Feasibility of Oral Function Evaluation According to Dementia Severity in Older Adults with Alzheimer's Disease.

Oral function evaluation in older adults with dementia is important for determining appropriate and practical dietary support plans; however, it can be challenging due to their difficulties in comprehending instructions and cooperating during assessments. The feasibility of oral function evaluation has not been well studied. This cross-sectional study aimed to determine the feasibility of oral function evaluation in older adults with Alzheimer's disease (AD) according to Functional Assessment Staging of Alzheimer's Disease (FAST) stages. In total, 428 older adults with AD (45 men and 383 women; mean age: 87.2 ± 6.2 years) were included. Multilevel logistic regression models were used to examine the prevalence of participants who were unable to perform oral function evaluations, including oral diadochokinesis (ODK), repeated saliva swallow test (RSST), and modified water swallow test (MWST). In comparison to the reference category (combined FAST stage 1-3), FAST stage 7 was associated with the infeasibility of ODK (adjusted odds ratio, 95% confidence interval = 26.7, 4.2-168.6), RSST (5.9, 2.2-16.1), and MWST (8.7, 1.6-48.5, respectively). Oral function evaluation is difficult in older adults with severe AD. Simpler and more practical swallowing function assessments and indicators that can be routinely observed are required.

Factors associated with the oral health status of patients with schizophrenia: A cross-sectional study.

BACKGROUND: Oral function deterioration attributed to ageing and medications is one of the main contributory factors of dysphagia. Therefore, oral health management is essential in older patients with schizophrenia. However, no previous studies have evaluated the oral function in patients with schizophrenia. OBJECTIVE: We surveyed patients with schizophrenia to identify factors associated with ageing-related variations in oral function. METHODS: This cross-sectional study included 34 male patients diagnosed with schizophrenia who were hospitalised at a psychiatric hospital between July and September 2021 and underwent a screening examination during dental care. The survey items included basic information, oral hygiene information, oral (oral diadochokinesis [ODK] and tongue pressure), physical function, and nutritional status. Thirty-six male community-dwelling older individuals were included as controls, and their outcomes were compared with those of patients with schizophrenia. RESULTS: Compared with healthy older adults, patients with schizophrenia demonstrated significantly lower teeth numbers, ODK, and calf circumference (CC) (p < .05). Multiple regression analysis revealed that ODK was associated with age and schizophrenia (p < .05). Conversely, tongue pressure was associated with CC (p < .05), suggesting different factors' association with the parameters indicating decreased oral function. CONCLUSIONS: Our study findings suggest that older patients with schizophrenia have decreased tongue pressure and generalised muscle mass, highlighting the need to manage oral function. Interventions for tongue pressure were more strongly associated with muscle mass and could be easier to manage than those with disease-dependent changes in ODK. TRIAL REGISTRATION: Retrospectively registered.

Anti-influenza A virus activity of flavonoids in vitro: a structure-activity relationship.

Secondary plant metabolites from food extracts, namely daidzein, quercetin, and luteolin, exhibit anti-influenza virus effects, with IC50 values of 143.6, 274.8, and 8.0 µM, respectively. The activities of these metabolites differ depending on the functional groups. Therefore, in this study, we focused on members of the flavonoid group, and investigated the anti-influenza viral effects of different flavonoid classes (flavone, isoflavone, flavonol, flavanone, and flavan-3-ol) in vitro. The IC50 values were 4.9-82.8 µM, 143.6 µM, 62.9-477.8 µM, 290.4-881.1 µM, and 22.9-6717.2 µM, respectively, confirming their activity. The modifying group factors (number, position, type) in the flavonoid skeleton may be significantly related to the anti-influenza virus activity. Moreover, time-of-addition assay revealed that the mechanism of inhibition varied for the different classes; for example, flavonoids that inhibit virus adsorption or the early stage of viral growth. Interestingly, all the examined flavonoids inhibited the late stages of viral growth, suggesting that flavonoids mainly inhibit the late events in viral growth before the release of viral particles. Additionally, apigenin might be effective against oseltamivir-resistant strains. Our results may be important in the development of anti-influenza virus therapeutic strategies in the future.

