Modulation of hepatic PPAR expression during Ft LVS LPS-induced protection from Francisella tularensis LVS infection

<p>Abstract</p> <p>Background</p> <p>It has been shown previously that administration of <it>Francisella tularensis </it>(<it>Ft</it>) Live Vaccine Strain (LVS) lipopolysaccharide (LPS) protects mice against subsequent challenge with <it>Ft </it>LVS and blunts the pro-inflammatory cytokine response.</p> <p>Methods</p> <p>To further investigate the molecular mechanisms that underlie <it>Ft </it>LVS LPS-mediated protection, we profiled global hepatic gene expression following <it>Ft </it>LVS LPS or saline pre-treatment and subsequent <it>Ft </it>LVS challenge using Affymetrix arrays.</p> <p>Results</p> <p>A large number of genes (> 3,000) were differentially expressed at 48 hours post-infection. The degree of modulation of inflammatory genes by infection was clearly attenuated by pre-treatment with <it>Ft </it>LVS LPS in the surviving mice. However, <it>Ft </it>LVS LPS alone had a subtle effect on the gene expression profile of the uninfected mice. By employing gene set enrichment analysis, we discovered significant up-regulation of the fatty acid metabolism pathway, which is regulated by peroxisome proliferator activated receptors (PPARs).</p> <p>Conclusions</p> <p>We hypothesize that the LPS-induced blunting of pro-inflammatory response in mouse is, in part, mediated by PPARs (α and γ).</p

An In Vivo and Cone Beam Computed Tomography Investigation of the Accuracy in Measuring Alveolar Bone Height and Detecting Dehiscence and Fenestration Defects.

PURPOSE: To investigate cone beam computed tomography (CBCT) accuracy in measuring facial bone height and detecting dehiscence and fenestration defects around teeth. MATERIALS AND METHODS: Patients who were treatment planned for periodontal flap or dental implant surgeries were enrolled (n = 25). CBCT imaging (Carestream CS 9300) was obtained at 0.09-mm voxels (n = 10 patients, 23 teeth) and at 0.18-mm voxels (n = 15 patients, 33 teeth). Facial bone height measurements, from cusp tip to crest of bone height along the long axis of the tooth, and presence or absence of dehiscence or fenestration defects were recorded from CBCT images in triplicates independently by two examiners. The corresponding clinical measurements were made at the time of surgery. Comparisons of CBCT and clinical measurements were made using paired t tests for teeth: anterior and posterior, maxillary and mandibular, with or without restorations, or root canal therapy. Level of agreement between investigators was assessed by concordance correlation coefficients (CCC), Pearson\u27s correlation coefficient (PCC), and Cohen\u27s Kappa. RESULTS: Comparing mean CBCT and clinical measurements, statistically significant differences were noted for 0.09-mm and 0.18-mm voxel sizes, for anterior and posterior teeth, for maxillary and mandibular teeth, for teeth with or without restorations, and for teeth without root canal therapy (P \u3c .05). Clinical and CBCT measurements were similar for teeth with crowns and with root canal therapy (P \u3e .05). CBCT measurements underestimated mean facial bone height from 0.33 ± 0.78 to 0.88 ± 1.14 mm (mean ± SD) and absolute facial bone height values from 0.56 ± 0.35 to 1.08 ± 0.92 mm. Intraexaminer and interexaminer reliability for measuring facial bone height ranged from poor to substantial (PCC = 0.78 to 0.97 and CCC = 0.63 to 0.96, respectively). Interexaminer reliability for detection of dehiscence and fenestration defects ranged from poor to moderate (Cohen\u27s Kappa = -0.09 to 0.66). CONCLUSION: CBCT imaging underestimated facial bone height and overestimated the presence of dehiscence and fenestration defects

Outcome assessment of orthodontic clear aligner vs fixed appliance treatment in a teenage population with mild malocclusions.

