Metformin Use and Long-term Clinical Outcomes in Kidney Transplant Recipients.

RATIONALE & OBJECTIVE: Metformin has been recommended for some patients with advanced chronic kidney disease. However, the value of metformin in kidney transplant recipients (KTRs) with pretransplant diabetes mellitus (DM) or posttransplant DM is uncertain. We investigated the clinical effects of metformin in KTRs. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: A total of 1,995 KTRs with diabetes from 6 tertiary referral centers in the Republic of Korea. EXPOSURE: Metformin usage was defined as the use of metformin for>90 days after kidney transplantation; 1,193 KTRs were metformin users, and 802 KTRs did not use metformin. Changing usage of metformin among those exposed for >90 days was also characterized. OUTCOME: Primary outcomes were all-cause mortality and death-censored graft failure (DCGF). Secondary outcomes were biopsy-proven acute rejection (BPAR) and lactic acidosis events. ANALYTICAL APPROACH: Survival analyses were conducted using multivariable Cox regression and competing risk analyses using Fine and Gray models. Changes in metformin use over time were modeled using a time-varying covariate. Metformin usage, mean daily dose, and hemoglobin A1c (HbA1c) changes were considered in the landmark analysis to address time-varying confounding. RESULTS: Metformin use was associated with a lower risk of DCGF (adjusted hazard ratio [AHR], 0.47 [95% CI, 0.23-0.96], P=0.038); there was no significant association with all-cause mortality (AHR, 0.94 [95% CI, 0.32-2.76], P=0.915) or BPAR (AHR 0.98 [95% CI, 0.62-1.54], P=0.942). In the subgroup analysis, metformin usage was associated with a reduced risk of all-cause mortality and a lower risk of DCGF for both pretransplantation DM and posttransplant DM groups. Metformin usage was associated with a lower risk of BPAR in the posttransplant DM group, although it was less effective in the pretransplantation DM group. There was no confirmed case of metformin-associated lactic acidosis (MALA) in the present cohort. A higher dose of metformin was correlated with lower risks of DCGF and BPAR. LIMITATIONS: Data on newer antidiabetic drugs such as SGLT2 inhibitors are limited, and there is potential limited generalizability to other populations. CONCLUSIONS: Metformin usage may benefit KTRs, as evidenced by its association with a reduced risk of DCGF and the absence of MALA events. Randomized controlled trials are needed to validate these observational findings.

Aminoacyl-tRNA synthetase inhibition activates a pathway that branches from the canonical amino acid response in mammalian cells.

Signaling pathways that sense amino acid abundance are integral to tissue homeostasis and cellular defense. Our laboratory has previously shown that halofuginone (HF) inhibits the prolyl-tRNA synthetase catalytic activity of glutamyl-prolyl-tRNA synthetase (EPRS), thereby activating the amino acid response (AAR). We now show that HF treatment selectively inhibits inflammatory responses in diverse cell types and that these therapeutic benefits occur in cells that lack GCN2, the signature effector of the AAR. Depletion of arginine, histidine, or lysine from cultured fibroblast-like synoviocytes recapitulates key aspects of HF treatment, without utilizing GCN2 or mammalian target of rapamycin complex 1 pathway signaling. Like HF, the threonyl-tRNA synthetase inhibitor borrelidin suppresses the induction of tissue remodeling and inflammatory mediators in cytokine-stimulated fibroblast-like synoviocytes without GCN2, but both aminoacyl-tRNA synthetase (aaRS) inhibitors are sensitive to the removal of GCN1. GCN1, an upstream component of the AAR pathway, binds to ribosomes and is required for GCN2 activation. These observations indicate that aaRS inhibitors, like HF, can modulate inflammatory response without the AAR/GCN2 signaling cassette, and that GCN1 has a role that is distinct from its activation of GCN2. We propose that GCN1 participates in a previously unrecognized amino acid sensor pathway that branches from the canonical AAR.

A Maternity Waiting Home Is an Alternative Approach for the Accessibility of Pregnant Women in an Obstetrically Underserved Area of Korea.

