Folate deficiency is associated with increased radiographic severity of osteoarthritis in knee joints but not in hand joints.

OBJECTIVES: No previous studies have explored the effect of folate deficiency on the severity of osteoarthritis (OA). Therefore, we investigated the relationship between folate level and features on knee and hand radiographs in a large, population-based OA cohort. METHODS: Among 9,260 subjects enrolled in the Dong-gu study, 2,489 who had knee and hand joint radiographs were included. Of these, subjects with a history of amputation or total knee replacement were excluded. Serum folate levels were measured using blood samples collected at the time of enrolment and stored. A semi-quantitative system was used to grade the severity of hand and knee x-ray changes. Linear regression was performed to assess relationships between serum folate levels and knee and hand radiographic scores after adjusting for age, sex, body mass index, smoking, alcohol consumption, education, physical activity, occupation, vitamin D, and ferritin. RESULTS: A total of 2,322 subjects were recruited. After adjusting for confounders, participants with folate deficiency (<4 ng/mL) had higher total (p<0.001), osteophyte (p<0.001), joint space narrowing (p=0.002), tibial attrition (p<0.001), and sclerosis (p=0.005) scores for knee joint radiographs compared to participants with a normal folate level. After adjusting for confounders, the radiographic scores for hand joints did not differ between the groups. CONCLUSIONS: Folate deficiency is associated with increased radiographic severity of OA in knee joints, but not in hand joints. Further studies are needed to explore the differential effects of folate on the severity of knee and hand OA.

Understanding of the Lower Extremity Motor Recovery After First-Ever Ischemic Stroke.

BACKGROUND: We aimed to verify the validity of the proportional recovery model for the lower extremity. METHODS: We reviewed clinical data of patients enrolled in the Korean Stroke Cohort for Functioning and Rehabilitation between August 2012 and May 2015. Recovery proportion was calculated as the amount of motor recovery over initial motor impairment, measured as the Fugl-Meyer Assessment of Lower Extremity score. We used the logistic regression method to model the probability of achieving the full Fugl-Meyer Assessment of Lower Extremity score, whereby we considered the ceiling effect of the score. To show the difference in the prevalence of achieving the full Fugl-Meyer Assessment of Lower Extremity score between 3 and 6 months poststroke, we constructed a marginal model through the generalized estimating equation method. We also performed the propensity score matching analysis to show the dependency of recovery proportion on the initial motor deficit at 3 and 6 months poststroke. RESULTS: We evaluated 1085 patients. The recovery proportions at 3 and 6 months poststroke were 0.67±0.42 and 0.75±0.39, respectively. A 1-unit decrease in the initial neurological impairment and the age at stroke onset increased the probability of achieving the full Fugl-Meyer Assessment of Lower Extremity score, which occurred at both 3 and 6 months poststroke. The prevalence of those who reach full lower limb motor recovery differs significantly between 3 and 6 months poststroke. We also found out that the recovery proportion at both 3 and 6 months poststroke is determined by the initial motor deficits of the lower limb. These results are not consistent with the proportional recovery model. CONCLUSIONS: Our results demonstrated that the proportional recovery model for the lower limb is invalid.

Association between alcohol and bone mineral density in a Mendelian randomization study: the Dong-gu study.

INTRODUCTION: Many previous studies have reported a positive relationship between alcohol and bone mineral density (BMD). However, the causality between alcohol and BMD has not been fully evaluated. MATERIALS AND METHODS: This study enrolled 8892 participants from the Dong-gu study. Mendelian randomization (MR) using two-stage least-squared regression was used to evaluate the association between the genetically predicted amount of alcohol consumption per day and BMD. The aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism was used as instrumental variables for alcohol consumption. Age, smoking history, and BMI were adjusted in the multivariate model. RESULTS: Self-reported alcohol consumption was positively related to total hip and lumbar spine BMD in both sexes. In multivariate Mendelian randomization analysis, the genetically predicted amount of alcohol consumption was positively associated with both total hip and lumbar spine BMD in men. Total hip BMD and lumbar spine BMD increased by 0.004 g/cm2 (95% confidence interval [CI] 0.002-0.007) and 0.007 g/cm2 (95% CI 0.004-0.011) with doubling of alcohol consumption. However, in women, genetically predicted alcohol consumption was not significantly associated with BMD. CONCLUSION: In our MR study, genetically predicted alcohol consumption was positively associated with BMD in men. This result suggests that the association between alcohol consumption and BMD is causal.

