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Pyroptosis, a type of inflammatory cell death, is dependent on the inflammatory caspase-mediated cleavage of gasdermin D (GSDMD), and the subsequent pore formation on plasma membranes through which interleukin (IL)-1β and IL-18 are released from cells. During proinflammatory activation, macrophages shift their metabolism from aerobic oxidative phosphorylation to anaerobic glycolysis. Hypoxia-inducible factor (HIF)1α is involved in the induction of IL-1β gene expression as well as the metabolic shift towards glycolysis. However, the relationships between pyroptosis and glycolysis, as well as between pyroptosis and HIF1α are poorly investigated. Here we show that lipopolysaccharide (LPS) stimulation of RAW264.7 murine macrophage cells results in pyroptosis when cells are cultured in high glucose medium. During pyroptosis, HIF1α activation occurs transiently followed by downregulation to sub-basal levels. HIF1α downregulation and pyroptosis are observed when cells are stimulated with LPS under high glucose conditions. We also found that intracellular levels of methylglyoxal (MGO), a side product of glycolysis, increase when cells are stimulated with LPS under high glucose conditions. The addition of glycolysis inhibitor and rapamycin suppresses HIF1α downregulation and pyroptosis. These results show that glycolysis plays a crucial role not only in pro-inflammatory activation, but also in pyroptosis in LPS-stimulated RAW264.7 macrophages.

Interprofessional education (IPE) is crucial in dentistry, medicine, and nursing. However, scant mixed methods studies have compared the IPE outcomes across these disciplines to develop evidence-based IPE. This study explored the differences in the readiness of dental, medical, and nursing students for interprofessional learning before and after IPE workshops and elucidated reasons for this disparity. Data were obtained from dental, medical, and nursing students who participated in IPE workshops conducted at Tokyo Medical and Dental University in Japan in 2019 and 2020. The participants filled the validated Japanese version of the Readiness for Interprofessional Learning Scale (RIPLS) before and after attending the workshops (n = 378). Paired t-tests were performed to assess differences between the pre- and post- workshop RIPLS scores. Welch's t-tests were deployed to evaluate interdisciplinary differences in their scores. Qualitative analyses were conducted using an explanatory sequential design with focus group discussions (FGDs) held with 17 dental students to explain the quantitative results. Total RIPLS scores increased significantly for every discipline after the workshops (p < 0.001). Dental students scored significantly lower pre- and post- workshop aggregates than medical and nursing students, respectively (p < 0.001). The FGDs yielded three principal themes in the explanations tendered by dental students on their lower scores: 1) dental students rarely felt the need for interprofessional collaborations, 2) dentists often worked without the need for interprofessional collaborations, and 3) dental students believed their contribution to the workshop was insufficient. The results revealed divergences in the readiness of dental, medical, and nursing students for interprofessional learning, and the study illuminated possible reasons for these disparities. These outcomes will help develop evidence-based IPE by indicating approaches to place a higher value on interprofessional collaborations in educational environments, ameliorate the awareness of educators, and enhance the workshop facilitation style.

CORM-3 is a water-soluble carbon monoxide (CO)-releasing molecule developed for possible therapeutic use of CO. CORM-3 belongs to a group of metal carbonyl compounds that contain transition metals and carbonyls as the central scaffold and coordinated ligands, respectively. CORM-3 has been reported to be reactive with many proteins in eukaryotes including mammals. Among them, several extracellular proteins, such as lysozyme, as well as plasma albumin and fibronectin, have been shown to interact directly with CORM-3. p62 is an intracellular adaptor protein required for targeting ubiquitinated (Ub) proteins to lysosomal degradation through autophagy. p62 has been shown to undergo self-oligomerization via covalent crosslinking in response to treatment with verteporfin, a benzoporphyrin derivative used for photodynamic therapy. Here we show that CORM-3 also interacts directly with p62. When applied to mouse embryonic fibroblasts (MEFs) at a high concentration (1 mM), CORM-3 causes the formation of reduction- and detergent-resistant high molecular weight (HMW)-p62. HMW-p62 accumulates more in atg5-/- MEFs than in wild type (WT) MEFs, showing the elimination of HMW-p62 through autophagy. HMW-p62 is also generated in H9c2 rat cardiomyoblastoma as well as A549 human alveolar epithelial cells, suggesting that HMW-p62 formation is not specific to MEFs, but, rather, is a general event in mammalian cells. HMW-p62 formation by CORM-3 can be reproduced using purified p62 in vitro, demonstrating the direct interaction between CORM-3 and p62. These results show that p62 is a CORM-3-interactive intracellular protein.