BACKGROUND: We analyzed whether a maternity waiting home (MWH) for pregnant women in an obstetrically underserved area of Gangwon-do in Korea, which has been in operation since August 2018, has improved the accessibility of a maternity hospital and pregnancy outcomes. METHODS: We compared and analyzed the accessibility of maternity hospitals for 170 pregnant women who applied for the MWH from August 2018 to May 2022. Among the 170 participants, 64 were MWH users and 106 non-users. The effect on pregnancy outcomes between MWH users and non-users was analyzed in the 160 people who achieved a pregnancy outcome. RESULTS: Although the average distance and travel time from the pregnant women's residence in the obstetrically underserved area to a maternity hospital were 56.4 ± 1.6 km and 63.4 ± 1.4 minutes, respectively, the average distance between the MWH and the MWH users' maternity hospital was 2.7 ± 0.2 km, and the travel time was 10.7 ± 0.6 minutes. The distance was 55.6 km closer on average and the travel time 54.1 minutes shorter. MWH users gave birth at a significantly later gestation age (38.9 ± 0.2 vs. 38.3 ± 0.15 weeks, P = 0.024) and to infants with heavier birth weights (3,300 ± 60 vs. 3,100 ± 50 gm, P = 0.024) compared with non-users. The rate of Cesarean section was significantly higher in the MWH users (47.5% vs. 44.6%, P = 0.047). The MWH users tended to be associated with a lower rate of neonatal intensive care unit admission (5.1% vs. 11.0%, P = 0.204), lower birth weight (< 2.5 kg) (1.7% vs. 8.0%, P = 0.155), and lower fetal death rate in the uterus (0% vs. 1.0%, P = 1.0) compared with non-users, but the differences were not significant. CONCLUSION: The MWH helped pregnant women in obstetrically underserved areas by improving accessibility to a maternity hospital and lengthening gestation. As a result, neonatal birth weight was heavier for MWH users than non-users. MWHs in Korea can provide an alternative way to improve accessibility to maternity healthcare for pregnant women in obstetrically underserved areas, where it is difficult to establish maternity hospitals, and thereby will improve their pregnancy outcomes.

Xenopus laevis FGF receptor substrate 3 (XFrs3) is important for eye development and mediates Pax6 expression in lens placode through its Shp2-binding sites.

Members of the fibroblast growth factor (FGF) family play important roles during various developmental processes including eye development. FRS (FGF receptor substrate) proteins bind to FGFR and serve as adapters for coordinated assembly of multi-protein complexes involved in Ras/MAPK and PI3 kinase/Akt pathways. Here, we identified Xenopus laevis Frs3 (XFrs3), a homolog of vertebrate Frs3, and investigated its roles during embryogenesis. XFrs3 is expressed maternally and zygotically with specific expression patterns throughout the early development. Knockdown of XFrs3 using a specific antisense morpholino oligonucleotide (MO) caused reduction of Pax6 expression in the lens placode, and defects in the eye ranging from microphthalmia to anophthalmia. XFrs3 MO-induced defects were alleviated by wild type XFrs3 or a mutant XFrs3 (XFrs3-4YF), in which the putative tyrosine phosphorylation sites served as Grb2-binding sites are mutated. However, another XFrs3 mutant (XFrs3-2YF), in which the putative Shp2-binding sites are mutated, could not rescue the defects of XFrs3 morphants. In addition, we found that XFrs3 is important for FGF or IGF-induced ERK activation in ectodermal tissue. Taken together, our results suggest that signaling through Shp2-binding sites of XFrs3 is necessary for the eye development in Xenopus laevis.

Halofuginone and other febrifugine derivatives inhibit prolyl-tRNA synthetase.

Febrifugine, the bioactive constituent of one of the 50 fundamental herbs of traditional Chinese medicine, has been characterized for its therapeutic activity, though its molecular target has remained unknown. Febrifugine derivatives have been used to treat malaria, cancer, fibrosis and inflammatory disease. We recently demonstrated that halofuginone (HF), a widely studied derivative of febrifugine, inhibits the development of T(H)17-driven autoimmunity in a mouse model of multiple sclerosis by activating the amino acid response (AAR) pathway. Here we show that HF binds glutamyl-prolyl-tRNA synthetase (EPRS), inhibiting prolyl-tRNA synthetase activity; this inhibition is reversed by the addition of exogenous proline or EPRS. We further show that inhibition of EPRS underlies the broad bioactivities of this family of natural product derivatives. This work both explains the molecular mechanism of a promising family of therapeutics and highlights the AAR pathway as an important drug target for promoting inflammatory resolution.

