low-frequency rTMS to target pathologic hyperconnectivity and reduce IEDs in children with SeLECTS and potentially other pediatric epilepsy syndromes, offering a promising avenue for therapeutic intervention.

Background: Despite recent advances in lung cancer therapeutics and improving overall survival, disparities persist among socially disadvantaged populations. This study aims to determine the effects of neighborhood deprivation indices (NDI) on lung cancer mortality. This is a multicenter retrospective cohort study assessing the relationship between NDI and overall survival adjusted for age, disease stage, and DNA methylation among biopsy-proven lung cancer patients. State-specific NDI for each year of sample collection were computed at the U.S. census tract level and dichotomized into low- and high-deprivation., Results: A total of 173 non small lung cancer patients were included, with n = 85 (49%) and n = 88 (51%) in the low and high-deprivation groups, respectively. NDI was significantly higher among Black patients when compared with White patients (p = 0.003). There was a significant correlation between DNA methylation and stage for HOXA7, SOX17, ZFP42, HOXA9, CDO1 and TAC1. Only HOXA7 DNA methylation was positively correlated with NDI. The high-deprivation group had a statistically significant shorter survival than the low-deprivation group (p = 0.02). After adjusting for age, race, stage, and DNA methylation status, belonging to the high-deprivation group was associated with higher mortality with a hazard ratio of 1.81 (95%CI: 1.03-3.19)., Conclusions: Increased neighborhood-level deprivation may be associated with liquid biopsy DNA methylation, shorter survival, and increased mortality. Changes in health care policies that consider neighborhood-level indices of socioeconomic deprivation may enable a more equitable increase in lung cancer survival., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

There is a little information about the effect of corn process conditions on the bioactive compounds of tortillas during gastrointestinal digestion. Tortillas elaborated with traditional and extrusion nixtamalization process were subjected to in vitro digestion. Extracts recovered from digestion were employed to determine the changes in phytochemicals, bioaccesibility and antioxidant capacity (DPPH, ABTS and FRAP). Digestion contributed to a greater solubilization of phenolic compounds in raw corn and tortillas, especially in the intestinal phase (311.4-583.2 mg GAE/100 g). With bioaccessibility indexes of 162.83 to 960.7 %. Intestinal phase affected the content of anthocyanins, reaching a lower bioaccessibility value than the found in undigested samples (17.90-29.91 %). Even though the traditional white tortilla showed the highest bioaccessibility values, blue tortilla showed a higher antioxidant activity in different phases of digestion. Both tortillas could function as prebiotic agents in the large intestine. Corn-based products are valuable as part of a healthy diet., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Background/objective: The University of Illinois at Chicago (UIC), along with many academic institutions worldwide, made significant efforts to address the many challenges presented during the COVID-19 pandemic by developing clinical staging and predictive models. Data from patients with a clinical encounter at UIC from July 1, 2019 to March 30, 2022 were abstracted from the electronic health record and stored in the UIC Center for Clinical and Translational Science Clinical Research Data Warehouse, prior to data analysis. While we saw some success, there were many failures along the way. For this paper, we wanted to discuss some of these obstacles and many of the lessons learned from the journey., Methods: Principle investigators, research staff, and other project team members were invited to complete an anonymous Qualtrics survey to reflect on the project. The survey included open-ended questions centering on participants' opinions about the project, including whether project goals were met, project successes, project failures, and areas that could have been improved. We then identified themes among the results., Results: Nine project team members (out of 30 members contacted) completed the survey. The responders were anonymous. The survey responses were grouped into four key themes: Collaboration, Infrastructure, Data Acquisition/Validation, and Model Building., Conclusion: Through our COVID-19 research efforts, the team learned about our strengths and deficiencies. We continue to work to improve our research and data translation capabilities., Competing Interests: The authors have no conflicts of interest to report., (© The Author(s) 2023.)

This study aims to perform a comprehensive genomic analysis to assess the influence of overexpression of MYO1E in non-small cell lung carcinoma (NSCLC) and whether there are differences in survival and mortality risk in NSCLC patients depending on both DNA methylation and RNA expression of MYO1E. The DNA methylation probe cg13887966 was inversely correlated with MYO1E RNA expression in both LUAD and LUSC subpopulations showing that lower MYO1E RNA expression was associated with higher MYO1E DNA methylation. Late stages of lung cancer showed significantly lower MYO1E DNA methylation and significantly higher MYO1E RNA expression for LUAD but not for LUSC. Low DNA methylation as well as high RNA expression of MYO1E are associated with a shorter median survival time and an increased risk of mortality for LUAD, but not for LUSC. This study suggests that changes in MYO1E methylation and expression in LUAD patients may have an essential role in lung cancer's pathogenesis. It shows the utility of MYO1E DNA methylation and RNA expression in predicting survival for LUAD patients. Also, given the low normal expression of MYO1E in blood cells MYO1E DNA methylation has the potential to be used as circulating tumor marker in liquid biopsies., (© 2023. The Author(s).)