OBJECTIVE: To assess the efficacy and efficiency of treatment in adolescents presenting with mild malocclusions, comparing outcomes using clear aligners to fixed appliances. MATERIALS AND METHODS: Patients identified retrospectively and consecutively from one private practice had been treated with either clear aligners (Invisalign, Align Technology, Santa Clara, Calif) or fixed appliances (0.022 Damon, Ormco, Orange, Calif; n = 26/group). Assessments of occlusion were made using the American Board of Orthodontics Discrepancy Index (DI) for initial records and Cast-Radiograph Evaluation (CRE) for final records. Number of appointments, number of emergency visits, and overall treatment time were determined from chart reviews. Data were analyzed using Pearson\u27s correlation, Wilcoxon rank tests, unpaired t-tests, and Chi-square tests, with significance set to P ≤ .05. RESULTS: Pretreatment, the aligner and fixed groups showed no significant difference in overall severity (DI: 11.9 ± 5.3 vs 11.6 ± 4.8) or in any individual DI category. Posttreatment scores showed finishes for the aligner group had fewer discrepancies from ideal relative to the fixed appliance group (CRE: 30.1 ± 8.3 vs 37.0 ± 9.3; P \u3c .01). Patients treated with aligners had fewer appointments (13.7 ± 4.4 vs 19.3 ± 3.6; P \u3c .0001), fewer emergency visits (0.8 ± 1.0 vs 3.6 ± 2.5; P \u3c .0001), and shorter overall treatment time (16.9 ± 5.7 vs 23.4 ± 4.4 months; P \u3c .0001). CONCLUSIONS: Outcomes for treatment of mild malocclusions in adolescents showed equivalent effectiveness of clear aligners compared to fixed appliances, with significantly improved results for clear aligner treatment in terms of tooth alignment, occlusal relations, and overjet. Assessment of the number of appointments, number of emergency visits, and overall treatment time showed better outcomes for treatment with clear aligners

Zonal expression of the thyroid hormone receptor α isoforms in rodent liver

Many metabolic processes occur simultaneously in the liver in different locations along the porto-central axis of the liver units. These processes are often regulated by hormones, one of which is thyroid hormone which for its action depends on the presence of the different isoforms of the thyroid hormone receptor (TR). These are encoded by two genes: c-erbA-alpha encoding TRalpha1 and TRalpha2 and their respective Delta isoforms, and c-erbA-beta which encodes TRbeta1, TRbeta2 and TRbeta3. We recently found a zonal (pericentral) expression of and a diurnal variation in the TRbeta1 isoform in rat liver. We were therefore also interested to see whether TRalpha1 and TRalpha2 expression showed similar characteristics. For this reason we raised both polyclonal and monoclonal antibodies against TRalpha1 and TRalpha2 isoforms and characterised these. Antibody specificity was tested using Western blots and immunohistochemistry in liver of TR isoform-specific knockout animals. Using these antibodies we found that the TRalpha1 and TRalpha2 isoforms are zonally expressed around the central vein in rat liver. The experiments show that the portal to central gradient of TRalpha1 is broader than that of TRbeta1. Moreover, the expression of the TRalpha2 protein showed a diurnal variation with a peak in the afternoon when the animals are least active whereas no such variation was found for the TRalpha1 protein.From our data it appears that both the TRalpha1 and TRalpha2 isoforms show a zonal distribution in liver. This finding, together with the observed diurnal rhythm, has major implications for interpreting and timing experiments concerning the TR and its downstream actions in live

A simplified pneumonia severity index (PSI) for clinical outcome prediction in COVID-19.

BackgroundThe Pneumonia Score Index (PSI) was developed to estimate the risk of dying within 30 days of presentation for community-acquired pneumonia patients and is a strong predictor of 30-day mortality after COVID-19. However, three of its required 20 variables (skilled nursing home, altered mental status and pleural effusion) are not discreetly available in the electronic medical record (EMR), resulting in manual chart review for these 3 factors. The goal of this study is to compare a simplified 17-factor version (PSI-17) to the original (denoted PSI-20) in terms of prediction of 30-day mortality in COVID-19.MethodsIn this retrospective cohort study, the hospitalized patients with confirmed SARS-CoV-2 infection between 2/28/20-5/28/20 were identified to compare the predictive performance between PSI-17 and PSI-20. Correlation was assessed between PSI-17 and PSI-20, and logistic regressions were performed for 30-day mortality. The predictive abilities were compared by discrimination, calibration, and overall performance.ResultsBased on 1,138 COVID-19 patients, the correlation between PSI-17 and PSI-20 was 0.95. Univariate logistic regression showed that PSI-17 had performance similar to PSI-20, based on AUC, ICI and Brier Score. After adjusting for confounding variables by multivariable logistic regression, PSI-17 and PSI-20 had AUCs (95% CI) of 0.85 (0.83-0.88) and 0.86 (0.84-0.89), respectively, indicating no significant difference in AUC at significance level of 0.05.ConclusionPSI-17 and PSI-20 are equally effective predictors of 30-day mortality in terms of several performance metrics. PSI-17 can be obtained without the manual chart review, which allows for automated risk calculations within an EMR. PSI-17 can be easily obtained and may be a comparable alternative to PSI-20