FOXL2 and FOXA1 cooperatively assemble on the TP53 promoter in alternative dimer configurations.

Although both the p53 and forkhead box (FOX) family proteins are key transcription factors associated with cancer progression, their direct relationship is unknown. Here, we found that FOX family proteins bind to the non-canonical homotypic cluster of the p53 promoter region (TP53). Analysis of crystal structures of FOX proteins (FOXL2 and FOXA1) bound to the p53 homotypic cluster indicated that they interact with a 2:1 stoichiometry accommodated by FOX-induced DNA allostery. In particular, FOX proteins exhibited distinct dimerization patterns in recognition of the same p53-DNA; dimer formation of FOXA1 involved protein-protein interaction, but FOXL2 did not. Biochemical and biological functional analyses confirmed the cooperative binding of FOX proteins to the TP53 promoter for the transcriptional activation of TP53. In addition, up-regulation of TP53 was necessary for FOX proteins to exhibit anti-proliferative activity in cancer cells. These analyses reveal the presence of a discrete characteristic within FOX family proteins in which FOX proteins regulate the transcription activity of the p53 tumor suppressor via cooperative binding to the TP53 promoter in alternative dimer configurations.

An efficient nickel hydrogen oxidation catalyst for hydroxide exchange membrane fuel cells.

The hydroxide exchange membrane fuel cell (HEMFC) is a promising energy conversion technology but is limited by the need for platinum group metal (PGM) electrocatalysts, especially for the hydrogen oxidation reaction (HOR). Here we report a Ni-based HOR catalyst that exhibits an electrochemical surface area-normalized exchange current density of 70 µA cm-2, the highest among PGM-free catalysts. The catalyst comprises Ni nanoparticles embedded in a nitrogen-doped carbon support. According to X-ray and ultraviolet photoelectron spectroscopy as well as H2 chemisorption data, the electronic interaction between the Ni nanoparticles and the support leads to balanced hydrogen and hydroxide binding energies, which are the likely origin of the catalyst's high activity. PGM-free HEMFCs employing this Ni-based HOR catalyst give a peak power density of 488 mW cm-2, up to 6.4 times higher than previous best-performing analogous HEMFCs. This work demonstrates the feasibility of efficient PGM-free HEMFCs.

Broncho-Vaxom bacterial lysate prevents asthma via acetate enhancement in mouse model.

PURPOSE: Broncho-Vaxom (BV) is known to attenuate allergic airway inflammation and chronic bronchitis in humans, but the underlying mechanism of this gut-mediated immunity remains unclear. This study investigated the effects of an oral BV on gut and systemic short-chain fatty acids (SCFAs) and immune responses. METHODS: Oral BV was administered daily for 15 days prior to commencing the study in an asthma mouse model. Asthma was induced by ovalbumin (OVA) sensitization followed by a challenge with 1% OVA by inhalation. Asthmatic phenotypes, gut- and systemic- immune responses, and SCFAs in the cecum and blood were then investigated. RESULTS: Airway hyperresponsiveness, total immunoglobulin E production, and pulmonary inflammation were all significantly suppressed by BV. The interleukin-13 level was also suppressed, whereas TGF-ß expression was increased, in the lungs of the BV-treated mice. The regulatory T (Treg) cell numbers were increased in the small intestine, and the acetate level was increased in the cecum and serum after BV treatment. The levels of acetate in the cecum and serum were negatively correlated with airway hyperresponsiveness and with the eosinophil numbers in the BAL fluid of the OVA-induced mice. There was a positive correlation between the acetate levels in the feces and serum and the lung expression of TGF-ß in the asthma mice. CONCLUSIONS: Oral BV administration appears to prevent allergic inflammation by enhancing Treg cell proliferation and acetate production in an asthmatic mouse model.

The alternative bile acid pathway can predict food allergy persistence in early childhood.

