Oral Condition and Incident Coronary Heart Disease: A Clustering Analysis

Poor oral health has been linked to coronary heart disease (CHD). Clustering clinical oral conditions routinely recorded in adults may identify their CHD risk profile. Participants from the Paris Prospective Study 3 received, between 2008 and 2012, a baseline routine full-mouth clinical examination and an extensive physical examination and were thereafter followed up every 2 y until September 2020. Three axes defined oral health conditions: 1) healthy, missing, filled, and decayed teeth; 2) masticatory capacity denoted by functional masticatory units; and 3) gingival inflammation and dental plaque. Hierarchical cluster analysis was performed with multivariate Cox proportional hazards regression models and adjusted for age, sex, smoking, body mass index, education, deprivation (EPICES score; Evaluation of Deprivation and Inequalities in Health Examination Centres), hypertension, type 2 diabetes, LDL and HDL serum cholesterol (low- and high-density lipoprotein), triglycerides, lipid-lowering medications, NT-proBNP and IL-6 serum level. A sample of 5,294 participants (age, 50 to 75 y; 37.10% women) were included in the study. Cluster analysis identified 3,688 (69.66%) participants with optimal oral health and preserved masticatory capacity (cluster 1), 1,356 (25.61%) with moderate oral health and moderately impaired masticatory capacity (cluster 2), and 250 (4.72%) with poor oral health and severely impaired masticatory capacity (cluster 3). After a median follow-up of 8.32 y (interquartile range, 8.00 to 10.05), 128 nonfatal incident CHD events occurred. As compared with cluster 1, the risk of CHD progressively increased from cluster 2 (hazard ratio, 1.45; 95% CI, 0.98 to 2.15) to cluster 3 (hazard ratio, 2.47; 95% CI, 1.34 to 4.57; P < 0.05 for trend). To conclude, middle-aged individuals with poor oral health and severely impaired masticatory capacity have more than twice the risk of incident CHD than those with optimal oral health and preserved masticatory capacity (ClinicalTrials.gov NCT00741728)

Phenotypic microarrays suggest Escherichia coli ST131 is not a metabolically distinct lineage of extra-intestinal pathogenic E. coli

Extraintestinal pathogenic E. coli (ExPEC) are the major aetiological agent of urinary tract infections (UTIs) in humans. The emergence of the CTX-M producing clone E. coli ST131 represents a major challenge to public health worldwide. A recent study on the metabolic potential of E. coli isolates demonstrated an association between the E. coli ST131 clone and enhanced utilisation of a panel of metabolic substrates. The studies presented here investigated the metabolic potential of ST131 and other major ExPEC ST isolates using 120 API test reagents and found that ST131 isolates demonstrated a lower metabolic activity for 5 of 120 biochemical tests in comparison to non-ST131 ExPEC isolates. Furthermore, comparative phenotypic microarray analysis showed a lack of specific metabolic profile for ST131 isolates countering the suggestion that these bacteria are metabolically fitter and therefore more successful human pathogens

Association of hearing impairment with incident depressive symptoms: a community-based prospective study

Objective: The aim was to investigate the potential association between hearing impairment and incident depressive symptoms.Methods: Using a prospective community-based cohort study in France (the Paris Prospective Study III), participants aged 50-75 years were recruited between 2008 and 2012 and thereafter followed up every 2 years up to 2018. Hearing impairment, measured at study recruitment by audiometry testing, was defined as a pure tone average >25 decibels in the better ear. Incident depressive symptoms, measured using the validated 13-item Questionnaire of Depression 2nd version, was assessed during follow-up. Multivariate generalized estimating equations were used to compute odds ratio (OR) and 95% confidence intervals (CI).Results: Among 7591 participants free of depressive symptoms at baseline (mean age 59.8 years, 63% of men), 14.3% had hearing impairment. Over 6 years of follow-up, 479 subjects (6.3%) had incident depressive symptoms. The OR for incident depressive symptoms was 1.36 for subjects with baseline hearing impairment (95% CI, 1.06-1.73). A pooled analysis of 4 published prospective studies yielded a multivariable relative risk of baseline hearing impairment for incident depressive symptoms of 1.29 (95% CI, 1.09-1.53).Conclusions: In this community-based prospective cohort study of participants aged 50 to 75 years, baseline hearing impairment was associated with a 36% increased odds of incident depressive symptoms