Health-related quality of life using WHODAS 2.0 and associated factors 1 year after stroke in Korea: a multi-centre and cross-sectional study.

BACKGROUND: Little is known about the self-perceived level of disability of stroke survivors in the community. We aimed to characterise Health-related quality of life (HRQoL) 1 year after stroke and investigate how sociodemographic and stroke-related factors and medical adherence explain the self-perceived level of disability in a Korean stroke population. METHODS: This was a multicentre cross-sectional study. A total of 382 ischaemic stroke survivors at 1 year after onset from 11 university hospitals underwent a one-session assessment, including socioeconomic variables, the modified Rankin Scale (mRS), various neurological sequelae, the Morisky, Green and Levin-Medication Adherence Questionnaire (MGL), and the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) 36-items. The relationship between disability and different variables was analysed using ordinal logistic regression. RESULTS: The prevalence of disability based on global WHODAS 2.0 was 62.6% (mild, 41.6%; moderate, 16.0%; severe, 5.0%). The prevalence of severe disability was higher in participation in society (16.8%) and getting around (11.8%) than in other domains. Low MGL- motivation was the only factor determining a significant association between all six domains of disability after adjustment. Different predictors for specific domains were age, mRS, dysarthria, trouble seeing, cognition problems, and MGL-motivation for understanding and communicating; age, recurrent stroke, mRS, hemiplegia, facial palsy, general weakness, and MGL-motivation for getting around; age, education, mRS, hemiplegia, and MGL-motivation for self-care; education, recurrent stroke, hemiplegia, dysarthria, and MGL-motivation for getting along with people; age, education, income, mRS, hemiplegia, dysarthria, MGL-knowledge, and MGL-motivation for life activities; living without a spouse, mRS, hemiplegia, dysarthria, trouble seeing, cognition problems, general weakness, and MGL-motivation for participation in society. CONCLUSIONS: Self-perceived disability according to the WHODAS 2.0 at 1 year after stroke was highly prevalent. Each disability domain showed a different prevalence and associated factors. Interventions promoting medical adherence to motivation seemed to help achieve high HRQoL in all domains.

The longitudinal associations between trajectory of and quantity of alcohol consumption and subsequent changes in blood pressure levels among non-hypertensive adults.

Given the dynamic characteristic of an individual's drinking behaviours, comprehensive consideration of alcohol consumption variation using repeated measures may improve insight into the nature of its association with blood pressure (BP) change. We examined the association between longitudinal alcohol consumption (trajectory and quantity) and changes in BP and pulse pressure (PP) among Korean aged ≥ 40 years living in rural areas. Totally, 1682 hypertension-free participants who completed all three health examinations (median, 5·3 years) were included. All three visits were used to determine the cumulative trajectory of and quantity of alcohol consumption and the latest two visits and the last visit were used for the recent trajectory and the most recent quantity of alcohol consumption, respectively. Changes in BP and PP from the baseline to the third visit were used as outcome. In men, ≥30 ml/d cumulative average alcohol consumption was associated with the greatest increase in systolic BP (SBP) in both baseline outcome-unadjusted (2·9 mmHg, P = 0·032) and -adjusted models (3·6 mmHg, P = 0·001), and the given association for the most recent alcohol consumption was observed in the baseline outcome-adjusted model (3·9 mmHg, P = 0·003). For PP, similar associations were observed only in the baseline outcome-adjusted model. No meaningful associations in diastolic BP in men and any BP or PP in women existed. The quantity of alcohol consumption rather than the trajectory may be significantly related to raised SBP, and a possible short-term influence of the most recent alcohol consumption may exist when baseline SBP is adjusted in men.

