Impact of Tongue Pressure and Peak Expiratory Flow Rate on Nutritional Status of Older Residents of Nursing Homes in Japan: A Cross-Sectional Study.

OBJECTIVES: Swallowing function is critical for continuing oral feeding to prevent frailty in older adults. In this study, we investigated the impact of tongue pressure and pulmonary function on the nutritional status of older adults. DESIGN, SETTING, PARTICIPANTS: This cross-sectional study was conducted in Kitakyushu, Japan from August 2017 to November 2018. Fifty-two residents aged >65 years of age from three nursing care insurance facilities in Kitakyushu City, Japan were recruited. MEASUREMENTS: Oral health status, swallowing function, nutritional status using a mini nutritional assessment short form (MNA-SF), cognitive function, activities of daily living, peak expiratory flow rate (PEFR) for pulmonary function, and tongue pressure were assessed. The associations between nutritional status and the above factors were analysed using a logistic regression model. RESULTS: Participants were divided into two groups: well-nourished group (MNA-SF ≤12) and undernutrition group (MNA-SF <12). Multivariate logistic regression analysis revealed that the correlations of PEFR [odds ratio (OR) = 0.23, 95% confidence interval (CI) = 0.23-0.89 p=0.033) and tongue pressure (OR = 0.88, 95% CI = 0.88-0.99, p=0.029) remained significant even after adjustment with possible confounders. CONCLUSION: Maximum tongue pressure and PEFR in older adults were significantly associated with their nutritional status. These findings suggest that maintaining oral and pulmonary function may be a preventive factor against a decrease in the nutritional status of older frail adults.

Dielectric-loaded surface plasmon polariton crossing waveguides using multimode interference.

A low-loss low-crosstalk multimode interference (MMI) crossing design for dielectric-loaded surface plasmon polariton waveguides (DLSPPWs), which are SiO2 stripes on Au films, is demonstrated numerically and experimentally. DLSPPWs are compatible with strong surface plasmon polariton (SPP) field confinement and maintain relatively low propagation losses. Unlike simpler crossings without MMI structures, low insertion loss of 0.65 dB and low crosstalk of -20.27 dB is confirmed numerically at a crossing angle of 10° when using tilted mirror-imaged MMI crossings. Similar insertion losses were also confirmed experimentally. The proposed structure will be beneficial for plasmonic device miniaturization and flexible patterning of optical interconnections.

Impact of antihypertensive medication adherence on blood pressure control in hypertension: the COMFORT study.

BACKGROUND: It has not been fully elucidated whether antihypertensive medication adherence affects blood pressure (BP) control in hypertension cases. AIM: To investigate the association of adherence to antihypertensive drug regimens and BP control using data from the Combination Pill of Losartan Potassium and Hydrochlorothiazide for Improvement of Medication Compliance Trial (COMFORT) study. DESIGN: An observational analysis from a randomized controlled trial. METHODS: A total of 203 hypertensive subjects were randomly assigned to a daily regimen of a combination pill (losartan 50 mg/hydrochlorothiazide 12.5 mg) or two pills, an angiotensin II receptor blocker and a thiazide diuretic. Medication adherence calculated based on pill counts and BPs was evaluated at 1, 3 and 6 months after randomization. RESULTS: The subjects were divided into three groups according to their adherence, i.e. relatively low-adherence (<90%; n = 19), moderate-adherence (90-99%; n = 71) and high-adherence (100%; n = 113) groups. Clinical characteristics of the subjects including BP, sex, randomized treatments and past medical history did not differ significantly among the three groups. Achieved follow-up BPs over the 6-month treatment period, which were adjusted for age, sex, baseline BP and randomized treatment, were significantly higher in the low-adherence group (135/78 mmHg) compared with the high-adherence (130/74 mmHg; P = 0.02/0.02) and the moderate-adherence (128/74 mmHg; P = 0.003/0.02) groups. CONCLUSION: Low adherence to an antihypertensive-drug regimen was associated with poor BP control.

Cut-off values of fasting and post-load plasma glucose and HbA1c for predicting Type 2 diabetes in community-dwelling Japanese subjects: the Hisayama Study.

