Improving the efficiency of complete denture treatment

In Japan, the number of elderly people with missing teeth has been decreasing. However, the number of patients wearing complete denture has not decreased. Therefore, suitable complete denture adjustment for the elderly people is important. The chair time and treatment contents (medical interview, medical examination, fitting, occlusion, adjustment, denture cleaning, patient’s instruction, polishing, postoperative instruction, denture score, blank time) involved in complete denture adjustment were investigated and it is confirmed that there was a lot of patient’s and blank time. The blank time is defined as “time not engaged in treatment” for the dentist, “observation time” for the assistant, and “time sitting in the chair doing nothing” for the patient. This research aimed to clarify a treatment procedure that allows for effective use of the blank time to provide appropriate treatment to each patient. The participants included 31 patients with complete dentures, 14 dentists, and 12 less experienced dentists. Treatment timetables were created using video data. Analyses were carried out to develop a more effective treatment protocol by changing treatment procedures and contents. Issues associated with treatment were also investigated. Treatment activities and chair time during denture adjustment (57 participants) were investigated to do treatment smoothly. As a result there were 22 out of 31 patients (deficiency of the denture cleaning etc.) whose treatment activities should be improved. The results suggested that treatment procedures that allow for effective use of patient’s and less experienced dentist’s blank time to provide appreciate treatment to each patient can be clarified

Cysteine oxidation targets peroxiredoxins 1 and 2 for exosomal release through a novel mechanism of redox-dependent secretion

Non-classical protein secretion is of major importance as a number of cytokines and inflammatory mediators are secreted via this route. Current evidence indicates that there are several mechanistically distinct methods of non-classical secretion. We have recently shown that peroxiredoxin (Prdx) 1 and Prdx2 are released by various cells upon exposure to inflammatory stimuli such as LPS or TNF-α. The released Prdx then acts to induce production of inflammatory cytokines. However, Prdx1 and 2 do not have signal peptides and therefore must be secreted by alternative mechanisms as has been postulated for the inflammatory mediators IL-1β and HMGB1. We show here that circulating Prdx1 and 2 are present exclusively as disulphide-linked homodimers. Inflammatory stimuli also induce in vitro release of Prdx1 and 2 as disulfide-linked homodimers. Mutation of cysteines Cys51 or Cys172 (but not Cys70) in Prdx2, and Cys52 or Cys173 (but not Cys71 or Cys83) in Prdx1 prevented dimer formation and this was associated with inhibition of their TNF-α-induced release. Thus, the presence and oxidation of key cysteine residues in these proteins are a prerequisite for their secretion in response to TNF-α and this release can be induced with an oxidant. In contrast, the secretion of the nuclear-associated danger signal HMGB1 is independent of cysteine oxidation, as shown by experiments with a cysteine-free HMGB1 mutant. Release of Prdx1 and 2 is not prevented by inhibitors of the classical secretory pathway; instead, both Prdx1 and 2 are released in exosomes from both HEK cells and monocytic cells. Serum Prdx1 and 2 are also associated with the exosomes. These results describe a novel pathway of protein secretion mediated by cysteine oxidation that underlines the importance of redox-dependent signalling mechanisms in inflammation

Comparison of three representative subjective evaluations of chewing function

In 2018, oral hypofunction was registered officially as a disease in Japan. It is important to detect oral hypofunction symptoms early in patients, before frank oral dysfunction symptoms occur. Subjective evaluations of chewing function, which help to identify foods that cannot be chewed, might be useful in diagnosing oral hypofunction. Previous evaluations used to identify patients with oral hypofunction used varying standards, making it impossible to compare and integrate them without first developing a unified screening method. This study aimed to compare and integrate known evaluation methods that are useful for diagnosing oral hypofunction. A total of 76 elderly participants （aged ＞65 years） were enrolled after providing consent to participate in this study. The established subjective evaluation methods of chewing function investigated for this study included the Yamamoto denture performance judgment table, the Sato table for evaluation of chewing function in complete denture wearers, and the Hirai evaluation method for the masticatory function in complete denture wearers. As the Yamamoto method lacks scoring, the total number of circles was used as the score. A time study was performed on the time taken for the description, entry, and analysis of these tables. There was a strong correlation between the Sato and Hirai methods （r＝0.71） and between the Sato and Yamamoto （r＝0.68） and Hirai and Yamamoto （r＝0.60） methods. During the time study, the description time was the shortest with the Yamamoto method, and the entry and analysis times were the shortest with the Sato method. The total time was significantly shorter with the Sato method than with the Yamamoto method. Three evaluation methods showed correlation, but the examination times varied. In future studies, we plan to clarify the selection criteria, including the relevance of objective evaluation and usability

Redox proteomics of the inflammatory secretome identifies a common set of redoxins and other glutathionylated proteins released in inflammation, influenza virus infection and oxidative stress