Outcomes of Various Classes of Oral Antidiabetic Drugs on Nonalcoholic Fatty Liver Disease.

Importance: Several oral antidiabetic drug (OAD) classes can potentially improve patient outcomes in nonalcoholic fatty liver disease (NAFLD) to varying degrees, but clinical data on which class is favored are lacking. Objective: To investigate which OAD is associated with the best patient outcomes in NAFLD and type 2 diabetes (T2D). Design, Setting, and Participants: This retrospective nonrandomized interventional cohort study used the National Health Information Database, which provided population-level data for Korea. This study involved patients with T2D and concomitant NAFLD. Exposures: Receiving either sodium-glucose cotransporter 2 (SGLT2) inhibitors, thiazolidinediones, dipeptidyl peptidase-4 (DPP-4) inhibitors, or sulfonylureas, each combined with metformin for 80% or more of 90 consecutive days. Main Outcomes and Measures: The main outcomes were NAFLD regression assessed by the fatty liver index and composite liver-related outcome (defined as liver-related hospitalization, liver-related mortality, liver transplant, and hepatocellular carcinoma) using the Fine-Gray model regarding competing risks. Results: In total, 80 178 patients (mean [SD] age, 58.5 [11.9] years; 43 007 [53.6%] male) were followed up for 219 941 person-years, with 4102 patients experiencing NAFLD regression. When compared with sulfonylureas, SGLT2 inhibitors (adjusted subdistribution hazard ratio [ASHR], 1.99 [95% CI, 1.75-2.27]), thiazolidinediones (ASHR, 1.70 [95% CI, 1.41-2.05]), and DPP-4 inhibitors (ASHR, 1.45 [95% CI, 1.31-1.59]) were associated with NAFLD regression. SGLT2 inhibitors were associated with a higher likelihood of NAFLD regression when compared with thiazolidinediones (ASHR, 1.40 [95% CI, 1.12-1.75]) and DPP-4 inhibitors (ASHR, 1.45 [95% CI, 1.30-1.62]). Only SGLT2 inhibitors (ASHR, 0.37 [95% CI, 0.17-0.82]), not thiazolidinediones or DPP-4 inhibitors, were significantly associated with lower incidence rates of adverse liver-related outcomes when compared with sulfonylureas. Conclusions and Relevance: The results of this cohort study suggest that physicians may lean towards prescribing SGLT2 inhibitors as the preferred OAD for individuals with NAFLD and T2D, considering their potential benefits in NAFLD regression and lower incidences of adverse liver-related outcomes. This observational study should prompt future research to determine whether prescribing practices might merit reexamination.

The effect of dialysis modality on annual mortality: A prospective cohort study.

Despite numerous studies on the effect of each dialysis modality on mortality, the issue remains controversial. We investigated the hazard rate of mortality in patients with incident end-stage renal disease (ESRD) concerning initial dialysis modality (hemodialysis vs. peritoneal dialysis). Using a nationwide, multicenter, prospective cohort in South Korea, we studied 2207 patients, of which 1647 (74.6%) underwent hemodialysis. We employed the weighted Fine and Gray model over the follow-up period using inverse probability of treatment and censoring weighting. Landmark analysis was used for identifying the changing effect of dialysis modality on individuals who remained event-free at each landmark point. No significant difference in hazard rate was observed overall. However, the peritoneal dialysis group had a significantly higher hazard rate than the hemodialysis group among patients under 65 years after 4- and 5- year follow-up. A similar pattern was observed among those with diabetes mellitus. Landmark analysis also showed the higher hazard rate for peritoneal dialysis at 2 years for the education-others group and at 3 years for the married group. These findings may inform dialysis modality decisions, suggesting a preference for hemodialysis in young patients with diabetes, especially for follow-ups longer than 3 years.

