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BackgroundThe alpha-protein kinase 3 (ALPK3) gene (OMIM: 617608) is associated with autosomal recessive familial hypertrophic cardiomyopathy-27 (CMH27, OMIM: 618052). Recently, several studies have shown that monoallelic premature terminating variants (PTVs) in ALPK3 are associated with adult-onset autosomal dominant hypertrophic cardiomyopathy (HCMP). However, these studies were performed on patient cohorts mainly from European Caucasian backgrounds.MethodsTo determine if this finding is replicated in the Korean HCMP cohort, we evaluated 2,366 Korean patients with non-syndromic HCMP using exome sequencing and compared the cohort dataset with three independent population databases.ResultsWe observed that monoallelic PTVs in ALPK3 were also significantly enriched in Korean patients with HCMP with an odds ratio score of 10–21.ConclusionsWe suggest that ALPK3 PTV carriers be considered a risk group for developing HCMP and be monitored for cardiomyopathies.

The effect of changes in immunosuppressive therapy during the acute phase post-heart transplantation (HTx) on clinical outcomes remains unclear. This study aimed to investigate the effects of changes in immunosuppressive therapy by corticosteroid (CS) weaning and everolimus (EVR) initiation during the first year post-HTx on clinical outcomes. We analyzed 622 recipients registered in the Korean Organ Transplant Registry (KOTRY) between January 2014 and December 2021. The median age at HTx was 56 years (interquartile range [IQR], 45–62), and the median follow-up time was 3.9 years (IQR 2.0–5.1). The early EVR initiation within the first year post-HTx and maintenance during the follow-up is associated with reduced the risk of primary composite outcome (all-cause mortality or re-transplantation) (HR, 0.24; 95% CI 0.09–0.68; p < 0.001) and cardiac allograft vasculopathy (CAV) (HR, 0.39; 95% CI 0.19–0.79; p = 0.009) compared with EVR-free or EVR intermittent treatment regimen, regardless of CS weaning. However, the early EVR initiation tends to increase the risk of acute allograft rejection compared with EVR-free or EVR intermittent treatment.

Patients with diabetes mellitus are highly susceptible to cardiovascular complications, which are directly correlated with cardiovascular morbidity and mortality. In addition to coronary artery disease, there is growing awareness of the risk and prevalence of heart failure (HF) in patients with diabetes. Echocardiography is an essential diagnostic modality commonly performed in patients with symptoms suggestive of cardiovascular diseases (CVD), such as dyspnea or chest pain, to establish or rule out the cause of symptoms. Conventional echocardiographic parameters, such as left ventricular ejection fraction, are helpful not only for diagnosing CVD but also for determining severity, treatment strategy, prognosis, and response to treatment. Echocardiographic myocardial strain, a novel echocardiographic technique, enables the detection of early changes in ventricular dysfunction before HF symptoms develop. This article aims to review the role of echocardiography in evaluating CVD in patients with diabetes mellitus and how to use it in patients with suspected cardiac diseases.

Summary: The mass production of polyhydrocarbons (PHCs) is achieved through electrochemical polymerization and its synthetic pathway is investigated using a combination of electrochemical techniques, NMR, and Fourier transform infrared (FTIR) spectroscopy. Here, we present a protocol for the electrochemical polymerization of PHCs from chlorinated methanes and an analysis of its polymerization reaction pathway. We describe steps for large-scale synthesis and characterization of PHCs and studying electrochemical polymerization reactions using cyclic voltammetry and chronoamperometry techniques along with NMR and FTIR spectroscopy using isotope-labeled reactants.For complete details on the use and execution of this protocol, please refer to Seo et al.,1 Lee et al.,2 and Seo et al.3 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Air pollution is a risk factor that increases cardiovascular morbidity and mortality. In this study, we investigated the cardiotoxicity of particulate matter (PM) exposure using a zebrafish embryo model. We found that PM exposure induced cardiotoxicity, such as arrhythmia, during cardiac development. PM exposure caused cardiotoxicity by altering the expression levels of cardiac development (T-box transcription factor 20, natriuretic peptide A, and GATA-binding protein 4)- and ion-channel (scn5lab, kcnq1, kcnh2a/b, and kcnh6a/b)-related genes. In conclusion, this study showed that PM induces the aberrant expression of cardiac development- and ion channel-related genes, leading to arrhythmia-like cardiotoxicity in zebrafish embryos. Our study provides a foundation for further research on the molecular and genetic mechanisms of cardiotoxicity induced by PM exposure.

