杉本 恵子

PURPOSE: High-frequency oscillation (HFO) in scalp electroencephalography is a promising new noninvasive prognostic epilepsy biomarker, but further data are needed to ascertain the utility of this parameter. The present work investigated the association between epileptic activity and scalp HFO in pediatric patients with various types of epilepsy, using multivariable regression models to correct for possible confounding factors. METHODS: The authors analyzed 97 subjects who were divided into groups with active epilepsy (within 1 year of seizure), seizure-free epilepsy (>1 year without seizure), and nonepilepsy. Regarding the frequency of seizure occurrence as an indicator of epileptic activity, we categorized subjects into four groups (Daily/Weekly, Monthly, Yearly, and Rarely). RESULTS: Multiple linear regression analysis showed that the scalp HFO detection rate was significantly higher in patients with active epilepsy than in those with nonepilepsy (β [95% confidence interval] = 2.77 [1.79-4.29]; P < 0.001). The association between scalp HFO detection rate and frequency of seizure occurrence was highest in the Daily/Weekly group (β [95% confidence interval] = 3.38 [1.57-7.27]; P = 0.002), followed by Monthly and Yearly groups (β [95% confidence interval] = 2.42 [1.02-5.73]; P = 0.046 and 0.36 [0.16-0.83]; P = 0.017). In addition, HFO duration, number of peaks, and number of channels detected were significantly higher in patients with active epilepsy. CONCLUSIONS: Pediatric patients with active epilepsy and high frequency of seizure occurrence exhibited a higher scalp HFO detection rate. These results may help to establish HFO detectable by noninvasive scalp electroencephalography as a biomarker of active epilepsy in pediatric patients.

OBJECTIVE: Epilepsy treatment with anti-seizure medications (ASMs) is based on careful assessment of the balance between the likelihood of further seizures and the risk of side effects of treatment. However, there is currently no established biomarker to ascertain seizure control status with ASMs. High-frequency oscillations (HFOs), transient bursts of EEG activity with frequencies beyond 80 Hz, are a new and promising noninvasive epilepsy biomarker. We compared the risk of scalp HFO appearance between pediatric patients with good and poor seizure control by treatment with ASMs. METHODS: A total of 72 epilepsy patients (aged 0-18 years, 39 males) with good and poor seizure control with ASMs participated in this study. We applied a validated automated detector to determine HFO and spike. We calculated the odds ratios (ORs) for scalp HFO and spike appearance according to seizure control status by multiple logistic regression analysis. RESULTS: Scalp HFO was seen more commonly and with a significantly higher detection rate in patients with poor seizure control as compared with patients with good seizure control for both ripple and fast ripple. These significant associations were found for both focal and generalized epilepsy. The ORs for scalp HFO appearance adjusted for confounding factors were significantly higher in patients with poor seizure control compared to those with good seizure control (ripple: OR [95% CI] = 11.91 [2.21-64.30], p = 0.004; fast ripple: 4.98 [1.03-24.09], p = 0.046). There were no significant associations between spike appearance and seizure control status. SIGNIFICANCE: We found an increased risk of scalp HFO appearance in patients with poor seizure control. The results of this study support that scalp HFO is associated with patients having frequent seizures after treatment in both ripple and fast ripple. PLAIN LANGUAGE SUMMARY: This study analyzed scalp high-frequency oscillations and spikes in pediatric patients with various types of epilepsy who were being treated using ASMs. The results showed that an increased risk of scalp HFO appearance was observed in patients with poor seizure control compared to those with good seizure control. These findings were observed in both the ripple (80-250 Hz) and fast ripple (250-500 Hz) bands. The scalp HFO is associated with patients having frequent seizures after treatment in both ripple and fast ripple.