A mutation in TGFB3 associated with a syndrome of low muscle mass, growth retardation, distal arthrogryposis and clinical features overlapping with Marfan and Loeys-Dietz syndrome.

The transforming growth factor ß (TGF-ß) family of growth factors are key regulators of mammalian development and their dysregulation is implicated in human disease, notably, heritable vasculopathies including Marfan (MFS, OMIM #154700) and Loeys-Dietz syndromes (LDS, OMIM #609192). We described a syndrome presenting at birth with distal arthrogryposis, hypotonia, bifid uvula, a failure of normal post-natal muscle development but no evidence of vascular disease; some of these features overlap with MFS and LDS. A de novo mutation in TGFB3 was identified by exome sequencing. Several lines of evidence indicate the mutation is hypomorphic suggesting that decreased TGF-ß signaling from a loss of TGFB3 activity is likely responsible for the clinical phenotype. This is the first example of a mutation in the coding portion of TGFB3 implicated in a clinical syndrome suggesting TGFB3 is essential for both human palatogenesis and normal muscle growth.

Direct observation of surface charge and stiffness of human metaphase chromosomes.

Metaphase chromosomes in which both polynucleotides and proteins are condensed with hierarchies are closely related to life phenomena such as cell division, cancer development, and cellular senescence. Nevertheless, their nature is rarely revealed, owing to their structural complexity and technical limitations in analytical methods. In this study, we used surface potential and nanomechanics mapping technology based on atomic force microscopy to measure the surface charge and intrinsic stiffness of metaphase chromosomes. We found that extra materials covering the chromosomes after the extraction process were positively charged. With the covering materials, the chromosomes were positively charged (ca. 44.9 ± 16.48 mV) and showed uniform stiffness (ca. 6.23 ± 1.98 MPa). In contrast, after getting rid of the extra materials through treatment with RNase and protease, the chromosomes were strongly negatively charged (ca. -197.4 ± 77.87 mV) and showed relatively non-uniform and augmented stiffness (ca. 36.87 ± 17.56 MPa). The results suggested undulating but compact coordination of condensed chromosomes. Additionally, excessive treatment with RNase and protease could destroy the chromosomal structure, providing an exceptional opportunity for multiscale stiffness mapping of polynucleotides, nucleosomes, chromatin fibers, and chromosomes in a single image. Our approach offers a new horizon in terms of an analytical technique for studying chromosome-related diseases.

Fast Responsive, Reversible Colorimetric Nanoparticle-Hydrogel Complexes for pH Monitoring.

Hydrogels containing redox-sensitive colorimetric nanoparticles (NPs) have been used to sense ambient pH in many fields owing to their simple and fast visualization capabilities. However, real-time pH monitoring still has limitations due to its poor response rate and irreversibility. Herein, we developed a fast responsive colorimetric hydrogel called ferrocene adsorption colorimetric hydrogel (FACH). Ferrocene, an organometallic compound, plays a vital role as an electron transfer mediator (i.e., redox catalyst) within the hydrogel network. FACH shows fast color change performance with high reactivity and penetrability to ambient pH changes. In detail, FACH shows distinct color change within 2 min under various pH conditions from four to eight, with good reliability. The speed for color change of FACH is approximately six times faster than that of previously developed colorimetric hydrogels, suggesting the fastest hydrogel-based colorimetric pH sensor. Furthermore, FACH shows reversibility and repeatability of the redox process, indicating scalable utility as a sustainable pH monitoring platform.

Primary Angiosarcoma of the Breast: A Single-Center Retrospective Study in Korea.