Abstract Background Cardiac evaluation using transthoracic echocardiography before noncardiac surgery is common in real-world practice. However, evidence supporting preoperative echocardiography is lacking. This study aims to evaluate the additional benefit of preoperative echocardiography in predicting postoperative cardiovascular events (CVE) in noncardiac surgery. Methods This study is designed as a multicenter, prospective study to assess the utility of preoperative echocardiography in patients undergoing intermediate- or high-risk noncardiac surgery. This trial comprises two studies: (1) a randomized controlled trial (RCT) for patients undergoing intermediate-risk surgery with fewer than three clinical risk factors from the revised cardiac risk index (intermediate-risk group) and (2) a prospective cohort study for patients undergoing intermediate-risk surgery with three or more clinical risk factors, or who undergo high-risk surgery regardless of the number of clinical risk factors (high-risk group). We hypothesize that the use of preoperative echocardiography will reduce postoperative CVEs in patients undergoing intermediate- to high-risk surgery through discovery of and further intervention for unexpected cardiac abnormalities before elective surgery. A total of 2330 and 2184 patients will be enrolled in the two studies. The primary endpoint is a composite of all-cause death; aborted sudden cardiac arrest; type I acute myocardial infarction; clinically diagnosed unstable angina; stress-induced cardiomyopathy; lethal arrhythmia, such as sustained ventricular tachycardia or ventricular fibrillation; and/or newly diagnosed or acutely decompensated heart failure within 30 days after surgery. Discussion This study will be the first large-scale prospective study examining the benefit of preoperative echocardiography in predicting postoperative CVE. The PREOP-ECHO trial will help doctors identify patients at risk of postoperative CVE using echocardiography and thereby reduce postoperative CVEs. Trial registration The Clinical Research Information Service KCT0006279 for RCT and KCT0006280 for prospective cohort study. Registered on June 21, 2021.

Background/Aims The optimal systolic blood pressure (SBP) goal for elderly patients with hypertension, especially to reduce cardiovascular disease (CVD) incidence and improve outcome, is unclear. This study aimed to evaluate the beneficial effects of intensive treatment for hypertension on the incidence of CVD in elderly Korean patients. Methods The HOW to Optimize eLDerly systolic Blood Pressure (HOWOLD-BP) trial is a multicenter, parallel-design, open-label, randomized controlled trial designed to evaluate whether intensive treatment (SBP ≤ 130 mmHg) will provide more benefits in lowering the incidence and mortality associated with CVD than standard treatment (SBP ≤ 140 mmHg) in elderly patients with hypertension aged ≥ 65 years. For this study, eleven university hospitals in Korea will enroll approximately 3,176 elderly patients with hypertension between 2019 and 2022. Patients will be requested to visit the clinic every 4 months for the first year and every 6 months thereafter for 36 months. Parameters, including clinic and home blood pressure, anthropometric and laboratory findings, and frailty assessments, will be collected according to the standardized protocol. The primary outcome is a composite of CVD (acute coronary syndrome, stroke, and heart failure) incidence and cardiovascular deaths. Results As of December 2021, 1,655 participants had been enrolled in the study, including 831 patients in the standard group and 824 patients in the intensive group. Conclusions The HOWOLD-BP trial is the first study performed in Korea to evaluate the beneficial effects of intensive blood pressure treatment on CVD in elderly patients with hypertension. The results of this study will help clarify the appropriate target SBP for this population.

In the original publication [...]

Background: Amyotrophic lateral sclerosis (ALS) is a systemic disease with multiple pathological effects, including neuroinflammation, oxidative stress, autophagy, mitochondrial dysfunction, and endoplasmic reticulum stress. Despite many studies seeking to identify and develop effective therapies, effective ALS treatment has yet to be approved. Hence, patients with ALS ultimately experience muscle atrophy and loss of motor neurons. Herbal medicines have been used to treat numerous diseases by modulating multiple biological processes and exerting pharmacological effects, including anti-inflammatory and antioxidant properties. In particular, Chaenomeles sinensis Koehne (CS) exhibits anti-hyperuricemic and nephroprotective effects and is used to treat anaphylaxis, viral infections, and neurodegenerative diseases, such as Alzheimer’s disease. This study monitored the effects of CS supplementation on muscle function and motor neurons in hSOD1G93A mice, an established ALS animal model. Methods: Body weight measurements and behavioral tests were performed; additionally, western blotting and immunohistochemistry analyses were conducted using the mice gastrocnemius, tibialis anterior, and spinal cord. Results: CS augmented anti-inflammatory and antioxidant effects in the muscle and spinal cord of hSOD1G93A mice. Furthermore, CS improved motor function and regulated autophagy in the muscles of the hSOD1G93A mice. Conclusions: CS might represent a promising supplement for improving motor function and delaying ALS progression. However, its development for clinical use warrants further investigation.