BACKGROUND: Mechanisms underlying persistent food allergy (FA) are not well elucidated. The intestinal mucosa is the primary exposure route of food allergens. However, no study has examined intestinal metabolites associated with FA persistence. The goal of this study was to investigate intestinal metabolites and associated microbiomes in early life that aid in determining the development and persistence of FA. METHODS: We identified metabolomic alterations in the stool of infants according to FA by mass spectrometry-based untargeted metabolome profiling. The targeted metabolomic analysis of bile acid metabolites and stool microbiome was performed. Bile acid metabolite composition in infancy was evaluated by characterizing the subjects at the age of 3 into FA remission and persistent FA. RESULTS: In untargeted metabolomics, primary bile acid biosynthesis was significantly different between subjects with FA and healthy controls. In targeted metabolomics for bile acids, intestinal bile acid metabolites synthesized by the alternative pathway were reduced in infants with FA than those in healthy controls. Subjects with persistent FA were also distinguished from healthy controls and those with FA remission by bile acid metabolites of the alternative pathway. These metabolites were negatively correlated with specific IgE levels in egg white. The abundance of intestinal Clostridia was decreased in the FA group and was correlated with ursodeoxycholic acid. CONCLUSION: Intestinal bile acid metabolites of the alternative pathway could be predictive biomarkers for persistent FA in early childhood. These findings require replication in future studies.

Machine learning-based prediction model for postoperative delirium in non-cardiac surgery.

BACKGROUND: Postoperative delirium is a common complication that is distressing. This study aimed to demonstrate a prediction model for delirium. METHODS: Among 203,374undergoing non-cardiac surgery between January 2011 and June 2019 at Samsung Medical Center, 2,865 (1.4%) were diagnosed with postoperative delirium. After comparing performances of machine learning algorithms, we chose variables for a prediction model based on an extreme gradient boosting algorithm. Using the top five variables, we generated a prediction model for delirium and conducted an external validation. The Kaplan-Meier and Cox survival analyses were used to analyse the difference of delirium occurrence in patients classified as a prediction model. RESULTS: The top five variables selected for the postoperative delirium prediction model were age, operation duration, physical status classification, male sex, and surgical risk. An optimal probability threshold in this model was estimated to be 0.02. The area under the receiver operating characteristic (AUROC) curve was 0.870 with a 95% confidence interval of 0.855-0.885, and the sensitivity and specificity of the model were 0.76 and 0.84, respectively. In an external validation, the AUROC was 0.867 (0.845-0.877). In the survival analysis, delirium occurred more frequently in the group of patients predicted as delirium using an internal validation dataset (p < 0.001). CONCLUSION: Based on machine learning techniques, we analyzed a prediction model of delirium in patients who underwent non-cardiac surgery. Screening for delirium based on the prediction model could improve postoperative care. The working model is provided online and is available for further verification among other populations. TRIAL REGISTRATION: KCT 0006363.

Indoor particulate matter induces epigenetic changes in companion atopic dogs.

The prevalence of atopic dermatitis (AD) is increasing and environmental factors are receiving attention as contributing causes. Indoor air pollutants (IAPs), especially particulate matter (PM) can alter epigenetic markers, DNA methylation (DNAm). Although DNAm-mediated epigenetic changes have been reported to modulate the pathogenesis of AD, their role at high risk of exposure to PM is still unclear. The study investigated the effects of exposure to IAPs in the development of AD and epigenetic changes through DNAm in companion atopic dogs that share indoor environment with their owners. Dogs were divided into two groups: AD (n = 47) and controls (n = 21). The IAPs concentration in each household was measured for 48 h, and a questionnaire on the residential environment was completed in all dogs. Eighteen dogs with AD and 12 healthy dogs were selected for DNAm analysis. In addition, clinical and immunological evaluations were conducted. The concentrations of PM2.5, PM10, and volatile organic compounds (VOCs) were significantly higher in the AD group. Moreover, there were more significant methylation differences in the LDLRAD4, KHSRP, and CTDSP2 genes in connection with PM10 in AD group compared to the controls. The degree of methylation of the LDLRAD4 and CTDSP2 genes was also correlated with related protein productions. The present study revealed that exposure to high indoor PM can cause epigenetic development of AD by methylation of the LDLRAD4, KHSRP, and CTDSP2 genes in dogs. Under the concept of "One Health," improving indoor environments should be considered to prevent the development of AD.