Protein cysteines can form transient disulfides with glutathione (GSH), resulting in the production of glutathionylated proteins, and this process is regarded as a mechanism by which the redox state of the cell can regulate protein function. Most studies on redox regulation of immunity have focused on intracellular proteins. In this study we have used redox proteomics to identify those proteins released in glutathionylated form by macrophages stimulated with lipopolysaccharide (LPS) after pre-loading the cells with biotinylated GSH. Of the several proteins identified in the redox secretome, we have selected a number for validation. Proteomic analysis indicated that LPS stimulated the release of peroxiredoxin (PRDX) 1, PRDX2, vimentin (VIM), profilin1 (PFN1) and thioredoxin 1 (TXN1). For PRDX1 and TXN1, we were able to confirm that the released protein is glutathionylated. PRDX1, PRDX2 and TXN1 were also released by the human pulmonary epithelial cell line, A549, infected with influenza virus. The release of the proteins identified was inhibited by the anti-inflammatory glucocorticoid, dexamethasone (DEX), which also inhibited tumor necrosis factor (TNF)-α release, and by thiol antioxidants (N-butanoyl GSH derivative, GSH-C4, and N-acetylcysteine (NAC), which did not affect TNF-α production. The proteins identified could be useful as biomarkers of oxidative stress associated with inflammation, and further studies will be required to investigate if the extracellular forms of these proteins has immunoregulatory functions

Toll-like receptor signaling adapter proteins govern spread of neuropathic pain and recovery following nerve injury in male mice.

BackgroundSpinal Toll-like receptors (TLRs) and signaling intermediaries have been implicated in persistent pain states. We examined the roles of two major TLR signaling pathways and selected TLRs in a mononeuropathic allodynia.MethodsL5 spinal nerve ligation (SNL) was performed in wild type (WT, C57BL/6) male and female mice and in male Tlr2-/-Tlr3-/-, Tlr4-/-, Tlr5-/-, Myd88-/-, Triflps2, Myd88/Triflps2, Tnf-/-, and Ifnar1-/- mice. We also examined L5 ligation in Tlr4-/- female mice. We examined tactile allodynia using von Frey hairs. Iba-1 (microglia) and GFAP (astrocytes) were assessed in spinal cords by immunostaining. Tactile thresholds were analyzed by 1- and 2-way ANOVA and the Bonferroni post hoc test was used.ResultsIn WT male and female mice, SNL lesions resulted in a persistent and robust ipsilateral, tactile allodynia. In males with TLR2, 3, 4, or 5 deficiencies, tactile allodynia was significantly, but incompletely, reversed (approximately 50%) as compared to WT. This effect was not seen in female Tlr4-/- mice. Increases in ipsilateral lumbar Iba-1 and GFAP were seen in mutant and WT mice. Mice deficient in MyD88, or MyD88 and TRIF, showed an approximately 50% reduction in withdrawal thresholds and reduced ipsilateral Iba-1. In contrast, TRIF and interferon receptor null mice developed a profound ipsilateral and contralateral tactile allodynia. In lumbar sections of the spinal cords, we observed a greater increase in Iba-1 immunoreactivity in the TRIF-signaling deficient mice as compared to WT, but no significant increase in GFAP. Removing MyD88 abrogated the contralateral allodynia in the TRIF signaling-deficient mice. Conversely, IFNβ, released downstream to TRIF signaling, administered intrathecally, temporarily reversed the tactile allodynia.ConclusionsThese observations suggest a critical role for the MyD88 pathway in initiating neuropathic pain, but a distinct role for the TRIF pathway and interferon in regulating neuropathic pain phenotypes in male mice

Aging aggravates ischemic stroke-induced brain damage in mice with chronic peripheral infection.

Ischemic stroke is confounded by conditions such as atherosclerosis, diabetes and infection, all of which alter peripheral inflammatory processes with concomitant impact on stroke outcome. The majority of the stroke patients are elderly, but the impact of interactions between aging and inflammation on stroke remains unknown. We thus investigated the influence of age on the outcome of stroke in animals predisposed to systemic chronic infection. Th1-polarized chronic systemic infection was induced in 18-22 month and 4-month-old C57BL/6j mice by administration of T. muris (gut parasite). One month after infection, mice underwent permanent middle cerebral artery occlusion and infarct size, brain gliosis and brain and plasma cytokine profiles were analyzed. Chronic infection increased the infarct size in aged but not in young mice at 24 hours. Aged, ischemic mice showed altered plasma and brain cytokine responses while the lesion size correlated with plasma pre-stroke levels of RANTES. Moreover, the old, infected mice exhibited significantly increased neutrophil recruitment and up-regulation of both plasma interleukin-17alpha and tumor necrosis factor alpha levels. Neither age nor infection status alone or in combination altered the ischemia-induced brain microgliosis. Our results show that chronic peripheral infection in aged animals renders the brain more vulnerable to ischemic insults, possibly by increasing the invasion of neutrophils and altering the inflammation status in the blood and brain. Understanding the interactions between age and infections is crucial for developing a better therapeutic regimen for ischemic stroke and when modeling it as a disease of the elderly. This article is protected by copyright. All rights reserved

Differential induction of nuclear factor-like 2 signature genes with toll-like receptors stimulation

