Obesity as predictive factor of periodontal therapy clinical outcomes: A cohort study

AIM: The study aim was to investigate the predictive role of obesity on clinical response following non-surgical periodontal therapy in individuals with severe periodontitis. METHODS: 57 BMI obese and 58 BMI normal non-smoker adults with periodontitis (defined as probing pocket depths (PPD) of ≥5 mm and alveolar bone loss of >30% with >50% of the teeth affected) received non-surgical periodontal therapy. Periodontal status was based upon PPD, clinical attachment level(CAL), and full mouth bleeding score(FMBS). Mean PPD, percentage sites PPD>4mm, percentage sites PPD>5mm, and FMBS at 2 and 6 months were outcome variables. Propensity score analysis was used to assess the effect of obesity on outcome variables after adjusting for confounders. RESULTS: Statistically significant higher clinical measures (mean PPD, mean percentage of sites with PPD>4mm, mean percentage of sites with PPD>5mm, and FMBS) were observed in the obese group than the normal group at baseline, 2 and 6 months after therapy(p4mm(p5mm(p<0.05), and FMBS (p<0.01), independent of age, gender, ethnicity or plaque levels. CONCLUSIONS: Obesity compared to normal BMI status was an independent predictor of poorer response following non-surgical periodontal therapy

Effect of treatment of periodontitis on incretin axis in obese and non-obese individuals: A cohort study

CONTEXT: Periodontitis confers an increased risk of developing type 2 diabetes and, in patients with obesity, it might interfere with the incretin axis. The effect of periodontal treatment on glucoregulatory hormones remains unknown. OBJECTIVE: To evaluate the effect of periodontal treatment on incretin axis in obese and lean non-diabetic individuals. SETTING: King's College Dental Hospital and Institute, London, UK. PARTICIPANTS AND METHODS: The metabolic profile of obese and BMI-normal individuals affected by periodontitis was studied at baseline, 2 and 6 months after intensive periodontal treatment, by measuring plasma insulin, glucagon, GLP-1 and GIP and markers of systemic inflammation and oxidative stress. MAIN OUTCOME MEASURE(S): Circulating levels of incretins and inflammatory markers. RESULTS: At baseline, periodontal parameters were worse for obese than non-obese; this was accompanied by higher levels of circulating hs-CRP, insulin and GLP-1. The response to periodontal treatment was less favourable in the obese group, without significant variations of hs-CRP or malondialdehyde. Gluco-regulatory hormones changed differently after treatment: while insulin and glucagon did not vary at 2 and 6 months, GLP-1 and GIP significantly increased at 6 months in both groups. In particular, GLP-1 increased more rapidly in obese participants, while the increase of GIP followed similar trends across visits in both groups. CONCLUSIONS: Nonsurgical treatment of periodontitis is associated with increased GLP-1 and GIP levels in non-obese and obese patients; changes in GLP-1 were more rapid in obese participants. This might have positive implications for the metabolic risk of these individuals

HOX transcription factors are potential targets and markers in malignant mesothelioma

YesBackground The HOX genes are a family of homeodomain-containing transcription factors that determine cellular identity during development and which are dys-regulated in some cancers. In this study we examined the expression and oncogenic function of HOX genes in mesothelioma, a cancer arising from the pleura or peritoneum which is associated with exposure to asbestos. Methods We tested the sensitivity of the mesothelioma-derived lines MSTO-211H, NCI-H28, NCI-H2052, and NCI-H226 to HXR9, a peptide antagonist of HOX protein binding to its PBX co-factor. Apoptosis was measured using a FACS-based assay with Annexin, and HOX gene expression profiles were established using RT-QPCR on RNA extracted from cell lines and primary mesotheliomas. The in vivo efficacy of HXR9 was tested in a mouse MSTO-211H flank tumor xenograft model. Results We show that HOX genes are significantly dysregulated in malignant mesothelioma. Targeting HOX genes with HXR9 caused apoptotic cell death in all of the mesothelioma-derived cell lines, and prevented the growth of mesothelioma tumors in a mouse xenograft model. Furthermore, the sensitivity of these lines to HXR9 correlated with the relative expression of HOX genes that have either an oncogenic or tumor suppressive function in cancer. The analysis of HOX expression in primary mesothelioma tumors indicated that these cells could also be sensitive to the disruption of HOX activity by HXR9, and that the expression of HOXB4 is strongly associated with overall survival. Conclusion HOX genes are a potential therapeutic target in mesothelioma, and HOXB4 expression correlates with overall survival.The authors gratefully acknowledge the support of the British Lung Foundation, grant number ICAPPG10-1. KJH acknowledges support from the ICR/RM NIHR Biomedical Research Centre

