Assessment of oral hypofunction and its association with age among Korean community-dwelling older adults.

BACKGROUND: Due to the increasing proportion of older adults in Korea and growing interest in aging, the concepts of oral aging and oral hypofunction have recently been introduced. Thus, it is necessary to investigate the age-specific oral function levels of Korean older adults and develop expert intervention methods for healthy aging. METHODS: Dysphagia, independence of daily living, and oral hypofunction were assessed in 206 older adults living in Wonju, Gangwon State, South Korea. Subjective dysphagia was assessed through self-report questionnaires using the Dysphagia Handicap Index (DHI), the Korean version of Eating Assessment Tool-10, and the Korean version of the Modified Barthel Index. In addition, the oral hypofunction assessment items included decreased chewing ability, occlusal pressure, tongue pressure, oral dryness, and oral cleanliness. RESULTS: DHI increased significantly with age, with those in their 80 s reporting the most difficulty swallowing. Oral function in terms of chewing ability (maximum occlusal pressure and number of remaining teeth), maximum occlusal pressure, and maximum tongue pressure also declined with increasing age. While there was no significant difference in oral dryness by age, those in their 80 s had dry mouth according to the criteria of the oral moisture checking device. CONCLUSIONS: In an assessment of oral function in community-dwelling, independent Korean older adults, the number of items that were assessed as oral hypofunction increased with age. The findings can be used to standardize the oral hypofunction assessment item and develop age-based individualized intervention plans for the early management of oral health and individual oral myofunctional rehabilitation in Korean community-dwelling older adults.

Differences in Korean adult inpatients' oral care behaviour in daily life and hospitals.

OBJECTIVES: The objectives of the study were to identify the differences in oral care methods between current and past hospitalizations and to investigate the need for inpatient oral care education for South Korean adults who have been hospitalized for more than 24 h. METHODS: This study employed a cross-sectional design. Between 23 December 2019 and 4 May 2020, a questionnaire was administered to 200 adult inpatients awaiting treatment and their guardians at university hospitals or clinics. Of these, the data of 195 patients were analysed. Frequency analysis, descriptive statistics and chi-square tests were used for data analysis. RESULTS: In daily life, the participants reported brushing their teeth thrice a day (52.3%) for 2 min (60%). A single product was the most used (51.3%). During hospitalization, 40% of the participants brushed their teeth thrice or more a day, 84.1% brushed for <1 min, and 83.6% did not use additional oral care products. CONCLUSIONS: Differences were observed between South Korean adults' oral care behaviours in daily life and those performed in hospitals. Oral hygiene habits, the frequency and duration of tooth brushing, and the use of oral care products decreased during hospitalization. Our findings can be applied to the development of oral care interventions for inpatients, while considering changes in the hospitalization environment and physical activity levels during hospitalization.

Occupational hazards among dental hygienists: Risk level assessment of scaling work.

OBJECTIVES: This study aimed to classify occupational hazards of ultrasonic scaling by factor and to identify the distribution of occupational risk levels of the study participants according to occupational hazards. In addition, the relationship between the general characteristics of dental hygienists and the occupational risk level of scaling was investigated. METHODS: This study was conducted on 237 dental hygienists. Exposure frequency and the degree of work loss were investigated on a five-point scale for each of the 15 occupational hazards of scaling. RESULTS: Among occupational hazards, the proportion of high-risk individuals for biological hazards (32.9%) was the highest. Dental clinics (33.6%) were found to have a higher proportion of high-risk individuals than dental hospitals (16.5%) (p < 0.05). The proportion of high-risk individuals was higher in the absence of an infection control coordinator (33.9%) (p < 0.05) and infection control education in the preceding 2 years (28.6%) (p < 0.05). CONCLUSION: To create a safe dental work environment, appropriate measures according to the risk level and measurement of occupational risk should be discussed.

Measuring workplace violence for clinical dental hygienists.

