Characterization of lymphocyte-rich hepatocellular carcinoma and the prognostic role of tertiary lymphoid structures.

BACKGROUND & AIMS: Lymphocyte-rich hepatocellular carcinoma (LR-HCC) is largely unknown and a rare subtype of HCC with immune-rich stroma. Tertiary lymphoid structures (TLS), frequently observed in LR-HCC, are known to be prognostically significant in various malignancies; however, their significance in HCC remains unevaluated. METHODS: Clinicopathologic data of 191 cases of surgically resected conventional HCC (C-HCC, n = 160) and LR-HCC (n = 31) were retrieved. Immunohistochemistry, multiplex immunofluorescence staining, RNA sequencing and proteomic analysis were conducted. Differences between the subtypes were statistically evaluated. RESULTS: LR-HCC was significantly correlated to larger tumour size, higher Edmondson-Steiner grade, presence of TLS and higher CD3-, CD8- and FOXP3-positive T cell, high PD-1 and PD-L1 expression (p < .001 for all) compared to C-HCC. Patients with LR-HCC exhibited significantly better overall survival (OS) (p = .044) and recurrence-free survival (RFS) (p = .025) than C-HCC. LR-HCC demonstrated TLS signatures with significantly higher proteomic-based immune scores in 14 of 17 types of tumour-infiltrating immune cells. Furthermore, C-HCC with secondary follicles, the most mature form of TLS, exhibited significantly better OS (p = .031) and RFS (p = .033) than those without. Across the global proteome, LR-HCC was well-differentiated from C-HCC and a map of protein-protein interactions between tumour-infiltrating lymphocytes and HCC in tumour microenvironment was completed. CONCLUSION: LR-HCC is clinicopathologically and molecularly distinct and shows better prognosis compared to C-HCC. Also, the presence of secondary follicle can be an important prognostic marker for better prognosis in both LR-HCC and C-HCC.

Discordant PD-L1 results between 28-8 and 22C3 assays are associated with outcomes of gastric cancer patients treated with nivolumab plus chemotherapy.

BACKGROUND: We evaluated the concordance/discordance of PD-L1 staining results between the 28-8 and 22C3 assays and its impact on the efficacy outcomes of advanced gastric cancer patients treated with nivolumab plus chemotherapy. METHODS: This retrospective study involved 143 gastric cancer patients treated with first-line nivolumab plus chemotherapy whose PD-L1 results with both 28-8 and 22C3 assays were available. The concordance/discordance between these assays and the inter-observer variability were evaluated for PD-L1 combined positive score (CPS) positivity. Discordant PD-L1 results were analyzed regarding survival outcomes. RESULTS: The agreement rates and Cohen's kappa values between the 28-8 and 22C3 assays were 78.3% and 0.56 (for CPS ≥ 1), 81.8% and 0.60 (for CPS ≥ 5), and 88.8% and 0.66 (for CPS ≥ 10), respectively. Inter-observer variability, as represented by the intra-class correlation coefficient, was 0.89 and 0.88 for the 28-8 and 22C3 assays, respectively. With PD-L1 CPS ≥ 5 defined as positive, 35 (24.5%) and 82 (57.3%) had concordantly positive and negative results, respectively, between the 28-8 and 22C3 assays, whereas 26 (18.2%) had discordant results. Progression-free survival was shorter for those who exhibited negatively concordant PD-L1 results and discordant PD-L1 positivity between the 28-8 and 22C3 assays relative to those with positively concordant PD-L1 results (P = 0.013). CONCLUSION: PD-L1 assays by 28-8 and 22C3 showed suboptimal concordance, while inter-observer variability was not critical in advanced gastric cancer. Discordant PD-L1 results between 28-8 and 22C3 assays may be associated with unfavorable efficacy outcomes in patients treated with nivolumab plus chemotherapy.

Anhydrous Alum Inhibits α-MSH-Induced Melanogenesis by Down-Regulating MITF via Dual Modulation of CREB and ERK.