Determination of the vRNA and cRNA promoter activity by M segment-specific non-coding nucleotides of influenza A virus.

Eight-segmented, negative-sense, single-stranded genomic RNAs of influenza A virus are terminated with 5' and 3' untranslated regions (UTRs). All segments have highly conserved extremities of 13 and 12 nucleotides at the 5' and 3' UTRs, respectively, constructing the viral RNA (vRNA) promoter. Adjacent to the duplex stem of 3 base pairs (bps) between the two conserved strands, additional 1-4 bps are existing in a segment-specific manner. We investigated the roles of the matrix (M) segment-specific base pair between the 14th nucleotide uridine (U14') of the 5' UTR and the 13th nucleotide adenosine (A13) of the 3' UTR by preparing possible vRNA promoters, named vXY, as well as cRNA promoters, named cYX. We analysed their RNA-dependent RNA replication efficiency using the minigenome replicon system and an enzyme assay system in vitro with synthetic RNA promoters. Notably, in contrast to vAC(s) that is a synthetic vRNA promoter with A14' and C13, base-pair disruption at the complementary RNA (cRNA) promoter in cAC(s), which has A13' and C14, not only reduced viral RNA replication in cells but also impaired de novo initiation of unprimed vRNA synthesis. Reverse genetics experiments confirmatively exhibited that this breakage in the cRNA promoter affected the rescue of infectious virus. The present study suggests that the first segment-specific base pair plays an essential role in generating infectious viruses by regulating the promoter activity of cRNA rather than vRNA. It could provide insights into the role of the segment-specific nucleotides in viral genome replication for sustainable infection.

Dietary iodine, seaweed consumption, and incidence risk of metabolic syndrome among postmenopausal women: a prospective analysis of the Korean Multi-Rural Communities Cohort Study (MRCohort).

PURPOSE: Despite a beneficial role of iodine and seaweed consumption against metabolic syndrome (MetS), which is high in postmenopausal women, few studies investigated such associations in a prospective study. This study aimed to investigate the association of dietary iodine and seaweed consumption with the incidence of MetS and its components in postmenopausal women. METHODS: A total of 2588 postmenopausal women aged ≥ 40 years were recruited between 2005 and 2011 in the Multi-Rural Communities Cohort (MRCohort). A validated semiquantitative food frequency questionnaire was used to collect dietary intake data. MetS was defined as three of five components [abdominal obesity, elevated blood pressure, glucose, triglyceride, and low-high density lipoprotein cholesterol (HDL-C)] and the incidence of MetS was checked every 2-4 years. The incidence rate ratio (IRR) was estimated using a modified Poisson regression model with a robust error estimator. RESULTS: During the mean follow-up period (3.4 ± 2.1 years), MetS occurred in 481 participants. The median cumulative average iodine intake was 108.9 µg/day (interquartile range, 60.8-190.2 µg/day). In multivariable analyses, average iodine and seaweed consumption were inversely associated with MetS (IRR = 0.61, 95% CI 0.47-0.78 in the highest quartile of iodine intake, P for trend = 0.0018; IRR = 0.52, 95% CI 0.39-0.69 in the highest quartile of seaweed consumption, P for trend = 0.0004). Among MetS components, blood glucose (> 100 mg/dL), blood pressure (≥ 130/85 mmHg), and lipid profiles (triglyceride, ≥ 150 mg/dL and HDL-C, < 50 mg/dL) were significantly inversely associated with dietary iodine and seaweed consumption, but there was no clear association for waist circumference (≥ 85 cm). CONCLUSION: Dietary iodine and seaweed consumption may be inversely associated with MetS incidence and its individual abnormalities in postmenopausal women.

Status Of Dysphagia After Ischemic Stroke: A Korean Nationwide Study.