Inflammation is associated with production of reactive oxygen species (ROS) and results in the induction of thioredoxin (TXN) and peroxiredoxins (PRDXs) and activation of nuclear factor-like 2 (Nrf2). In this study we have used the mouse RAW 264.7 macrophage and the human THP-1 monocyte cell line to investigate the pattern of expression of three Nrf2 target genes, PRDX1, TXN reductase (TXNRD1) and heme oxygenase (HMOX1), by activation of different Toll-like receptors (TLR). We found that, while the TLR4 agonist lipopolysaccharide (LPS) induces all three genes, the pattern of induction with agonists for TLR1/2, TLR3, TLR2/6 and TLR7/8 differs depending on the gene and the cell line. In all cases, the extent of induction was HMOX1>TXNRD1>PRDX1. Since LPS was a good inducer of all genes in both cell lines, we studied the mechanisms mediating LPS induction of the three genes using mouse RAW 264.7 cells. To assess the role of ROS we used the antioxidant N-acetylcysteine (NAC). Only LPS induction of HMOX1 was inhibited by NAC while that of TXNRD1 and PRDX1 was unaffected. These three genes were also induced by phorbol myristate acetate (PMA), a ROS-inducer acting by activation of protein kinase C (PKC). The protein kinase inhibitor staurosporine inhibited the induction of all three genes by PMA but only that of HMOX1 by LPS. This indicates that activation of these genes by inflammatory agents is regulated by different mechanisms involving either ROS or protein kinases, or both

Ischemic neurons recruit natural killer cells that accelerate brain infarction

Brain ischemia and reperfusion activate the immune system. The abrupt development of brain ischemic lesions suggests that innate immune cells may shape the outcome of stroke. Natural killer (NK) cells are innate lymphocytes that can be swiftly mobilized during the earliest phases of immune responses, but their role during stroke remains unknown. Herein, we found that NK cells infiltrated the ischemic lesions of the human brain. In a mouse model of cerebral ischemia, ischemic neuron-derived fractalkine recruited NK cells, which subsequently determined the size of brain lesions in a T and B cell-independent manner. NK cell-mediated exacerbation of brain infarction occurred rapidly after ischemia via the disruption of NK cell tolerance, augmenting local inflammation and neuronal hyperactivity. Therefore, NK cells catalyzed neuronal death in the ischemic brain

Relationship between education and age-related cognitive decline: A review of recent research

The association between level of educational attainment and cognitive performance is well studied. People with higher education perform better across a broad range of cognitive tasks. However, there is uncertainty as to whether education moderates the trajectory of age-related cognitive decline. This review paper addresses the potential link between education and age-related cognitive decline by evaluating relevant research published since 2000. Studies reporting data on education and its association with the rate of cognitive decline across various cognitive domains were reviewed. A total of 10 studies were identified with a mean follow-up period of 7.6 years; each contained a population-based, non-demented sample. In the majority of studies, results showed that education did not moderate age-associated cognitive decline. The few studies that did find an association between education and decline in specific cognitive functions should be interpreted with caution because of methodological issues. The literature reveals little consistent evidence that normal age-related cognitive decline is moderated by education attainment. This supports a passive theory of cognitive reserve: people with a higher level of education will continue to perform at a higher level of cognitive functioning than their lower educated peers, which may delay the onset of impairment in the future. Psychogeriatric

CD38 Exacerbates Focal Cytokine Production, Postischemic Inflammation and Brain Injury after Focal Cerebral Ischemia

BACKGROUND: Converging evidence suggests that inflammatory processes significantly influence brain injury and clinical impairment in ischemic stroke. Although early studies suggested a key role of lymphocytes, recent data has emphasized the orchestrating function of innate immunity, i.e., macrophages and microglia. The bifunctional receptor and ectoenzyme CD38 synthesizes calcium-mobilizing second messengers (e.g., cyclic ADP-ribose), which have been shown to be necessary for activation and migration of myeloid immune cells. Therefore, we investigated the dynamics of CD38 in stroke and the impact of CD38-deficiency on cytokine production, inflammation and cerebral damage in a mouse model of cerebral ischemia-reperfusion. METHODOLOGY/PRINCIPAL FINDINGS: We show that the local expression of the chemokine MCP-1 was attenuated in CD38-deficient mice compared with wildtype mice after focal cerebral ischemia and reperfusion. In contrast, no significant induction of MCP-1 expression was observed in peripheral blood after 6 hours. Flow cytometry analysis revealed less infiltrating macrophages and lymphocytes in the ischemic hemisphere of CD38-deficient mice, whereas the amount of resident microglia was unaltered. An up-regulation of CD38 expression was observed in macrophages and CD8(+) cells after focal cerebral ischemia in wildtype mice, whereas CD38 expression was unchanged in microglia. Finally, we demonstrate that CD38-deficiency decreases the cerebral ischemic injury and the persistent neurological deficit after three days of reperfusion in this murine temporary middle cerebral artery occlusion (tMCAO) model. CONCLUSION/SIGNIFICANCE: CD38 is differentially regulated following stroke and its deficiency attenuates the postischemic chemokine production, the immune cell infiltration and the cerebral injury after temporary ischemia and reperfusion. Therefore CD38 might prove a therapeutic target in ischemic stroke