Ruminococcus gnavus ameliorates atopic dermatitis by enhancing Treg cell and metabolites in BALB/c mice.

BACKGROUND: Ruminococcus gnavus (R. gnavus) are mucin-degrading gut bacteria that play a key role in the early colonization of the gut by serving as endogenous sources of nutrients. They can also influence immune development. We had previously reported a lower abundance of R. gnavus in infants with atopic dermatitis (AD) compared with that in healthy subjects. However, the underlying mechanisms remain unclear. In this study, we investigated the effect of orally administered R. gnavus on antibiotic treatment-induced gut dysbiosis (and the underlying mechanism) in a mouse model of AD. METHODS: Four-week-old female BALB/C mice were administered antibiotic cocktails for 2 weeks. R. gnavus was orally administered throughout the study duration. At 6 weeks of age, AD was induced by epidermal sensitization with ovalbumin. AD phenotypes and systemic and gut immune responses were investigated. RESULTS: Orally administered R. gnavus significantly reduced AD-associated parameters (i.e., transepidermal water loss, clinical score, total serum immunoglobulin (Ig) E level, OVA-specific IgE level, and skin inflammation). R. gnavus treatment also resulted in significant downregulation of T helper 2-related cytokine mRNA and upregulation of interleukin (IL)-10 and Foxp3 in the skin. The population of CD4+ FOXP3+ T cells in mesenteric- and skin-draining lymph nodes and butyrate levels in the cecum increased in R. gnavus-administered AD mice. CONCLUSIONS: Immune modulation by orally administered R. gnavus may alleviate AD symptoms through the enhancement of regulatory T-cell counts and short-chain fatty acids production in AD mice.

Host-microbial interactions between PTGR2 and Bifidobacterium in the early life gut of atopic dermatitis children.

BACKGROUND: Gut microbiota dysbiosis is linked to the development and responses of the immune system and can play an important role in the onset of allergic diseases including atopic dermatitis (AD). This study investigated the association between host genetics and the gut microbiota in AD. METHODS: A global gene expression profiling of the gut epithelial colonocytes, genetic variations analysis, and the gut microbial composition analysis were performed. RESULTS: This study identified the upregulation of PTGR2 (p = .028), a gene involved in prostaglandin catalysis and inflammatory responses, as a potential risk factor for AD. In subsequent fine mapping analysis using 17 single nucleotide polymorphisms (SNPs) of PTGR2 in 864 Korean subjects (420 AD patients and 444 unaffected controls), several SNPs and haplotypes showed significant associations with AD and its SCORing AD (SCORAD) values (p = .002). To investigate host-microbial interactions, further gut microbiota data and genotypes were obtained from an independent cohort of 176 subjects (91 AD patients and 85 controls). From correlation analysis, a significantly negative association between SNP and Bifidobacterium abundance was observed in AD patients (p = .005). In additional observations of PTGR2-associated downstream molecules, NRF2 (p = .004) and several antioxidant genes (GSTT1, GCLC, GPX1; p < .05) showed significantly reduced expression in AD patients. CONCLUSIONS: Our current findings suggest that the interaction between PTGR2 dysregulated expression and a Bifidobacterium abundance affects a higher risk of AD and a more severe onset.

Comprehensive LC-MS/MS method combined with tandem hybrid hydrolysis for multiple exposure assessment of multiclass environmental pollutants.