OBJECTIVE: This study aimed to develop and assess a tool for measuring violence experienced by clinical dental hygienists in the workplace. METHODS: The basic questionnaire used in this study was created by referring to previous studies, the Negative Acts Questionnaire-Revised (NAQ-R) and the Workplace Bullying in Nursing-Type Inventory (WPBN-TI). The content feasibility was verified by ten experts in the field, and irrelevant questions were deleted, based on a content validity index value of 0.8. This study surveyed 205 clinical dental hygienists to test the tool's validity and reliability. Frequency analysis was conducted on items related to general characteristics and workplace violence. RESULTS: The questionnaire set was 31 questions, which, comprised five domains, were finalized through reliability verification. These domains were verbal attacks and alienation (9 questions), inappropriate work experiences (6 questions), physical threats (4 questions), workplace sexual harassment (6 questions) and verbal violence (6 questions) from patients and their family members. Among the study participants, 47.3% said they received rude signals from others, 17.9% said they were subjected to sexual evaluations regarding their appearance, and 29.4% said their abilities were ignored by patients and family members of patients. CONCLUSIONS: Clinical dental hygienists have been exposed to various types of violence in their workplaces, such as sexual and verbal harassment, by patients and their family members. This tool can be used in the dental setting to conduct surveys on workplace violence and establish a monitoring and support system.

Oral health care provided by nurses for hospitalized patients in Korea.

OBJECTIVES: To investigate registered nurses' awareness and implementation of oral health care in patients who are hospitalized in general wards or intensive care units (ICUs) in South Korea. METHODS: This research was performed as a descriptive survey of 149 nurses working in nine general hospitals with at least 100 beds in major Korean cities. RESULTS: Approximately half (40.9%) of the survey respondents reported providing oral health care for hospitalized patients but that relevant protocols were not available at most hospitals or wards (89.5%). Nurses working in an ICU were significantly more likely to provide oral health care than those working in general wards (83.9% vs 15.1%; P < .001). Most respondents (83.2%) were aware of the importance of providing oral health care for hospitalized patients; however, the proportion considering that such care should be provided by dental hygienists was greater than that considering it should be provided by nurses (36.4% vs 26.0%; P < .001). Agreement that oral health care should be provided for hospitalized patients by dental hygienists was highest in nurses working in ICUs (53.3%; P < .001). CONCLUSIONS: According to this survey, oral healthcare provision is generally low in hospitalized patients and differs between ICUs and general wards. Most respondents considered that dental hygienists should provide oral health care for hospitalized patients. There is an opportunity for nurses and dental hygienists to work collaboratively towards development of an evidence-based protocol for oral health care in hospitalized patients.

Effect of interferential current therapy on forward head posture.

[Purpose] The purpose of this study was to examine the effects of interferential current therapy on the shoulder muscles of subjects with forward head posture. [Subjects and Methods] Thirty volunteers (15 forward head posture, 15 control) participated in this study. Interferential current therapy treatment was conducted for 10 min, three times per week, for 3 weeks on both the upper trapezius and levator scapulae. Subjects were measured anterior both acromion distance and posterior both acromial distance using a ruler, and the forward head posture angle using an electronic application. [Results] Both groups showed significant increases in anterior acromial distance, and decreases in posterior acromial distance and forward head posture angle. [Conclusion] Subjects were concluded that electrical therapy could improve structural alignment; therefore, the implementation of interferential current therapy is expected to be effective for the treatment of forward head posture.

Novel inhibitors of lysine (K)-specific Demethylase 4A with anticancer activity.

Lysine (K)-specific demethylase 4A (KDM4A) is a histone demethylase that removes methyl residues from trimethylated or dimethylated histone 3 at lysines 9 and 36. Overexpression of KDM4A is found in various cancer types. To identify KDM4A inhibitors with anti-tumor functions, screening with an in vitro KDM4A enzyme activity assay was carried out. The benzylidenehydrazine analogue LDD2269 was selected, with an IC50 of 6.56 µM of KDM4A enzyme inhibition, and the binding mode was investigated using in silico molecular docking. Demethylation inhibition by LDD2269 was confirmed with a cell-based assay using antibodies against methylated histone at lysines 9 and 36. HCT-116 colon cancer cell line proliferation was suppressed by LDD2269, which also interfered with soft-agar growth and migration of HCT-116 cells. AnnexinV staining and PARP cleavage experiments showed apoptosis induction by LDD2269. Derivatives of LDD2269 were synthesized and the structure-activity relationship was explored. LDD2269 is reported here as a strong inhibitor of KDM4A in in vitro and cell-based systems, with anti-tumor functions.