AIMS: We examined the optimal cut-off values of fasting plasma glucose, 2-h post-load glucose and HbA(1c) for predicting Type 2 diabetes in community-dwelling Japanese subjects. METHODS: A total of 1982 subjects without diabetes aged 40-79 years who underwent a 75-g oral glucose tolerance test were followed prospectively for 14 years by annual health examination. RESULTS: During the follow-up, 295 subjects developed Type 2 diabetes. Compared with the first decile, the crude hazard ratio for incident Type 2 diabetes was significantly higher in the fifth fasting plasma glucose decile [5.4-5.4 mmol/l (97-98 mg/dl)] or higher, in the seventh 2-h post-load glucose decile [6.9-7.2 mmol/l (124-131 mg/dl)] or higher, and in the fifth HbA(1c) decile [34-36 mmol/mol (5.3-5.4%)] or higher. These associations remained substantially unchanged even after adjustment for confounding factors. The receiver operating characteristic curve analysis showed that the optimal cut-off values for predicting Type 2 diabetes were 5.6 mmol/l (101 mg/dl) for fasting plasma glucose, 6.9 mmol/l (124 mg/dl) for 2-h post-load glucose and 37 mmol/mol (5.5%) for HbA(1c). In a stratified analysis, the cut-off values were approximately 5.6 mmol/l (101 mg/dl) for fasting plasma glucose and 37 mmol/mol (5.5%) for HbA(1c), and these values were unchanged over BMI quartile levels, whereas the 2-h post-load glucose cut-off values declined with decreasing BMI levels. CONCLUSIONS: Our findings suggest that the cut-off value for predicting Type 2 diabetes in the Japanese population is 5.6 mmol/l (101 mg/dl) for fasting plasma glucose and 37 mmol/mol (5.5%) for HbA(1c), while the 2-h post-load glucose cut-off value is lower than the diagnostic criterion for impaired glucose tolerance.

A novel Hansenula polymorpha transcriptional factor HpHAP4-B, able to functionally replace the S. cerevisiae HAP4 gene, contains an additional bZip motif.

The transcriptional regulator HAP4, whose expression is induced on respiratory substrates, has been shown to be involved in the balance between fermentation and respiration in Saccharomyces cerevisiae. We have previously identified a HAP4 orthologue in the yeast Hansenula polymorpha, called HpHAP4-A, which, despite its very limited sequence conservation (a 16 amino acid N-terminal motif), is fully functional in S. cerevisiae. Based on the same N-terminal motif, a second gene has now been identified in the same organism. It was shown to contain an additional cis-binding motif of the bZip type. We report on the cloning, heterologous expression and analysis in S. cerevisiae of this novel ScHAP4 orthologue. From these experiments we could conclude that, as with HpHAP4-A, the novel orthologue, designated HpHAP4-B, could functionally replace the S. cerevisiae gene but to a lesser extent. The relationship between the presence of the additional cis-binding motif and the weaker potential as a HAP4 functional homologue is discussed.

Syndrome of inappropriate secretion of antidiuretic hormone associated with limbic encephalitis in a patient with drug-induced hypersensitivity syndrome.

Drug-induced hypersensitivity syndrome (DIHS)/drug rash with eosinophilia and systemic symptoms (DRESS) is a severe multiorgan reaction with reactivation of herpesviruses. Various features are often seen during the course of the disease. Many aspects of this syndrome suggest close similarities between DIHS/DRESS and graft-versus-host disease. We describe a patient with phenobarbital-induced hypersensitivity syndrome who revealed syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with limbic encephalitis during the course of the disease. In view of previous reports that SIADH and limbic encephalitis are caused by reactivation of latent herpesviruses after transplantation, both conditions may be secondarily caused by reactivation of latent herpesviruses, which is typically observed in DIHS/DRESS. These neurological symptoms should be added to a growing list of important complications of DIHS/DRESS because of the high mortality rate associated with them.

A novel stepwise analysis procedure of genome-wide expression profiles identifies transcript signatures of thiamine genes as classifiers of mitochondrial mutants.