Abstract This Korean nationwide, multicenter, noninterventional, prospective cohort study aimed to analyze physician adherence to guideline-recommended therapy for heart failure (HF) with reduced ejection fraction (HFrEF) and its effect on patient-reported outcomes (PROs). Patients diagnosed with or hospitalized for HFrEF within the previous year were enrolled. Treatment adherence was considered optimal when all 3 categories of guideline-recommended medications (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or angiotensin receptor-neprilysin inhibitors; beta-blockers; and mineralocorticoid receptor antagonists) were prescribed and suboptimal when ≤ 2 categories were prescribed. The 36-Item Short Form Survey (SF-36) scores were compared at baseline and 6 months between the 2 groups. Overall, 854 patients from 30 hospitals were included. At baseline, the optimal adherence group comprised 527 patients (61.7%), whereas during follow-up, the optimal and suboptimal adherence groups comprised 462 (54.1%) and 281 (32.9%) patients, respectively. Patients in the suboptimal adherence group were older, with a lower body mass index, and increased comorbidities, including renal dysfunction. SF-36 scores were significantly higher in the optimal adherence group for most domains (P

Particulate matter 2.5 (PM2.5) levels are associated with adverse pregnancy outcomes. In this retrospective cohort study, we examined whether the concentration of indoor PM2.5 affected pregnancy outcomes. Additionally, we evaluated biomarkers of pregnancy-related complications caused by fine dust. We collected clinical information and data based on residential addresses from the Air Korea database to assess PM2.5 exposure levels. As a multicenter prospective cohort study, we measured the indoor PM2.5 concentration and inflammatory and oxidative stress markers. The PM2.5 concentration of the low-birth-weight (LBW) delivery group was 27.21 μg/m3, which was significantly higher than that of the normal-birth-weight (NBW) group (26.23 μg/m3) (p = 0.02). When the newborns were divided by sex, the PM2.5 concentration of the LBW group was 27.89 μg/m3 in male infants, which was significantly higher than that of the NBW group (26.26 μg/m3) (p = 0.01). In the prospective study, 8-hydroxy-2-deoxyguanosine significantly increased in the high-concentration group (113.55 ng/mL, compared with 92.20 ng/mL in the low-concentration group); in the high-concentration group, the rates of preterm birth (PTB) and small size for gestational age significantly increased (p < 0.01, p = 0.01). This study showed an association between PM2.5, oxidative stress, and fetal growth, with the PTB group being more vulnerable.

The aim of this study was to examine the neutrophil-to-lymphocyte ratio (NLR) in patients diagnosed with a deep neck infection (DNI) to identify helpful indicators for the initial differential diagnosis. This study was conducted as a single-center, retrospective cohort study that utilized data from the electronic medical records of patients who visited the emergency department in a tertiary university hospital between February 2018 and April 2022. The study enrolled patients aged ≥18 years who were diagnosed with tonsillitis with or without DNI during the study period. The NLR of patients without DNI was 6.1 ± 5.03, and the NLR of patients with acute tonsillitis with DNI was 8.0 ± 5.67, showing significant differences. The rate of admission in the general wards (GWs) and ICUs was significantly higher in patients with DNI, and the length of hospital stay was also significantly longer in patients with DNI. Older age, male, lower body temperature, C-reactive protein, and NLR were significant independent risk factors for DNI in patients with tonsillitis. The cutoff value for predicting DNI in patients with body temperature

This study aimed to demonstrate clinical feasibility of deep learning (DL)-based fully automated coronary artery calcium (CAC) scoring software using non-electrocardiogram (ECG)-gated chest computed tomography (CT) from patients with cancer. Overall, 913 patients with colorectal or gastric cancer who underwent non-contrast-enhanced chest CT between 2013 and 2015 were included. Agatston scores obtained by manual segmentation of CAC on chest CT were used as reference. Reliability of automated CAC score acquisition was evaluated using intraclass correlation coefficients (ICCs). The agreement for cardiovascular disease (CVD) risk stratification was assessed with linearly weighted k statistics. ICCs between the manual and automated CAC scores were 0.992 (95% CI, 0.991 and 0.993, p