Effect of Structural Differences in Naringenin, Prenylated Naringenin, and Their Derivatives on the Anti-Influenza Virus Activity and Cellular Uptake of Their Flavanones.

Vaccines and antiviral drugs are widely used to treat influenza infection. However, they cannot rapidly respond to drug-resistant viruses. Therefore, new anti-influenza virus strategies are required. Naringenin is a flavonoid with potential for new antiviral strategies. In this study, we evaluated the antiviral effects of naringenin derivatives and examined the relationship between their cellular uptake and antiviral effects. Madin-Darby canine kidney (MDCK) cells were infected with the A/PR/8/34 strain and exposed to the compound-containing medium for 24 h. The amount of virus in the supernatant was calculated using focus-forming reduction assay. Antiviral activity was evaluated using IC50 and CC50 values. Cells were exposed to a constant concentration of naringenin or prenylated naringenin, and intracellular uptake and distribution were evaluated using a fluorescence microscope. Prenylated naringenin showed strong anti-influenza virus effects, and the amount of intracellular uptake was revealed by the strong intracellular fluorescence. In addition, intracellular distribution differed depending on the position of the prenyl group. The steric factor of naringenin is deeply involved in influenza A virus activity, and prenyl groups are desirable. Furthermore, the prenyl group affects cellular affinity, and the uptake mechanism differs depending on its position. These results provide important information on antiviral strategies.

Comparison of the Amount of Used and the Ease of Oral Care between Liquid and Gel-Type Oral Moisturizers Used with an Oral Care Simulators.

Oral care involving the removal of dry sputum is effective for older patients who require nursing care or hospitalization. However, safe and efficient oral care methods for such patients remain unclear. We aimed to simulate the oral cavity of older adults with dry mouth and elucidate the differences between two moisturization agents, water and gel-like oral moisturizer, and investigate the effect of occupation and experience on the amount of use and the ease of oral care. Using an oral care simulator (MANABOT®, Nissin Dental Products Inc., Kyoto, Japan), 42 students and 48 dental professionals (13 dentists and 35 dental hygienists) performed oral care using moisturization agents to facilitate dry sputum removal. The time required for oral care, amount of water or gel used, amount of pharyngeal inflow, and ease of oral care when using water or gel were compared. The simulations revealed that the amount of use and pharyngeal inflow for gel (2.9 ± 1.6 and 0.3 ± 0.3, respectively) were significantly lower than those for water (6.8 ± 4.1 and 1.2 ± 1.5, respectively) in all participants. Using a gel-like moisturizer might reduce the aspiration risk in older patients requiring nursing care or hospitalization, regardless of occupation and experience.

Association between oral health and advisability of oral feeding in advanced cancer patients receiving palliative care: a cross-sectional study.

PURPOSE: Maintenance of oral feeding is important in terms of maintaining and improving the quality of life in terminal cancer patients receiving palliative care. Although adequate oral health status is essential for oral feeding in hospitalized patients, the relationship between oral health and oral feeding in patients receiving palliative care remains unclear. This cross-sectional study aimed to examine how the general condition and oral health status of these patients relate to decisions regarding their nutritional intake methods. METHODS: This retrospective cross-sectional study included 103 terminal cancer patients (59 men and 44 women; mean age, 73.8 ± 10.9 years) who received palliative care between April 2017 and August 2019. The nutritional method was assessed using the Functional Oral Intake Scale (FOIS). We assessed two types of nutritional methods: (1) the method advised by the attending physician until the initial dental examination (FOIS-I) and (2) the recommended method based on consultation with a palliative care doctor and dentist after the initial oral examination (FOIS-R). Furthermore, the participants' basic information and Dysphagia Severity Scale (DSS) and Oral Health Assessment Tool (OHAT) scores were assessed. RESULTS: There was a divergence between FOIS-I and FOIS-R. FOIS-R was significantly higher than FOIS-I (p < 0.001). Multiple regression analysis revealed that the time until death, DSS score, and OHAT score had a significant impact on determining the food form for oral feeding. CONCLUSIONS: Appropriate oral health assessment is important in determining the food form and indication for oral feeding among patients receiving palliative care.