Carotid artery stiffness and incident depressive symptoms: The Paris Prospective Study III

Background: Arterial stiffness may contribute to late-life depression via cerebral microvascular damage, but evidence is scarce. No longitudinal study has evaluated the association between arterial stiffness and risk of depressive symptoms. Therefore, we investigated the association between carotid artery stiffness and incident depressive symptoms in a large community-based cohort study.Methods: This longitudinal study included 7013 participants (mean age 59.7 ± 6.3 years; 35.8% women) free of depressive symptoms at baseline. Carotid artery stiffness (high-resolution echo tracking) was determined at baseline. Presence of depressive symptoms was determined at baseline and at 4 and 6 years of follow-up, and was defined as a score ≥7 on the validated Questionnaire of Depression, Second Version, Abridged and/or new use of antidepressant medication. Logistic regression and generalized estimating equations were used.Results: In total, 6.9% (n = 484) of the participants had incident depressive symptoms. Individuals in the lowest tertile of carotid distensibility coefficient (indicating greater carotid artery stiffness) compared with those in the highest tertile had a higher risk of incident depressive symptoms (odds ratio: 1.43; 95% confidence interval: 1.10-1.87), after adjustment for age, sex, living alone, education, lifestyle, cardiovascular risk factors, and baseline Questionnaire of Depression, Second Version, Abridged scores. Results were qualitatively similar when we used carotid Young's elastic modulus as a measure of carotid stiffness instead of carotid distensibility coefficient, and when we used generalized estimating equations instead of logistic regression.Conclusions: Greater carotid stiffness is associated with a higher incidence of depressive symptoms. This supports the hypothesis that carotid stiffness may contribute to the development of late-life depression

Efflux Pump, the Masked Side of ß-Lactam Resistance in Klebsiella pneumoniae Clinical Isolates

International audienceBACKGROUND: Beta-lactamase production and porin decrease are the well-recognized mechanisms of acquired beta-lactam resistance in Klebsiella pneumoniae isolates. However, such mechanisms proved to be absent in K. pneumoniae isolates that are non susceptible to cefoxitin (FOX) and susceptible to amoxicillin+clavulanic acid in our hospital. Assessing the role of efflux pumps in this beta-lactam phenotype was the aim of this study. METHODOLOGY/FINDINGS: MICs of 9 beta-lactams, including cloxacillin (CLX), and other antibiotic families were tested alone and with an efflux pump inhibitor (EPI), then with both CLX (subinhibitory concentrations) and EPI against 11 unique bacteremia K. pneumoniae isolates displaying the unusual phenotype, and 2 ATCC strains. CLX and EPI-dose dependent effects were studied on 4 representatives strains. CLX MICs significantly decreased when tested with EPI. A similar phenomenon was observed with piperacillin+tazobactam whereas MICs of the other beta-lactams significantly decreased only in the presence of both EPI and CLX. Thus, FOX MICs decreased 128 fold in the K. pneumoniae isolates but also 16 fold in ATCC strain. Restoration of FOX activity was CLX dose-dependent suggesting a competitive relationship between CLX and the other beta-lactams with regard to their efflux. For chloramphenicol, erythromycin and nalidixic acid whose resistance was also due to efflux, adding CLX to EPI did not increase their activity suggesting differences between the efflux process of these molecules and that of beta-lactams. CONCLUSION: This is the first study demonstrating that efflux mechanism plays a key role in the beta-lactam susceptibility of clinical isolates of K. pneumoniae. Such data clearly evidence that the involvement of efflux pumps in beta-lactam resistance is specially underestimated in clinical isolates

Self-reported body silhouette trajectories across the lifespan and excessive daytime sleepiness in adulthood: a retrospective analysis. The Paris Prospective Study III.