To extract functional information on genes and processes from large expression datasets, analysis methods are required that can computationally deal with these amounts of data, are tunable to specific research questions, and construct classifiers that are not overspecific to the dataset at hand. To satisfy these requirements, a stepwise procedure that combines elements from principal component analysis and discriminant analysis, was developed to specifically retrieve genes involved in processes of interest and classify samples based upon those genes. In a global expression dataset of 300 gene knock-outs in Saccharomyces cerevisiae, the procedure successfully classified samples with similar 'cellular component' Gene Ontology annotations of the knock-out gene by expression signatures of limited numbers of genes. The genes discriminating 'mitochondrion' from the other subgroups were evaluated in more detail. The thiamine pathway turned out to be one of the processes involved and was successfully evaluated in a logistic model to predict whether yeast knock-outs were mitochondrial or not. Further, this pathway is biologically related to the mitochondrial system. Hence, this strongly indicates that our approach is effective and efficient in extracting meaningful information from large microarray experiments and assigning functions to yet uncharacterized genes.

Number of teeth and serum lipid peroxide in 85-year-olds.

OBJECTIVES: To investigate influence of dental status on systemic oxidative stress, we evaluated the association between number of teeth and serum lipid peroxide, an oxidative stress index, in 85-years old residents of Japan. METHODS: In October 2003, 207 subjects 85-years old agreed to participate in the present follow-up study after five years from the 8020 Data Bank Survey of Fukuoka prefecture in 1998. Dental health condition including number of teeth was examined by dentists. Data from 204 subjects (88 male, 116 female) who completed nonfasting venous blood examination including lipid peroxide and blood chemistry were analyzed. The examination included a medical questionnaire regarding smoking history, physical activity, alcohol consumption, educational duration, and regular dental care, anthropometric and manometric measurements. RESULTS: Albumin, lipids, and lipid peroxide in serum all were within the normal range. Number of teeth correlated positively with height and white blood cell count, and correlated negatively with lipid peroxide. In a multiple regression analysis to adjust for confounding factors, tooth number retained this correlation with lipid peroxide. By analysis of variance with a Bonferroni-Dunn correction, edentulous subjects showed significantly higher lipid peroxide than those retaining 20 teeth or more. CONCLUSION: The negative association between number of teeth and lipid peroxide links more teeth remaining with less oxidative stress in an 85-year-old population; this may decrease risk of atherosclerotic complications.

Relationship between chewing ability and 4-year mortality in a cohort of 80-year-old Japanese people.

OBJECTIVE: Poor oral health has been reported to be a risk indicator of mortality, however, few data are available regarding the relationship between chewing ability and mortality. We examined the relationship between self-assessed chewing ability and mortality in elderly subjects. DESIGN: Prospective study. SUBJECTS AND METHODS: Participating in the study were 697 people (277 males, 420 females) from 1282 individuals (80 years old) residing in Fukuoka Prefecture, Japan. Data on oral and systemic health status through questionnaires, accompanied by physical and laboratory blood examinations were obtained. Chewing ability was assessed based on the number of types of food each subject reported as able to chew by questionnaire. RESULTS: A total of 108 subjects died between 1998 and 2002. Those with the lowest number of chewable foods were associated with higher risk of mortality than those with the ability to chew all of the 15 types of food surveyed [hazard ratio (HR) = 2.38, 95% confidence interval (95% CI) = 1.07-5.29], though other parameters including current smoking, low serum albumin, and poor physical health status were more significant. Further, reduced chewing ability of soft foods increased the risk (HR = 2.65, 95% CI = 1.20-5.87). CONCLUSION: Chewing ability was associated with mortality in a population of 80-year-old community residents, and may be a predictor for survival rate.

Mutations in yeast mt tRNAs: specific and general suppression by nuclear encoded tRNA interactors.