Objective To evaluate the predictive performance of optic nerve sheath thickness (ONST) on the outcomes of traumatic brain injury (TBI) and to compare the inter-observer agreement To evaluate the predictive performance of optic nerve sheath thickness (ONST) for traumatic brain injury (TBI) and to compare the predictive performance and inter-observer agreement between ONST and optic nerve sheath diameter (ONSD) on facial computed tomography (CT). Methods We retrospectively enrolled patients with a history of facial trauma and who underwent both facial CT and brain CT. Two reviewers independently measured ONST and ONSD of each patient using facial CT images. Final brain CT with clinical outcome was used as the reference standard for TBI. Multivariate logistic regression analyses, receiver operating characteristic (ROC) curves, and intraclass correlation coefficients were used for statistical analyses. Results Both ONST (P=0.002) and ONSD (P=0.001) on facial CT were significantly independent factors to distinguish between TBI and healthy brains; an increase in ONST and ONSD values corresponded with an increase in the risk of TBI by 8.9- and 7.6-fold, respectively. The predictive performances of the ONST (sensitivity, 96.2%; specificity, 94.3%; area under the ROC curve, 0.968) and ONSD (sensitivity, 92.6%; specificity, 90.2%; area under the ROC curve, 0.955) were excellent and exhibited similar sensitivity, specificity, and area under the curve (P=0.18–0.99). Interobserver and intraobserver intraclass correlation coefficients for ONST were significantly higher than those for ONSD (all P

Background/Aims Pheochromocytoma and paraganglioma (PPGL) are catecholamine-producing tumors that can cause blood pressure (BP) elevation and cardiovascular complications. Clinical presentation of these tumors may be changed through widespread use of imaging studies, which enables detection of PPGLs before onset of symptoms. We investigated clinical profiles of patients with surgically resected PPGLs. Methods From 2005 to 2017, 111 consecutive patients with surgically resected PPGLs in two tertiary hospitals in Korea were studied. Results Mean age was 52 ± 16 years, 57 patients (51.4%) were male and 54 (48.6%) were hypertensive. Twenty-nine PPGLs (26.1%) were extra-adrenal paragangliomas. Sixteen (14.4%) and seven patients (6.3%) (Group 1, n = 23) were diagnosed during work-up of hypertension and transient cardiomyopathy respectively, and the remainder (Group 2, n = 88) were incidentalomas detected during routine abdominal imaging. Patients in the Group 1 were younger and more frequently symptomatic, and had higher BPs, heart rates and levels of urinary catecholamines than those in the Group 2. Paragangliomas were less frequent and secretion of epinephrine and metanephrine was more predominant in the Group 1 than in Group 2. After the surgical resections, 18.2% of patients still needed antihypertensive medications. Conclusions Out of 111 patients with surgically resected PPGLs, 88 (79.3%) were diagnosed as incidentalomas. Seven patients presented with transient cardiomyopathy and 16 with hypertension. Tumor location and secretion of catecholamine may vary depending on the presence of symptoms.

Amyotrophic lateral sclerosis (ALS), a multicomplex neurodegenerative disease, has multiple underlying pathological factors and can induce other neuromuscular diseases, leading to muscle atrophy and respiratory failure. Currently, there is no effective drug for treating patients with ALS. Herbal medicine, used to treat various diseases, has multitarget effects and does not usually induce side effects. Each bioactive component in such herbal combinations can exert a mechanism of action to increase therapeutic efficacy. Herein, we investigated the efficacy of an herbal formula, comprising Achyranthes bidentata Blume, Eucommia ulmoides Oliver, and Paeonia lactiflora Pallas, in suppressing the pathological mechanism of ALS in male hSOD1G93A mice. Herbal formula extract (HFE) (1 mg/g) were orally administered once daily for six weeks, starting at eight weeks of age, in hSOD1G93A transgenic mice. To evaluate the effects of HFE, we performed footprint behavioral tests, western blotting, and immunohistochemistry to detect protein expression and quantitative PCR to detect mRNA levels in the muscles and spinal cord of hSOD1G93A mice. HFE-treated hSOD1G93A mice showed increased anti-inflammation, antioxidation, and regulation of autophagy in the muscles and spinal cord. Thus, HEF can be therapeutic candidates for inhibiting disease progression in patients with ALS. This study has some limitations. Although this experiment was performed only in male hSOD1G93A mice, studies that investigate the efficacy of HEF in various ALS models including female mice, such as mice modeling TAR DNA-binding protein 43 (TDP43) and ORF 72 on chromosome 9 (C9orf72) ALS, are required before it can be established that HEF are therapeutic candidates for patients with ALS.