OBJECTIVE: To identify the incidence of dysphagia after ischemic stroke and determine factors affecting the presence of dysphagia. DESIGN: Retrospective case-control study. This was an interim analysis of a prospective multicenter Korean stroke cohort. SETTING: Acute care university hospitals. PARTICIPANTS: Patients (N=6000) with first-ever acute ischemic stroke. Patients were divided into 2 groups according to the presence or absence of dysphagia confirmed at 7 days after onset using the American Speech-Language-Hearing Association National Outcomes Measurement System (ASHA-NOMS) scale, which was determined after conducting screening or standardized tests. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Age at stroke onset, body mass index (BMI), premorbid modified Rankin Scale (mRS), brainstem lesions, National Institutes of Health Stroke Scale (NIHSS), poststroke mRS, and ASHA-NOMS swallowing level at poststroke day 7 were evaluated. RESULTS: Among patients with ischemic stroke, 32.3% (n=1940) had dysphagia at 7 days after stroke onset. At discharge, 80.5% (n=1561) still had dysphagia. The prediction model for the presence of dysphagia identified age at onset, underweight (BMI <18.5 kg/m2), premorbid mRS, brainstem lesions, and NIHSS as independent predictors. The odds ratio (OR) for the presence of dysphagia significantly increased with underweight (OR, 1.6684; 95% confidence interval [CI], 1.27-2.20), increased age at onset (OR, 1.0318; 95% CI, 1.03-1.04), premorbid mRS (OR, 1.1832; 95% CI, 1.13-1.24), brainstem lesions (OR, 1.6494; 95% CI, 1.39-1.96), and NIHSS (OR, 1.2073; 95% CI, 1.19-1.23). CONCLUSIONS: The incidence of dysphagia after ischemic stroke was 32.3%. The prediction model for the presence of dysphagia identified age, low BMI, premorbid disabilities, brainstem lesions, and NIHSS as predictive factors.

Mechanism for coordinate regulation of rpoS by sRNA-sRNA interaction in Escherichia coli.

RpoS is a key regulator of general stress responses in Escherichia coli. Its expression is post-transcriptionally up-regulated by the small RNAs (sRNAs), ArcZ, DsrA and RprA, through sRNA-rpoS mRNA interactions. Although overexpression of the sRNA, CyaR, was reported to down-regulate rpoS expression, how CyaR regulates rpoS has not been determined. Here, we report that CyaR represses rpoS expression by base-pairing with a region next to the ArcZ binding site in the 5' UTR of rpoS mRNA and that CyaR expression itself is down-regulated by ArcZ through sRNA-sRNA interaction. The short form of ArcZ, but not the full-length form, can base-pair with CyaR. This ArcZ-CyaR interaction triggers degradation of CyaR by RNase E, alleviating the CyaR-mediated rpoS repression. These results suggest that ArcZ not only participates in rpoS translation as an activator, but also acts as a regulator of the reciprocally acting CyaR, maximizing its rpoS-activating effect.

Serum level vitamin D and parathyroid hormone, and mortality, with or without chronic kidney disease.

Levels of vitamin D and parathyroid hormone (PTH) are closely associated with renal function. We evaluated the associations among 25-hydroxyvitamin D (25OHD) levels, PTH levels, and mortality, and whether these associations varied by renal function. We used data from the Dong-gu Study, a population-based cohort in Korean adults. We analyzed the associations among intact PTH, 25OHD levels and mortality in 8580 participants. Hazard ratios (HRs) for mortality were calculated using Cox proportional hazards regression after adjusting for age, sex, month of sampling, lifestyle, and comorbidities. We also evaluated the effects of chronic kidney disease (CKD). A total of 860 deaths occurred during the follow-up period of 7.6 years. Compared to the first 25OHD quartile, the HRs of the second, third, and fourth quartiles were 0.96 [95% confidence interval (CI) 0.79-1.16], 0.84 (95% CI 0.68-1.02), and 0.71 (95% CI 0.57-0.89), respectively. The association between intact PTH levels and mortality varied by renal function, and was both nonlinear and significant only in subjects with CKD. Compared to the second intact PTH quartile in such subjects, the HRs for the first, third, and fourth quartiles were 1.61 (95% CI 0.92-2.81), 1.97 (95% CI 1.17-3.31), and 2.19 (95% CI 1.33-3.59), respectively. In conclusion, we demonstrated that low serum levels of 25OHD are associated with an increased risk of mortality. Serum levels of intact PTH are nonlinearly associated with mortality only in subjects with CKD, with the lowest risk for mortality being evident in the second quartile.