Patients with mild cognitive impairment diagnosed at dementia clinic display decreased maximum occlusal force: a cross-sectional study.

BACKGROUND: Previous research indicates that patients with mild cognitive impairment (MCI) are more likely to have poor oral health and impairments in oral functions, which may be due to few remaining teeth and impaired tongue and lip motor function. However, the oral health of those patients following comprehensive cognitive assessment by a dementia specialist has not been sufficiently investigated. Therefore, this study aimed to clarify the oral function of patients with MCI and the association between oral health and lower cognitive function. METHODS: This cross-sectional study included 96 participants (men: 35; women: 61; mean age: 73.3 ± 8.5 years) who visited a dementia clinic between December 2017 and January 2020. Participants' cognitive function was assessed by a dementia specialist using neuropsychological and hematological tests and neuroimaging immediately after enrollment. The participants were divided into the healthy and MCI groups according to comprehensive cognitive assessment. Participants' age, sex, body mass index, primary disease, education level, drinking habits, smoking habits, living environment, employment status, and exercise habits were evaluated. Moreover, oral outcomes, including the number of existing teeth, number of functional teeth (natural and prosthetic teeth which were occluded with antagonists), denture use, oral dryness, tongue and lip motor function, tongue pressure, occlusal force, masticatory ability, and swallowing ability were recorded. The Mann-Whitney U test, χ2, and Fisher's exact tests were used for between-group comparisons. Furthermore, logistic regression analysis using MCI diagnosis as the target variable was performed. RESULTS: A comprehensive evaluation of the cognitive function of the study participants by the dementia specialist revealed that 48 participants (mean age: 69.8 ± 8.8 years) were healthy and 48 (mean age: 76.9 ± 6.7 years) had MCI. MCI participants were significantly older (p < 0.001) and had significantly fewer existing teeth (p = 0.031) and lower maximum occlusal force (p = 0.019) than healthy participants. Age (odds ratio: 1.126, p = 0.002) and maximum occlusal force (odds ratio: 0.978, p = 0.048) were significantly associated with lower cognitive function. CONCLUSIONS: Patients with MCI had poorer oral health than healthy individuals. Decreased maximum occlusal force was independently associated with lower cognitive function, even when adjusted for age and sex.

Association between Improvement of Oral Health, Swallowing Function, and Nutritional Intake Method in Acute Stroke Patients.

Stroke and poor oral health are common in older people, and the brain injuries associated with stroke are often accompanied by a decline in oral function. In this study, we investigated the characteristics of stroke patients who could not recover oral ingestion until discharge and the association between improved oral health, swallowing function, and nutritional intake methods in acute care. The subjects were 216 consecutive stroke patients who were admitted to Tokyo Medical and Dental University hospital and received oral health management. Nutritional intake, dysphagia, and oral health were evaluated using the Functional Oral Intake Scale (FOIS), Dysphagia Severity Scale (DSS), and Oral Health Assessment Tool (OHAT), respectively. Patients in the tube feeding group (FOIS level 1-2, N = 68) tended to have a worse general condition, fewer functional teeth, and a worse DSS level than those in the oral nutrition group (FOIS level 3-7, N = 148). Multiple analysis with improvement in FOIS score as the dependent variable showed that number of functional teeth (odds ratio [OR]: 1.08, p = 0.04) and improved DSS (OR: 7.44, p < 0.001) and OHAT values (OR: 1.23, p = 0.048) were associated with improvement in nutritional intake methods in acute care. Therefore, recovery of swallowing function and oral health might be important for stroke patients to recover oral ingestion in acute care.