Purpose: The US Preventive Services Task Force has recommended lung cancer screening (LCS) with low-dose CT (LDCT) in high-risk individuals since 2013. Because LDCT encompasses the lower neck, chest, and upper abdomen, many incidental findings (IFs) are detected. The authors created a quick reference guide to describe common IFs in LCS to assist LCS program navigators and ordering providers in managing the care continuum in LCS., Methods: The ACR IF white papers were reviewed for findings on LDCT that were age appropriate for LCS. A draft guide was created on the basis of recommendations in the IF white papers, the medical literature, and input from subspecialty content experts. The draft was piloted with LCS program navigators recruited through contacts by the ACR LCS Steering Committee. The navigators completed a survey on overall usefulness, clarity, adequacy of content, and user experience with the guide., Results: Seven anatomic regions including 15 discrete organs with 45 management recommendations were identified as relevant to the age of individuals eligible for LCS. The draft was piloted by 49 LCS program navigators from 32 facilities. The guide was rated as useful and clear by 95% of users. No unexpected or adverse experiences were reported in using the guide. On the basis of feedback, relevant sections were reviewed and edited., Conclusions: The ACR Lung Cancer Screening CT Incidental Findings Quick Reference Guide outlines the common IFs in LCS and can serve as an easy-to-use resource for ordering providers and LCS program navigators to help guide management., (Copyright © 2022 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

We validate a deep learning model predicting comorbidities from frontal chest radiographs (CXRs) in patients with coronavirus disease 2019 (COVID-19) and compare the model's performance with hierarchical condition category (HCC) and mortality outcomes in COVID-19. The model was trained and tested on 14,121 ambulatory frontal CXRs from 2010 to 2019 at a single institution, modeling select comorbidities using the value-based Medicare Advantage HCC Risk Adjustment Model. Sex, age, HCC codes, and risk adjustment factor (RAF) score were used. The model was validated on frontal CXRs from 413 ambulatory patients with COVID-19 (internal cohort) and on initial frontal CXRs from 487 COVID-19 hospitalized patients (external cohort). The discriminatory ability of the model was assessed using receiver operating characteristic (ROC) curves compared to the HCC data from electronic health records, and predicted age and RAF score were compared using correlation coefficient and absolute mean error. The model predictions were used as covariables in logistic regression models to evaluate the prediction of mortality in the external cohort. Predicted comorbidities from frontal CXRs, including diabetes with chronic complications, obesity, congestive heart failure, arrhythmias, vascular disease, and chronic obstructive pulmonary disease, had a total area under ROC curve (AUC) of 0.85 (95% CI: 0.85-0.86). The ROC AUC of predicted mortality for the model was 0.84 (95% CI,0.79-0.88) for the combined cohorts. This model using only frontal CXRs predicted select comorbidities and RAF score in both internal ambulatory and external hospitalized COVID-19 cohorts and was discriminatory of mortality, supporting its potential use in clinical decision making., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Pyrros et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The blue corn-based products are considered functional foods due to their high concentration of anthocyanins. The aim of this study was to estimate the kinetic and thermodynamic parameters of the thermal degradation of anthocyanins from extruded nixtamalized corn products. A comparative study of anthocyanins thermal stability in these matrices in a buffer solution (pH 2.5) was investigated at different temperatures (60, 75 or 90 °C). Results showed the mechanism of anthocyanins degradation followed first-order reaction kinetics. The values of the reaction rate constant (k) were found to be in a range of 0.027-0.037 h -1 at 60 °C, 0.107-0.113 h -1 at 75 °C and 0.340-0.354 h -1 at 90 °C. The higher the k value was, the shorter the half-life time and D-value. The activation energy (Ea) and z-values were in the range of 75.1-89.2 kJ/mol and 28.8-35.1 °C, respectively. The coefficient Q 10 indicated the reaction rate approximately doubles with every 10 °C temperature increase. ∆H, ∆S and ∆G indicated the degradation of anthocyanins was an endothermic and nonspontaneous reaction. Even the major susceptibility of the anthocyanins in extruded nixtamalized corn products at the time-temperature combination applied, there was not difference between flour and tortilla, this imply that most of the anthocyanins were degraded during the nixtamalization extrusion process and no significative further degradation occur in the cooking step. This study provides and advance in the knowledge on the effect of nixtamalization extrusion process and tortillas making on the stability of anthocyanins from blue corn. However, further studies are needed., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Early studies showed positive associations fine particulate matter (PM 2.5), course particulate matter PM 10, nitrogen dioxide (NO 2 ) and Ozone (O 3 ) concentrations with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) confirmed cases in the United States. One study showed that a1 μg/m3 increase in PM 2.5 is associated with an 8% increase in the COVID-19 death rate. Specifically, Chicago and surrounding suburbs have been labeled hot spots in the United States and correlation with air pollutants concentration will help identify specific communities most at risk. A number of studies have identified demographic variables associated with increased positive SARS-CoV-2 and the importance of air quality and socioeconomic factors must be further understood for more targeted public health responses. The results of this analysis noted positive relationships between zip code SARS-CoV-2 incidence rate and environmental and demographic EJ indicators. Evaluation of race and SARS-CoV-2 incidence rate at the zip code level found positive moderate correlations for ethnic minority individuals., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors.)