Excessive daytime sleepiness (EDS) is a common sleep complaint in the population and is increasingly recognised as deleterious for health. Simple and sensitive tools allowing identifying individuals at greater risk of EDS would be of public health importance. Hence, we determined trajectories of body silhouette from early childhood to adulthood and evaluated their association with EDS in adulthood. A retrospective analysis in a prospective community-based study. 6820 men and women self-reported their silhouette at ages 8, 15, 25, 35 and 45 using the body silhouettes proposed by Stunkard &lt;i&gt;et al&lt;/i&gt; . EDS was defined by an Epworth Sleepiness Scale score ≥11. Presence of EDS in adulthood. The study population comprised 6820 participants (mean age 59.8 years, 61.1% men). Five distinct body silhouettes trajectories over the lifespan were identified: 31.9% 'lean stable', 11.1% 'lean increase', 16.1% 'lean-marked increase', 32.5% 'moderate stable' and 8.4% 'heavy stable'. Subjects with a 'heavy-stable' trajectory (OR 1.24, 95% CI 0.94 to 1.62) and those with a 'lean-marked increase' trajectory (OR 1.46, 95% CI 1.18 to 1.81) were more likely to have EDS when compared with the 'lean-stable' group after adjusting for confounding. Further adjustment for birth weight strengthened the magnitude of the ORs. Increasing body silhouette and to a lesser extent constantly high body silhouette trajectory from childhood to adulthood are associated with increased likelihood of EDS, independently of major confounding variables. NCT00741728; Pre-results

Body Silhouette Trajectories Over the Lifespan and Insomnia Symptoms: The Paris Prospective Study 3.

Insomnia symptoms are highly prevalent and associated with several adverse medical conditions, but only few determinants, including non-modifiable ones, have been highlighted. We investigated associations between body silhouette trajectories over the lifespan and insomnia symptoms in adulthood. From a community-based study, 7 496 men and women aged 50-75 years recalled their body silhouette at age 8, 15, 25, 35 and 45, and rated the frequency of insomnia symptoms on a standardized sleep questionnaire. An Epworth Sleepiness Scale ≥11 defined excessive daytime sleepiness (EDS). Using a group-based trajectory modeling, we identified five body silhouette trajectories: a 'lean-stable' (32.7%), a 'heavy-stable' (8.1%), a 'moderate-stable' (32.5%), a 'lean-increase' (11%) and a 'lean-marked increase' (15.7%) trajectory. In multivariate logistic regression, compared to the 'lean-stable' trajectory, the 'lean-marked increase' and 'heavy-stable' trajectories were associated with a significant increased odd of having ≥1 insomnia symptoms as compared to none and of having a proxy for insomnia disorder (≥1 insomnia symptom and EDS). The association with the 'lean-marked increase' trajectory' was independent from body mass index measured at study recruitment. In conclusion, increasing body silhouette over the lifespan is associated with insomnia symptoms in adulthood, emphasizing the importance of weight gain prevention during the entire lifespan

Virulence Potential and Genomic Mapping of the Worldwide Clone Escherichia coli ST131

Recently, the worldwide propagation of clonal CTX-M-15-producing Escherichia coli isolates, namely ST131 and O25b:H4, has been reported. Like the majority of extra-intestinal pathogenic E. coli isolates, the pandemic clone ST131 belongs to phylogenetic group B2, and has recently been shown to be highly virulent in a mouse model, even though it lacks several genes encoding key virulence factors (Pap, Cnf1 and HlyA). Using two animal models, Caenorhabditis elegans and zebrafish embryos, we assessed the virulence of three E. coli ST131 strains (2 CTX-M-15- producing urine and 1 non-ESBL-producing faecal isolate), comparing them with five non-ST131 B2 and a group A uropathogenic E. coli (UPEC). In C. elegans, the three ST131 strains showed intermediate virulence between the non virulent group A isolate and the virulent non-ST131 B2 strains. In zebrafish, the CTX-M-15-producing ST131 UPEC isolates were also less virulent than the non-ST131 B2 strains, suggesting that the production of CTX-M-15 is not correlated with enhanced virulence. Amongst the non-ST131 B2 group isolates, variation in pathogenic potential in zebrafish embryos was observed ranging from intermediate to highly virulent. Interestingly, the ST131 strains were equally persistent in surviving embryos as the non-ST131-group B2 strains, suggesting similar mechanisms may account for development of persistent infection. Optical maps of the genome of the ST131 strains were compared with those of 24 reference E. coli strains. Although small differences were seen within the ST131 strains, the tree built on the optical maps showed that these strains belonged to a specific cluster (86% similarity) with only 45% similarity with the other group B2 strains and 25% with strains of group A and D. Thus, the ST131 clone has a genetic composition that differs from other group B2 strains, and appears to be less virulent than previously suspected