no study has examined the longitudinal association between hand-grip strength and mental health, such as depressive symptoms.
we investigated the relationship between baseline hand-grip strength and ...the risk of depressive symptoms.
a prospective cohort study.
a prospective cohort study with a 1-year follow-up was conducted using 4,314 subjects from community-dwelling individuals aged 40-79 years in two Japanese municipalities, based on the Locomotive Syndrome and Health Outcomes in Aizu Cohort Study (LOHAS, 2008-10).
we assessed baseline hand-grip strength standardised using national representative data classified by age and gender, and depressive symptoms at baseline and after the follow-up using the five-item version of the Mental Health Inventory (MHI-5).
the 4,314 subjects had a mean age of 66.3 years, 58.5% were women, and mean unadjusted hand-grip strength was 29.8 kg. Multivariable random-effect logistic regression analysis revealed that subjects with lower hand-grip strength (per 1SD decrease) had higher odds of having depressive symptoms at baseline adjusted odds ratio (AOR) 1.15, 95% confidence interval (CI) 1.06-1.24; P = 0.001. Further, lower hand-grip strength (per 1SD decrease) was associated with the longitudinal development of depressive symptoms after 1 year (AOR 1.13, 95% CI 1.01-1.27; P = 0.036).
using a large population-based sample, our results suggest that lower hand-grip strength, standardised using age and gender, is both cross-sectionally and longitudinally associated with depressive symptoms.
Background
The infection route of Helicobacter pylori has been recognized to be mainly intrafamilial, preferentially mother‐to‐child, especially in developed countries. To determine the transmission ...route, we examined whether multilocus sequence typing (MLST) was useful for analysis of intrafamilial infection. The possibility of intraspousal infection was also evaluated.
Materials and Methods
Clonal relationships between strains derived from 35 index Japanese pediatric patients, and their family members were analyzed by two genetic typing procedures, MLST and random amplified polymorphic DNA (RAPD) fingerprinting.
Results
Mostly coincident results were obtained by MLST and RAPD. By MLST, the allele of loci in the isolates mostly matched between the index child and both the father and mother for 9 (25.7%) of the 35 patients, between the index child and the mother for 25 (60.0%) of the 35 patients.
Conclusions
MLST is useful for analyzing the infection route of H. pylori as a highly reproducible method. Intrafamilial, especially mother‐to‐children and sibling, infection is the dominant transmission route. Intraspousal infection is also thought to occur in about a quarter in the Japanese families.
Abstract
Background
Inadequate sleep is correlated with morbidity and mortality among older adults. However, the longitudinal relationship between subjective sleep quality and risk of falls in the ...elderly population remains to be clarified.
Methods
Study participants were from Locomotive Syndrome and Health Outcome in Aizu Cohort Study (LOHAS) sites (1,071 community-dwelling people ≧65 years of age, mean: 71 years). Subjective sleep quality was measured by the Pittsburgh Sleep Quality Index (PSQI). Occurrence of falls (defined as experiencing at least one fall) during the subsequent year was ascertained by a self-reported questionnaire.
Results
Mean global PSQI score was 4.3 (SD 3.2), with 28.9% of participants rating their sleep quality as poor (PSQI > 5). A total of 210 participants (19.6%) fell at least once in the year following sleep examination. Multivariable analysis revealed that participants reporting worse subjective sleep quality had significantly higher odds of experiencing falls during the 1-year follow-up period (adjusted odds ratio AOR = 1.50 for each three-point increase in global PSQI score; 95% confidence interval CI = 1.20, 1.89). Participants in the highest global PSQI score (PSQI > 5) quartile had significantly increased odds of experiencing falls compared to those in the lowest global score quartile (PSQI < 2; AOR = 2.14; 95% CI = 1.09, 4.22). This association was similarly significant in subgroup analyses for older men and women, nonusers of sleep medication, and those without a history of falls at baseline.
Conclusion
Subjective poor sleep quality, as measured by the PSQI, is longitudinally associated with greater risk of experiencing falls in community-dwelling older adults.