Mutations in mitochondrial tRNA genes can produce alterations in tRNA structure resulting in defective mitochondrial protein synthesis and hence respiratory defects. Such defects are often at the origin of neurodegenerative diseases in humans and can be easily studied in yeast since respiratory deficient mutants are viable. Several nuclear encoded tRNA interactors have been shown to rescue the mitochondrial defects due to mutations in mitochondrial tRNAs. Among these, we have identified the gene for the mitochondrial protein synthesis elongation factor EF-Tu and the specific mt aminoacyl-tRNA synthetases. We also observed that the respiratory defects and the effect of the TUF1 over-expression were strongly strain dependent. The importance of the nuclear background in which the mitochondrial mutation is expressed was investigated by changing the nuclear context. Finally, we demonstrated, using the RT-PCR method, the existence of significantly variable levels of the TUF1 transcript among strains with functional and dysfunctional mitochondria.

Chewing ability and quality of life in an 80-year-old population.

As quality of life (QOL) could be influenced by oral status in the elderly, we examined whether chewing ability or number of teeth affected QOL in 80-year olds. A cross-sectional survey included dental examination, chewing self-assessment, and a QOL questionnaire. A total of 823 people who were 80 years old participated in this study. QOL was assessed in terms of satisfaction with physical condition, meals, daily living and social interactions, and with face-scale scores. After adjustment for gender, spouse and activities of daily living, dissatisfaction with social interactions was 3.9 times more prevalent in individuals able to chew four foods or fewer than in those chewing 15. Dissatisfaction with physical condition, meals and daily living, and poor face-scale scores, were 2.7, 2.4, 3.4, and 2.4 times more prevalent, respectively, in subjects chewing four foods or fewer. The number of teeth showed little effect. In conclusion, self-assessed chewing ability but not number of teeth was associated with QOL in 80-year-old subjects.

Relationship of number of remaining teeth to health-related quality of life in community-dwelling elderly.

OBJECTIVE: The aim of this study was to evaluate the relationship between number of remaining teeth and health-related quality of life in community-dwelling elderly. SUBJECTS: A total of 207 participants who were community-dwelling, 85 years of age. Data were from a population-based study of age-related general and oral health in Fukuoka Prefecture, Japan. MEASUREMENTS: The Japanese version of the Short Form 36 Health Survey (SF-36). RESULTS: The mental component score for the participants, from the SF-36, was higher than the Japanese national norm for those aged > or = 70 years. There were no significant differences in the mean of any scores on the SF-36 by having spouse, living with family, or education level. The mean of the SF-36 scores of physical functioning (PF) and of the physical component scores were significantly higher in the 85-year-old participants with > or = 20 teeth than in those with < or = 19 teeth (p < 0.05 and p < 0.01 respectively). In addition, a significant difference (p < 0.05) was observed between the mean of participants with > or = 20 teeth and those with < or = 19 teeth after adjustment for region where the participant lived, activities of daily living (ADL), and sex. The PF (p < 0.001), role-physical (p < 0.005), bodily pain (p < 0.001), vitality (p < 0.001), social functioning (p < 0.05), and physical component (p < 0.001) scores were significantly higher in participants with a good activities of daily living (ADL) assessment. However, ADL was not associated with the number of teeth. CONCLUSIONS: The findings of the present study indicated that 85-year-old participants with > or = 20 teeth had better subjective physical health than those with < or = 19 teeth.

DNA-binding activity of LndI protein and temporal expression of the gene that upregulates landomycin E production in Streptomyces globisporus 1912.

The gene lndI is involved in the pathway-specific positive regulation of biosynthesis of the antitumour polyketide landomycin E in Streptomyces globisporus 1912. LndI was overexpressed in Escherichia coli as a protein C-terminally fused to the intein-chitin-binding-domain tag and purified in a one-step column procedure. Results of in vivo LndI titration, DNA gel mobility-shift assays and promoter-probing experiments indicate that LndI is an autoregulatory DNA-binding protein that binds to its own gene promoter and to the promoter of the structural gene lndE. Enhanced green fluorescent protein was used as a reporter to study the temporal and spatial pattern of lndI transcription. Expression of lndI started before cells entered mid-exponential phase and peak expression coincided with maximal accumulation of landomycin E and biomass. In solid-phase analysis, lndI expression was evident in substrate mycelia but was absent from aerial hyphae and spores.

A new Hansenula polymorpha HAP4 homologue which contains only the N-terminal conserved domain of the protein is fully functional in Saccharomyces cerevisiae.

