Compliance costs and productivity: an approach from working hours.

This study proposes a new approach of measuring compliance costs of rules and regulations by focusing on labor input, and estimates the compliance costs in Japan based on a survey of workers. According to the results, the working hours required to comply with rules and regulations account for more than 20% of total labor input. By industry, this cost is higher in the finance and insurance industry followed by the health and welfare industry, and by firm size, it is higher in large firms. If these costs were halved, overall economic productivity would increase by about 8%.

Breakfast Skipping and Declines in Cognitive Score Among Community-Dwelling Older Adults: A Longitudinal Study of the HEIJO-KYO Cohort.

Previous studies outlined the correlation of adverse effects of breakfast skipping with cognitive function. However, the majority of these studies have focused on the short-term effects; to date, the long-term effect of breakfast skipping on cognitive function among older adults remains unclear. In this prospective cohort study of 712 older adults (mean age, 70.8 years), breakfast skipping was defined as skipping breakfast one or more times per week, and declines in cognitive score was defined as decreases in Mini-Mental State Examination (MMSE) score of two or more in the observed period. During follow-up (median, 31 months), 135 of 712 participants developed declines in cognitive score. Poisson regression models revealed that the incidence rate for declines in cognitive score was significantly higher in breakfast skipper (n = 29) than breakfast eaters (n = 683) [incidence rate ratio (IRR), 2.10; 95% CI, 1.28-3.44]. Additional propensity score adjustments related to breakfast skipping from baseline parameters (age, gender, smoking and drinking status, BMI, household income, educated level, depressive symptoms, hypertension, diabetes, sleep medication, physical activity, caloric intake, and baseline cognition) produced consistent results (IRR, 2.21; 95% CI, 1.33-3.68). Sensitivity analysis, when the cut-off value of decreases in MMSE score was changed to three points, suggested a significant and stronger association (IRR, 3.03; 95% CI, 1.72-5.35). Regarding daily intakes of food groups, breakfast skippers consumed a significantly lower amount of vegetables, fruits, and fish than breakfast eaters. In conclusion, our findings suggest that breakfast skipping is longitudinally associated with declines in cognitive score among older adults.

Elevation of enterococcus-specific antibodies associated with bacterial translocation is predictive of survival rate in chronic liver disease.

Introduction/purpose: The gut-liver axis contributes to disease progression, a rise in infection rate, organ failure and a poor overall outcome in chronic liver diseases (CLD). Monitoring of the gut-liver axis is critical in understanding disease status, but biomarkers have not been elucidated. The aim of this study is to determine the level of serum antibodies against Enterococcus (E.) faecalis in evaluating patients with CLD, including those treated with rifaximin (a minimally absorbed antibiotic), and in patients with alcohol-associated liver disease (ALD). Materials and methods: We enrolled 109 CLD patients (cohort 1), 30 hepatic encephalopathy patients treated with rifaximin (cohort 2), 53 inpatients with ALD undergoing alcohol cessation (cohort 3) and 33 healthy subjects. To assess the consequences of E. faecalis translocation, we developed an assay for the detection of a serum antibody against E. faecalis capsular polysaccharide (E.CPS). Results: Serum E.CPS antibody titer was elevated only in those patients with advanced CLD and ALD. The E.CPS antibody titer was an independent prognostic factor (p < 0.05), while Mac-2 binding protein and albumin-bilirubin score were not independent predictors of survival. The improvement of predictive model in integrated factors was significant [continuous net reclassification index (value 0.699, p < 0.05) and integrated discrimination improvement (value 0.164, p = 0.051)]. Furthermore, rifaximin treatment led to a decrease of serum E.CPS antibody titer resulting in a significantly longer overall rate of survival. Conclusion: The E.CPS antibody titer appears to be a strong predictor of survival in CLD patients. Serum E.CPS levels decrease in CLD patients receiving rifaximin, and may be associated with an overall improvement in rate of survival.

Work-from-home productivity during the COVID-19 pandemic: Evidence from Japan.