The Keap1-Nrf2 system plays a central role in the oxidative stress response; however, the identity of the reactive oxygen species sensor within Keap1 remains poorly understood. Here, we show that a ...Keap1 mutant lacking 11 cysteine residues retains the ability to target Nrf2 for degradation, but it is unable to respond to cysteine-reactive Nrf2 inducers. Of the 11 mutated cysteine residues, we find that 4 (Cys226/613/622/624) are important for sensing hydrogen peroxide. Our analyses of multiple mutant mice lines, complemented by MEFs expressing a series of Keap1 mutants, reveal that Keap1 uses the cysteine residues redundantly to set up an elaborate fail-safe mechanism in which specific combinations of these four cysteine residues can form a disulfide bond to sense hydrogen peroxide. This sensing mechanism is distinct from that used for electrophilic Nrf2 inducers, demonstrating that Keap1 is equipped with multiple cysteine-based sensors to detect various endogenous and exogenous stresses.
Display omitted
•Keap1 H2O2 sensor is distinct from that used for sensing electrophilic inducers•Keap1 uses Cys226, Cys613, and Cys622/624 residues to sense H2O2•Keap1 uses these cysteine residues to set up an elaborate fail-safe mechanism
The Keap1-Nrf2 system plays a central role in the oxidative stress response. Suzuki et al. show that the H2O2 sensor of Keap1 is distinct from those used for electrophilic inducers. Keap1 exploits Cys226, Cys613, and Cys622/624 residues for sensing H2O2, and these residues set up an elaborate fail-safe mechanism.
Abstract
Metabolic syndrome and lumbar spinal stenosis (LSS) are common age-related diseases. However, the causal relationship between them remains unclear. This study aimed to identify the effects ...of LSS on metabolic syndrome incidence in community-dwelling adults. This prospective cohort study included participants of the Aizu cohort study (LOHAS) aged < 75 years as of 2008. Participants with metabolic syndrome at baseline were excluded. The primary outcome measure was metabolic syndrome incidence, and the main explanatory variable was the presence of LSS, as assessed by a self-reported questionnaire. A multivariate Cox proportional hazard regression model was used to estimate hazard ratios (HRs) for metabolic syndrome incidence during the 6-year follow-up period. Complete-case analyses were compared with the multiple imputation results. Among 1599 participants, 1390 complete cases were analyzed (mean SD age 62.3 9.0 years; females, 734 52.8%). Among those participants, 525 (37.8%) developed metabolic syndrome during the follow-up of 3.89 1.96 years. The presence of LSS was associated with developing metabolic syndrome (HR, 1.41; 95% confidence interval CI 1.02–1.95). Multiple imputation results showed similar trends of those having complete-case data (HR, 1.47; 95% CI 1.08–2.00). This finding suggests the importance of prevention and management of LSS in community settings.
The structural kinetics of surface events on a Pt3Co/C cathode catalyst in a polymer electrolyte fuel cell (PEFC) was investigated by operando time-resolved X-ray absorption fine structure (XAFS) ...with a time resolution of 500 ms. The rate constants of electrochemical reactions, the changes in charge density on Pt, and the changes in the local coordination structures of the Pt3Co alloy catalyst in the PEFC were successfully evaluated during fuel-cell voltage-operating processes. Significant time lags were observed between the electrochemical reactions and the structural changes in the Pt3Co alloy catalyst. The rate constants of all the surface events on the Pt3Co/C catalyst were significantly higher than those on the Pt/C catalyst, suggesting the advantageous behaviors (cell performance and catalyst durability) on the Pt3Co alloy cathode catalyst.
Aims
To describe the prevalence, overlap, and prognostic implications of physical and social frailties and cognitive dysfunction in hospitalized elderly patients with heart failure.
Methods and ...results
The FRAGILE‐HF study was a prospective multicentre cohort study enrolling consecutive hospitalized patients with heart failure aged ≥65 years. The study objectives were to examine the prevalence, overlap, and prognostic implications of the coexistence of multiple frailty domains. Physical frailty, social frailty, and cognitive dysfunction were evaluated by the Fried phenotype model, Makizako's 5 items, and Mini‐Cog, respectively. The primary study outcome was the combined endpoint of heart failure rehospitalization and all‐cause death within 1 year. Among 1180 enrolled hospitalized patients (median age, 81 years; 57.4% male), physical frailty, social frailty, and cognitive dysfunction were identified in 56.1%, 66.4%, and 37.1% of the patients, respectively. The number of identified frailty domains was 0, 1, 2, and 3 in 13.5%, 31.4%, 36.9%, and 18.2% of the patients, respectively. During follow‐up, the combined endpoint occurred in 383 patients. Adjusted hazard ratios for 1, 2, and 3 domains, with 0 domains as the reference, were 1.38 95% confidence interval (CI) 0.89–2.13; P = 0.15, 1.60 (95% CI 1.04–2.46; P = 0.034), and 2.04 (95% CI 1.28–3.24; P = 0.003), respectively. Incorporating the number of frailty domains into the pre‐existing risk model yielded a 22.0% (95% CI 0.087–0.352; P = 0.001) net reclassification improvement for the primary outcome.