The Role of Kinase Modulators in Cellular Senescence for Use in Cancer Treatment.

Recently, more than 30 small molecules and eight monoclonal antibodies that modulate kinase signaling have been approved for the treatment of several pathological conditions, including cancer, idiopathic pulmonary fibrosis, and rheumatoid arthritis. Among them, kinase modulators have been a primary focus for use in cancer treatment. Cellular senescence is believed to protect cells from tumorigenesis by irreversibly halting cell cycle progression and avoiding the growth of damaged cells and tissues. Senescence can also contribute to tumor suppression and be utilized as a mechanism by anti-cancer agents. Although the role of kinase modulators in cancer treatment and their effects on senescence in tumor development have been extensively studied, the relationship between kinase modulators for cancer treatment and senescence has not been fully discussed. In this review, we discuss the pro- and anti-tumorigenesis functions of senescence and summarize the key roles of kinase modulators in the regulation of senescence against tumors.

The discovery of 2,5-isomers of triazole-pyrrolopyrimidine as selective Janus kinase 2 (JAK2) inhibitors versus JAK1 and JAK3.

Members of the Janus kinase (JAK) family are potential therapeutic targets. Abnormal signaling by mutant JAK2 is related to hematological malignancy, such as myeloproliferative neoplasms (MPNs), and tyrosine kinase inhibitor (TKI)-resistance in non-small cell lung cancer (NSCLC). We discovered a potent and highly selective inhibitor of JAK2 over JAK1 and -3 based on the structure of 4-(2,5-triazole)-pyrrolopyrimidine. Among all triazole compounds tested, 2,5-triazole regioisomers more effectively inhibited JAK2 kinase activity than isomers with substitutions of various alkyl groups at the R2 position, except for methyl-substituted 1,5-triazole, which was more potent than the corresponding 1,4- and 2,5-triazoles. None of the synthesized 1,4-isomers inhibited all three JAK family members. Compounds with phenyl or tolyl group substituents at the R1 position were completely inactive compared with the corresponding analogues with a methyl substituted at the R1 position. As a result of this structure-activity relationship, 54, which is substituted with a cyclopropylmethyl moiety, exhibited significant inhibitory activity and selectivity (IC50=41.9nM, fold selectivity JAK1/2 10.6 and JAK3/2 58.1). Compound 54 also exhibited an equivalent inhibition of wild type JAK2 and the V617F mutant. Moreover, 54 inhibited the proliferation of HEL 92.1.7 cells, which carry JAK2 V617F, and gefitinib-resistant HCC827 cells. Compound 54 also suppressed STAT3 phosphorylation at Y705.

Does denture-wearing status in edentulous South Korean elderly persons affect their nutritional intakes?

OBJECTIVE: The aim of this cross-sectional study was to determine whether denture-wearing status in edentulous South Korean elders affected their nutritional intakes, using the 2008-2010 data from the Korean National Health and Nutrition Examination Survey (KNHANES). BACKGROUND: Good nutritional status is a requirement for healthy aging in the elders. Tooth loss is the key to lead to low masticatory ability and alterative food choice, which may increase the risks of systemic disease. Therefore, denture treatment is important to improve general health of edentulous persons. MATERIALS AND METHODS: From KNHANES data, 1168 edentulous older people were selected as the participants of the present study. Nutrient intake data collected via participants' 24-h dietary recalls were used to determine the ratio of nutrient intake to the Recommended Dietary Allowance for Koreans, the percentage of individuals with inadequate nutrient and the effects of denture wearing on the risk of undernourishment. RESULTS: The results showed that compared to denture wearers, edentulous persons without dentures had lower intakes of potassium, niacin and vitamin C. In addition, the distribution of inadequate nutrient intake among participants without dentures was higher than among participants with dentures; the risk of undernourishment was 1.89 times that of denture wearers. [Correction made on 21 March 2014, after first online publication: "[…] participants with dentures was higher than among participants without dentures" was corrected to "[…] participants without dentures was higher than among participants with dentures"] CONCLUSION: Denture wearing was seen to have a significant effect on the level of nutrient intake in edentulous elders.

