Some modifiable risk factors for dementia are closely related to oral health. Although eating and speaking abilities are fundamental oral functions, limited studies have focused on the effect of malnutrition and lack of social interaction between oral health and dementia. We investigated the mediating effects of nutritional and social factors on the association between the number of teeth and the incidence of dementia. This 6-y cohort study used data from the Japan Gerontological Evaluation Study targeting older adults aged 65 y and above. The number of teeth (exposure) and covariates in 2010 (baseline survey), mediators (weight loss, vegetable and fruit intake, homeboundness, social network) in 2013, and the onset of dementia (outcome) between 2013 and 2016 were obtained. The Karlson–Holm–Breen mediation method was applied. A total of 35,744 participants were included (54.0% women). The mean age at baseline was 73.1 ± 5.5 y for men and 73.2 ± 5.5 y for women. A total of 1,776 participants (5.0%) had dementia during the follow-up period. There was a significant total effect of the number of teeth on the onset of dementia (hazard ratio, 1.14; 95% CI, 1.01–1.28). Controlling for nutritional and social mediators, the effect of the number of teeth was reduced to 1.10 (95% CI, 0.98–1.25), leaving an indirect effect of 1.03 (95% CI, 1.02–1.04). In the sex-stratified analysis, the proportion mediated by weight loss was 6.35% for men and 4.07% for women. The proportions mediated by vegetable and fruit intake and homeboundness were 4.44% and 4.83% for men and 8.45% and 0.93% for women, respectively. Furthermore, the proportion mediated by social networks was 13.79% for men and 4.00% for women. Tooth loss was associated with the onset of dementia. Nutritional and social factors partially mediated this association.

The complete nucleotide sequence of pKDSC50, a large virulence plasmid from Salmonella enterica serovar Choleraesuis strain RF-1, has been determined. We identified 48 of the open reading frames (ORFs) encoded by the 49,503-bp molecule. pKDSC50 encodes a known virulence-associated operon, the spv operon, which is composed of genes essential for systemic infection by nontyphoidal Salmonella. Analysis of the genetic organization of pKDSC50 suggests that the plasmid is composed of several virulence-associated genes, which include the spvRABCD genes, plasmid replication and maintenance genes, and one insertion sequence element. A second virulence-associated region including the pef (plasmid-encoded fimbria) operon and rck (resistance to complement killing) gene, which has been identified on the virulence plasmid of S. enterica serovar Typhimurium, was absent. Two different replicon regions, similar to the RepFIIA and RepFIB replicons, were found. Both showed high similarity to those of the pO157 plasmid of enterohemorrhagic Escherichia coli O157:H7 and the enteropathogenic E. coli ( Plasmid-encoded gene products are required for full expression of virulence in many enteropathogenic bacteria, including those of the genera Shigella (53, 54) and Yersina (17,20), as well as Salmonella (12,33,35,47,56). Nontyphoidal Salmonella serovars are important agents of gastroenteritis and can cause systemic infection, such as bacteremia (septicemia), in animals and humans. Many of these serotypes typically carry large plasmids which are essential to the production of systemic infection in animal models (21,23). Although the virulence plasmids of these Salmonella strains are variable in size, ranging from 50 to 94 kb, their distribution is dependent on the serotype. For example, S. enterica serovar Choleraesuis, S. enterica serovar Enteritidis, S. enterica serovar Dublin, S. enterica serovars Gallinarum and Pullorum, and S. enterica serovar Typhimurium harbor the 50-, 60-, 80-, 90-, and 94-kb virulence plasmids, respectively.Strains of serovar Typhimurium cured of the virulence plasmid are strongly attenuated in their subsequent spreading infection to the mesenteric lymph nodes, spleen, and liver (23), while the presence of the virulence plasmid of Salmonella does not appear to be required for bacterial adherence to and invasion of cultured eukaryotic cells or for colonization of the cecum or invasion of Peyer's patches in the mouse (24, 42). All of these virulence plasmids contain a highly conserved 8-kb region, which contains the spv (Salmonella plasmid virulence) locus that can confer complete virulence on a strain of serovar Typhimurium cured of the plasmid (25).The spv region consists of spvR, a gene that encodes a transcriptional factor of the LysR family, and the spvABCD operon of structural genes (1,2,22,25,37). The spv operon is required for the systemic phase of disease in specific hosts, i.e., serovar Choleraesuis in pigs (15), serovar Dublin in cattle (39, 61), serovars Gallinarum and Pullorum in fowl (5, 6), and serova...

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We have isolated and sequenced several cDNAs derived from the sea squirt Ciona intestinalis that encode vitamin K-dependent proteins. Four of these encode ␥-carboxyglutamic acid (Gla) domain-containing proteins, which we have named Ci-Gla1 through Ci-Gla4. Two additional cDNAs encode the apparent orthologs of ␥-glutamyl carboxylase and vitamin K epoxide reductase. Ci-Gla1 undergoes ␥-glutamyl carboxylation when expressed in CHO cells and is homologous to Gla-RTK, a putative receptor tyrosine kinase previously identified in a related ascidian. The remaining three Gla domain proteins are similar to proteins that participate in fundamental developmental processes, complement regulation, and blood coagulation. These proteins are generally expressed at low levels throughout development and exhibit either relatively constant expression (Ci-Gla1, ␥-glutamyl carboxylase, and vitamin K epoxide reductase) or spatiotemporal regulation (Ci-Gla2, -3, and -4). These results demonstrate the evolutionary emergence of the vitamin K-dependent Gla domain before the divergence of vertebrates and urochordates and suggest novel functions for Gla domain proteins distinct from their roles in vertebrate hemostasis. In addition, these findings highlight the usefulness of C. intestinalis as a model organism for investigating vitamin K-dependent physiological phenomena, which may be conserved among the chordate subphyla.ascidian ͉ ␥-carboxyglutamic acid ͉ urochordate ͉ warfarin

Objectives Weight loss is a critical health issue in older adults. Oral function is essential for nutrient intake and can be restored using dental prosthetic treatments in patients with tooth loss. This study aimed to investigate the relationship between tooth loss and weight loss among the older adults and to evaluate the magnitude of its risk reduction by dental prosthetic treatment. Design Three‐year follow‐up longitudinal study based on a self‐reported questionnaire. Setting Community‐dwelling older adults in Japan. Participants Adults aged 65 and older (n = 53,690). Measurements We used >10% weight loss during follow‐up, the number of remaining teeth, and the use of dental prostheses as the outcome variable, exposure variable, and mediator, respectively. We fitted the logistic regression model including possible confounders and calculated the odds ratios (ORs) and 95% confidence intervals (95% CIs) of the controlled direct effect (CDE) at the level of use or nonuse of the dental prosthesis based on a causal mediation analysis framework. Additionally, we calculated the proportion eliminated by the dental prosthesis. Results The mean age of participants was 72.6 years (1 SD = 5.5), and 47.4% were males. About 5.8% (n = 3132) of them experienced >10% weight loss during the follow‐up. Weight loss was observed in 6.8% of the participants with 0–19 remaining teeth and in 4.3% of them with ≥20 remaining teeth. The CDE of 0–19 remaining teeth was greater when no one used dental prosthesis (OR = 1.41; 95% CI = 1.26–1.59) compared with that when all participants used dental prosthesis (OR = 1.26; 95% CI = 1.08–1.46). This indicated that dental prosthesis decreased the risk of weight loss by 37.3%. Conclusion Our study revealed that tooth loss increased the risk of clinically critical levels of weight loss among community‐dwelling older adults. However, this risk was reduced by dental prosthetic treatment.