Background: The increasing prevalence of non-alcoholic fatty liver disease (NAFLD) has become a global health problem. NAFLD has few initial symptoms and may be difficult to detect early, so there is need for a minimally invasive early detection marker. We hypothesized that miR-122 and miR-20a levels combined, as the miR-122/miR-20a ratio might detect NAFLD more sensitively. Methods: This study involved 167 participants with low alcohol intake. Those who had an increase in echogenicity of the liver parenchyma and hepato-renal contrast on ultrasonography were classified as the NAFLD group (n = 44), which was further classified into mild (n = 26) and severe (n = 18) groups based on echogenic intensity and hepatic vessel and diaphragm visualization. Participants without fatty liver were included in the normal group, except for those with an abnormal body mass index, glycated hemoglobin, and systolic blood pressure (n = 123) values. Serum miR-122 and miR-20a expression levels in participants were measured by real-time polymerase chain reaction, and the miR-122/miR-20a was calculated. Results: In the NAFLD group, miR-122 expression was significantly higher and the miR-20a was significantly lower than in the normal group, in agreement with previous studies. miR-122/miR-20a was also significantly higher in the NAFLD group. Receiver operating characteristic curve analysis was performed with miR-122/miR-20a as an NAFLD detection marker, and the area under the curve of miR-122/miR-20a was significantly larger than that of miR-122 or miR-20a alone. Conclusions: The miR-122/miR-20a ratio, combined with miR-122 and miR-20a levels, is a useful biomarker to detect NAFLD with high sensitivity.

The increasing prevalence of nonalcoholic fatty liver disease (NAFLD) is a global health problem. In recent years, the inhibitory effect of brain-derived neurotrophic factor (BDNF) on diabetes mellitus and fatty liver has been clarified. The purpose of this study was to analyze the relationship between serum BDNF and NAFLD which caused by abnormal metabolism of glucose and lipids. This cross-sectional study involved 429 participants (mean age, 63.5 years: men, 38.5%) with low alcohol intake. Of the participants, those who had an increase in echogenicity of the liver parenchyma and hepato-renal contrast on ultrasonography were classified as the NAFLD group (n = 88), and the others were classified as the normal (n = 341) group. The NAFLD group was further classified into a mild group (n = 60) and a severe group (n = 28) based on the intensity of echogenicity and visualization of the hepatic vessels and diaphragm. Median BDNF levels were higher in the NAFLD group than the normal group (35.5 vs. 42.3 ng/mL, p < 0.01). Furthermore, BDNF levels tended to be associated with the severity of NAFLD (p < 0.01). In addition to the univariate analysis, in the sex- and age-adjusted model, there was a significant association between the BDNF levels and NAFLD severity (p < 0.01). The fully adjusted regression analysis also showed a positive association between the serum BDNF level and NAFLD (p < 0.01). These results suggest that NAFLD patients have a compensatory increase in circulating BDNF levels.

The early detection of acute myocardial infarction, which is caused by lifestyle-related risk factors, is essential because it can lead to chronic heart failure or sudden death. Echocardiography, among the most common methods used to detect acute myocardial infarction, is a noninvasive modality for the early diagnosis and assessment of abnormal wall motion. However, depending on disease range and severity, abnormal wall motion may be difficult to distinguish from normal myocardium. As abnormal wall motion can lead to fatal complications, high accuracy is required in its detection over time on echocardiography. This study aimed to develop an automatic detection method for acute myocardial infarction using convolutional neural networks (CNNs) and long short-term memory (LSTM) in echocardiography. The short-axis view (papillary muscle level) of one cardiac cycle and left ventricular long-axis view were input into VGG16, a CNN model, for feature extraction. Thereafter, LSTM was used to classify the cases as normal myocardium or acute myocardial infarction. The overall classification accuracy reached 85.1% for the left ventricular long-axis view and 83.2% for the short-axis view (papillary muscle level). These results suggest the usefulness of the proposed method for the detection of myocardial infarction using echocardiography.

INTRODUCTION: DNA methylation in the CpG sites of intron 1 of HIF3A is associated with body mass index (BMI). This cross-sectional study investigated correlations between DNA methylation of HIF3A and BMI or adiposity parameters in the Japanese population. METHOD: DNA methylation of HIF3A was quantified via pyrosequencing. RESULT: DNA methylation of HIF3A differed only in women; DNA methylation level at cg27146050 was associated with visceral adipose tissue thickness and correlated with BMI and percent (%) body fat after excluding smokers. CONCLUSION: Peripheral blood DNA methylation at the CpG site (cg27146050) of HIF3A correlated with VAT thickness in Japanese women.