Bicontinuous Nanoporous Frameworks: Caged Longevity for Enzymes.

The preparation of bicontinuous nanoporous covalent frameworks, which are promising for caging active enzymes, is demonstrated. The frameworks have three- dimensionally continuous, hydrophilic pores with widths varying between 5 and 30 nm. Enzymes were infiltrated into the bicontinuous pore by applying a pressured enzyme solution. The new materials and methods allowed the amount of caged proteins to be controlled precisely. The resulting enzyme-loaded framework films could be recycled many times with nearly no loss of catalytic activity. Entropic trapping of proteins by a bicontinuous pore with the right size distribution is an unprecedented strategy toward facile in vitro utilization of biocatalysts.

Effects of KRC-108 on the Aurora A activity and growth of colorectal cancer cells.

Aurora A is involved in regulating multiple steps of mitosis. Over-expression of Aurora A is related to tumorigenesis and poor prognosis. KRC-108 is a novel multi-kinase inhibitor which has anti-tumor activity in vivo. In this study, we identified the inhibitory effects of KRC-108 on Aurora A kinase and growth-inhibitory characteristics of KRC-108. The in vitro kinase activity assay, immunoblot, and immunofluorescence analyses demonstrated that KRC-108 inhibited Aurora A activity. KRC-108 exhibited cytotoxicity against human colorectal cancer cell line HT-29. Colony formation assays showed that KRC-108 reduced the colony growth of HT-29 cells. KRC-108 also inhibited migration of HT-29 cells. The expression levels of cyclin B1 and CDC2 were decreased by KRC-108 in HT-29 cells. Cell cycle analysis and flow cytometry indicated that the inhibitory effects of KRC-108 on cell growth are due to induction of G2/M arrest and apoptosis by inhibition of Aurora A. KRC-108 induces cell-cycle arrest and apoptosis in colorectal cancer cell line by Aurora A inhibition. The reported in vivo anti-tumor effects of KRC-108 might partly be due to anti-Aurora A effects. This study suggests that KRC-108 has potential for development as an anti-tumor agent, although further studies are needed.

Discovery of quinolinone derivatives as potent FLT3 inhibitors.

Recently some fms-like tyrosine kinase 3 (FLT3) inhibitors have shown good efficacy in acute myeloid leukemia (AML) patients. In an effort to develop anti-leukemic drugs, we investigated quinolinone derivatives as novel FLT3 inhibitors. Two substituted quinolinones, KR65367 and KR65370 were subjected to FLT3 kinase activity assay and showed potent inhibition against FLT3 kinase activity in vitro, with IC50 of 2.7 and 0.57 nM, respectively. As a measure of selectivity, effects on the activity of other kinases were also tested. Both compounds have negligible activity against Met, Ron, epidermal growth factor receptor, Aurora A, Janus kinase 2, and insulin receptor; with IC50 greater than 10 µM. KR compounds showed strong growth inhibition in MV4;11 AML cells and increased the apoptotic cell death in flow cytometric analyses. A decrease in STAT5 phosphorylation by KR compounds was observed in MV4;11 cells. Furthermore, in vitro evaluation of compounds structurally related to KR65367 and KR65370 showed a good structure-activity relationship.

Simultaneous determination of nine lignans from Schisandra chinensis extract using ultra-performance liquid chromatography with tandem mass spectrometry in rat plasma, urine, and gastrointestinal tract samples: application to the pharmacokinetic study of Schisandra chinensis.

The fruit of Schisandra chinensis is a well-known herbal medicine and dietary supplement due to a variety of biological activities including antihepatotoxic and antihyperlipidemic activities. However, the simultaneous validation methodology and pharmacokinetic investigation of nine lignans of S. chinensis extract in biological samples have not been proved yet. Thus, the present study was undertaken to develop the proper sample preparation method and simultaneous analytical method of schisandrol A, gomisin J, schisandrol B, tigloylgomisin H, angeloylgomisin H, schisandrin A, schisandrin B, gomisin N, and schisandrin C in the hexane-soluble extract of S. chinensis to apply for the pharmacokinetic study in rats. All intra- and interprecisions of nine lignans were below 13.7% and accuracies were 85.1-115% and it is enough to evaluate the pharmacokinetic parameters after both intravenous and oral administration of hexane-soluble extract of S. chinensis to rats.