Structural Equation Modeling of Tongue Function and Tongue Hygiene in Acute Stroke Patients.

In acute stroke patients, it is important to maintain tongue hygiene and tongue function for prognosis management. However, the direct relationship between these factors is unclear, since these are often assessed by multiple observables. In this study, we used structural equation modeling (SEM) analysis, a tool to analyze the relationship between concepts that cannot be measured directly, to analyze the relationship between tongue hygiene and tongue function. The subjects were 73 patients with acute stroke admitted to a university hospital who underwent dental intervention. Age, sex, nutritional intake method, clinical severity classification of dysphagia, number of current teeth, number of functional teeth, oral health, tongue movement, tongue coating, number of microorganisms on the tongue surface, tongue surface moisture level, and tongue pressure were measured at the first visit. SEM analysis showed that the relationship between tongue function and tongue hygiene was 0.05 between tongue function and swallowing function was 0.90, and that between tongue hygiene and swallowing function was 0.09. We found no statistical relationship between tongue function and tongue hygiene in acute stroke patients. However, it was reconfirmed that tongue function is strongly related to feeding and swallowing functions.

Effect of oral health intervention on cognitive decline in community-dwelling older adults: A randomized controlled trial.

PURPOSE: The incidence of dementia is rapidly increasing worldwide, especially in developed countries. Little is known regarding the effectiveness of dental intervention to prevent dementia or a decline in cognitive functions among community-dwelling older adults, but a few studies have reported a correlation between the lack of regular dental checkups and dementia. For that reason, this study aimed to investigate the effects of oral health intervention on cognitive functions in community-dwelling subjects with a mild cognitive decline via a randomized controlled trial. PATIENTS AND METHODS: Fifty-five community-dwelling older adults with a Mini-Mental State Examination score of ≥21 to ≤26 who had not visited a dental clinic in the previous year were randomized to an intervention group (n = 28) or a control group (n = 29). The intervention group received monthly oral health intervention by dental hygienists for 8 months while the control group did not. Data on demographics, cognitive function and oral parameters were collected before and after the intervention. RESULTS: Twenty-five subjects in the intervention group (mean age 77.0 years) and 25 in the control group (mean age 72.8 years) completed the study. Significant improvements were observed in the Trail Making Test (TMT)-A, TMT-B, bleeding on probing rate, oral diadochokinesis, tongue pressure and chewing ability in the intervention group (P < 0.05). There were also significant interactions between the TMT-A and TMT-B scores, oral diadochokinesis, tongue pressure and chewing ability (P < 0.05). CONCLUSION: Oral health intervention by dental hygienists may be effective for improving the oral health and executive function of cognitive function assessed via TMT.

Factors associated with the number of microorganisms on the tongue surface in patients following acute stroke.

BACKGROUND: Oral hygiene management of patients with acute stroke is important for preventing aspiration pneumonia and ensuring oral intake. The tongue coating score can be useful for evaluating the oral hygiene level since it reflects the microorganism number on the tongue surface in elderly patients. However, the relationship between the number of oral microorganisms and the tongue coating score in patients with acute stroke remains unclear. OBJECTIVES: We aimed to investigate the relationships between the microorganism number on the tongue surface and oral factors, including tongue coating score, tongue surface moisture level and tongue function. METHODS: This cross-sectional study enrolled 73 patients with acute stroke who were hospitalised at an acute care hospital and underwent dental intervention. Potential explanatory factors, including sex, age, Glasgow Coma Scale score, tongue coating score, tongue surface moisture level, nutrition intake method, number of functional teeth and tongue function, were evaluated. Logistic regression analysis determined their association with the microorganism number on the tongue surface. RESULTS: The tongue coating score (odds ratio: 1.31) and tongue surface moisture level (odds ratio: 1.10) were significantly associated with increased microorganism numbers on the tongue surface. CONCLUSION: The tongue coating score, which reflects the actual number of microorganisms on the tongue surface, could be an effective tool for evaluating oral hygiene level in patients with stroke. Moreover, reducing oral microorganisms in saliva through oral hygiene management, including removing the tongue coating, could contribute towards the prevention of aspiration pneumonia.