Environmental pollutants (EPOLs), such as phthalates, volatile organic compounds, phenols, parabens, polycyclic aromatic hydrocarbons, pyrethroids, and environmental tobacco smoke, are highly heterogeneous compounds. Recently, attention has been drawn to the assessment of the combinatory effects of multiple EPs. To correlate multiple exposures with potential health implications, advanced comprehensive analytical methods covering multiclass EPOLs are essential. However, because of several technical problems associated with enzyme hydrolysis, simultaneous extraction, and multiresidue liquid chromatography-tandem mass spectrometry analysis, it is difficult to establish a comprehensive method covering a number of EPOLs in a single sample preparation and analytical run. We developed tandem hybrid hydrolysis, modified direct injection, and a comprehensive mobile phase to overcome these technical problems and established a comprehensive analytical method for simultaneous biomonitoring of multiclass EPOLs. Tandem hybrid hydrolysis using ß-glucuronidase and consecutive acid hydrolysis allowed selective hydrolysis of glucuronide- and sulfate-conjugated metabolites without phthalate degradation. The comprehensive mobile phase composed of 0.01% acetic acid and acetonitrile enabled us to simultaneously analyze 86 EPOLs, with good chromatographic behavior and ionization efficiency. Modified direct injection allowed a small amount of sample and simultaneous urinary extraction. The method was validated and applied to 39 urine samples from 19 mother-newborn pairs for multiple exposure assessment. Results showed that BP-3, a general component in sunblock products, and monoethyl phthalate, a metabolite of diethyl phthalate, exhibit a clear positive correlation between mothers and newborns. Therefore, the developed method has potential as a novel analytical tool for long-term, large-scale, and data-rich human biomonitoring of EPOLs.

Accuracy of Cloud-Based Speech Recognition Open Application Programming Interface for Medical Terms of Korean.

BACKGROUND: There are limited data on the accuracy of cloud-based speech recognition (SR) open application programming interfaces (APIs) for medical terminology. This study aimed to evaluate the medical term recognition accuracy of current available cloud-based SR open APIs in Korean. METHODS: We analyzed the SR accuracy of currently available cloud-based SR open APIs using real doctor-patient conversation recordings collected from an outpatient clinic at a large tertiary medical center in Korea. For each original and SR transcription, we analyzed the accuracy rate of each cloud-based SR open API (i.e., the number of medical terms in the SR transcription per number of medical terms in the original transcription). RESULTS: A total of 112 doctor-patient conversation recordings were converted with three cloud-based SR open APIs (Naver Clova SR from Naver Corporation; Google Speech-to-Text from Alphabet Inc.; and Amazon Transcribe from Amazon), and each transcription was compared. Naver Clova SR (75.1%) showed the highest accuracy with the recognition of medical terms compared to the other open APIs (Google Speech-to-Text, 50.9%, P < 0.001; Amazon Transcribe, 57.9%, P < 0.001), and Amazon Transcribe demonstrated higher recognition accuracy compared to Google Speech-to-Text (P < 0.001). In the sub-analysis, Naver Clova SR showed the highest accuracy in all areas according to word classes, but the accuracy of words longer than five characters showed no statistical differences (Naver Clova SR, 52.6%; Google Speech-to-Text, 56.3%; Amazon Transcribe, 36.6%). CONCLUSION: Among three current cloud-based SR open APIs, Naver Clova SR which manufactured by Korean company showed highest accuracy of medical terms in Korean, compared to Google Speech-to-Text and Amazon Transcribe. Although limitations are existing in the recognition of medical terminology, there is a lot of rooms for improvement of this promising technology by combining strengths of each SR engines.

Reinforcement Learning Based Multipath QUIC Scheduler for Multimedia Streaming.

