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

Absence of intestinal PPARγ aggravates acute infectious colitis in mice through a lipocalin-2-dependent pathway.

To be able to colonize its host, invading Salmonella enterica serovar Typhimurium must disrupt and severely affect host-microbiome homeostasis. Here we report that S. Typhimurium induces acute infectious colitis by inhibiting peroxisome proliferator-activated receptor gamma (PPARγ) expression in intestinal epithelial cells. Interestingly, this PPARγ down-regulation by S. Typhimurium is independent of TLR-4 signaling but triggers a marked elevation of host innate immune response genes, including that encoding the antimicrobial peptide lipocalin-2 (Lcn2). Accumulation of Lcn2 stabilizes the metalloproteinase MMP-9 via extracellular binding, which further aggravates the colitis. Remarkably, when exposed to S. Typhimurium, Lcn2-null mice exhibited a drastic reduction of the colitis and remained protected even at later stages of infection. Our data suggest a mechanism in which S. Typhimurium hijacks the control of host immune response genes such as those encoding PPARγ and Lcn2 to acquire residence in a host, which by evolution has established a symbiotic relation with its microbiome community to prevent pathogen invasion

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

Early Weight Gain in Infants With Cleft Lip and Palate Treated With and Without Nasoalveolar Molding: A Retrospective Study.

OBJECTIVE:: To assess weight gain of infants with cleft lip and/or palate (CL ± P) treated with nasoalveolar molding (NAM). DESIGN:: Retrospective, case-control chart review. SETTING:: Doernbecher Children\u27s Hospital, Oregon Health & Science University, Portland, Oregon. PATIENTS, PARTICIPANTS:: Infants with nonsyndromic CL ± P and noncleft controls. INTERVENTIONS:: Prior to primary lip surgery, NAM was either included (+NAM) or not included (-NAM) in the cleft treatment protocol. MAIN OUTCOME MEASURE(S):: Weight gain and percentage weight gain relative to initial weight were compared among +NAM, -NAM, and control groups from birth to 7 months and from birth to 36 months. RESULTS:: Comparing +NAM and -NAM groups, no significant difference in weight or percentage weight gain was found in either time window. Compared to controls, from birth to 7 months, both CL ± P groups weighed less ( P \u3c .001), while percentage weight gain was greater for the +NAM ( P \u3c .001) and did not differ for -NAM. From birth to 36 months relative to controls, weight for +NAM showed no significant difference and -NAM weighed less ( P \u3c .01), while percentage weight gain was greater for both CL ± P groups ( P \u3c .001). CONCLUSIONS:: Comparisons of CL ± P infants treated with and without NAM showed that with the NAM appliance, despite its added complexity, there was no adverse impact on weight gain. Comparisons to noncleft, control infants suggests that NAM treatment may have a beneficial impact on weight gain

Measurement and comparison of bracket transfer accuracy of five indirect bonding techniques

OBJECTIVE: To measure and compare bracket transfer accuracy of five indirect bonding (IDB) techniques. MATERIALS AND METHODS: Five IDB techniques were studied: double polyvinyl siloxane (double-PVS), double vacuum-form (double-VF), polyvinyl siloxane vacuum-form (PVS-VF), polyvinyl siloxane putty (PVS-putty), and single vacuum-form (single-VF). Brackets were bonded on 25 identical stone working models. IDB trays were fabricated over working models (n  =  5 per technique) to transfer brackets to another 25 identical stone patient models. The mesiodistal (M-D), occlusogingival (O-G), and faciolingual (F-L) positions of each bracket were measured on the working and patient models using digital photography (M-D, O-G) and calipers (F-L). Paired t-tests were used to compare bracket positions between working and patient models, and analysis of variance was used to compare bracket transfer accuracy among the five techniques. RESULTS: Between the working and patient models, double-VF had the most teeth with significant differences (n  =  6) and PVS-VF the fewest (n  =  1; P < .05). With one exception, all significant differences were ≤0.26 mm and most (65%) were ≤0.13 mm. When the techniques were compared, bracket transfer accuracy was similar for double-PVS, PVS-putty, and PVS-VF, whereas double-VF and single-VF showed significantly less accuracy in the O-G direction. CONCLUSIONS: Although overall differences in bracket position were relatively small, silicone-based trays had consistently high accuracy in transferring brackets, whereas methods that exclusively used vacuum-formed trays were less consistent