Melanogenesis, the intricate process of melanin synthesis, is central to skin pigmentation and photoprotection and is regulated by various signaling pathways and transcription factors. To develop potential skin-whitening agents, we used B16F1 melanoma cells to investigate the inhibitory effects of anhydrous alum on melanogenesis and its underlying molecular mechanisms. Anhydrous alum (KAl(SO4)2) with high purity (>99%), which is generated through the heat-treatment of hydrated alum (KAl(SO4)2·12H2O) at 400 °C, potentiates a significant reduction in melanin content without cytotoxicity. Anhydrous alum downregulates the master regulator of melanogenesis, microphthalmia-associated transcription factor (MITF), which targets key genes involved in melanogenesis, thereby inhibiting α-melanocyte-stimulating hormone (α-MSH)-induced melanogenesis. Phosphorylation of the cAMP response element-binding protein, which acts as a co-activator of MITF gene expression, is attenuated by anhydrous alum, resulting in compromised MITF transcription. Notably, anhydrous alum promoted extracellular signal-regulated kinase phosphorylation, leading to the impaired nuclear localization of MITF. Overall, these results demonstrated the generation and mode of action of anhydrous alum in B16F1 cells, which constitutes a promising option for cosmetic or therapeutic use.

Cumulative average nut consumption in relation to lower incidence of hypertension: a prospective cohort study of 10,347 adults.

PURPOSE: Maintaining optimal blood pressure (BP) levels can be an effective preventive strategy for reducing disease burden. Nut consumption may play a preventive role against hypertension, which is a lifelong condition. We aimed to prospectively examine the association between cumulative average nut consumption and the incidence of hypertension in Korean adults aged 40 years and older. METHODS: A total of 10,347 participants who were free of hypertension at baseline, were included. Hypertension was defined as having a physician diagnosis and taking antihypertensive medications or having abnormal BP (systolic ≥ 140 mmHg or diastolic ≥ 90 mmHg). As an exposure, cumulative average nut consumption was calculated using repeated food-frequency questionnaires (mean: 2.1). We used a modified Poisson regression model with a robust error estimator to estimate the incidence rate ratios (IRRs) with 95% confidence intervals (CIs) for hypertension. RESULTS: We identified 2047 incident cases of hypertension during 44,614 person-years of follow-up. Among both men and women, an average nut consumption of ≥ 1 serving/week (15 g/week]) was inversely associated with hypertension incidence (IRR = 0.74, 95% CI = 0.58-0.96, p for trend = 0.013 for men; IRR = 0.72, 95% CI = 0.59-0.88, p for trend = 0.002 for women) and these significant associations were consistently observed across the strata of potential confounders. CONCLUSION: An average consumption of at least one serving (15 g) per week of peanuts, almonds, and/or pine nuts may be inversely associated with the risk of hypertension among Korean adults aged 40 years and older, in a dose-response manner.

Field study of the indoor environments for preventing the spread of the SARS-CoV-2 in Seoul.

Despite the prolonged global spread of COVID-19, few studies have investigated the environmental influence on the spread of SARS-CoV-2 RNA with a metropolitan scale, particularly the detection of SARS-CoV-2 after disinfection at multi-use facilities. Between February 2020 and January 2021, 1,769 indoor air samples and object surfaces were tested at 231 multi-use facilities where confirmed cases were known to have occurred in Seoul, to determine whether SARS-CoV-2 RNA could be detected even after disinfection. Samples were collected by air scanner and swab pipette and detected by real-time RT-PCR. As a result, 10 (0.56%) positive samples were detected despite disinfection. The common environmental features of all 10 were surfaces that contained moisture and windowless buildings. With the aim of preventing the spread of COVID-19, from January to February 2021, we next conducted 643 preemptive tests before the outbreak of infections at 22 multi-use facilities where cluster infections were frequent. From these preemptive inspections, we obtained five (0.78%) positive results from two facilities, which enabled us to disinfect the buildings and give all the users a COVID-19 test. Based on the study purpose of finding and investigating cases of positive detection even after disinfection in the field through long-term environmental detection in a large city, our preemptive investigation results helped to prevent the spread of infectious diseases by confirming the potential existence of an asymptomatic patient.

Validity and reliability of a Korean version of the Consultation and Relational Empathy (CARE) measure.