With the recent advances in computing devices such as smartphones and laptops, most devices are equipped with multiple network interfaces such as cellular, Wi-Fi, and Ethernet. Multipath TCP (MPTCP) has been the de facto standard for utilizing multipaths, and Multipath QUIC (MPQUIC), which is an extension of the Quick UDP Internet Connections (QUIC) protocol, has become a promising replacement due to its various advantages. The multipath scheduler, which determines the path to which each packet should be transmitted, is a key function that affects the multipath transport performance. For example, the default minRTT scheduler typically achieves good throughput, while the redundant scheduler gains low latency. While the legacy schedulers may generally give a desirable performance in some environments, however, each application renders different requirements. For example, Web applications target low latency, while video streaming applications require low jitter and high video quality. In this paper, we propose a novel MPQUIC scheduler based on deep reinforcement learning using the Deep Q-Network (DQN) that enhances the quality of multimedia streaming. Our proposal first takes into account both delay and throughput as a reward for reinforcement learning to achieve a low video chunk download time. Second, we propose a chunk manager that informs the scheduler of the video chunk information, and we also tune the learning parameters to explore new random actions adequately. Finally, we implement our new scheduler on the Linux kernel and give results using the Mininet experiments. The evaluation results show that our proposal outperforms legacy schedulers by at least 20%.

Development of a Quantitative Method for Detection of Multiclass Veterinary Drugs in Feed Using Modified QuPPe Extraction and LC-MS/MS.

A method was developed for the rapid and quantitative analysis of 30 veterinary drugs belonging to 17 classes (amphenicols (1), anthelmintics (1), cephalosporins (4), coccidiostats (1), lincosamides (1), macrolide (1), nitroimidazole (1), penicillins (3), phenylhydrazines (1), polypeptides (1), pyrethrins (1), quinolones (5), sulfonamides (3), tetracycline (3), neuroleptic agents (1), triazene trypanocidal agents (1), other. (1)) in feeds. The proposed method with a modified Quick Polar Pesticides (QuPPe) sample preparation was validated for the determination of 30 veterinary drugs in feed samples by liquid chromatography triple-quadrupole mass spectrometry (LC-MS/MS). The sample was extracted with methanol containing 1% acetic acid and purified by dispersive solid-phase extraction (d-SPE) with C18. Good linearity (r2 ≥ 0.98) was observed, and the LOQ values ranged from 10 to 200 µg/kg. Average recoveries ranged from 70.8 to 118.4%, and the relative standard deviation was ≤ 18.7%. This validated method was used in the determination of 30 veterinary drugs in 142 feed samples obtained from South Korea. The results show that lincomycin was present in only one of the tested feed samples, although it was detected at a value lower than the LOQ. In conclusion, this multi-residue method can be used for screening through the detection and quantitation of residual multiclass veterinary drugs in feed samples.

Assessment of organochlorine pesticides in the atmosphere of South Korea: spatial distribution, seasonal variation, and sources.

Organochlorine pesticides (OCPs) are widely used in certain countries. We determined atmospheric concentrations, distribution patterns, and seasonal variations of OCPs at four sites in South Korea for 1 year. Samples of 22 OCPs were collected using a high-volume air sampler, and measured via the isotope dilution method with HRGC/HRMS. In South Korea, pentachlorobenzene (PeCB), hexachlorocyclohexane (HCB), and endosulfan (EnSF) were dominant, accounting for > 87% of total OCPs. Spatial distributions showed significant differences and the highest levels were observed in Seosan (295.2 pg·m-3), indicating the compounding potential of diverse sources as Seosan has concentrated large-scale industrial complexes and agricultural activity (Seoul: 243.6 pg·m-3 > Jeju: 193.5 pg·m-3 > Baengnyeong: 178.2 pg·m-3). The isomeric ratios of OCPs in the South Korean atmosphere indicated that the dominant sources of HCB and dichlorodiphenyltrichloroethane were primarily used in the past; meanwhile, chlordane (CHL) and EnSFs were derived from recent material inputs. Seasonally, OCP concentrations largely peaked in summer with minimum values in winter. This apparent temperature dependence suggests the re-volatilization of accumulated chemicals into the atmosphere. Additionally, an air mass back trajectory indicated the influence of pollutants released from a reservoir through long-range atmospheric transport in the summer. In particular, restricted OCPs are primarily released into the atmosphere by inadvertent sources, such as industrial activities and volatilization from contaminated areas. Thus, severe OCP pollution in Korea is due to the mobile nature of the particles. These data can be useful for the continuous monitoring of long-range transported air pollutants that are transferred between countries.