The older adult population in Japan is expected to increase. Therefore, long-term care and frailty prevention are important. However, the relationship between masticatory performance, nutritional intake, and frailty remains unclear. This cross-sectional study aimed to examine energy, protein, and vitamin D intake and its association with frailty and masticatory performance in older adults. Patients between January 2022 and January 2023 were recruited and divided into robust and frail groups. Masticatory performance, nutrition, frailty, and other data, such as age and sex, were evaluated through onsite measurements and a questionnaire. Logistic regression analysis was conducted with frailty as a dependent variable and masticatory performance as an independent variable, adjusting for age, sex, skeletal muscle mass, living alone, energy intake, protein–energy ratio, and vitamin D intake. No significant differences were observed between the groups regarding age or sex. The robust group showed significantly better results for protein–energy ratio, vitamin D intake, and subjective and objective masticatory performance than the frail group. Logistic regression analysis revealed a significant correlation between skeletal muscle mass, protein–energy ratio, and objective masticatory performance with frailty. Masticatory performance was associated with frailty, independent of the intake of nutrients such as energy, protein, and vitamin D.

Purpose Lisdexamfetamine (LDX), which is used for the treatment of attention-deficit/hyperactivity disorder and narcolepsy, is composed of l -lysine attached to dextroamphetamine ( d -amphetamine). In this article, we report a forensic autopsy case in which prescription drugs were unknown at autopsy. While amphetamine was detected, methamphetamine could not be detected by liquid chromatography–tandem mass spectrometry (LC–MS/MS) in any of samples collected. Thus, we aimed to quantify LDX concentrations in autopsy samples and to prove that the amphetamine detected in this case was due to metabolized LDX. Methods Femoral vein blood, cardiac whole blood, urine, and gastric content samples were taken at autopsy for toxicological analysis. Qualitative and quantitative analyses were performed using LC–MS/MS. In addition, optical isomer separation for the amphetamine detected was conducted. The stability of LDX in whole blood and urine was also examined at three different temperatures. Results The concentrations of LDX were < 4.00, 30.9, and 4.42 ng/mL in whole blood, urine, and gastric content samples, respectively. The concentrations of amphetamine were 329, 510, 2970, and 915 ng/mL in femoral vein blood, heart whole blood, urine, and gastric contents, respectively. The amphetamine detected in this case was identified to be only d -amphetamine by optical isomer separation. The d -amphetamine detected was considered to be derived from LDX. Stability experiments revealed that LDX in whole blood decreased at ambient temperature. Conclusions The results in the present case report may be useful in interpreting whether or not the amphetamine detected in a cadaver is a metabolite of LDX.

Background With the global rise in the aging population, the relationship between oral function and risk of long-term care is attracting attention. One method for subjective assessment of masticatory function is the use of a food acceptance questionnaire. Although it is hypothesized that objective oral functions such as tongue pressure and swallowing function are associated with subjective masticatory performance, this relationship has yet to be investigated. The aim of this study is to elucidate the association between overall oral function and subjective masticatory performance using a food questionnaire. Methods Patients aged ≥ 65 years were recruited from an outpatient dental clinic at Tokyo Medical and Dental University. Subjective masticatory performance was assessed using the food acceptance score as described in a previous study. Seven oral function parameters defined by the Japanese Society of Gerodontology, were measured. Age, sex, number of functional teeth, geriatric depression, cognitive function, and oral health-related quality of life were assessed. Variables for which normality was rejected were transformed into tertile values. Multiple regression analysis was conducted with the food acceptance score as the objective variable, and each oral function parameter and other items as explanatory variables. Results This study included 201 participants (87 males and 114 females). Multiple regression analysis revealed that the number of functional teeth, geriatric depression, oral health-related quality of life, objective masticatory performance, tongue pressure, and swallowing function were substantially associated with the food acceptance scores. Conclusions This study demonstrated that subjective masticatory performance was independently associated with tongue pressure, objective masticatory performance, swallowing function, number of functional teeth, geriatric depression, and oral health-related quality of life.

Direct exposure of cardiomyocytes to ethanol causes cardiac damage such as cardiac arrythmias and apoptotic cell death. Cardiomyocytes are connected to each other through intercalated disks (ID), which are composed of a gap junction (GJ), adherens junction, and desmosome. Changes in the content as well as the subcellular localization of connexin43 (Cx43), the main component of the cardiac GJ, are reportedly involved in cardiac arrythmias and subsequent damage. Recently, the hippo-YAP signaling pathway, which links cellular physical status to cell proliferation, differentiation, and apoptosis, has been implicated in cardiac homeostasis under physiological as well as pathological conditions. This study was conducted to explore the possible involvement of junctional intercellular communication, mechanotransduction through cytoskeletal organization, and the hippo-YAP pathway in cardiac damage caused by direct exposure to ethanol. HL-1 murine atrial cardiac cells were used since these cells retain cardiac phenotypes through ID formation and subsequent synchronous contraction. Cells were exposed to 0.5-2% ethanol; significant apoptotic cell death was observed after exposure to 2% ethanol for 48 hours. A decrease in Cx43 levels was already observed after 3 hours exposure to 2% ethanol, suggesting a rapid degradation of this protein. Upon exposure to ethanol, Cx43 translocated into lysosomes. Cellular cytoskeletal organization was also dysregulated by ethanol, as demonstrated by the disruption of myofibrils and intermediate filaments. Coinciding with the loss of cell-cell adherence, decreased phosphorylation of YAP, a hippo pathway effector, was also observed in ethanol-treated cells. Taken together, the results provide evidence that cells exposed directly to ethanol show 1) impaired cell-cell adherence/communication, 2) decreased cellular mechanotransduction by the cytoskeleton, and 3) a suppressed hippo-YAP pathway. Suppression of hippo-YAP pathway signaling should be effective in maintaining cellular homeostasis in cardiomyocytes exposed to ethanol.