BACKGROUND: No validated tool is available to assess patients' perception of physician empathy in Korea. The objective of this study was to establish a Korean version of the Consultation and Relational Empathy (CARE) measure-originally developed in English and widely used internationally-and to examine its reliability and validity. METHODS: The CARE measure was translated into Korean and tested on 240 patients from one secondary care hospital and one tertiary care hospital in Korea. Internal consistency by Cronbach's alpha, exploratory analysis, and confirmatory factor analysis were conducted to verify the 10 items of the Korean CARE measure. RESULTS: The Korean CARE measure demonstrated high acceptability and face validity, excellent internal reliability (Cronbach's alpha = 0.97) and moderate test-retest reliability (Pearson correlation coefficient = 0.53; Spearman correlation coefficient = 0.51). Distribution of scores showed negative skewedness. Corrected item-total correlations ranged from 0.77-0.92, indicating homogeneity. The Kaiser-Meyer-Olkin measure of sampling adequacy was 0.949, and Bartlett's test of sphericity was good (χ2 = 3157.11, P < 0.001). Factor analysis yielded a single dimensional structure of physician empathy with all factor loadings exceeding 0.80 and showing excellent goodness of fit. CONCLUSION: This study supports the reliability and validity of the Korean CARE measure in a university hospital setting in Korea.

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

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

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

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

Impact of a screening protocol for blood pressure level for hypertension in the Korean community health survey.

PURPOSE: A community program is an efficient model for improving the management of chronic diseases such as hypertension, diabetes, and dyslipidemia. A specific blood pressure (BP) measurement protocol was developed for community settings in which BP was measured by the interviewer at the interviewee's home. MATERIALS AND METHODS: In the 2018 Korean Community Health Survey, BP was measured twice at a five-minute interval after a five-minute resting period at the beginning of the survey. In 2019, BP was measured at the end of the survey after a two-minute rest and was obtained as three measurements at one-minute intervals. As factors related to BP level, stressful stimuli within 30 min before BP measurement such as smoking, caffeine, and/or exercise; duration of rest; and survey year were analysed. RESULTS: The mean age of participants was 55.2 years, and females accounted for 55.4% of the participants (n = 399,838). Stressful stimuli were observed in 21.9% of the participants in 2018 (n = 188,440) and 11.3% in 2019 (n = 211,398). Duration of rest was 0 min (2.1%), two minutes (55.0%), and five minutes (47.9%). When adjusted for age, sex, body mass index, antihypertensive medication, the arm of measurement, survey year (beta= -4.092), stressful stimuli (beta = 0.834), and resting time (beta = -1.296 per one minute of rest) were significant factors for mean systolic BP. A two-minute rest was not a significant factor in mean BP. The differences in adjusted mean systolic BPs were significant for rest times of five minutes vs. two minutes (3.1 mmHg, p < 0.0001), for stressful stimuli (0.8 mmHg, p < 0.0001), and for survey year (127.8 ± 0.2 mmHg vs. 122.2 ± 0.3 mmHg for 2018 vs. 2019, p < 0.0001). CONCLUSION: For the community-based home visit survey, avoidance of stressful stimuli, five-minute rest, and allocation of BP measurement in the last part of the survey was useful for obtaining a stable BP level.

May Measurement Month 2019: an analysis of blood pressure screening results from Korea.

Hypertension is the biggest contributing risk factor to cerebrovascular disease and is associated with increased risk of coronary artery disease. The May Measurement Month (MMM) campaign is a global initiative aimed at raising awareness of hypertension and acting as a temporary solution to the lack of screening programs worldwide. An opportunistic cross-sectional survey of participants aged ≥18 was carried out during May 2019 in Korea. Over 10 000 participants were recruited in the MMM campaign in Korea, with a slogan of 'A simple measure to save lives-#checkyourpressure'. A total of 9975 participants with valid clinical and blood pressure (BP) data were used for analysis. All participants were Korean in ethnicity, mean age was 57.2 (SD ± 21.2) years, 57.7% were females, and the mean body mass index was 23.4 kg/m2 (SD ± 3.3). In total, 37.7% of the participants reported a previous diagnosis of hypertension, and 91.3% of those diagnosed were on antihypertensive medications. For other comorbidities, 11.6% reported having diabetes mellitus, 2.0% had previous stroke, and 1.0% had previous myocardial infarction. Mean BP was 130.0/81.0 mmHg in the overall population. After multiple imputation, 47.6% of participants were classified as hypertensive (systolic BP ≥140 mmHg and/or diastolic BP ≥90 mmHg or on treatment for raised BP). Among all hypertensive participants, the awareness rate, the treatment rate, and the control rate (systolic BP <140 mmHg and diastolic BP <90 mmHg) were 76.2%, 74.0%, and 50.5%, respectively. Of those on antihypertensive medication, the control rate was 68.2%. While awareness and treatment rates were relatively high in the MMM19 campaign, the BP control rate of the total hypertensive population was still only ∼50%, which demands more emphasis on strict BP control.