Objective: Assess the effect of Whole-Body Vibration (WBV) therapy in functional balance status of Parkinson's disease (PD) patients and compare this to conventional and combined therapy., Introduction: PD patients experience a decreased mobility, inactivity, and loss of independence as consequence of disturbances in gait, posture, and balance. Rehabilitation therapy is a non-pharmacological way of improving functionality. One of the most studied modalities is WBV, with multiple studies showing improvement in motor function. However, results in this manner are inconsistent., Methods: Forty-five patients were enrolled in a non-randomized controlled trial and divided into three groups. Group 1 received conventional therapy (thermotherapy, stretching, strengthening, coordination and balance). Group 2 received WBV therapy, and group 3 patients underwent a combined therapy protocol. A total of 20 sessions (3 per week) were conducted, assessing Berg Balance Scale (BBS) before initial and after final session., Results: The 3 intervention groups showed significant improvement in BBS scores after concluding the 20-session trial compared to initial assessment. When comparing mean change in BBS score from initial to final assessment, the combined therapy group had a greater increase compared to conventional therapy, but no significant differences were observed comparing to WBV group. Mean change in BBS score showed no significant difference between conventional therapy and WBV therapy group., Conclusions: WBV therapy is a useful tool as co-adjuvant in conventional therapy. The combination of both therapies is a significant therapeutic alternative for the improvement of functional balance status in PD patients compared to conventional therapy alone.

The aim of this study was to evaluate the effect of extrusion factors on the properties of extruded nixtamalized corn flours (ENCFs), determine the optimal conditions, and produce a tortilla with texture and nutraceutical characteristics acceptable for consumers. The processing factors used were feed moisture (FM, 15 to 30%), extruder temperature (T, 70 to 110 °C), and screw speed (SS, 50 to 145 rpm). The properties evaluated in the flours were total anthocyanins (TA), subjective water absorption capacity, and peak viscosity (PV). Response surface methodology and analysis of variance were used in the evaluation. The linear and quadratic terms of FM had a greater effect on all evaluated parameters. The optimization was performed using the numerical method of global desirability. The response variables that were optimized in the ENCF were TAs (maximize) and PV (maximize). The optimal region was the following: FM (18.17%), T (92.03 °C), and SS (76.61 rpm). The experimental value for the TA in the optimized ENCF was 226.07 mg/kg, and the PV was 1063.9 cP. The results of this study could help develop nixtamalized corn flours with desirable characteristics to make tortillas using the extrusion process. PRACTICAL APPLICATION: The results obtained would be useful for the tortilla industry, developing nixtamalized corn flours with desirable characteristics to make healthy tortillas using the extrusion process, with minimum losses in biologically active compounds such as anthocyanins (health promoters) without affect negatively the eating quality of the product (good texture)., (© 2020 Institute of Food Technologists®.)

Paclitaxel is a chemotherapeutic agent used for the treatment of metastatic breast cancer. 2,5,7,8-Tetramethyl-2R-(4R, 8R-12-trimethyltridecyl) chroman-6-yloxyacetic acid (alpha-TEA) is an analog of vitamin E that inhibits primary tumor growth and the incidence of lymphatic and pulmonary metastases in preclinical animal models. Here, the efficacy of sequential treatment with paclitaxel and alpha-TEA was tested in the BALB/c syngeneic 66cl-4-GFP mammary cancer model. Both agents were formulated into liposomes and delivered by inhalation in an effort to increase anti-tumor efficacy and minimize paclitaxel toxicity. Combination treatment consisting of twelve days of every-other-day treatment with aerosolized paclitaxel (approximately 0.46 microg/mouse/treatment) followed by a daily regimen of aerosolized alpha-TEA (36 microg/mouse/treatment) significantly decreased primary tumor burden when compared to untreated or liposome control groups and was significantly better than individual treatments (P < 0.05). Importantly, combination treatment was significantly better at reducing lung and lymph node micrometastatic foci when compared to control and individual treatment groups (P < 0.05). Immunohistochemical analyses of tumor sections showed combination treatment when compared to liposome control or individual treatments to significantly decrease total number of cells staining positive for the endothelial cell marker CD31 or for the Ki67 marker of cellular proliferation and increase the number of apoptotic (TUNEL positive) tumor cells (P < 0.001). Studies addressing the toxicity of alpha-TEA demonstrated that alpha-TEA formulated in liposomes and delivered by aerosol (72 microg/mouse/day) or gavage (5 mg/mouse/day) for 25 days did not cause blood, liver, or kidney toxicity. In conclusion, sequential inhalation delivery of liposomal-formulated paclitaxel and alpha-TEA produces significantly better anti-tumor outcomes than single treatments.