This study examines the productivity of working from home (WFH) practices during the COVID-19 pandemic. The results reveal that the mean WFH productivity relative to working at the usual workplace was about 60%-70%, and it was lower for employees and firms that started WFH practice only after the spread of the COVID-19 pandemic. However, there was a large dispersion of WFH productivity, both by individual and firm characteristics. Highly educated and high-wage employees tended to exhibit a small reduction in WFH productivity. The results obtained from the employee and employer surveys were generally consistent with each other.

Analysis of nucleotide insertion opposite urea and translesion synthesis across urea by DNA polymerases.

Urea (Ua) is produced in DNA as the result of oxidative damage to thymine and guanine. It was previously reported that Klenow fragment (Kf) exo- incorporated dATP opposite Ua, and that DNA polymerase ß was blocked by Ua. We report here the following nucleotide incorporations opposite Ua by various DNA polymerases: DNA polymerase α, dATP and dGTP (dATP > dGTP); DNA polymerase δ, dATP; DNA polymerase ζ, dATP; Kf exo-, dATP; Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4), dGTP and dATP (dGTP > dATP); and DNA polymerase η, dCTP, dGTP, dATP, and dTTP (dCTP > dGTP > dATP > dTTP). DNA polymerases ß and ε were blocked by Ua. Elongation by DNA polymerases δ and ζ stopped after inserting dATP opposite Ua. Importantly, the elongation efficiency to full-length beyond Ua using DNA polymerase η and Dpo4 were almost the same as that of natural DNA.

Accuracy of carbohydrate-deficient transferrin as a biomarker of chronic alcohol abuse during treatment for alcoholism.

AIM: Clinical evaluations are generally used to verify the effectiveness of detoxification treatments for alcohol dependence, but new objective biomarkers are essential for accurate diagnosis. We aim to assess the accuracy of carbohydrate-deficient transferrin (%CDT) in a cohort of Japanese patients admitted to a psychiatric hospital specializing in alcohol dependence. In addition, we investigated the kinetics of %CDT during alcohol moderation or cessation. METHODS: The study cohort consisted of 126 alcohol-dependent patients. The levels of serum %CDT were assessed by the N Latex CDT direct immunonephelometric assay. RESULTS: Alcohol consumption was significantly correlated with %CDT. The only independent predictive factor of alcohol consumption was %CDT, with glutamyltranspeptidase (GGT) and albumin-bilirubin score proving insufficient. The cut-off value of %CDT was 1.9% with high sensitivity and specificity in detecting alcohol abstinence beyond 30 days (68.6% sensitivity, 91.8% specificity) and excessive alcohol drinking (77.9% sensitivity, 77.1% specificity). The %CDT levels were significantly decreased at 30 days of abstinence when compared with baseline. Notably, %CDT values were significantly changed even in the light alcohol drinking cohort (p = 0.0009), whereas GGT levels were not significantly changed. CONCLUSIONS: Our results indicate that %CDT is an accurate and specific biomarker of alcohol consumption and is useful in detecting alcohol abstinence even in a low alcohol intake patient cohort. These results suggest that %CDT could be a useful objective biomarker of chronic alcohol abuse during clinical treatment for alcoholism.

Productivity of firms using relief policies during the COVID-19 crisis.

This study, based on an original survey of Japanese firms, analyzes the productivity of firms that used relief policy measures during the COVID-19 pandemic. The productivity of firms using these relief measures was lower than that of non-user firms prior to the pandemic, suggesting that inefficient firms have been affected seriously. The result cautions against the excessive and prolonged relief policies.

Products of Oxidative Guanine Damage Form Base Pairs with Guanine.