Blood pressure levels and cardiovascular risk according to age in patients with diabetes mellitus: a nationwide population-based cohort study.

BACKGROUND: Little is known about age-specific target blood pressure (BP) in hypertensive patients with diabetes mellitus (DM). The aim of this study was to determine the BP level at the lowest cardiovascular risk of hypertensive patients with DM according to age. METHODS: Using the Korean National Health Insurance Service database, we analyzed patients without cardiovascular disease diagnosed with both hypertension and DM from January 2002 to December 2011. Primary end-point was composite cardiovascular events including cardiovascular death, myocardial infarction and stroke. RESULTS: Of 241,148 study patients, 35,396 had cardiovascular events during a median follow-up period of 10 years. At the age of < 70 years, the risk of cardiovascular events was lower in patients with BP < 120/70 mmHg than in those with BP 130-139/80-89 mmHg. At the age of ≥ 70, however, there were no significant differences in the risk of cardiovascular events between patients with BP 130-139/80-89 mmHg and BP < 120/70 mmHg. The risk of cardiovascular events was similar between patients with BP 130-139/80-89 mmHg and BP 120-129/70-79 mmHg, and it was significantly higher in those with BP ≥ 140/90 mmHg than in those with BP 130-139/80-89 mmHg at all ages. CONCLUSIONS: In a cohort of hypertensive patients who had DM but no history of cardiovascular disease, lower BP was associated with lower risk of cardiovascular events especially at the age of < 70. However, low BP < 130-139/80-89 mmHg was not associated with decreased cardiovascular risk, it may be better to keep the BP of 130-139/80-89 mmHg at the age of ≥ 70.

WHO implementation workshop on guidelines on procedures and data requirements for changes to approved biotherapeutic products, Seoul, Republic of Korea, 25-26 June 2019.

The first global workshop on implementation of the WHO guidelines on procedures and data requirements for changes to approved biotherapeutic products adopted by the WHO Expert Committee in 2018 was held in June 2019. The workshop participants recognized that the principles based on sound science and the potential for risk, as described in the WHO Guidelines on post-approval changes, which constitute the global standard for product life-cycle management are providing clarity and helping national regulatory authorities in establishing guidance while improving time-lines for an efficient regulation of products. Consequently, the regulatory situation for post-approval changes and guideline implementation is changing but there is a disparity between different countries. While the guidelines are gradually being implemented in some countries and also being considered in other countries, the need for regional workshops and further training on post-approval changes was a common theme reiterated by many participants. Given the complexities relating to post-approval changes in different regions/countries, there was a clear understanding among all participants that an efficient approach for product life-cycle management at a national level is needed to ensure faster availability of high standard, safe and efficacious medicines to patients as per the World Health Assembly Resolution 67.21.

Age-dependent pulmonary reactivity to house dust mite allergen: a model of adult-onset asthma?

Asthma is a heterogeneous disease differentiated by factors like allergen sensitivity, inflammation, sex, and age at onset. The mouse model is widely used to study the early-life development of allergic asthma. However, age-dependent allergen responses later in life remain relatively understudied and lack a widely accepted model. To differentiate age-dependent responses to the ubiquitous house dust mite (HDM), 3- and 9-mo-old female C57BL/6 mice were randomized into two groups each and exposed to HDM or phosphate-buffered saline (control) via intranasal instillation for sensitization and challenge phases. At 24 h after challenge, all mice underwent pulmonary function testing and methacholine challenge. Bronchoalveolar lavage fluid (BALF) was collected for assessment of cell differentials, and right lung lobes were fixed, sectioned, and stained for histopathology and immunohistochemistry. Both age groups demonstrated strong inflammatory/allergic responses to HDM exposure. However, only 9-mo-old HDM-exposed mice demonstrated significant airway hyperresponsiveness compared with age-matched controls. These HDM-exposed mice also had 1) statistically significant increases in tissue bronchiolitis, perivasculitis, and BALF neutrophilia relative to their younger counterparts and 2) significantly increased extent of immunostaining compared with all other groups. This study presents a potential model for adult-onset asthma, focusing specifically on the atopic, perimenopausal female phenotype. Our findings suggest that lung function declines with age and that the inflammatory profile of this adult subgroup is a mixed, rather than a simple, atopic, Th2 response. This model may enhance our understanding of how age influences the development of asthmic-like symptoms in older subgroups.