Cross-sectional study of age-specific differences in salivary occult blood test results in older adults.

This study aimed to identify factors associated with poor oral health status, as indicated by salivary occult blood (SOB) level, in community-dwelling older adults. A total of 592 community-dwelling participants aged 70 to 84 years with 20 to 28 teeth participated in the survey and SOB evaluation. Survey items included behaviors during dental visits, systemic diseases, smoking habit, cognitive function, and findings of intraoral examination. To identify factors associated with high SOB levels, binomial logistic regression analysis was performed after classifying participants as having high and low SOB on the basis of 75th-percentile SOB measurements. Presence of dental plaque (odds ratio [OR]: 2.26), poor subjective oral health (OR: 2.99) (for the age group 70 to 74 years), fewer remaining teeth (OR: 0.80), no dental visits during the previous year (OR: 2.80) (for the age group 75 to 79 years), and no dental visits during the previous year (OR: 3.93) (for the age group 80 to 84 years) were significantly associated with high SOB levels. The factors associated with high SOB, which indicates poor oral health status, differed by age group in community-dwelling older adults. Therefore, oral health management may improve oral health by providing different age groups with care that accounts for their physical and social functional abilities.

Survey on the oral health status of community-dwelling older people with visual impairment.

AIMS: Little is known about the impact of low vision (LV) on dental care in the elderly population. The present study aimed to clarify the oral health status and oral health behavior of older people with LV. METHODS AND RESULTS: We surveyed community-dwelling older people (age ≥ 65 years, non-LV = 35, LV = 23); and collected data on sex, age, systemic diseases, oral health status, and oral health behavior. Although there was no difference in dental clinic visits within one year, the LV group received significantly lesser oral health instructions by dental hygienists and dentists than the non-LV (60.9% vs 85.7%, P < 0.05) group. Additionally, the LV group was more than twice as aware of the "8020 Campaign," written by the Ministry of Health, Labor and Welfare in Japan than the non-LV group. The non-LV group had higher awareness of thickening agents and denture cleaners, both of which may require visual input. Although we had assumed that LV would lead to poor results for the oral health status, there were no demonstrable differences between both groups. CONCLUSION: Older individuals with LV require suitable forms of nonvisual communication to receive oral health instruction and literacy.

Effect of a collaborative transdisciplinary team approach on oral health status in acute stroke patients.

BACKGROUND: Oral function deteriorates easily during the acute phase of cerebral stroke. Therefore, oral health care involving a transdisciplinary approach consisting of dental and medical professionals might be important, but has not been studied in detail. OBJECTIVE: This study assessed the oral health status of patients with cerebral stroke in the acute phase, with the aim of elucidating the efficacy of collaborative, transdisciplinary oral health care involving dentists, dental hygienists, nurses and speech therapists. METHODS: The participants were 115 consecutive acute cerebral stroke patients, who received oral health care while hospitalised at the university hospital. Their oral health status was assessed using the oral health assessment tool (OHAT) on admission and discharge. RESULTS: Patients with acute cerebral stroke had high OHAT scores on admission, meaning poor oral health status. The collaborative oral health care resulted in significant decrease of OHAT scores at discharge, indicative of the improvement of oral health status. Multivariate analysis identified OHAT score for tongue, dentures and oral cleanliness on admission as the significant variables associated with poor oral health status at discharge. CONCLUSIONS: Thus, the oral health of cerebral stroke patients in the acute phase can be improved by implementing transdisciplinary collaboration of medical and dental professionals. Particularly, patients with problems pertaining to the tongue, dentures and oral cleanliness as revealed through OHAT on admission may require more intensive intervention.