Conclusions
The coexistence of multiple frailty domains is prevalent in hospitalized elderly patients with heart failure. Holistic assessment of multi‐domain frailty provides additive value to known prognostic factors.
Although the human papillomavirus (HPV) vaccine is effective for preventing cervical cancers, this vaccine does not eliminate pre‐existing infections, and alternative strategies have been warranted. ...Here, we report that FOXP4 is a new target molecule for differentiation therapy of cervical intraepithelial neoplasia (CIN). An immunohistochemical study showed that FOXP4 was expressed in columnar epithelial, reserve, and immature squamous cells, but not in mature squamous cells of the normal uterine cervix. In contrast with normal mature squamous cells, FOXP4 was expressed in atypical squamous cells in CIN and squamous cell carcinoma lesions. The FOXP4‐positive areas significantly increased according to the CIN stages from CIN1 to CIN3. In monolayer cultures, downregulation of FOXP4 attenuated proliferation and induced squamous differentiation in CIN1‐derived HPV 16‐positive W12 cells via an ELF3‐dependent pathway. In organotypic raft cultures, FOXP4‐downregulated W12 cells showed mature squamous phenotypes of CIN lesions. In human keratinocyte‐derived HaCaT cells, FOXP4 downregulation also induced squamous differentiation via an ELF3‐dependent pathway. These findings suggest that downregulation of FOXP4 inhibits cell proliferation and promotes the differentiation of atypical cells in CIN lesions. Based on these results, we propose that FOXP4 is a novel target molecule for nonsurgical CIN treatment that inhibits CIN progression by inducing squamous differentiation.
Downregulation of FOXP4 inhibits cell proliferation and promotes differentiation of atypical cells in CIN lesions. We propose that FOXP4 is a novel target molecule for non‐surgical CIN treatment that inhibits CIN progression by inducing squamous differentiation.
Escherichia coli survives under acid stress conditions by the glutamic acid-dependent acid resistance (GAD) system, which enzymatically decreases intracellular protons. We found a linkage between GAD ...and flagellar systems in E. coli. The
gene, one of the GAD cluster genes, encodes an uncharacterized membrane protein. A reporter assay showed that the
promoter was induced in a GadE-dependent manner when grown in the M9 glycerol medium. Transcriptome analysis revealed that most of the transcripts were from genes involved in flagellum synthesis, and cell motility increased not only in the
-deficient mutant but also in the
-deficient mutant. Defects in both the
and
increased the intracellular level of FliA, an alternative sigma factor for flagellum synthesis, activated by the master regulator FlhDC. The promoter activity of the
gene, which encodes repressor for the
operon, was found to decrease in both the
- and
-deficient mutants. Transmission electron microscopy showed that the number of flagellar filaments on the
-,
-, and
-deficient cells increased, and all three mutants showed higher motility than the parent strain. Thus, HdeD in the GAD system activates the
promoter, resulting in a decrease in flagellar filaments in E. coli cells. We speculated that the synthesis of HdeD, stimulated in E. coli exposed to acid stress, could control the flagellum biosynthesis by sensing slight changes in pH at the cytoplasmic membrane. This could help in saving energy through termination of flagellum biosynthesis and improve bacterial survival efficiency within the animal digestive system.
E. coli cells encounter various environments from the mouth down to the intestines within the host animals. The pH of gastric juice is lower than 2.0, and the bacterial must quickly respond and adapt to the following environmental changes before reaching the intestines. The quick response plays a role in cellular survival in the population, whereas adaptation may contribute to species survival. The GAD and flagellar systems are important for response to low pH in E. coli. Here, we identified the novel inner membrane regulator HdeD, encoding in the GAD cluster, to repress the synthesis of flagella. These insights provide a deeper understanding of how the bacteria enter the animal digestive system, survive, and form colonies in the intestines.