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

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

Prevalence of Fabry Disease in Korean Men with Left Ventricular Hypertrophy.

BACKGROUND: Fabry disease is an X-linked recessive disorder caused by deficiency of the lysosomal enzyme α-galactosidase A (α-Gal A). Previous studies identified many cases of Fabry disease among men with left ventricular hypertrophy (LVH). The purpose of this study was to define the frequency of Fabry disease among Korean men with LVH. METHODS: In this national prospective multicenter study, we screened Fabry disease in men with LVH on echocardiography. The criterion for LVH diagnosis was a maximum LV wall thickness 13 mm or greater. We screened 988 men with LVH for plasma α-Gal A activity. In patients with low α-Gal A activity (< 3 nmol/hr/mL), we searched for mutations in the α-galactosidase gene. RESULTS: In seven men, α-Gal A activity was low. Three had previously identified mutations; Gly328Arg, Arg301Gln, and His46Arg. Two unrelated men had the E66Q variant associated with functional polymorphism. In two patients, we did not detect GLA mutations, although α-Gal A activity was low on repeated assessment. CONCLUSION: We identified three patients (0.3%) with Fabry disease among unselected Korean men with LVH. Although the prevalence of Fabry disease was low in our study, early treatment of Fabry disease can result in a good prognosis. Therefore, in men with unexplained LVH, differential diagnosis of Fabry disease should be considered.

GAREM1 regulates the PR interval on electrocardiograms.

PR interval is the period from the onset of P wave to the start of the QRS complex on electrocardiograms. A recent genomewide association study (GWAS) suggested that GAREM1 was linked to the PR interval on electrocardiograms. This study was designed to validate this correlation using additional subjects and examined the function of Garem1 in a mouse model. We analyzed the association of rs17744182, a variant in the GAREM1 locus, with the PR interval in 5646 subjects who were recruited from 2 Korean replication sets, Yangpyeong (n = 2471) and Yonsei (n = 3175), and noted a significant genomewide association by meta-analysis (P = 2.39 × 10-8). To confirm the function of Garem1 in mice, Garem1 siRNA was injected into mouse tail veins to reduce the expression of Garem1. Garem1 transcript levels declined by 53% in the atrium of the heart (P = 0.029), and Garem1-siRNA injected mice experienced a significant decrease in PR interval (43.27 ms vs. 44.89 ms in control, P = 0.007). We analyzed the expression pattern of Garem1 in the heart by immunohistology and observed specific expression of Garem1 in intracardiac ganglia. Garem1 was expressed in most neurons of the ganglion, including cholinergic and adrenergic cells. We have provided evidence that GAREM1 is involved in the PR interval of ECGs. These findings increase our understanding of the regulatory signals of heart rhythm through intracardiac ganglia of the autonomic nervous system and can be used to guide the development of a therapeutic target for heart conditions, such as atrial fibrillation.

Mediating effects of nocturnal blood pressure and morning surge on the contributions of arterial stiffness and sodium intake to morning blood pressure: A path analysis.

BACKGROUND: The aim of this study was to evaluate the mediating effects of nocturnal blood pressure (BP) and morning surge on the contribution of arterial stiffness and sodium intake to morning BP in a middle-aged general population. METHODS: The study included 124 subjects aged 30-59 years, from rural Yeoju County, Gyeonggi Province, South Korea. Ambulatory BP monitoring, 24 h urinary sodium excretion (24 h UNa) and brachial-ankle pulse wave velocity (baPWV) measurements were performed in all subjects. RESULTS: The mean ± SD age was 48.1 ± 8.2 years and the proportion of male subjects was 41.1%. After adjusting for covariates, morning systolic blood pressure (SBP) was significantly correlated with morning surge [coefficient = 0.761, 95% confidence interval (CI) 0.651-0.872, p < 0.001], nocturnal SBP (coefficient = 0.576, 95% CI 0.454-0.698, p < 0.001) and baPWV (coefficient = 3.550, 95% CI 1.447-5.653, p = 0.001). Path analysis modeling revealed that baPWV had significant direct (0.035, p = 0.013) and indirect effects (0.042, p = 0.012) on morning SBP. The indirect effect mediated by nocturnal SBP was statistically significant (0.054, p = 0.005), but the indirect effect mediated by the morning surge was not significant. The 24 h UNa had no significant direct or indirect effects on morning SBP. CONCLUSION: baPWV had significant direct and indirect effects on morning SBP. The indirect effect was mediated by nocturnal SBP, but not by morning surge. The 24 h UNa had neither significant direct nor indirect effects on morning SBP.