Validation of the Korean Academy of Geriatric Dentistry screening questionnaire and oral frailty diagnostic criteria in community-dwelling older adults.

OBJECTIVES: This study aimed to establish the validity-specifically, the sensitivity and specificity-of the screening questionnaire and diagnostic criteria for oral frailty proposed by the Korean Academy of Geriatric Dentistry (KAGD) among community-dwelling older adults. METHODS: This study enrolled 100 participants. Among various definitions of oral frailty, this study used the criteria proposed by Tanaka as the reference test. The screening questionnaire consisted of 11 items for screening physical frailty, chewing ability, swallowing difficulties, oral dryness, and tongue and lip motor function. Each question had a different scoring weight, and if the total score was 1 or higher, an oral frailty diagnostic examination proposed by the KAGD would be recommended. The diagnostic test was the oral frailty diagnostic criteria proposed by the KAGD including 6 measures: chewing ability, occlusal force, tongue pressure, oral dryness, swallowing difficulty, and oral hygiene. If a participant exhibited 2 or more positive measures, this participant was classified as "oral frail." The screening questionnaire was analyzed using a cut-off value of 1 or higher, while the diagnostic criteria utilized a cut-off of 2 or more positive measures. Sensitivity and specificity were calculated. RESULTS: The screening questionnaire showed significant power for screening oral frailty (area under the receiver operating characteristic curve, 0.783; sensitivity, 87.8%; specificity, 52.5%). The diagnostic accuracy of the newly proposed diagnostic criteria was acceptable (sensitivity, 95.1%; specificity, 42.4%). CONCLUSIONS: The newly proposed screening questionnaire and diagnostic criteria in Korea appear to be a useful tool to identify oral frailty in community-dwelling older adults.

A role of CPEB1 in the modulation of proliferation and neuronal maturation of rat primary neural progenitor cells.

Cytoplasmic polyadenylation binding protein 1 (CPEB1) is a RNA binding protein, which regulates translation of target mRNAs by regulating polyadenylation status. CPEB1 plays important roles in the regulation of germline cell development by modulating cell cycle progression through the polyadenylation of target mRNAs such as cyclin B1. Similar mechanism is reported in proliferating astrocytes by us, although CPEB1 is involved in the transport of target mRNAs as well as local translation at dendritic spines. In this study, we found the expression of CPEB1 in cultured rat primary neural progenitor cells (NPCs). EGF stimulation of cultured NPCs induced rapid phosphorylation of CPEB1, a hallmark of CPEB1-dependent translational control along with cyclin B1 polyadenylation and translation. EGF-induced activation of ERK1/2 and Aurora A kinase was responsible for CPEB1 phosphorylation. Pharmacological inhibition studies suggested that ERK1/2 is involved in the activation of Aurora A kinase and regulation of CPEB1 phosphorylation in cultured NPCs. Long-term incubation in EGF resulted in the down-regulation of CPEB1 expression, which further increased expression of cyclin B1 and cell cycle progression. When we down-regulated the expression of CPEB1 in NPCs by siRNA transfection, the proliferation of NPCs was increased. Increased NPCs proliferation by down-regulation of CPEB1 resulted in eventual up-regulation of neuronal differentiation with increase in both pre- and post-synaptic proteins. The results from the present study may suggest the importance of translational control in the regulation of neuronal development, an emerging concept in many neurodevelopmental and psychiatric disorders such as autism spectrum disorder.

Flavonoids as receptor tyrosine kinase FLT3 inhibitors.

The Fms-like tyrosine kinase 3 (FLT3), a receptor tyrosine kinase, is involved in the proliferation, differentiation and apoptosis of hematopoietic cells. FLT3 is highly overexpressed in acute myeloid leukemia (AML) of the majority of patients. Screening for flavonoids including flavones, flavanones, flavonols, and flavanonols disclosed that luteolin was potent FLT3 enzyme inhibitor. Furthermore, luteolin suppressed cell proliferation in MV4;11 cells with constitutively activated FLT3.