This study aimed to identify (1) what newly graduated dental hygienists and reinstated dental hygienists consider important for preventing early turnover in their own professions and for encouraging them to continue in the profession more generally and (2) relevant factors among hygienists intending to continue working in the field. An anonymous, self-administered questionnaire survey was distributed to 215 Japanese dental hygienists who participated in the technical training programs (response rate: 72.6%). Of them, 143 participants were classified into two groups: newly graduated (NGDH, n = 32) and those reinstated to work (RDH, n = 111). Follow-up for lack of skills was most often selected as important for preventing early turnover among both groups and follow-up for lack of knowledge was significantly selected in the RDH group (p < 0.001). Regarding factors important for career continuation, NGDHs significantly selected gaining job satisfaction, whereas RDHs significantly selected working support. Relevant factors contributing to participants’ intentions to continue in the profession were job satisfaction (NGDH, OR = 8.37; RDH, OR = 8.83), career outlook (RDH, OR = 3.11), and job turnover experience because of marriage and parenting (RDH, OR = 2.70), thereby suggesting the importance of raising awareness regarding career progression and job-related rewards among dental hygienists, their educators, and the government through ongoing career education.

Patients tend to feel stress in association with dental treatment due to uneasiness and fear. We investigated the effects of providing advance notice and stress-coping traits on the physiological stress of patients during dental treatment. Sixty non-dental professionals (male, n = 26; female, n = 34; mean age, 49.9 years) were recruited for this study and informed consent was obtained. Subjects were given simulated dental treatment including three stimuli, air, percussion and running of an air turbine, with or without advance notice of the stimulation during dental treatment. Real-time sympathetic nerve activity (SN) and parasympathetic nerve activity (PN) during the treatment were measured using a biological information monitor. The stress-coping traits of each subject were examined using the Lazarus-Type Stress Coping Inventory (SCI). Correlations between the nerve-activity and scores of eight stress-coping strategies of SCI and the presence/absence of advance notice were analyzed. Age, types of stimuli and order of stimuli significantly affected SN, while age, types of stimuli, and the pattern of stimulation significantly affected PN. The interaction of the stress-coping trait and presence/absence of advance notice significantly affected PN. Providing advance notice may have different effects on physiological stress depending on how the patient copes with stress.

Preventing adverse pregnancy outcomes is crucial for maternal and child health. Periodontal disease is a risk factor for many systemic diseases including adverse pregnancy outcomes, such as preterm birth and low birth weight. In addition, the administration of the periodontopathic bacterium Porphyromonas gingivalis exacerbates obesity, glucose tolerance, and hepatic steatosis and alters endocrine function in the brown adipose tissue (BAT). However, the effects of having periodontal disease during pregnancy remain unclear. Thus, this study investigates the effect of P. gingivalis administration on obesity, liver, and BAT during pregnancy. Sonicated P. gingivalis (Pg) or saline (Co) was injected intravenously and administered orally to pregnant C57BL/6J mice three times per week. Maternal body weight and fetal body weight on embryonic day (ED) 18 were evaluated. Microarray analysis and qPCR in the liver and BAT and hepatic and plasma triglyceride quantification were performed on dams at ED 18. The body weight of Pg dams was heavier than that of Co dams; however, the fetal body weight was decreased in the offspring of Pg dams. Microarray analysis revealed 254 and 53 differentially expressed genes in the liver and BAT, respectively. Gene set enrichment analysis exhibited the downregulation of fatty acid metabolism gene set in the liver and estrogen response early/late gene sets in the BAT, whereas inflammatory response and IL6/JAK/STAT3 signaling gene sets were upregulated both in the liver and BAT. The downregulation of expression levels of Lpin1 , Lpin2 , and Lxra in the liver, which are associated with triglyceride synthesis, and a decreasing trend in hepatic triglyceride of Pg dams were observed. P. gingivalis administration may alter lipid metabolism in the liver. Overall, the intravenous and oral administration of sonicated P. gingivalis -induced obesity and modified gene expression in the liver and BAT in pregnant mice and caused fetuses to be underweight.