High sodium intake and sodium to potassium ratio may be linked to subsequent increase in vascular damage in adults aged 40 years and older: the Korean multi-rural communities cohort (MRCohort).

PURPOSE: Subclinical vascular damage is a chronic intermediate process in cardiovascular disease (CVD) and high sodium (Na) has been regarded as an adverse factor in subclinical vascular health; however, the longitudinal relationship between Na intake and subclinical vascular damage has not been studied. We aimed to evaluate the longitudinal relationship of dietary Na intake and sodium to potassium ratio (Na:K) with brachial-ankle pulse wave velocity (baPWV) and carotid intima media thickness (cIMT) in healthy adults aged 40 years and older in Korea. METHODS: The present study was based on participants (n = 2145 for baPWV analysis and n = 2494 for cIMT analysis) who visited three times during 2005-2013 (median 5.3 years of follow-up). We used both dietary Na intake and Na:K at baseline and its average (baseline, 2nd, 3rd), which was obtained from food frequency questionnaire (FFQ) as exposure at every visit. baPWV and cIMT levels at the third visit and change from baseline to the third visit were used to represent the level of subclinical vascular damage. RESULTS: After adjustment for potential confounders, significant positive relationships between dietary Na intake and both baPWV3rd and cIMT3rd were observed (baPWV: p for trend ≤ 0.0001 for Naaverage; cIMT: p for trend = 0.013 for Naaverage). Compared with Na:Ks less than 1.0, the levels of both baPWV and cIMT were higher for participants with Na:Ks over 1.0 (baPWV: p for trend = 0.0002 for Na:Kaverage; cIMT: p for trend = 0.005 for Na:Kaverage). Similar significant trends were shown in relationships between dietary Na intake and Na:K and changes in baPWV and cIMT levels. CONCLUSIONS: In conclusion, dietary Na intake and Na:K may be positively linked to subsequent baPWV and cIMT levels in adults aged 40 years and older in Korea. Our findings may provide informative evidence on subclinical vascular damage, particularly for populations with relatively high dietary Na intake and low dietary K intake.

Habitual consumption of soy protein and isoflavones and risk of metabolic syndrome in adults ≥ 40 years old: a prospective analysis of the Korean Multi-Rural Communities Cohort Study (MRCohort).

PURPOSE: Although considerable attention has been paid to the potential benefits of soy protein and isoflavones for preventing metabolic syndrome (MetS) and its components, findings linking habitual consumption of these factors to MetS are limited. This study aimed to evaluate the association of MetS incidence with habitual intake of soy protein/isoflavones among Korean men and women aged ≥ 40 years old who did not have MetS at baseline (n = 5509; 2204 men and 3305 women). METHODS: Dietary intake of soy protein/isoflavones at baseline and average consumption during follow-up were used. RESULTS: A significant inverse association between dietary intake and incidence of MetS was found in women (incidence rate ratios, IRR = 0.60, 95% CI = 0.46-0.78, P for trend = 0.0094 for the highest quintile of average soy protein intake compared with the lowest quintile; IRR = 0.57, 95% CI = 0.44-0.74, P for trend = 0.0048 for the highest quintile of average isoflavones intake compared with the lowest quintile). A tendency towards an inverse association was also found in men, although it was not significant for the highest quintile (IRR = 0.80, 95% CI = 0.58-1.11, P for trend = 0.9759, comparing the lowest to the highest quintile of average soy protein intake; IRR = 0.73, 95% CI = 0.53-1.01, P for trend = 0.8956, comparing the lowest to the highest quintile of average isoflavones intake). In terms of individual abnormalities, a significant inverse association was found between soy protein and isoflavones and the incidence of low-high-density lipoprotein cholesterol in both men and women. Abdominal obesity and elevated blood pressure were inversely related to soy protein/isoflavones only in women, and an inverse association of elevated triglyceride appeared only in men. CONCLUSION: Our findings suggest that habitual intake of soy protein and isoflavones is inversely associated with the risk of MetS and its components. There is likely to be a reverse J-shaped association of average intake with MetS.