Caspase Cleavage of Receptor Tyrosine Kinases in the Dependence Receptor Family.

Dependence receptors are a group of receptor proteins with shared characteristics of transducing two different signals within cells. They can transduce a positive signal of survival and differentiation in the presence of ligands. On the other hand, dependence receptors can transduce an apoptosis signal in the absence of ligands. The function of these receptors depends on the availability of their ligands. Several receptor tyrosine kinases (RTKs) have been reported as dependence receptors. When cells undergo apoptosis by dependence receptors, the intracellular domain of some RTKs is cleaved by the caspases. Among the RTKs that belong to dependence receptors, we focused on eight RTKs (RET, HER2, MET, ALK, TrkC, EphA4, EphB3, and c-KIT) that are cleaved by caspases. In this review, we describe the features of the receptors, their cleavage sites, and the fate of the cleaved products, as well as recent implications on them being used as potential therapeutics for cancer treatment.

Development and evaluation of simulation-based scenario education program for professional oral hygiene care in intubated patient.

PURPOSE: This study was conducted to develop a professional oral hygiene care (POHC) simulation education program for intubated patients and to evaluate the suitability of education by evaluating the performance confidence (PC), critical thinking disposition (CT), and learning satisfaction (LS) of dental hygiene students. METHODS: This study developed a POHC simulation education program (theory, skill training, scenario education, and debriefing) for intubated patients through expert validation and consisted of a single-group pre- and postexperiment design. The subjects were 3rd and 4th year students at the Department of Dental Hygiene in Wonju City, and a total of 30 people were enrolled. The collected data were analyzed using the PASW Statistics version 23.0. The content validity test was measured by the CVI (Content validity index) value, and the PC, CT, and LS of the subjects before and after participating in the program were analyzed using a paired t-test. The significance level (α) was based on .05. RESULTS: After the program, the PC improved from 4.29 ± 0.43 to 4.54 ± 0.44, and there was a significant difference (p = .004). CT improved from 3.73 ± 0.36 to 3.84 ± 0.36, but there was no significant difference (p = .062), and prudence improved from 4.21 ± 0.33 to 4.43 ± 0.27, and there was significant difference. (p = .001). LS increased from 4.66 ± 0.36 to 4.90 ± 0.16 after education, and there was a significant difference (p = .002). CONCLUSION(S): Simulation education program improved dental hygiene students' POHC performance confidence. Various scenarios will need to be developed in the future, and it is necessary to evaluate simulation education within the dental hygiene curriculum and identify areas for improvement.

Discovery of benzimidazole-indazole derivatives as potent FLT3-tyrosine kinase domain mutant kinase inhibitors for acute myeloid leukemia.

The FMS-like tyrosine kinase 3 (FLT3) gene encodes a class III receptor tyrosine kinase that is expressed in hematopoietic stem cells. The mutations of FLT3 gene found in 30% of acute myeloid leukemia (AML), leads to an abnormal constitutive activation of FLT3 kinase of the receptor and results in immature myeloblast cell proliferation. Although small molecule drugs targeting the FLT3 kinase have been approved, new FLT3 inhibitors are needed owing to the side effects and drug resistances arising from kinase domain mutations, such as D835Y and F691L. In this study, we have developed benzimidazole-indazole based novel inhibitors targeting mutant FLT3 kinases through the optimization of diverse chemical moieties substituted around the core skeleton. The most optimized compound 22f exhibited potent inhibitory activities against FLT3 and FLT3/D835Y, with IC50 values of 0.941 and 0.199 nM, respectively. Furthermore, 22f exhibited strong antiproliferative activity against an AML cell line, MV4-11 cells with a GI50 of 0.26 nM. More importantly, 22f showed single-digit nanomolar GI50 values in the mutant FLT kinase expressed Ba/F3 cell lines including FLT-D835Y (GI50 = 0.29 nM) and FLT3-F691L (GI50 = 2.87 nM). Molecular docking studies indicated that the compound exhibits a well-fitted binding mode as a type 1 inhibitor in the homology model of active conformation of FLT3 kinase.