Amyotrophic lateral sclerosis (ALS) is a complex disease characterized by motor neuron loss and muscle atrophy. There is no prominent treatment for ALS as the pathogenic process in the skeletal muscle and spinal cord is complex and multifactorial. Therefore, we investigated the effects of a herbal formula on the multi-target effects in the skeletal muscle and spinal cord in hSOD1G93A transgenic mice. We prepared a herbal extract (HE) from Glycyrrhiza uralensis, Atractylodes macrocephala Koidzumi, Panax ginseng, and Astragalus membranaceus. Control and HE-treated mice underwent rotarod and footprint tests. We also performed immunohistochemical and Western blotting analyses to assess expression of inflammation-related and oxidative stress-related proteins in the muscle and spinal cord tissues. We found that the HE increased motor activity and reduced motor neuron loss in hSOD1G93A mice. In addition, the HE significantly reduced the levels of inflammatory proteins and oxidative stress-related proteins in the skeletal muscles and spinal cord of hSOD1G93A mice. Furthermore, we demonstrated that the HE regulated autophagy function and augmented neuromuscular junction in the muscle of hSOD1G93A mice. Based on these results, we propose that the HE formula may be a potential therapeutic strategy for multi-target treatment in complex and multifactorial pathological diseases.

Purpose Contrast media extravasation (CME) is an adverse reaction after administration of contrast media during CT examinations. The purpose of this study was to evaluate the frequency, management, and outcomes of extravasations and to assess the risk factors for CME in the emergency department (ED) and the ward. Materials and Methods This retrospective study was conducted at a single academic urban hospital from January 2013 to December 2015. We analyzed the medical records of all patients who experienced CME after undergoing a CT scan. We compared the patients’ age, sex, underlying disease, injection site, injection flow rate, time of CT examination, type of CT examination, and severity of injury between those in the ED and the ward. Results CME occurred in 41 (0.36%) of 114767 patients, which included 16 (0.34%) in the ED and 25 (0.37%) in the ward. Both groups were more frequent in those aged older than 60 years and in female. Additionally, the abdominopelvic CT type and 2–3 mL/s as the injection rate were more common in both groups. However, CME was more frequent during the nighttime (10, 62.5%) in the ER, while it was more common in the daytime (14, 56.0%) in the ward. Severe complications were more frequent in the ER (9, 56.3%) compared with the ward (8, 32.8%). There were no significant differences in CME between the ED and the ward. When comparing the clinical manifestations in the mild and severe groups, the antecubital fossa (33.3% and 0%, respectively; p = 0.013) for the injection site and abdominopelvic CT (41.7% and 82.4%, respectively; p = 0.012) and CT angiography (41.7% and 5.87%, respectively; p = 0.014) for the CT examination showed significant differences between the mild and severe groups. Conclusion In this study, there were no significant clinical differences in CME between the ED and ward. Thus, prevention is more important than the place of admission. Radiologists and emergency physicians should pay attention to CME in the ED because it frequently occurs at night and results in more severe complications.

Cognitive impairment in end-stage renal disease patients is associated with an increased risk of mortality. We examined the cognitive function in hemodialysis (HD) patients and compared the Korean versions of the Montreal Cognitive Assessment (K-MoCA) and of the Mini-Mental State Examination (K-MMSE) to identify the better cognitive screening instrument in these patients. Thirty patients undergoing hemodialysis and 30 matched reference group of apparently healthy control were included. All subjects underwent the K-MoCA, K-MMSE and a neuropsychological test battery to measure attention, visuospatial function, language, memory and executive function. All cognitive data were converted to z-scores with appropriate age and education level prior to group comparisons. Cognitive performance 1.0 SD below the mean was defined as modest cognitve impairment while 1.5 below the mean was defined as severe cognitive impairment. Modest cognitive impairment in memory plus other cognitive domains was detected in 27 patients (90%) while severe cognitive impairment in memory plus other cognitive domains was detected in 23 (77%) patients. Total scores in the K-MoCA were significantly lower in HD patients than in the reference group. However, no significant group difference was found in the K-MMSE. The K-MMSE ROC AUC (95% confidence interval) was 0.72 (0.59–0.85) and K-MoCA ROC AUC was 0.77 (0.65–0.89). Cognitive impairment is common but under-diagnosed in this population. The K-MoCA seems to be more sensitive than the K-MMSE in HD patients.