Species of Cercospora associated with grey leaf spot of maize

Grey leaf spot is a serious yield-reducing disease of maize (Zea mays) in many parts of the world where this crop is cultivated. The causal organism associated with the disease is Cercospora zeae-maydis. Two potential sibling species have been recognized as Groups I and II. The DNA sequences for the internal transcribed spacers (ITS1 & ITS2), the 5.8S rRNA gene, elongation factor 1-α, histone H3, actin and calmodulin gene regions suggest that Groups I and II are two distinct species. Furthermore, Cercospora zeae-maydis (Group I) can be distinguished from C. zeina sp. nov. (Group II) by its faster growth rate on artificial media, the ability to produce cercosporin, longer conidiophores, and broadly fusiform conidia. A PCR-based test that distinguishes the two species was developed using species-specific primers designed from the histone H3 gene

Evaluating clinical utility of subgingival and salivary endotoxin activity levels as periodontal biomarkers.

OBJECTIVES: The use of periodontal biomarkers for identification and monitoring of unique patient populations could foster better stratification of at-risk groups, increase access to treatment for those most in need, facilitate preventive measures and improve personalised care plans. The aim of this study was to examine the diagnostic and prognostic utility of oral lipopolysaccharides as bacterially-derived periodontal biomarkers. METHODS: Periodontal parameters were recorded, and saliva and subgingival plaque samples were collected at the beginning of the study from periodontally healthy volunteers and periodontitis patients, and three months after completion of conventional periodontal treatment in the periodontitis group. Endotoxin activity in the samples was measured using the recombinant factor C assay. Associations between clinical periodontal parameters and subgingival and salivary endotoxin activities were analysed using a multivariate regression model, while the ROC curve was applied to estimate the sensitivity, specificity and c-statistics for salivary and subgingival endotoxin activities as diagnostic biomarkers for periodontitis. RESULTS: Significant correlations were found between subgingival endotoxin activities, probing pocket depth and periodontal diagnosis, which were independent from patients' age, gender and smoking status. In addition, subgingival endotoxin levels had high specificity and sensitivity in detecting periodontal health and disease (0.91 and 0.85 respectively). Salivary endotoxin activity was positively associated with periodontal diagnosis, mean probing pocket depth, percentages of sites over 4 mm and full mouth bleeding score. However, it was inferior in discriminating patients with stable periodontium from those with periodontitis (sensitivity = 0.69, specificity = 0.61) compared to subgingival endotoxin activity. CONCLUSIONS: Subgingival endotoxin activity has good diagnostic and prognostic values as a site-specific periodontal biomarker and is not influenced by the patient's age, gender or smoking status. In contrast, salivary endotoxin activity, as a patient-level biomarker, is dependent on patient's age, has poorer diagnostic and prognostic capability, but shows good correlations with disease susceptibility and both its extent and severity

Efficacy and safety of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor in patients with stage IIIB/C and IVM1a melanoma: subanalysis of the Phase III OPTiM trial