Among the natural bases, guanine is the most oxidizable base. The damage caused by oxidation of guanine, commonly referred to as oxidative guanine damage, results in the formation of several products, including 2,5-diamino-4H-imidazol-4-one (Iz), 2,2,4-triamino-5(2H)-oxazolone (Oz), guanidinoformimine (Gf), guanidinohydantoin/iminoallantoin (Gh/Ia), spiroiminodihydantoin (Sp), 5-carboxamido-5-formamido-2-iminohydantoin (2Ih), urea (Ua), 5-guanidino-4-nitroimidazole (NI), spirodi(iminohydantoin) (5-Si and 8-Si), triazine, the M+7 product, other products by peroxynitrite, alkylated guanines, and 8,5'-cyclo-2'-deoxyguanosine (cG). Herein, we summarize the present knowledge about base pairs containing the products of oxidative guanine damage and guanine. Of these products, Iz is involved in G-C transversions. Oz, Gh/Ia, and Sp form preferably Oz:G, Gh/Ia:G, and Sp:G base pairs in some cases. An involvement of Gf, 2Ih, Ua, 5-Si, 8-Si, triazine, the M+7 product, and 4-hydroxy-2,5-dioxo-imidazolidine-4-carboxylic acid (HICA) in G-C transversions requires further experiments. In addition, we describe base pairs that target the RNA-dependent RNA polymerase (RdRp) of RNA viruses and describe implications for the 2019 novel coronavirus (SARS-CoV-2): When products of oxidative guanine damage are adapted for the ribonucleoside analogs, mimics of oxidative guanine damages, which can form base pairs, may become antiviral agents for SARS-CoV-2.

The interaction effect between physical and cultural leisure activities on the subsequent decline of instrumental ADL: the Fujiwara-kyo study.

BACKGROUND: Maintenance of instrumental activities of daily living (IADL) and social role (SR) is crucial to keep independent life because the decline in SR and IADL was a significant predictor of dependence in basic ADL in later. The independent effect of physical and cultural leisure activities and their effect modification on the IADL remains unknown. METHODS: We prospectively observed 3241 elderly with intact IADL at baseline for 5 years. Higher level functional capacity such as IADL and SR was assessed using the Tokyo Metropolitan Institute of Gerontology Index of competence (TMIG index). RESULTS: The mean age of the participants was 72.3 years (standard deviation 5.1), and 46.9% were male, and 90.9% of them received a follow-up assessment. Of the participants, 10.4% developed an IADL decline. Engagement in leisure physical activity was associated with a significantly lower risk of IADL decline (adjusted risk ratio, 0.73; 95% confidence interval [CI], 0.60 to 0.89), and cultural leisure activity was also associated with lower risk of IADL decline (adjusted risk ratio, 0.77; 95% CI, 0.63 to 0.95) independent of potential confounders. We also found significant and positive interaction between physical and cultural leisure activities at risk for IADL decline (P = 0.024) and SR decline (P = 0.004). CONCLUSIONS: We found an independent association of physical and cultural leisure activities with a lower risk for functional decline in IADL and SR with positive interaction. Combined engagement in physical and cultural activities may effectively prevent from IADL decline and SR decline.

Effect of cataract surgery on cognitive function in elderly: Results of Fujiwara-kyo Eye Study.

PURPOSE: To determine whether there is a significant association between prior cataract surgery and cognitive function in an elderly Japanese cohort. SETTING: Nara Medical University, Nara, Japan. DESIGN: The Fujiwara-kyo Eye Study was a cross-sectional epidemiological study. METHODS: The subjects were ≥ 68-years who lived in the Nara Prefecture and responded to recruitment notices. All of the subjects received comprehensive ophthalmological examinations, and answered questionnaires on their socio-demographic and medical history including prior cataract surgery. The association between prior cataract surgery and cognitive function was determined. RESULTS: A total of the 2764 subjects whose mean age was 76.3±4.8 years (±standard deviation) was studied. Of these, 668 individuals (24.2%) had undergone cataract surgery. Of these, 150 (5.4%) had dementia as determined by the Mini-Mental State Examination (MMSE) score ≤23, and 877 individuals (31.7%) had mild cognitive impairment (MCI; MMSE score 24-26). The subjects who had prior cataract surgery had significantly lower odds ratio (OR) of having MCI (OR = 0.78, 95% confidence interval; CI 0.64-0.96, P = 0.019) than those who had not had cataract surgery after adjusting for age, sex, body mass index, education, hypertension, diabetes, depression, and history of stroke. The OR was still lower when the visual acuity was also added to the adjusted factors (OR 0.79, 95% CI 0.64-0.97, P = 0.025). However, prior cataract surgery did not contribute significantly to the low OR for dementia. CONCLUSIONS: Cataract surgery may play a role in reducing the risk of developing MCI independently of visual acuity but not for dementia.