NAADP-mediated Ca2+ signaling promotes autophagy and protects against LPS-induced liver injury.

LPS has been shown to induce hepatocyte autophagy, but little is known about how LPS is able to do this during acute toxic liver injury. Our aim was to determine the existence of any selective Ca2+ signaling coupling to hepatocyte autophagy in response to LPS. LPS increased the autophagic process in hepatocytes, and CD38 knockdown prevented this response. Ned19, a specific inhibitor for nicotinic acid adenine dinucleotide phosphate (NAADP), prevented LPS-mediated Ca2+ signaling and autophagosome formation in hepatocytes. CD38 overexpression protected the liver from LPS/d-galactosamine (GalN)-induced injury, and NAADP administration promoted autophagosome formation and protected hepatocytes from injury induced by LPS/GalN. Autophagy was promoted by the up-regulation of autophagy-related gene expression via NAADP-mediated Ca2+ signaling in response to LPS. However, CD38-knockout mice displayed down-regulation in hepatocyte gene expression. Ned19 also inhibited the NAADP-stimulated induction of gene expression by inhibiting the LPS-induced nuclear translocation of transcription factor EB (TFEB). Hepatocyte autophagy protects against LPS-induced liver injury via the CD38/NAADP/Ca2+/TFEB pathway. The role of NAADP-mediated Ca2+ signaling in the autophagic process will help elucidate the complexities of autophagy regulation, which is essential toward the discovery of new therapeutic tools against acute liver injury.-Rah, S.-Y., Lee, Y.-H., Kim, U.-H. NAADP-mediated Ca2+ signaling promotes autophagy and protects against LPS-induced liver injury.

The small RNA, SdsR, acts as a novel type of toxin in Escherichia coli.

Most small noncoding RNAs (sRNAs) are known to base pair with target mRNAs and regulate mRNA stability or translation to trigger various changes in the cell metabolism of Escherichia coli. The SdsR sRNA is expressed specifically during the stationary phase and represses tolC and mutS expression. However, it was not previously known whether the growth-phase-dependent regulation of SdsR is important for cell growth. Here, we ectopically expressed SdsR during the exponential phase and examined cell growth and survival. We found that ectopic expression of SdsR led to a significant and Hfq-dependent cell death with accompanying cell filamentation. This SdsR-driven cell death was alleviated by overexpression of RyeA, an sRNA transcribed on the opposite DNA strand, suggesting that SdsR/RyeA is a novel type of toxin-antitoxin (T/A) system in which both the toxin and the antitoxin are sRNAs. We defined the minimal region required for the SdsR-driven cell death. We also performed RNA-seq analysis and identified 209 genes whose expression levels were altered by more than two-fold following pulse expression of ectopic SdsR at exponential phase. Finally, we found that that the observed SdsR-driven cell death was mainly caused by the SdsR-mediated repression of yhcB, which encodes an inner membrane protein.

Relationships among medication adherence, lifestyle modification, and health-related quality of life in patients with acute myocardial infarction: a cross-sectional study.