Due to the rarity of primary angiosarcoma of the breast, optimal management is based on expert opinion. The aim of this study was to review all primary angiosarcomas of the breast obtained from a single center in terms of clinicopathologic characteristics, treatment, and survival outcomes. From 1997 to 2020, 15 patients with primary angiosarcoma of the breast underwent either mastectomy or wide excision. We analyzed the clinicopathologic data to assess disease-free survival and overall survival. Fifteen women with primary angiosarcoma of the breast were identified. The mean age at diagnosis was 33 years (range: 14-63 years). The overall mean tumor size was 7.7 cm (range 3.5-20 cm). Upon histological grading, there were three cases of low grade, five intermediate grade, six high grade, and one unidentified grade. The five-year disease-free survival rate was 24.4%, and the five-year survival rate was 37.2%. The survival rate of the low-grade patient group was statistically higher than that of the intermediate- or high-grade patient groups (p = 0.024). Primary angiosarcoma of the breast is a rare aggressive tumor characterized by high grade and poor outcome. Histologic grade appears to be a reliable predictor of survival. There are no standard treatment guidelines; thus, optimal R0 surgical resection remains the best approach. The roles of neoadjuvant, adjuvant chemotherapy, and radiotherapy remain unclear.

Akt phosphorylates and regulates the function of Dlx5.

Akt, a phosphoinositide-dependent serine/threonine protein kinase, acts as a key regulator in bone formation. Akt can be activated by several osteogenic signaling molecules, but its precise function and downstream targets in bone development are unknown. Dlx5 transcription factor plays important roles during bone development and osteoblast differentiation. Its expression is regulated by several osteogenic signals. In addition, Dlx5 function is also regulated through post-translational modification by several kinases. In this report, we have investigated a potential regulation of Dlx5 function by Akt. Our results indicate that Akt interacts with and phosphorylates Dlx5. In addition, we provide evidences that Akt kinase activity is important for Akt to enhance the protein stability and transcriptional activity of Dlx5. These results suggest that Dlx5 is a novel target of Akt and that the activity of Dlx5 could be modulated by a novel mechanism involving Akt during osteoblast differentiation.

Web-Based Text Analysis of the Patient Safety Concerns of Various Healthcare Stakeholders.

Patient safety is a fundamental aspect of the quality of healthcare and there is a growing interest in improving safety among healthcare stakeholders in many countries. The Korean government recognized that patient safety is a threat to society following several serious adverse events, and so the Ministry of Health and Welfare of the Korean government set up the Patient Safety Act in January 2015. This study analyzed text data on patient safety collected from web-based, user-generated documents related to the legislation to see if they accurately represent the specific concerns of various healthcare stakeholders. We adopted the unsupervised natural language processing method of probabilistic topic modeling and also Latent Dirichlet Allocation. The results showed that text data are useful for inferring the latent concerns of healthcare consumers, providers, government bodies, and researchers as well as changes therein over time.

The Relationship of Lifestyle Factors with the Prevalence of Major Depressive Disorder by Ecological Factors.

OBJECTIVE: The association between ecological/lifestyle factors and major depressive disorder (MDD) have been provided but was inconsistent as characteristics of population including race, gender, etc. METHODS: Data were extracted from the Korean National Health and Nutrition Examination Survey and consisted of 35,839 adults including 1,537 with MDD. Ecological factors included age, sex, married status, education, family income, residence, occupation, BMI, self-recognition stress, and history of non-communicable disease. Smoking, drinking, regular exercise, total energy intake, and sleep was consisted for lifestyle factors. The relationship between MDD and ecological/lifestyle factors, was evaluated using the multiple logistic regression model after adjustment for covariates. RESULTS: The increased prevalence of MDD in men was related aged, unmarried, low educated, unoccupied, high BMI, and high self-recognition stress. To women, MDD prevalence was increased as aged, low educated and family income, resided in urban, unoccupied, high self-recognition stress and history of non-communicable disease. Current smoking/drinking and lack of sleep was positively related with prevalence of MDD in women. The relationship between lifestyle factors and MDD prevalence was influenced by ecological status, predominantly in women. CONCLUSION: The relationship of lifestyle factors with MDD prevalence were observed and could be attenuated by various ecological factors, in women.

Macronutrient Intake in Adults Diagnosed with Metabolic Syndrome: Using the Health Examinee (HEXA) Cohort.