Allosteric activation of cytochrome P450 3A4 by efavirenz facilitates midazolam binding.

1. The purpose of this study is to investigate the heteroactivation mechanism of CYP3A4 by efavirenz, which enhances metabolism of midazolam in vivo, in terms of its binding to CYP3A4 with in vitro spectroscopic methods. 2. Efavirenz exhibited a type II spectral change with binding to CYP3A4 indicating a possible inhibitor. Although dissociation constant (K d) was approximated as 520 µM, efavirenz enhanced binding affinity of midazolam as a co-existing drug with an estimated iK d value of 5.6 µM which is comparable to a clinical concentration. 3. Efavirenz stimulated the formation of 1'-hydroxymidazolam, and the product formation rate (V max) concentration-dependently increased without changing the K m. Besides, an efavirenz analogue, [6-chloro-1,4-dihydro-4-(1-pentynyl)-4-(trifluoromethyl)-2H-3,1-benzoxazin-2-one] (efavirenz impurity) slightly facilitated the binding affinity of midazolam in a concentration-dependent manner. These results propose that efavirenz affects midazolam-binding via binding to the peripheral site which is apart from the active site of CYP3A4. 4. A molecular dynamics simulation also suggested the bound-efavirenz was repositioned to effector-binding site. As a consequence, our spectroscopic studies clarified the heteroactivation of CYP3A4 caused by efavirenz with a proper affinity to the peripheral site, and we concluded the method can be a useful tool for characterising the potential for drug-drug interactions.

Nuclear receptor-mediated cell-autonomous oscillatory expression of the circadian transcription factor, neuronal PAS domain protein 2 (NPAS2).

NPAS2 (MOP4) is a heme-containing sensor transcription factor responsive to a wide range of intra- and extracellular stimuli, which also functions as a circadian transcription factor. This molecule forms a heterodimer with another circadian transcription factor, BMAL1, and activates transcription via E-box elements, indicating that circadian phase synchronization between NPAS2 and BMAL1 expression is important for the efficient transcriptional activation of target genes. However, details of the mechanism of cell-autonomous circadian transcription of Npas2 remain unclear. Here, we show that one of the ROREs (retinoid-related orphan receptor response elements) in the upstream region of the transcription start site is essential for circadian transcription of the Npas2 gene. Furthermore, we also show that endogenous RORα indeed plays an essential role in cell-autonomous circadian transcription of Npas2, because a damped transcriptional oscillation was observed not only by introduction of a dominant negative form or small interfering RNA but also in embryonic fibroblasts obtained from RORα-mutant (sg/sg) mice. These results indicate that circadian transcription of Npas2 is synchronized with that of Bmal1 in a cell-autonomous nuclear receptor-mediated fashion.

Genome-wide profiling of the core clock protein BMAL1 targets reveals a strict relationship with metabolism.

Circadian rhythms are common to most organisms and govern much of homeostasis and physiology. Since a significant fraction of the mammalian genome is controlled by the clock machinery, understanding the genome-wide signaling and epigenetic basis of circadian gene expression is essential. BMAL1 is a critical circadian transcription factor that regulates genes via E-box elements in their promoters. We used multiple high-throughput approaches, including chromatin immunoprecipitation-based systematic analyses and DNA microarrays combined with bioinformatics, to generate genome-wide profiles of BMAL1 target genes. We reveal that, in addition to E-boxes, the CCAATG element contributes to elicit robust circadian expression. BMAL1 occupancy is found in more than 150 sites, including all known clock genes. Importantly, a significant proportion of BMAL1 targets include genes that encode central regulators of metabolic processes. The database generated in this study constitutes a useful resource to decipher the network of circadian gene control and its intimate links with several fundamental physiological functions.