In Saccharomyces cerevisiae, the HAP transcriptional complex is involved in the fermentation-respiration shift. This complex is composed of four subunits. Three subunits are necessary for DNA-binding, whereas the Hap4p subunit, glucose-repressed, contains the transcriptional activation domain. Hap4p is the key regulator of the complex activity in response to carbon sources in S. cerevisiae. To date, no HAP4 homologue has been identified, except in Kluyveromyces lactis. Examination of these two HAP4 sequences led to the identification of two very short conserved peptides also identified in other yeasts. In the yeast Hansenula polymorpha, two possible HAP4 homologues have been found. Their deduced amino acid sequences are similar to the ScHap4p and KlHap4p proteins only in the N-terminal 16-amino-acid basic motif. Since molecular genetic tools exist and complete genome sequence is known for this yeast, we expressed one of these putative HpHap4 proteins in S. cerevisiae and showed that this protein is able to restore the growth defect of the S. cerevisiae hap4-deleted strain. A set of experiments was performed to confirm the functional homology of this new gene with ScHAP4. The discovery of a Hap4-regulatory protein in H. polymorpha with only the N-terminal conserved domain of the S. cerevisiae protein indicates that this domain may play a crucial role during evolution.

Activities of daily living and chewing ability in an 80-year-old population.

OBJECTIVES: The aim of this study was to determine whether chewing ability or number of intact teeth was related to performance of activities of daily living in 80-year olds. DESIGN: This was a cross-sectional survey including dental examinations, chewing self-assessment, and everyday function. SUBJECTS AND METHODS: A total of 823 people (309 males, 514 females) who were 80 years of age and resident in the Fukuoka Prefecture, Japan participated in this study. RESULTS: The mean number of intact teeth was 7.5 +/- 8.7; of the 15 food items offered, the mean number of foods chewed was 11.2 +/- 3.8. Function was independent in 713 subjects, and dependent in 93. After adjustment for gender, we found the number of foods chewed being linked to independent function by the multiple regression analysis (beta = 0.223, P < 0.0001); the number of intact teeth was only weakly related (beta = 0.077, P = 0.03). By logistic regression analysis, functional dependency was 7.5 times more prevalent in individuals capable of chewing four foods or fewer, and 3.3 times more prevalent in those chewing five to nine, than in those chewing all 15 items. No significant functional difference was related to the number of intact teeth. CONCLUSION: Chewing ability may be independently related with functional status in 80-year olds.

Relationship of physical fitness to chewing in an 80-year-old population.

OBJECTIVE: Although tooth loss causes a decrease in masticatory ability, which may influence nutritional status, and impair an individual's general health including physical activity, little is known whether a decrease in chewing ability could result in deterioration in physical fitness in a very elderly population. Thus, the present study evaluated the relationship of chewing ability or teeth number with measures of physical fitness in a sample of 80-years-old in Japan. DESIGN: Cross-sectional survey. SUBJECTS AND METHODS: A total of 1282 people who were 80-years old and resided in the Fukuoka Prefecture were approached. A total of 697 individuals (277 male, 420 female) agreed to participate. RESULTS: Chewing food number and teeth number were related positively with physical fitness measurements of hand grip strength, leg extensor strength, leg extensor power, stepping rate, and one-leg standing time. However, the significant relationship between the number of teeth and physical ability disappeared after adjustment for various confounders, using multiple regression analysis or logistic regression analysis. On the other hand, the relationship of chewing ability with physical fitness measurements of leg extensor strength, one-leg standing time, or isokinetic leg extensor power remained significant even after adjustment for these confounders. CONCLUSION: There is a relationship between perceived chewing ability (number of foods considered chewable) and physical fitness in this 80-year-old population. Chewing ability may be an independent predictor of physical fitness, thus preventative dental care aimed at preserving chewing ability may be able to enhance activities of daily life and quality of life in very elderly individuals.

CpG methylation of MGMT and hMLH1 promoter in hepatocellular carcinoma associated with hepatitis viral infection.