Generation, repair and replication of guanine oxidation products.

Guanine is the most readily oxidized of the four DNA bases, and guanine oxidation products cause G:C-T:A and G:C-C:G transversions through DNA replication. 8-Oxo-7,8-dihydroguanine (8-oxoG) causes G:C-T:A transversions but not G:C-C:G transversions, and is more readily oxidized than guanine. This review covers four major findings. (i) 2,2,4-Triamino-5(2H)-oxazolone (Oz) is produced from guanine and 8-oxoG under various oxidative conditions. Guanine is incorporated opposite Oz by DNA polymerases, except REV1. (ii) Several enzymes exhibit incision activity towards Oz. (iii) Since the redox potential of GG is lower than that of G, contiguous GG sequences are more readily oxidized by a one-electron oxidant than a single guanine, and OzOz is produced from GG in double-stranded DNA. Unlike most DNA polymerases, DNA polymerase ζ efficiently extends the primer up to full-length across OzOz. (iv) In quadruplex DNA, 3'-guanine is mainly damaged by one-electron oxidation in quadruplex DNA, and this damage depends on the highest occupied molecular orbital (HOMO). The oxidation products in quadruplex DNA are different from those in single-stranded or double-stranded DNA.

Effects of Tooth Loss and the Apolipoprotein E ɛ4 Allele on Mild Memory Impairment in the Fujiwara-kyo Study of Japan: A Nested Case-Control Study.

BACKGROUND: Several studies have suggested that periodontal disease can exacerbate the pro-inflammatory status of the brain. Tooth loss is one of the alternative evaluation indices of periodontal disease. There are few data on the relationship between tooth loss and memory impairment, depending on the apolipoprotein E (APOE) ɛ4 genotype. OBJECTIVE: To determine if tooth loss is associated with mild memory impairment (MMI) and if this association is modified by the presence of the APOEɛ4 allele. METHODS: A nested case-control study was conducted from 2007 to 2012 in Japan. Five hundred and thirty-seven Japanese subjects aged 65 years and over who were cognitively intact at baseline were analyzed. MMI at follow-up was evaluated. RESULTS: The median number of teeth at baseline was significantly lower in MMI participants (n = 179) than in controls (n = 358) (MMI: median 21.0, interquartile range 10.0-25.0 versus controls: 24.0, 14.0-27.0). After adjustment for demographics, vascular risk factors, and APOEɛ4 allele, the multivariate adjusted odds ratio (OR) of ≤8 teeth was 1.97 (95% confidence interval [CI], 1.13-3.44) compared to 25-32 teeth. Participants with both the presence of at least 1 APOEɛ4 allele and ≤8 teeth had a higher risk of MMI compared with those with neither (OR, 2.82; 95% CI, 1.15-6.91). Those with either risk factor alone did not have a higher risk of MMI. CONCLUSIONS: A lower number of teeth is related to risk of MMI. This may be primarily true for those individuals with an APOEɛ4 allele.

Association of Visual Acuity and Cognitive Impairment in Older Individuals: Fujiwara-kyo Eye Study.