Objectives: Talimogene laherparepvec is the first oncolytic immunotherapy to receive approval in Europe, the USA and Australia. In the randomized, open-label Phase III OPTiM trial (NCT00769704), talimogene laherparepvec significantly improved durable response rate (DRR) versus granulocyte-macrophage colony-stimulating factor (GM-CSF) in 436 patients with unresectable stage IIIB-IVM1c melanoma. The median overall survival (OS) was longer versus GM-CSF in patients with earlier-stage melanoma (IIIB-IVM1a). Here, we report a detailed subgroup analysis of the OPTiM study in patients with IIIB-IVM1a disease. Patients and methods: The patients were randomized (2:1 ratio) to intralesional talimogene laherparepvec or subcutaneous GM-CSF and were evaluated for DRR, overall response rate (ORR), OS, safety, benefit-risk and numbers needed to treat. Descriptive statistics were used for subgroup comparisons. Results: Among 249 evaluated patients with stage IIIB-IVM1a melanoma, DRR was higher with talimogene laherparepvec compared with GM-CSF (25.2% versus 1.2%; P < 0.0001). ORR was also higher in the talimogene laherparepvec arm (40.5% versus 2.3%; P < 0.0001), and 27 patients in the talimogene laherparepvec arm had a complete response, compared with none in GM-CSF-treated patients. The incidence rates of exposure-adjusted adverse events (AE) and serious AEs were similar with both treatments. Conclusion: The subgroup of patients with stage IIIB, IIIC and IVM1a melanoma (57.1% of the OPTiM intent-to-treat population) derived greater benefit in DRR and ORR from talimogene laherparepvec compared with GM-CSF. Talimogene laherparepvec was well tolerated

Extended thromboprophylaxis with betrixaban in acutely ill medical patients

BACKGROUND: Patients with acute medical illnesses are at prolonged risk for venous thrombosis. However, the appropriate duration of thromboprophylaxis remains unknown. METHODS: Patients who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (at a dose of 40 mg once daily) for 10±4 days plus oral betrixaban placebo for 35 to 42 days or subcutaneous enoxaparin placebo for 10±4 days plus oral betrixaban (at a dose of 80 mg once daily) for 35 to 42 days. We performed sequential analyses in three prespecified, progressively inclusive cohorts: patients with an elevated d-dimer level (cohort 1), patients with an elevated d-dimer level or an age of at least 75 years (cohort 2), and all the enrolled patients (overall population cohort). The statistical analysis plan specified that if the between-group difference in any analysis in this sequence was not significant, the other analyses would be considered exploratory. The primary efficacy outcome was a composite of asymptomatic proximal deep-vein thrombosis and symptomatic venous thromboembolism. The principal safety outcome was major bleeding. RESULTS: A total of 7513 patients underwent randomization. In cohort 1, the primary efficacy outcome occurred in 6.9% of patients receiving betrixaban and 8.5% receiving enoxaparin (relative risk in the betrixaban group, 0.81; 95% confidence interval [CI], 0.65 to 1.00; P=0.054). The rates were 5.6% and 7.1%, respectively (relative risk, 0.80; 95% CI, 0.66 to 0.98; P=0.03) in cohort 2 and 5.3% and 7.0% (relative risk, 0.76; 95% CI, 0.63 to 0.92; P=0.006) in the overall population. (The last two analyses were considered to be exploratory owing to the result in cohort 1.) In the overall population, major bleeding occurred in 0.7% of the betrixaban group and 0.6% of the enoxaparin group (relative risk, 1.19; 95% CI, 0.67 to 2.12; P=0.55). CONCLUSIONS: Among acutely ill medical patients with an elevated d-dimer level, there was no significant difference between extended-duration betrixaban and a standard regimen of enoxaparin in the prespecified primary efficacy outcome. However, prespecified exploratory analyses provided evidence suggesting a benefit for betrixaban in the two larger cohorts. (Funded by Portola Pharmaceuticals; APEX ClinicalTrials.gov number, NCT01583218.)

Overcoming data scarcity of Twitter: using tweets as bootstrap with application to autism-related topic content analysis

Notwithstanding recent work which has demonstrated the potential of using Twitter messages for content-specific data mining and analysis, the depth of such analysis is inherently limited by the scarcity of data imposed by the 140 character tweet limit. In this paper we describe a novel approach for targeted knowledge exploration which uses tweet content analysis as a preliminary step. This step is used to bootstrap more sophisticated data collection from directly related but much richer content sources. In particular we demonstrate that valuable information can be collected by following URLs included in tweets. We automatically extract content from the corresponding web pages and treating each web page as a document linked to the original tweet show how a temporal topic model based on a hierarchical Dirichlet process can be used to track the evolution of a complex topic structure of a Twitter community. Using autism-related tweets we demonstrate that our method is capable of capturing a much more meaningful picture of information exchange than user-chosen hashtags.Comment: IEEE/ACM International Conference on Advances in Social Networks Analysis and Mining, 201