Inactivations of DNA repair genes, O(6)-methylguanine-DNA methyltransferase (MGMT) and hMLH1, by promoter hypermethylation have been reported in several types of primary human neoplasia. This epigenetic inactivation mechanism remains elusive in hepatocellular carcinoma (HCC). To investigate the relation between the expression of MGMT and hMLH1 and the CpG methylation within their promoters in HCCs with or without hepatitis viral infection, we performed immunohistochemistry and urea/bisulphite sequencing on 46 HCCs, corresponding noncancerous tissues, and 20 normal liver tissues. MGMT- and hMLH1-negative HCCs were 60.9% (28 out of 46) and 21.8% (10 out of 46), respectively. HCCs lacking both proteins were 10.9% (five out of 46). The frequency and extent of CpG methylation in the MGMT promoter increased along with hepatitis viral infection and pathological progression. MGMT-negative tumours showed very frequent and widespread methylation in the promoter compared with MGMT-positive tumours. Half of the hMLH1-negative HCCs showed promoter hypermethylation. These data suggested that MGMT gene silencing in a subset of HCCs was likely caused by epigenetic alteration, such as promoter hypermethylation, and that the promoter hypermethylation silenced the hMLH1 gene in half of the hMLH1-negative tumours. A correlation between the promoter methylation status and viral infection, although it was weak, intimated that hepatitis viral infections could play a role in the CpG methylation of the MGMT promoter.

The yeast counterparts of human 'MELAS' mutations cause mitochondrial dysfunction that can be rescued by overexpression of the mitochondrial translation factor EF-Tu.

We have taken advantage of the similarity between human and yeast (Saccharomyces cerevisiae) mitochondrial tRNA(Leu)(UUR), and of the possibility of transforming yeast mitochondria, to construct yeast mitochondrial mutations in the gene encoding tRNA(Leu)(UUR) equivalent to the human A3243G, C3256T and T3291C mutations that have been found in patients with the neurodegenerative disease MELAS (for mitochondrial 'myopathy, encephalopathy, lactic acidosis and stroke-like episodes'). The resulting yeast cells (bearing the equivalent mutations A14G, C26T and T69C) were defective for growth on respiratory substrates, exhibited an abnormal mitochondrial morphology, and accumulated mitochondrial DNA deletions at a very high rate, a trait characteristic of severe mitochondrial defects in protein synthesis. This effect was specific at least in the pathogenic mutation T69C, because when we introduced A or G instead of C, the respiratory defect was absent or very mild. All defective phenotypes returned to normal when the mutant cells were transformed by multicopy plasmids carrying the gene encoding the mitochondrial elongation factor EF-Tu. The ability to create and analyse such mutated strains and to select correcting genes should make yeast a good model for the study of tRNAs and their interacting partners and a practical tool for the study of pathological mutations and of tRNA sequence polymorphisms.

The S. Cerevisiae HAP complex, a key regulator of mitochondrial function, coordinates nuclear and mitochondrial gene expression.

We have compared Saccharomyces cerevisiae global gene expression in wild-type and mutants (Deltahap2 and Deltahap4) of the HAP transcriptional complex, which has been shown to be necessary for growth on respiratory substrates. Several hundred ORFs are under positive or negative control of this complex and we analyse here in detail the effect of HAP on mitochondria. We found that most of the genes upregulated in the wild-type strain were involved in organelle functions, but practically none of the downregulated ones. Nuclear genes encoding the different subunits of the respiratory chain complexes figure in the genes more expressed in the wild-type than in the mutants, as expected, but in this group we also found key components of the mitochondrial translation apparatus. This control of mitochondrial translation may be one of the means of coordinating mitochondrial and nuclear gene expression in elaborating the respiratory chain. In addition, HAP controls the nuclear genes involved in several other mitochondrial processes (import, mitochondrial division) that define the metabolic state of the cell, but not mitochondrial DNA replication and transcription. In most cases, a putative CCAAT-binding site is present upstream of the ORF, while in others no such sites are present, suggesting the control to be indirect. The large number of genes regulated by the HAP complex, as well as the fact that HAP also regulates some putative transcriptional activators of unknown function, place this complex at a hierarchically high position in the global transcriptional regulation of the cell.