Sex difference in long-term clinical outcomes after percutaneous coronary intervention: A propensity-matched analysis of National Health Insurance data in Republic of Korea.

OBJECTIVE: We investigated the gender difference in the 5-year outcome after percutaneous coronary intervention (PCI) using an unselected population data. BACKGROUND: Sex-specific outcome after percutaneous coronary intervention (PCI) is not consistent among studies. METHODS: A total of 48,783 patients were enrolled from a Korean nationwide cohort of PCI in year 2011. Outcomes adjusted with age and propensity for clinical characteristics were compared. Primary outcome was 5-year cumulative incidence of all-cause death. Nonfatal major adverse clinical event (MACE) consisting of revascularization, shock, or stroke was also assessed. RESULTS: In unadjusted analysis, women were older and had higher frequency of comorbidities including hypertension, hyperlipidemia, and diabetes compared to men (p < .001, all). Women had higher 5-year death risk than men (21.8 vs. 17.3%; hazard ratio [HR] 1.29, 95% confidential interval [CI] 1.23-1.34). In propensity score-matched analysis (N = 28,924), women had lower 5-year death risk (20.2 vs. 26.1%, HR 0.75, 95% CI 0.71-0.78). This lower death risk in women was consistent in subgroup analyses of age, risk factors, and clinical diagnosis including angina or acute myocardial infarction (p < .05, all). CONCLUSIONS: Older age and more common comorbidities in women contributed to the apparent worse outcome after PCI in women. After adjusting these disadvantages, women had better outcome after PCI than men.

Medication Adherence and Clinical Outcome of Fixed-Dose Combination vs. Free Combination of Angiotensin Receptor Blocker and Statin.

BACKGROUND: Non-compliance with angiotensin receptor blockers (ARB) or statin is one of the major hurdles to optimal medical treatment. This study investigated whether fixed-dose combination (FDC) improved compliance to medication compared with traditional free combination (FC).Methods and Results:In this retrospective nationwide cohort study, medication persistency, medication adherence measured by proportion of days covered (PDC), and all-cause death of 123,992 patients who started ARB and stain were investigated for 540 days. Patients had a mean age of 63 years and 48% were male. Persistency, PDC, and proportion of PDC ≥80% of FDC (N=34,776) were higher than those for FC (N=89,216) in both unadjusted analysis (54.5% vs. 27.8%; 84.1% vs. 63.1%; 75.5% vs. 48.1%) and propensity-score matched analysis (P<0.001, all). Death risk for the investigation period (0-540 days) was lower in FDC in unadjusted (1.8% vs. 2.6%, P<0.001) and adjusted cohort (P<0.05). In landmark analyses at days 180 and 360, there was no significant difference of death risk between FDC and FC (P>0.05). CONCLUSIONS: In this real-world data analysis, patients taking FDC of ARB and statin showed higher medication persistence and adherence compared to patients taking FC of ARB and statin up to 540 days. The risk of all-cause death was not different between FDC and FC despite better medication compliance in the FDC patients.

Prognosis of Myocardial Injury After Non-Cardiac Surgery in Adults Aged Younger Than 45 Years.