Macronutrient intake is important in the prevention and management of metabolic syndrome (MetS). This study aimed to evaluate total energy and macronutrient intake of participants diagnosed with MetS at recruitment of the health examinees (HEXA) cohort, considering the plant and animal sources of each macronutrient. We included 130,423 participants aged 40-69 years for analysis. Odds ratios (OR) and 95% confidence intervals (CI) were estimated to evaluate the intake of macronutrients stratified by gender. Energy and macronutrient intake were estimated by linking food frequency questionnaire data to the Korean food composition database, and were calculated separately for plant and animal foods. Low energy (men: OR = 0.95, 95% CI: 0.92-0.98; women: OR = 0.97, 95% CI: 0.95-0.99), and fat intake (men: OR = 0.93, 95% CI: 0.90-0.96; women: OR = 0.80, 95% CI: 0.77-0.83) were observed. Only postmenopausal women had lower intake of total energy (OR = 0.95, 95% CI: 0.92-0.97), whereas low fat intake was observed in all women (OR = 0.80, 95% CI: 0.77-0.83). For carbohydrate intake, the OR were 1.14 (95% CI: 1.08-1.22) and 1.17 (95% CI: 1.08-1.27) among women in their 50s and 60s, respectively. Protein intake was low (OR = 0.90, 95% CI: 0.86-0.95; and OR = 0.88, 95% CI: 0.82-0.94) among women in their 50s and 60s, respectively. High intake of plant carbohydrates in women (OR = 1.16, 95% CI: 1.12-1.20), and plant protein in both genders (OR = 1.09, 95% CI: 1.05-1.13) were observed, but low intake of total energy, fat, and animal-source carbohydrates in both genders was also observed. Fat intake was low regardless of food source. In conclusion, high consumption of plant-source macronutrients, and low consumption of animal-source macronutrients was observed in Korean adults diagnosed with MetS. Attention should be directed to plant sources of carbohydrates and proteins when designing population interventions for metabolic syndrome reduction in Korea.

Comparison of Nicotine Dependence and Biomarker Levels among Traditional Cigarette, Heat-Not-Burn Cigarette, and Liquid E-Cigarette Users: Results from the Think Study.

This study aimed to compare Korean smokers' smoking-related biomarker levels by tobacco product type, including heat-not-burn cigarettes (HNBC), liquid e-cigarettes (EC), and traditional cigarettes (TC). Nicotine dependence levels were evaluated in Korean adult study participants including TC-, EC-, HNBC-only users and nonsmokers (n = 1586) from March 2019 to July 2019 in Seoul and Cheonan/Asan South Korea using the Fagerström Test Score. Additionally, urine samples (n = 832) were collected for the measurement of urinary nicotine, cotinine, OH-cotinine, NNAL(4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol), CYMA(N-acetyl-S-(2-cyanoehtyl)-L-cysteine), or CEMA (2-cyanoethylmercapturic acid) using LC-MS/MS. The median(interquartile range) nicotine dependence level was not different among the three types of smokers, being 3.0 (2.0-5.0) for TC- (n = 726), 3.0 (1.0-4.0) for EC- (n = 316), and 3.0 (2.0-4.0) for HNBC- (n = 377) only users. HNBC-only users presented similar biomarker levels compared to TC-only users, except for NNAL (HNBC: 14.5 (4.0-58.8) pg/mL, TC: 32.0 (4.0-69.6) pg/mL; p = 0.0106) and CEMA (HNBC: 60.4 (10.0-232.0) ng/mL, TC: 166.1 (25.3-532.1) ng/mL; p = 0.0007). TC and HNBC users showed increased urinary cotinine levels as early as the time after the first smoke of the day. EC users' biomarker levels were possibly lower than TC or HNBC users' but higher than those of non-smokers.

What are the main patient safety concerns of healthcare stakeholders: a mixed-method study of Web-based text.