BACKGROUND: The healthy adherer effect is a phenomenon in which patients who adhere to medical therapies tend to pursue health-seeking behaviors. Although the healthy adherer effect is supposed to affect health outcomes in patients with coronary artery disease, evaluation of its presence and extent is not easy. This study aimed to assess the relationship between medication adherence and lifestyle modifications and health-related quality of life among post-acute myocardial infarction (AMI) patients. METHODS: A cross-sectional study was conducted in 417 post-AMI patients who underwent percutaneous coronary intervention (PCI). Patients were recruited from 11 university hospitals from December 2015 to March 2016 in South Korea. Details regarding socio-demographic factors, six health behaviors (low-salt intake, low-fat diet and/or weight-loss diet, regular exercise, stress reduction in daily life, drinking in moderation, and smoking cessation), medication adherence using the Modified Morisky Scale (MMS), and HRQoL using the Coronary Revascularization Outcome Questionnaire (CROQ) were surveyed in a one-on-one interview. RESULTS: In the univariate logistic analysis, sex (female), age (≥70 years), MMS score (≥5), and CROQ score were associated with adherence to lifestyle modification. In the multiple logistic analysis, a high MMS score (≥5) was associated with adherence to lifestyle modification after adjusting for sex, age, marital status, education, and family income (adjusted odds ratio [OR] = 11.7, 95% confidence interval [CI] = 1.5-91.3). After further adjusting for the CROQ score, the association between high MMS score and adherence to lifestyle modification was significant (adjusted OR = 11.5, 95% CI = 1.4-93.3). CONCLUSIONS: Adherence to medication was associated with adherence to lifestyle modification, suggesting the possible presence of the healthy adherer effect in post-AMI patients. After further adjusting for HRQoL, the association remained. To improve health outcome in post-AMI patients, early detection of patients with poor adherence to medication and lifestyle modification and motivational education programs to improve adherence are important. In addition, the healthy adherer effect should be considered in clinical research, in particular, in studies evaluating the effects of therapies on health outcomes.

Structural features of influenza A virus panhandle RNA enabling the activation of RIG-I independently of 5'-triphosphate.

Retinoic acid-inducible gene I (RIG-I) recognizes specific molecular patterns of viral RNAs for inducing type I interferon. The C-terminal domain (CTD) of RIG-I binds to double-stranded RNA (dsRNA) with the 5'-triphosphate (5'-PPP), which induces a conformational change in RIG-I to an active form. It has been suggested that RIG-I detects infection of influenza A virus by recognizing the 5'-triphosphorylated panhandle structure of the viral RNA genome. Influenza panhandle RNA has a unique structure with a sharp helical bending. In spite of extensive studies of how viral RNAs activate RIG-I, whether the structural elements of the influenza panhandle RNA confer the ability to activate RIG-I signaling has been poorly explored. Here, we investigated the dynamics of the influenza panhandle RNA in complex with RIG-I CTD using NMR spectroscopy and showed that the bending structure of the panhandle RNA negates the requirement of a 5'-PPP moiety for RIG-I activation.

Association between Plasma Pentraxin 3 Levels and Bone Mineral Density in Elderly Koreans: the Dong-gu Study.

BACKGROUND: We investigated the association between pentraxin 3 (PTX3), a novel inflammatory marker, and bone mineral density (BMD) in the general Korean population. METHODS: We selected a sub-cohort of 1,440 subjects (757 men and 683 women) from participants in the community-based Dong-gu Study. The mean age was 66.0 ± 8.1 years for men and 63.7 ± 7.9 years for women. The plasma PTX3 levels were measured using an enzyme-linked immunosorbent assay, and BMD was measured in the femoral neck and lumbar spine using dual-energy X-ray absorptiometry. Linear regression analyses were used to evaluate the association between the plasma PTX3 levels and BMD. RESULTS: PTX3 was inversely associated with the BMD of the lumbar spine (P = 0.010) and femoral neck (P < 0.001) in men but not in women. For men, the association with the BMD of the femoral neck remained after adjustment for multiple comparison (P = 0.020). CONCLUSION: This study suggests that PTX3 levels might be inversely associated with BMD in elderly men.

Effects of Lithium and Phosphorus on the Efficacy of a Liner for Increasing the Shear Bond Strength Between Lithium Disilicate and Zirconia.