Both visual impairment and cognitive impairment are essential factors that determine the quality of life in the aged population. The aim of this study was to determine if a correlation existed between visual acuity and cognitive impairment in an elderly Japanese population. The Fujiwara-kyo Eye Study was a cross-sectional study of individuals aged ≥68 years who lived in Nara Prefecture of Japan. Participants underwent ophthalmological examinations and cognitive function test. A mild visual impairment was defined as having a best corrected visual acuity (BCVA) >0.2 logarithm of the minimum angle of resolution (logMAR) units in the better eye. Cognitive impairment was defined as having a Mini-Mental State Examination (MMSE) score of ≤23 points. A total to 2818 individuals completed the examinations. The mean age of the participants was 76.3 ± 4.8 years (mean ± standard deviation). The mean BCVA of the better eye was -0.02 ± 0.13 logMAR units and 6.6% subjects were classified as being mildly visually impaired. The mean MMSE score was 27.3 ± 2.3 and 5.7% subjects were classified as being cognitively impaired. The proportion of subjects with cognitive or moderate visual impairment increased with age, and there was a significant correlation between the visual acuity and MMSE score (r = -0.10, p < 0.0001). Subjects with mild visual impairments had 2.4 times higher odds of having cognitive impairment than those without visual impairment (odds ratio 2.4, 95% confidence interval, 1.5-3.8, p < 0.001) after adjusting for age, sex, and length of education. We conclude that it may be important to maintain good visual acuity to reduce the risk of having cognitive impairment.

Two-year prognosis after residential treatment for patients with alcohol dependence: three chief guidelines for sobriety in Japan.

BACKGROUND: In Japan, the three chief traditional guidelines for sobriety (3CGS) are regular medical checkups, participation in self-help groups, and pharmacotherapy with antidipsotropics. However, the official record of the origins of 3CGS is not clear. The aim of this current study was to assess 3CGS by an examination of the prognosis of patients with alcohol dependence 2 years after their discharge from a residential treatment program. SUBJECTS AND METHODS: The association between subjects' abstinence from alcohol and their regular medical checkups, participation in self-help groups, and treatment with antidipsotropics were prospectively examined. Two years after discharge, the relationship between the 3CGS compliance and abstinence rates was investigated as the primary outcome. In addition, the following were examined as secondary outcomes: the time taken till the first drink after discharge, whether the participants were readmitted to residential treatment, the number of days to readmission, the number of heavy drinking days, and recovery. RESULTS: A total of 98 patients participated. The perfect and partial abstinence rates for patients who followed all the principles of 3CGS were significantly higher than those for patients who followed no guidelines (P<0.05 and P<0.01, respectively). The perfect abstinence rates for patients who had continued attending checkup sessions (P<0.001) and who were taking antidipsotropics (P<0.05) were significantly higher than those for patients who did not follow these components of 3CGS. However, the perfect abstinence rates were not higher for patients who had continued to participate in self-help groups. In addition, the perfect abstinence rate was statistically associated with regular medical checkups (adjusted odds ratio =5.33, 95% confidence interval =1.35-21.0) and participation in self-help groups (adjusted odds ratio =3.79, 95% confidence interval =1.17-12.3). CONCLUSION: This study, reports the effectiveness of 3CGS for the first time. The recovery rate of alcoholics 2 years after discharge from residential treatment was examined. However, due to the chronic nature of alcoholism, further studies are required to investigate the efficacy of 3CGS beyond 2 years.

Diffusion tensor studies and voxel-based morphometry of the temporal lobe to determine the cognitive prognosis in cases of Alzheimer's disease and mild cognitive impairment: Do white matter changes precede gray matter changes?

PURPOSE: The purpose of the current study was to assess the feasibility of diffusion tensor imaging (DTI) parameters for determining the prognosis of Alzheimer's disease (AD). We also analyzed the correlation among DTI, voxel-based morphometry (VBM), and results of the mini-mental state examination (MMSE). METHODS: The subjects of this prospective study were patients with AD and mild cognitive impairment. We performed annual follow-ups with DTI, VBM, and MMSE for 2 or 3 years. On DTI, the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) of the uncinate fascicles were measured. VBM was performed to provide a z-score for the parahippocampal gyrus. The correlations among these factors were evaluated in the same period and the next period of the follow-up study. RESULTS: For evaluation of the same period, both DTI parameters and z-scores showed statistically significant correlations with the MMSE score. Also for evaluation of the next period, both DTI parameters and z-scores showed statistically significant correlations with the MMSE score of the next period. We observed a statistically significant correlation between the ADC value of the uncinate fascicles and the z-score of the next period. CONCLUSIONS: Diffusion tensor parameters (ADC and FA) of the uncinate fascicles correlated well with cognitive function in the next year and seemed to be feasible for use as biomarkers for predicting the progression of AD. In addition, the white matter changes observed in the ADC seemed to precede changes in the gray matter volume of the parahippocampal gyrus that were represented by z-scores of VBM.