Validation study of candidate single nucleotide polymorphisms associated with left ventricular hypertrophy in the Korean population.

BACKGROUND: Left ventricular hypertrophy (LVH) is a valid predictor for cardiovascular mortality and morbidity regardless of age, gender, and race. The HyperGEN study conducted a genome-wide association study and identified twelve single nucleotide polymorphisms (SNPs) associated with LVH. The aim of this study was to validate these candidate SNPs in the Korean population. METHODS: Among 1637 individuals from the Korean Multi-Rural Communities Cohort Study (MRCohort) of the Korean Genome Epidemiology Study (KoGES), we carried out a linear regression analysis with left ventricular mass index (LVMI) and a logistic regression analysis for LVH status. RESULTS: The rs4129218 on chromosome 12 tended to be associated with LVM/body surface area (adjusted ß = -0.023; p = 0.036) and LVM/height(2.7) (adjusted ß = -0.027; p = 0.016), and was marginally protective against LVH after adjustment for age, sex, body mass index, serum creatinine, systolic blood pressure, heart rate and antihypertensive medication (adjusted odds ratio = 0.766 and 0.731; p = 0.027 and 0.007 according to indexation by BSA and height(2.7), respectively). CONCLUSIONS: In the Korean population, the minor allele of rs4129218 had borderline association with lower LVM. This study suggests that rs4129218 on chromosome 12 showed consistent tendency of possibly related loci for LVH independent of ethnic background.

Correlations between molecular subtypes and pathologic response patterns of breast cancers after neoadjuvant chemotherapy.

BACKGROUND: The relationship between the pathologic response patterns after neoadjuvant chemotherapy (NAC) and specific subtypes of breast cancer is unclear. METHODS: This study retrospectively analyzed 351 tumors from 348 women with breast cancer who received anthracycline and taxane-based NAC and subsequent surgery. Various histopathologic factors were assessed in the pretreatment biopsy and surgery specimens based on molecular subtypes defined by immunohistochemistry. RESULTS: The tumors without a pathologic complete response in each subtype retained their morphologic features after NAC. Lymphocytic infiltration was higher in the hormone receptor-negative (HR-) tumors than in the HR+ tumors. The HR- tumors showed more necrosis and histiocytic infiltration in the tumor bed than the HR+ tumors. The overall (including in situ carcinoma) and invasive pathologic cancer sizes were similar for the triple-negative tumors only. Although all the subtypes showed significantly reduced tumor size after NAC, the difference between the pre-NAC magnetic resonance imaging (MRI) tumor size and the overall pathologic cancer size was significantly smaller for the HR+/human epidermal growth factor receptor 2-negative (HER2-) subgroup than for the triple-negative subgroup. The triple-negative tumors showed the highest correlation between post-NAC tumor size measured by MRI and overall or invasive pathologic tumor size. CONCLUSION: The molecular subtypes of breast cancer have characteristic pathologic patterns of response to NAC.

Analysis of Removal Torque of Injection Molded Zirconia Implants; An Experimental Study on Beagles.

This study compared the removal torque between injection molded zirconia implants and titanium implants with resorbable blast media (RBM) surfaces in beagle humeri. Fifteen screw-shaped implants were classified into 3 groups; titanium implant with RBM surface (Group RT), injection molded zirconia implant (Group Zr) and injection molded zirconia implant with sand-blasted surface (Group ZrS). Implants were inserted into beagle humeri. After 12 weeks, removal torque values were measured. The Zr group has a slightly higher removal torque value than the RT and ZrS groups but there were no significant differences among groups. Zirconia implants shows a similar removal torque to RBM titanium implants. This in vivo study showed injection molded zirconia implants could be an alternative to RBM titanium implants in terms of removal torque.