PURPOSE: To evaluate the effect of the chemical formulation of liners on the shear bond strength (SBS) between lithium disilicate veneering ceramic and zirconia core. MATERIALS AND METHODS: Four experimental groups (n = 12) were designed according to liner composition: negative control group (lithium and phosphorus removed from the conventional liner), Li group (lithium added to the negative control group), P group (phosphorus added to the negative control group), and Li+P group as the positive control (conventional liner). After applying the liner, lithium disilicate was pressed on zirconia. Specimens were stored in distilled water (37°C, 24 h) before testing the SBS. To test the SBS, shear force was applied perpendicular to the lithium disilicate-zirconia interface. The differences in the SBS between the veneer lithium disilicate and zirconia substructure were evaluated with one-way ANOVA (significance level of 0.05). RESULTS: The presence or absence of lithium and phosphorus influenced the efficacy of the liner. The negative control and P groups showed mainly cohesive failures, and the Li group mainly showed mixed failures. Both adhesive and mixed failures were observed in the Li+P group. The groups including lithium showed significantly higher SBS than the negative control or Li+P group (p < 0.05). The group including phosphorus, which showed higher crystallinity, showed significantly lower SBS than the negative control and Li+P groups (p < 0.05). CONCLUSIONS: The differences in the composition of the liner can affect the wettability and reactivity, and as a result, the SBS was different.

Protein kinase C downregulation induces senescence via FoxO3a inhibition in HCT116 and HEK293 cells.

We investigated the impact of protein kinase C (PKC) on cellular senescence. The PKC activity and expression of conventional PKC (cPKC) and atypical PKC (aPKC) isoforms decreased during replicative senescence in IMR-90 cells. Forced inhibition of cPKC or aPKC induced the activation of senescence markers, including senescence-associated ß-galactosidase activity and reactive oxygen species (ROS)-p53-p21Cip1/WAF1 axis in HCT116 and HEK293 cells. PKC inhibition triggered the nuclear exportation of FoxO3a via stimulation of AKT-mediated phosphorylation of FoxO3a, and thereby decreased the transcription of FoxO3a target genes. Conversely, ectopic expression of the PKC isoforms led to stimulation of the nuclear import of FoxO3a and expression of the FoxO3a target genes. Ectopic FoxO3a expression attenuated ROS accumulation and senescent phenotypes induced by PKC inhibition. Therefore, this study suggests for the first time that downregulation of PKC induces senescence through the AKT-FoxO3a-ROS-p53-p21Cip1/WAF1 pathway in HCT116 and HEK293 cells.

A prospective association between dietary folate intake and type 2 diabetes risk among Korean adults aged 40 years or older: the Korean Multi-Rural Communities Cohort (MRCohort) Study.

It has not been well established whether dietary folate intake reduces the risk of diabetes development. We aimed to clarify the prospective association between dietary folate intake and type 2 diabetes (T2D) risk among 7333 Korean adults aged 40 years or older who were included in the Multi-Rural Communities Cohort. Dietary folate intake was estimated from all 106 food items listed on a FFQ, not including folate intake from supplements. Two different measurements of dietary folate intake were used: the baseline consumption and the average consumption from baseline until just before the end of follow-up. The association between folate intake and T2D risk was determined through a modified Poisson regression model with a robust error estimator controlling for potential confounders. For 29 745 person years, 319 cases of diabetes were ascertained. In multivariable analyses, dietary folate intake was inversely associated with risk of T2D for women, not for men. For women, the incidence rate ratio of diabetes in the third tertile compared with the first tertile was 0·57 (95 % CI 0·38-0·87, P for trend=0·0085) in the baseline consumption model and 0·64 (95 % CI 0·43-0·95, P for trend=0·0244) in the average consumption model. These inverse associations was found in both normal fasting blood glucose group and impaired fasting glucose group among women. Among non-users of multinutrients and vitamin supplements, the significant inverse association remained. Thus, higher dietary intake of folate is prospectively associated with lower risk of diabetes for women.