OBJECTIVES: Various healthcare stakeholders define quality of care in different ways. Public policy could advocate all these concerns. This study was conducted to identify the main themes on patient safety of stakeholders expressed before and after the Patient Safety Act was enacted in Korea in 2015. DESIGN: Longitudinal observational study of the interests of healthcare stakeholders generated between January 2014 and September 2018. MATERIALS AND METHODS: Text data were collected from 2,487 documents on 18 websites that were identified as representative healthcare stakeholder groups of consumers, providers, government, and researchers. A Korean natural language processing (NLP) package, manual review, and synonym dictionary were used for data preprocessing, and we adopted the unsupervised NLP method of probabilistic topic modeling and latent Dirichlet allocation. A linear trend analysis over time, a qualitative step involving two external experts, and original text reviews were performed to validate the identified topics. RESULTS: Forty-one topics were identified, and the most common concerns of stakeholders were institutional infection control as triggered by the Middle East respiratory syndrome outbreak in early 2015, and infusion-related infection from late 2017 until the middle of 2018. The other top-three concerns of the stakeholder groups were highly similar, while research topics were limited to the perceptions of providers and the activities and culture of hospitals. Five topics showed statistically significant increasing trends over time, while another five showed decreasing trends (both P < 0.05). In the qualitative step, we confirmed 35 themes and revised the other 6. CONCLUSIONS: A common concern among stakeholders was hospital infection control, ranging from nosocomial infections to those brought in by family visiting patients. Government policies and systemic approaches to patient safety were highlighted by different stakeholders. Researchers were focused on hospital sociocultural factors at both the organizational and clinician levels. These identified concerns all should be advocated by the public health policy.

Effect of Psychological Distance on Intention in Self-Affirmation Theory.

In previous studies, self-affirmation has been shown to have no effect or have a negative impact on intention to change. We applied construal level theory to examine possible reasons for inconsistencies among findings in existing self-affirmation studies. In Study 1, when female college students in their 20s (N = 113) received health threat information with a psychologically proximal breast cancer message, it induced low-level construal and increased specific physical activity intention. In Study 2, when self-affirmed participants were exposed to health threat information with a psychologically distal Alzheimer's disease message, there was no increase in specific physical activity intention. These results suggest that when a discrepancy exists between the psychological distance of health threat information and the intention reflecting the construal level, no change of intention occurs, even in self-affirmed individuals.

The Association of Dietary Macronutrients with Lung Function in Healthy Adults Using the Ansan-Ansung Cohort Study.

This study is aimed to examine the association between macronutrient intake and lung function in healthy adults (n = 5880) using the Ansan-Ansung cohort study. To identify the index of lung function, we used the percentage difference of predicted Forced Expiratory Volume (%FEV1_diff) between baseline and follow-up. Based on the median %FEV1_diff, subjects were classified by two groups as "decreased vs. unchanged/improved". The dietary macronutrients were estimated and validated using the food-frequency questionnaire. Multiple logistic regression models were used to evaluate the association after adjusting for confounders. Advanced analysis examined the association after stratifying by age and obesity. The average of %FEV1 is 114.1 and 112.5 at baseline and follow-up, respectively. The positive association of protein and fiber intake with lung function was observed in men. Low fat and high carbohydrate intake decreased the lung function in women only. After stratification by age, the association of protein, fat, and carbohydrate intake with lung function was observed in young men and old women only. Otherwise, the association of protein and fiber with lung function was influenced by abdominal obesity. In conclusion, the lung function was positively associated with high protein and fat intake, but was negatively associated with high carbohydrate intake, which could be influenced by age and obesity.

Acetylation of histone deacetylase 6 by p300 attenuates its deacetylase activity.

Protein acetyltransferases and deacetylases affect the activities of each other. This is well documented by the acetylation and inhibition of HDAC1 by p300, a transcriptional co-activator with protein acetyltransferase activity. However, the relationship between HDAC6 and p300 is poorly understood. HDAC6 is a class II histone deacetylase and differs from other members of HDAC family in that it contains two HDAC domains and an ubiquitin-binding motif. HDAC6 is a microtubule-associated deacetylase. It predominantly deacetylates non-histone proteins, including alpha-tubulin, and regulates cell motility. Here, we report that p300 interacts with and acetylates HDAC6 resulting down-regulation of HDAC6 deacetylase activity. Furthermore, we provide evidences that acetylation of HDAC6 by p300 inhibits tubulin deacetylation and suppression of Sp1 transcriptional activity by HDAC6. Our results demonstrate that p300 can inactivate HDAC6 by acetylation, and that p300 may regulate the activity of Sp1 indirectly through HDAC6 in addition to its direct modification of Sp1.