Abstract Background Diabetes mellitus (DM) is a chronic progressive metabolic disease that involves uncontrolled elevation of blood glucose levels. Among various therapeutic approaches, GLP-1 prevents type 2 diabetes mellitus (T2DM) patients from experiencing hyperglycemic episodes. However, the short half-life (

Objective Most patients with head trauma require brain computed tomography (CT) in the emergency department. However, the requirement for facial CT remains controversial. The aim of this study was to evaluate the diagnostic value of brain CT alone for detection of facial fractures and its ability to determine the requirement for additional facial CT. Methods This retrospective multicenter study was conducted in two tertiary hospitals in Seoul, Republic of Korea, between January 2014 and December 2015. Data were collected from the medical records of adult patients (aged over 18 years) who had undergone both brain and facial CT on the same day as their presentation to the emergency department with blunt trauma to the head and face. The same radiologist analyzed all brain and facial CT images. Results Eight hundred and sixty patients (668 men, 192 women; mean age 48.60±18.2 years) were identified to have had facial fractures. There was a statistically significant predominance of men but not of any particular age group. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of brain CT were 83.72%, 98.87%, 97.17%, 92.92%, and 94.08%, respectively. Conclusion These findings suggest that brain CT has high diagnostic value for detection of upper facial bone fractures with high accuracy and can aid emergency physicians when determining the requirement for additional facial CT.

Abstract Background Cognitive decline is a major concern in patients with migraine. Depression, anxiety, and/or poor sleep quality are well-known comorbidities of migraine, but available evidence on the subjective cognitive decline (SCD) is limited. This study aimed to investigate the presence and frequency of SCD and its relationship with anxiety, depression and sleep quality in patients with migraine. Methods We enrolled patients with migraine who scored within the normal range of the Korean-Mini Mental State Examination and the Korean-Montreal Cognitive Assessment. Using the Subjective Cognitive Decline Questionnaire (SCD-Q), participants with ≥7 were assigned to the SCD group. The Headache Impact Test-6, Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, and Pittsburgh Sleep Quality Index were used and analyzed between the two groups. Results A total of 188 patients with migraine, aged 38.1 ± 9.9 years, were enrolled. The mean SCD-Q score was 6.5 ± 5.5, and 44.7% of participants were identified as SCD. Migraineurs with SCD reported higher headache pain intensity and headache impact, as well as greater prevalence of anxiety, depression, reduced quality of sleep, and shorter sleep duration during weekdays compared to migraineurs without SCD. There were no significant differences in terms of age, sex, migraine type (chronic/episodic), medication, or sleep duration during weekends between the two groups. Upon multivariate logistic analysis adjusted for age, sex, headache characteristics, and psychological variables, depression was associated with increased risk of SCD (Odds ratio 1.31, 95% confidence interval 1.16–1.49) and sleep duration during weekdays was associated with decreased risk of SCD (Odds ratio 0.66, 95% confidence interval 0.44–0.97). Conclusions A non-negligible number of patients with migraine complained of SCD. Depression and short sleep duration during weekdays were related to SCD among adult migraineurs.

PurposeThe gut microbiota can influence several diseases through immune modulation; however, the exact role of microbes such as Clostridium difficileand the relationship between microbiota colonization and allergic diseases are not well known. This study aimed to determine the relationship between C. difficilecolonization and/or infection (CDCI) during infancy and allergic diseases during early childhood.MethodsInfants 1–12 months of age presenting changes in bowel habits for more than 2 weeks were enrolled in this study. After dividing them into 2 groups according to the presence and absence of C. difficile, the risk of allergic disease development during childhood was identified and compared.ResultsSixty-five patients were included in this study; 22 (33.8%) were diagnosed with CDCI. No significant differences were observed in baseline characteristics between the C. difficile-positive and -negative groups except for antibiotic exposure (22.7% vs. 60.5%, P=0.004). Compared to the C. difficile-negative group, the risk of developing at least one allergic disease was higher in the C. difficile-positive group after adjusting other variables (adjusted odds ratios, 5.61; 95% confidence interval, 1.52–20.74; P=0.007). Furthermore, food allergies were more prevalent in the C. difficile-positive group (P=0.03).ConclusionCDCI during infancy were associated with a higher risk of developing allergic diseases during early childhood. These results suggest that CDCI during infancy might reflect the reduced diversity of the intestinal microbiota, which is associated with an increased risk of allergic sensitization. To identify the underlying mechanism, further investigation and a larger cohort study will be needed.