BACKGROUND: This study compared myocardial injury after non-cardiac surgery (MINS) and mortalities between patients under and over the age of 45 years.Methods and Results:From January 2010 and June 2019, patients with cardiac troponin measurement within 30 days after non-cardiac surgery were enrolled and divided into groups according to age: >45 (≥45 years) and <45 (<45 years). Further analyses were conducted only in patients who were diagnosed with MINS. The outcomes were MINS and 30-day mortality. Of the 35,223 patients, 31,161 (88.5%) patients were in the >45-year group and 4,062 (11.5%) were in the <45-year group. After adjustment with inverse probability of weighting, the <45-years group showed a lower incidence of MINS and cardiovascular mortality (16.6% vs. 11.7%; odds ratio, 0.77; 95% confidence interval [CI], 0.69-0.84; P<0.001 and 0.4% vs. 0.2%; hazard ratio [HR], 0.41; 95% CI, 0.19-0.88; P=0.02, respectively). In a comparison of only the <45-years group, MINS was associated with increased 30-day mortality (0.7% vs. 10.3%; HR, 10.48; 95% CI, 6.18-17.78; P<0.001), but the mortalities of patients with MINS did not differ according to age. CONCLUSIONS: MINS has a comparable prognostic impact in patients aged under and over 45 years; therefore, future studies need to also consider patients aged <45 years regarding risk factors of MINS and screening of perioperative troponin elevation.

Mid-pregnancy PM2.5 exposure affects sex-specific growth trajectories via ARRDC3 methylation.

Prenatal particulate matter <2.5 µm (PM2.5) is associated with adverse birth growth. However, the longitudinal growth impacts have been little studied, and no mechanistic relationships have been described. We investigated the association between prenatal PM2.5 exposure and growth trajectories, and the possible role of epigenetics. We enrolled 1313 neonates with PM2.5 data measured by ordinary kriging from the COhort for Childhood Origin of Asthma and allergic diseases, followed up at 1, 3, and 5 years to evaluate growth. Differential DNA methylation and pyrosequencing of cord blood leukocytes was evaluated according to the prenatal PM2.5 levels and birth weight (BW). PM2.5 exposure during the second trimester (T2) caused the lowest BW in both sexes, further adjusted for indoor PM2.5 levels [female, aOR 1.39 (95% CI 1.05-1.83); male, aOR 1.36 (95% CI 1.04-1.79)]. Bayesian distributed lag models with indoor PM2.5 adjustments revealed a sensitive window for BW effects at 10-26 weeks gestation, but only in females. Latent class mixture models indicated that a persistently low weight-for-height percentile trajectory was more prevalent in the highest PM2.5 exposure quartile at T2 in females, compared to a persistently high trajectory (36.5% vs. 20.3%, P = 0.022). Also, in the females only, the high PM2.5 and low BW neonates showed significantly greater ARRDC3 methylation changes. ARRDC3 methylation was also higher only in females with low weight at 5 years of age. Higher fetal PM2.5 exposure during T2 may cause a decreased growth trajectory, especially in females, mediated by ARRDC3 hyper-methylation-associated energy metabolism.

Association Between High Body Mass Index and Mortality Following Myocardial Injury After Noncardiac Surgery.

BACKGROUND: Despite an association between obesity and increased risks for various diseases, obesity has been paradoxically reported to correlate with improved mortality in patients with established cardiovascular disease. However, its effect has not been evaluated to date in patients with myocardial injury after noncardiac surgery (MINS). METHODS: From January 2010 to June 2019, of a total of 35,269 adult patients with postoperative cardiac troponin level data, 5633 (16.0%) patients had MINS as diagnosed by postoperative cardiac troponin I above the 99th-percentile upper reference of 40 ng·L-1 using the TnI-Ultra immunoassay. Patients with MINS were divided into 3 groups according to body mass index (BMI), with 3246 (57.6%) were in the normal (18.5-25 kg·m-2), 425 (7.5%) in the low BMI (<18.5 kg·m-2), and 1962 (34.8%) in the high BMI (≥25 kg·m-2) groups, respectively. The primary outcome was mortality during the first year after surgery, and the mortality during 30 days was also compared. RESULTS: Following adjustment for confounding with inverse probability of treatment weighting, mortality within the first year appeared to be significantly lower in the high BMI group compared with the normal (14.8% vs 20.9%; hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.66-0.85; P < .001) and the low BMI (14.8% vs 25.6%; HR: 0.56; 95% CI, 0.48-0.66; P < .001) groups. CONCLUSIONS: High BMI may be associated with decreased mortality following MINS. Further investigations are needed to support this finding.

