OBJECTIVES Although chronic periodontitis has been associated with Alzheimer's disease, the effect of chronic periodontitis on vascular dementia as well as the role of lifestyle behaviors such as smoking, alcohol consumption, and physical activity in this association are still unclear. DESIGN Retrospective cohort study. SETTING Population based. PARTICIPANTS The study population was derived from the Korean National Health Insurance Service‐Health Screening Cohort. Among 262 349 participants, diagnosis of chronic periodontitis was determined during 2003‐2004. MEASUREMENTS Starting from 2005, participants were followed up for overall dementia, Alzheimer's disease, and vascular dementia until 2015. Cox proportional hazards regression was used to determine the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of dementia according to chronic periodontitis. RESULTS Compared with nonchronic periodontitis participants, chronic periodontitis patients had elevated risk for overall dementia (aHR = 1.06; 95% CI = 1.01‐1.11) and Alzheimer's disease (aHR = 1.05; 95% CI = 1.00‐1.11). There was a tendency toward increased vascular dementia risk among chronic periodontitis patients (aHR = 1.10; 95% CI = 0.98‐1.22). The risk‐increasing effect of chronic periodontitis on dementia tended to be stronger among participants with healthy lifestyle behaviors including never‐smokers and those who exercised and did not consume alcohol. CONCLUSION Chronic periodontitis may be associated with a higher risk of developing dementia. Future studies that investigate whether preventing chronic periodontitis may lead to reduced risk of dementia are needed.

The constitutively expressed AcrAB multidrug efflux system of Escherichia coli shows a high degree of homology with the normally silent AcrEF system. Exposure of a strain with acrAB deleted to antibiotic selection pressure frequently leads to the insertion sequence-mediated activation of the homologous AcrEF system. In this study, we used strains constitutively expressing either AcrAB or AcrEF from their normal chromosomal locations to resolve a controversy about whether phenylalanylarginine ␤-naphthylamide (PA␤N) inhibits the activities of AcrAB and AcrEF and/or acts synergistically with antibiotics by destabilizing the outer membrane permeability barrier. Real-time efflux assays allowed a clear distinction between the efflux pump-inhibiting activity of PA␤N and the outer membrane-destabilizing action of polymyxin B nonapeptide (PMXBN). When added in equal amounts, PA␤N, but not PMXBN, strongly inhibited the efflux activities of both AcrAB and AcrEF pumps. In contrast, when outer membrane destabilization was assessed by the nitrocefin hydrolysis assay, PMXBN exerted a much greater damaging effect than PA␤N. Strong action of PA␤N in inhibiting efflux activity compared to its weak action in destabilizing the outer membrane permeability barrier suggests that PA␤N acts mainly by inhibiting efflux pumps. We concluded that at low concentrations, PA␤N acts specifically as an inhibitor of both AcrAB and AcrEF efflux pumps; however, at high concentrations, PA␤N in the efflux-proficient background not only inhibits efflux pump activity but also destabilizes the membrane. The effects of PA␤N on membrane integrity are compounded in cells unable to extrude PA␤N. IMPORTANCEThe increase in multidrug-resistant bacterial pathogens at an alarming rate has accelerated the need for implementation of better antimicrobial stewardship, discovery of new antibiotics, and deeper understanding of the mechanism of drug resistance. The work carried out in this study highlights the importance of employing real-time fluorescence-based assays in differentiating multidrug efflux-inhibitory and outer membrane-destabilizing activities of antibacterial compounds. Multidrug resistance among human bacterial pathogens remains a grave social concern. Numerous strategies have been proposed to curtail the rampant increase in multidrug resistance among human pathogens, ranging from the effective integration of pharmacokinetic and pharmacodynamic parameters and implementation of antimicrobial stewardship (1) to the development of novel antibiotics based on either an existing or a novel chemical scaffold, exploitation of new cellular targets, and directly tackling the cellular mechanisms that confer multidrug resistance (2). Efflux of antibiotics from the cell is one of the common mechanisms of antibiotic resistance in bacteria, with resistance developing when the rate of drug efflux across the membrane exceeds that of drug influx (3).Bacterial genomes encode several membrane-bound multidrug efflux systems (4, 5). These systems are usually under t...

Liver cirrhosis is a major cause of mortality and a common end of various progressive liver diseases. Since the effective treatment is currently limited to liver transplantation, stem cell-based therapy as an alternative has attracted interest due to promising results from preclinical and clinical studies. However, there is still much to be understood regarding the precise mechanisms of action. A number of stem cells from different origins have been employed for hepatic regeneration with different degrees of success. The present review presents a synopsis of stem cell research for the treatment of patients with liver cirrhosis according to the stem cell type. Clinical trials to date are summarized briefly. Finally, issues to be resolved and future perspectives are discussed with regard to clinical applications.

While 6-year-old children who had not ingested fluoridated water showed higher dft in the WF-ceased area than in the non-WF area, 11-year-old children in the WF-ceased area who had ingested fluoridated water for approximately 4 years after birth showed significantly lower DMFT than those in the non-WF area. This suggests that the systemic effect of fluoride intake through water fluoridation could be important for the prevention of dental caries.