Epigastric pain is a common symptom in the emergency department. Most epigastric pain is not fatal, except in acute myocardial infarction, aortic dissection, and abdominal aneurysm rupture. Epigastric pain can also be the only symptom of isolated spontaneous gastric artery dissection. We report the case of a 51-year-old woman diagnosed with neurofibromatosis who initially presented with only epigastric pain. She was initially misdiagnosed with gastritis, treated conservatively, and discharged. Two hours later, she returned to the emergency department with persistent epigastric pain and rebound tenderness in the epigastric area. Angiography revealed a left hepatic arterial aneurysm and right gastric artery dissection, which were subsequently embolized. Although extremely rare, patients presenting with epigastric pain at risk of vasculopathies should be considered for isolated spontaneous gastric artery dissection. Early recognition and definitive therapy lead to a favorable outcome.

Although acute bronchitis is quite common, there is relatively limited information regarding the microorganisms that are involved in this illness.We performed a prospective study of acute bronchitis at 31 hospitals and clinics in Korea from July 2011 to June 2012. Sputum specimens were collected for polymerase chain reaction (PCR) and culture of microorganisms.Of the 811 enrolled patients, 291 had acceptable sputum specimens that were included for analysis of the etiologic distribution. With multiplex PCR testing, viruses were identified in 36.1% (105/291), most commonly rhinovirus (25.8%) and coronavirus (3.8%). Typical bacteria were isolated in 126/291 (43.3%) patients. Among these patients Haemophilus influenzae (n = 39) and Streptococcus pneumoniae (n = 30) were isolated most commonly; atypical bacteria were identified in 44 (15.1%) patients. Bacteria-only, virus-only, and mixed infections (bacteria plus virus) accounted for 36.7% (98/291), 17.2% (50/291), and 18.9% (55/291) of infections, respectively. In particular, 52.4% of patients with viral infection had a concurrent bacterial infection, and rhinovirus was the most common virus in mixed infections (40/55). Additionally, infections with typical bacteria were more common in patients with chronic lung disease (p = 0.029), and typical bacterial infections showed a trend towards a higher prevalence with older age (p = 0.001).Bacteria were associated with almost half of community-acquired acute bronchitis cases. Additional studies are required to further illuminate the role of bacteria and to identify patient groups most likely to benefit from antibiotic treatment.

ABSTRACT Central to NF-κB signaling pathways is IKKγ/NEMO, a regulatory subunit of the cytoplasmic IκB kinase (IKK) complex, which undergoes various posttranslational modifications, specifically phosphorylation, to regulate its function. Furthermore, Kaposi’s sarcoma-associated herpesvirus (KSHV) FADD-like interleukin-1β (IL-1β) converting enzyme (FLICE) inhibitory protein (vFLIP) activates the NF-κB signaling pathway by directly interacting with IKKγ/NEMO. However, the exact functions of IKKγ/NEMO phosphorylation and its KvFLIP interaction in NF-κB activation remain elusive. Here, we report two novel phosphorylation sites of IKKγ/NEMO and their negative effect on the IKKγ/NEMO-mediated NF-κB signaling pathway. First, the Src family protein tyrosine kinases (SF-PTKs), including Src, Fyn, Lyn, and Fgr, interact with and phosphorylate tyrosine residue 374 (Y374) of IKKγ/NEMO. Mutation of the Y374 residue to phenylalanine (Y374F) specifically abolished SF-PTK-mediated tyrosine phosphorylation, leading to increased tumor necrosis factor alpha (TNF-α)-induced NF-κB activity. Moreover, our mass spectrometry analysis found that the serine 377 residue (S377) of IKKγ/NEMO underwent robust phosphorylation upon KvFLIP expression. Replacement of the IKKγ/NEMO S377 residue by alanine (S377A) or glutamic acid (S377E) resulted in a significant increase or decrease of NF-κB activity and TNF-α-mediated IL-6 cytokine production, respectively. Our study thus demonstrates that the Y374 or S377 residue located at the C-terminal proline-rich domain of human IKKγ/NEMO undergoes phosphorylation upon TNF-α treatment or KvFLIP expression, respectively, resulting in the suppression of IKKγ/NEMO activity to induce NF-κB activation. This study suggests the potential phosphorylation-mediated feedback negative regulation of IKKγ/NEMO activity in the NF-κB signaling pathway. IMPORTANCE Since unchecked regulation of NF-κB has been linked to uncontrolled proliferation and cell death, the downregulation of the NF-κB signaling pathway is as important as its activation. Specifically, the phosphorylation-mediated modification of IKKγ/NEMO is a critical regulatory mechanism of NF-κB activity. Here, we report two novel phosphorylations of IKKγ/NEMO and their negative effects on the NF-κB signaling pathway. First, the Src family protein tyrosine kinase interacts with and phosphorylates tyrosine residue 374 of IKKγ/NEMO, suppressing tumor necrosis factor alpha (TNF-α)-induced NF-κB activity. Additionally, Kaposi’s sarcoma-associated herpesvirus (KSHV) FADD-like interleukin-1β (IL-1β) converting enzyme (FLICE) inhibitory protein (KvFLIP) expression induces a robust phosphorylation of the serine 377 residue of IKKγ/NEMO, resulting in a significant decrease of NF-κB activity. Our study thus demonstrates that the Y374 or S377 residue of IKKγ/NEMO undergoes phosphorylation upon TNF-α treatment or KvFLIP expression, respectively, resulting in the suppression of IKKγ/NEMO activity to induce NF-κB activation. This also suggests the potential phosphorylation-mediated feedback negative regulation of IKKγ/NEMO activity in the NF-κB signaling pathway.