Elevated high-sensitivity C-reactive protein concentrations may be associated with increased postdischarge mortality in patients with myocardial injury after noncardiac surgery: A retrospective observational study.

BACKGROUND: Myocardial injury after noncardiac surgery (MINS) is one of the most common cardiovascular complications associated with mortality and morbidity during the first 2 years after surgery. However, the relevant variables associated with mortality after discharge in patients with MINS have not been fully investigated. OBJECTIVES: This study aimed to evaluate the association between persistent inflammation detected by high-sensitivity C-reactive protein (hsCRP) at discharge and postdischarge mortality after MINS. DESIGN: Retrospective observational analysis of acquired data from Samsung Medical Center Troponin in Noncardiac Operation (SMC-TINCO) registry. SETTING: A tertiary hospital from January 2010 to June 2019. PATIENTS: Patients who were discharged alive after a diagnosis of MINS. MAIN OUTCOME MEASURES: The primary endpoint was postdischarge 1-year mortality, and 30-day mortality and the mortality from 30 days to 1 year was also compared. RESULTS: Data from a total of 4545 adult patients were divided into two groups according to hsCRP concentration at discharge. There were 757 (16.7%) patients in the normal hsCRP group and 3788 (83.3%) patients in the elevated hsCRP group. After inverse probability weighting, 1-year mortality was significantly higher in the elevated group than the normal group (hazard ratio 1.93, 95% CI 1.45 to 2.57, P  < 0.001). Thirty-day mortality and the mortality from 30 days to 1 year were also increased in the elevated group. CONCLUSION: In patients with MINS, an elevated hsCRP concentration at discharge appeared to be associated with increased mortality. Further research is needed to determine whether controlling inflammation can be helpful in reducing mortality.

Pre-operative anaemia and myocardial injury after noncardiac surgery: A retrospective study.

BACKGROUND: Pre-operative anaemia is associated with adverse outcomes of noncardiac surgery, but its association with myocardial injury after noncardiac surgery (MINS) has not been fully investigated. OBJECTIVE: The association between pre-operative anaemia and MINS. DESIGN: A single-centre retrospective cohort study. SETTING: Tertiary care referral centre. PATIENTS: Patients with measured cardiac troponin (cTn) I levels after noncardiac surgery. INTERVENTIONS: Patients were separated according to pre-operative anaemia (haemoglobin <13 g dl-1 in men and <12 g dl-1 in women). Anaemia was further stratified into mild and moderate-to-severe at a haemoglobin level threshold of 11 g dl-1. MAIN OUTCOME MEASURES: The primary outcome was MINS, defined as a peak cTn I level more than 99th percentile of the upper reference limit within 30 postoperative days. RESULTS: Data from a total of 35 170 patients were collected, including 22 062 (62.7%) patients in the normal group and 13 108 (37.3%) in the anaemia group. After propensity score matching, 11919 sets of patients were generated, and the incidence of MINS was significantly associated with anaemia [14.5 vs. 21.0%, odds ratio (OR) 1.57, 95% confidence interval (CI) 1.47 to 1.68, P < 0.001]. For the entire population, multivariable analysis showed a graded association between anaemia severity and MINS (OR 1.32, 95% CI 1.22 to 1.43, P < 0.001 for mild anaemia and OR 1.80, 95% CI 1.66 to 1.94, P < 0.001 for moderate-to-severe anaemia compared with the normal group) and a significantly higher incidence of MINS for moderate-to-severe anaemia than mild anaemia (18.6 vs. 28.6%, OR 1.37, 95% CI 1.25 to 1.50, P < 0.001). The estimated threshold for pre-operative haemoglobin associated with MINS was 12.2 g dl-1, with an area under the curve of 0.622. CONCLUSIONS: Pre-operative anaemia was independently associated with MINS, suggesting that MINS may be related to the association between anaemia and postoperative mortality. TRIAL REGISTRATION: SMC 2019-08-048.