Higher Cognitive Function in Elderly Individuals with Previous Cataract Surgery: Cross-Sectional Association Independent of Visual Acuity in the HEIJO-KYO Cohort.

Cataract surgery improves visual acuity and drastically increases the capacity for light reception to the retina. Although previous studies suggested that both light exposure and visual acuity were associated with cognitive function, the relationships between cataract surgery, visual acuity, and cognitive function have not been evaluated in large populations. In this cross-sectional study, we measured cognitive function using the Mini-Mental State Examination and best-corrected visual acuity in pseudophakic (previous cataract surgery) and phakic (no previous cataract surgery) elderly individuals. Of 945 participants (mean age 71.7 years), 166 (17.6%) had pseudophakia and 317 (33.5%) had impaired cognitive function (score ≤26). The pseudophakic group showed significantly better visual acuity than the phakic group (p = 0.003) and lower age-adjusted odds ratio (ORs) for cognitive impairment (OR 0.66; p = 0.038). Consistently, in multivariate logistic regression models, after adjusting for confounding factors, including visual acuity and socioeconomic status, ORs for cognitive impairment were significantly lower in the pseudophakic group than in the phakic group (OR 0.64; 95% confidence interval 0.43-0.96; p = 0.031). This association remained significant in sensitivity analysis, excluding participants with low cognitive score ≤23 (n = 36). In conclusion, in a general elderly population, prevalence of cognitive impairment was significantly lower in pseudophakic individuals independently of visual acuity. The association was also independent of several major causes of cognitive impairment such as aging, gender, obesity, socioeconomic status, hypertension, diabetes, sleep disturbances, depressive symptoms, and physical inactivity.

Contiguous 2,2,4-triamino-5(2H)-oxazolone obstructs DNA synthesis by DNA polymerases α, ß, η, ι, κ, REV1 and Klenow Fragment exo-, but not by DNA polymerase ζ.

Guanine is the most easily oxidized of the four DNA bases, and contiguous guanines (GG) in a sequence are more readily oxidized than a single guanine in a sequence. Continued oxidation of GGs results in a contiguous oxidized guanine lesion. Two contiguous 2,5-diamino-4H-imidazol-4-ones, an oxidized form of guanine that hydrolyses to 2,2,4-triamino-5(2H)-oxazolone (Oz), are detected following the oxidation of GG. In this study, we analysed translesion synthesis (TLS) across two contiguous Oz molecules (OzOz) using Klenow Fragment exo(-) (KF exo(-)) and DNA polymerases (Pols) α, ß, ζ, η, ι, κ and REV1. We found that KF exo(-) and Pols α, ß, ι and REV1 inserted one nucleotide opposite the 3' Oz of OzOz and stalled at the subsequent extension, and that Pol κ incorporated no nucleotide. Pol η only inefficiently elongated the primer up to full-length across OzOz; the synthesis of most DNA strands stalled at the 3' or 5' Oz of OzOz. Surprisingly, however, Pol ζ efficiently extended the primer up to full-length across OzOz, unlike the other DNA polymerases, but catalysed error-prone nucleotide incorporation. We therefore believe that Pol ζ is required for efficient TLS of OzOz. These results show that OzOz obstructs DNA synthesis by DNA polymerases except Pol ζ.

Self-Reported Hearing Loss Predicts 5-Year Decline in Higher-Level Functional Capacity in High-Functioning Elderly Adults: The Fujiwara-Kyo Study.