Epigenetic modifications of the herpesviral genome play a key role in the transcriptional control of latent and lytic genes during a productive viral lifecycle. In this study, we describe for the first time a comprehensive genome-wide ChIP-on-Chip analysis of the chromatin associated with the Kaposi's sarcoma-associated herpesvirus (KSHV) genome during latency and lytic reactivation. Depending on the gene expression class, different combinations of activating [acetylated H3 (AcH3) and H3K4me3] and repressive [H3K9me3 and H3K27me3] histone modifications are associated with the viral latent genome, which changes upon reactivation in a manner that is correlated with their expression. Specifically, both the activating marks co-localize on the KSHV latent genome, as do the repressive marks. However, the activating and repressive histone modifications are mutually exclusive of each other on the bulk of the latent KSHV genome. The genomic region encoding the IE genes ORF50 and ORF48 possesses the features of a bivalent chromatin structure characterized by the concomitant presence of the activating H3K4me3 and the repressive H3K27me3 marks during latency, which rapidly changes upon reactivation with increasing AcH3 and H3K4me3 marks and decreasing H3K27me3. Furthermore, EZH2, the H3K27me3 histone methyltransferase of the Polycomb group proteins (PcG), colocalizes with the H3K27me3 mark on the entire KSHV genome during latency, whereas RTA-mediated reactivation induces EZH2 dissociation from the genomic regions encoding IE and E genes concurrent with decreasing H3K27me3 level and increasing IE/E lytic gene expression. Moreover, either the inhibition of EZH2 expression by a small molecule inhibitor DZNep and RNAi knockdown, or the expression of H3K27me3-specific histone demethylases apparently induced the KSHV lytic gene expression cascade. These data indicate that histone modifications associated with the KSHV latent genome are involved in the regulation of latency and ultimately in the control of the temporal and sequential expression of the lytic gene cascade. In addition, the PcG proteins play a critical role in the control of KSHV latency by maintaining a reversible heterochromatin on the KSHV lytic genes. Thus, the regulation of the spatial and temporal association of the PcG proteins with the KSHV genome may be crucial for propagating the KSHV lifecycle.

In the title compound, [ZnI2(C6H8N2)2], the ZnII ion is coordinated by two iodide anions and two N atoms from 2,6-dimethylpyrazine in a distorted tetrahedral geometry.

Since 15 November 2012, the South Korean government amended the law to make some medicines available at 24-hour convenient stores that had previously been sold at pharmacies only. The aim of this study was to evaluate the impact of this legislation on drug poisoning in youth patients, who may be affected by increased access. This study retrospectively analyzed data registered in the Emergency Department-based Injury In-depth Surveillance (EDIIS) database from January 2007 to December 2018. Patients aged 15 to 24 years old were selected to analyze the incidence and outcomes of acetaminophen (AAP) poisoning in youth patientsBefore the deregulation of over-thecounter (OTC) medication sales, 1994 youth patients visited the emergency department (ED) from 2007-2012. By contrast, 5440 youth visited the ED from 2013-2018 after deregulation. In particular, there were 263 (13.2%) and 820 (15.1%) cases of AAP poisoning intentionally before and after deregulation, respectively, which was not significantly different (p = 0.085). However, the number of patients who were admitted to the general ward (GW) due to AAP poisoning significantly increased from 93 (35.4%) to 339 (41.3%) (p = 0.041). Furthermore, the number of patients who were admitted to the intensive care unit (ICU) after ingesting AAP significantly increased from 9 (3.4%) to 93 (11.3%) (p<0.001). There was no significant difference in intentional AAP poisoning ratios following the deregulation of OTC drug sales; however, GW and ICU admission rates significantly increased. This study demonstrated that there is positive relationship between intentional AAP poisoning and severity in youth patients after the deregulation legislation. [ABSTRACT FROM AUTHOR]