Manatees (Trichechus manatus latirostris) are afflicted with inflammatory and infectious disease secondary to human interaction, such as boat strike and entanglement, as well as "cold stress syndrome" and pneumonia. White-blood-cell count and fever, primary indicators of systemic inflammation in most species, are insensitive in diagnosing inflammatory disease in manatees. Acute phase-response proteins, such as haptoglobin and serum amyloid A, have proven to be sensitive measures of inflammation/infection in domestic large animal species. This study assessed diagnosis of generalized inflammatory disease by different methods including total white-blood-cell count, albumin: globulin ratio, gel electrophoresis analysis, C-reactive protein, alpha, acid glycoprotein, haptoglobin, fibrinogen, and serum amyloid A. Samples were collected from 71 apparently healthy and 27 diseased animals during diagnostic medical examination. Serum amyloid A, measured by ELISA, followed by albumin:globulin ratio, measured by plasma gel electrophoresis, were most sensitive in diagnosing inflammatory disease, with diagnostic sensitivity and specificity of approximately 90%. The reference interval for serum amyloid A is <10-50 microg/ml with an equivocal interval of 51-70 microg/ml. The reference interval for albumin:globulin ratio by plasma gel electrophoresis is 0.7-1.1. Albumin: globulin ratio, calculated using biochemical techniques, was not accurate due to overestimation of albumin by bromcresol green dye-binding methodology. Albumin:globulin ratio, measured by serum gel electrophoresis, has a low sensitivity of 15% due to the lack of fibrinogen in the sample. Haptoglobin, measured by hemoglobin titration, had a reference interval of 0.4-2.4 mg/ml, a diagnostic sensitivity of 60%, and a diagnostic specificity of 93%. The haptoglobin assay is significantly affected by hemolysis. Fibrinogen, measured by heat precipitation, has a reference interval of 100-400 mg/dl, a diagnostic sensitivity of 40%, and a diagnostic specificity of 95%.

A nonhydrolyzable ether analogue of RRR-alpha-tocopherol, 2,5,7,8-tetramethyl-2R-(4R, 8R, 12-trimethyltridecyl)chroman-6-yloxyacetic acid, called RRR-alpha-tocopheryloxyacetic acid or RRR-alpha-tocopherol ether-linked acetic acid analogue (alpha-TEA), exhibits antitumor activity in vitro and in vivo using a syngeneic BALB/c mouse mammary tumor model (line 66 clone 4 stably transfected with green fluorescent protein). Treatment of cells with 5, 10, and 20 micro g/ml alpha-TEA for 3 days produced 6, 34, and 50% apoptosis, respectively, and treatment of cells with 10 micro g/ml for 2, 3, 4, and 5 days produced 20, 35, 47, and 58% apoptosis, respectively. A liposomal formulation of alpha-TEA administered by aerosol reduced s.c. tumor growth and lung metastasis. Alpha-TEA-treated animals showed a significant decrease in tumor volumes over 17 days of aerosol treatment (P < 0.001). Forty percent of aerosol as well as untreated control mice had visible, macroscopic lung metastases versus none (0%) of the alpha-TEA-treated mice. On the basis of fluorescence microscopic examination of the surface (top and bottom) of flattened whole left lung lobes, an average of 60 +/- 15 and 102 +/- 17 versus 11 +/- 4 fluorescent microscopic metastases was observed in aerosol control and untreated control versus alpha-TEA-treated animals, respectively. Alpha-TEA formulated in ethanol + peanut oil (5 mg/mouse/day) delivered by gavage did not reduce s.c. primary tumor burden; however, fluorescent microscopic lung metastases were significantly reduced (P < 0.0021). In summary, alpha-TEA formulated in liposomes and delivered by aerosol is a potent antitumor agent and reduces lung metastasis.