OBJECTIVES: To clarify the relationship between self-reported hearing loss (HL) and 5-year decline in higher-level functional capacity in high-functioning elderly adults. DESIGN: Population-based, prospective cohort study. SETTING: The Fujiwara-Kyo Study, Nara, Japan. PARTICIPANTS: Community-dwelling individuals aged 65 and older with a perfect baseline and valid follow-up instrumental activity of daily living (IADL) (n = 3,267), intellectual activity (IA) (n = 2,925), and social role (SR) (n = 2,698) scores. MEASUREMENTS: Self-reported HL was evaluated using a single question: "Do you feel you have hearing loss?" IADLs, IA, and SR were measured using the Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC) subscales. Geriatric syndromes (depressive symptoms, cognitive impairment, sleep disturbance, falls, urinary incontinence, visual impairment) were self-reported at baseline. Blood tests were performed to measure cardiovascular risk factors. RESULTS: During 5-year follow-up, new declines developed for 213 participants in IADLs, 272 in IA, and 327 in SR. After adjustment for all covariates, including geriatric syndromes, using multiple logistic regression analysis, self-reported HL at baseline was associated with a decline in IA (odds ratio (OR) = 1.39, 95% confidence interval (CI) = 1.04-1.86) and SR (OR = 1.34, 95% CI = 1.02-1.76) but not IADLs (OR = 1.07, 95% CI = 0.76-1.48). CONCLUSION: Self-reported HL was found to be a significant predictor of decline in IA and SR. Preventive intervention against age-related HL may contribute to maintaining high-level functional capacity in independent elderly adults.

G-Quadruplex DNA- and RNA-Specific-Binding Proteins Engineered from the RGG Domain of TLS/FUS.

Human telomere DNA (Htelo) and telomeric repeat-containing RNA (TERRA) are integral telomere components containing the short DNA repeats d(TTAGGG) and RNA repeats r(UUAGGG), respectively. Htelo and TERRA form G-quadruplexes, but the biological significance of their G-quadruplex formation in telomeres is unknown. Compounds that selectively bind G-quadruplex DNA and RNA are useful for understanding the functions of each G-quadruplex. Here we report that engineered Arg-Gly-Gly repeat (RGG) domains of translocated in liposarcoma containing only Phe (RGGF) and Tyr (RGGY) specifically bind and stabilize the G-quadruplexes of Htelo and TERRA, respectively. Moreover, RGGF inhibits trimethylation of both histone H4 at lysine 20 and histone H3 at lysine 9 at telomeres, while RGGY inhibits only H3 trimethylation in living cells. These findings indicate that G-quadruplexes of Htelo and TERRA have distinct functions in telomere histone methylation.

Association of Tooth Loss With Development of Swallowing Problems in Community-Dwelling Independent Elderly Population: The Fujiwara-kyo Study.

BACKGROUND: Tooth loss induces changes to the anatomy of the oral cavity. We hypothesized that tooth loss may disturb smooth swallowing in healthy elderly people. The purpose of this study was to investigate the effect of tooth loss on the development of swallowing problems in an independent elderly population. METHODS: This was a 5-year prospective cohort study conducted in Nara, Japan. Included in this analysis were 1,988 community residents aged 65 years or older without swallowing problems at baseline. The participants were classified into quartile groups according to the number of remaining teeth at the baseline survey: 0-12, 13-22, 23-26, and 27-32 teeth. A decrease in the number of teeth during the survey was calculated by subtracting follow-up number from baseline number. Main outcome was the development of swallowing problems at follow-up. RESULTS: During follow-up, 312 individuals developed swallowing problems. After adjustment for confounding factors by multiple logistic regression analysis, the odds ratios for developing swallowing problems in participants with 13-22 or 0-12 teeth were 2.42 (95% confidence interval [CI], 1.61-3.63) and 2.49 (95% CI, 1.68-3.69), respectively, compared to participants with 27-32 teeth, demonstrating a significant relationship. The odds ratio of per 1 tooth decrease over 5 years was 1.08 (95% CI, 1.02-1.13), showing a significant association. CONCLUSIONS: Swallowing problems due to aging are more likely to develop in individuals with fewer teeth.