Non-alcoholic fatty liver disease (NAFLD) is closely associated with obesity, metabolic syndrome, and type II diabetes mellitus. Recently, circulating microRNAs (miRNAs) have been proposed as useful disease biomarkers. We examined whether circulating miRNAs, such as miR-20a, miR-27a, and miR-126, were useful biomarkers for NAFLD. We conducted a cross-sectional analysis of 527 subjects aged 39 years or older who had undergone a health examination in the Yakumo Study. Of the residents, 92 were diagnosed with NAFLD using a registered medical sonographer. Serum miR-20a, miR-27a and miR-126 levels were measured by quantitative real-time PCR. We then calculated the odds ratios for serum miRNA level changes according to the severity of NAFLD using normal liver status as the reference group. Serum levels of miR-20a and 27a, but not miR-126, were significantly lower in NAFLD subjects than normal subjects. Serum miR-20a and miR-27a levels were significantly lower in both male and female severe NAFLD subjects. Logistic regression analysis showed a significant relationship between low circulating miR-20a and 27a levels and severe NAFLD. Down-regulated circulating miR-20a and 27a levels were significantly associated with severe NAFLD in the general population. Circulating miR-20a and miR-27a may be useful biomarkers for severe NAFLD.

BACKGROUND: Cardiac wall motion abnormality (WMA) is a common complication in patients with subarachnoid hemorrhage (SAH) and is one determinant of their prognosis. The aim of this study was to examine whether the electrocardiography (ECG) findings at admission could predict WMA commonly observed after SAH. MATERIALS AND METHODS: We studied 161 SAH patients with SAH who were hospitalized in our institution between April 2007 and November 2010. We performed bedside 2-dimensional transthoracic echocardiography and 12-lead surface ECG within 24hours of SAH onset. Each of the following ECG changes was scored as having 1 point: ST elevation, ST depression and T wave inversion. We summed up the points in every patient and compared with WMA evaluated by echocardiography. RESULTS: The study subjects were classified into 2 groups based on the presence of WMA. Multivariate analysis revealed that ST elevation, ST depression and T wave inversion were strong independent predictors of WMA. Receiver operating characteristic curve determined that the threshold value to predict WMA was 4 points (sensitivity 86.5%, specificity 83.1%, AUC 0.94, P < .0001). CONCLUSIONS: In conclusion, a novel ECG score may well predict WMA after SAH which may associate with an increased risk of mortality.

Purpose It has been demonstrated that circulating microRNA profiles are affected by physiological conditions. Several studies have demonstrated that microRNAs play important roles in the regulation of adiposity. However, few have investigated the relationship between circulating microRNAs and obesity, which has become a major public health problem worldwide. This study investigated the association between circulating microRNAs and obesity in a Japanese population. Methods Obesity parameters, such as subcutaneous and visceral fat adipose tissue, body fat percentage, and body mass index were assessed in a cross-sectional sample of 526 participants who attended health examinations in Yakumo, Japan. In addition, five circulating microRNAs (miR-20a, -21, -27a, -103a, and -320), which are involved in adipocyte proliferation and differentiation, were quantified using real-time polymerase chain reaction amplification. Results We compared the circulating microRNA concentrations in a percentile greater than 75th (high) with below the value (low) of subcutaneous adipose tissue, visceral fat adipose tissue, body mass index, and per cent body fat. For visceral fat adipose tissue, significant decrease in miR-320 expression was observed in high group. Also, for body mass index, significant change of miR-20a, -27a, 103a, and 320 expression level was observed in high group. Multiple linear regression analysis demonstrated that circulating levels of some microRNA such as miR-27a were significantly associated with subcutaneous adipose tissue, visceral fat adipose tissue, and body mass index. Conclusions Our findings support the need for further studies to determine whether such changes are consistent across different populations and whether the identified microRNAs may represent novel biomarkers to predict the susceptibility and progression of obesity-related disorders.

PURPOSE: The ratio of the left atrial volume index (LAVI) and late diastolic mitral annular velocity (A') is a useful echocardiographic index for identifying advanced left ventricular (LV) diastolic dysfunction in patients with dyspnoea. We investigated the clinical implications and prognostic value of the aforementioned ratio (LAVI/A') in patients with ST elevation (STE) or non-STE (NSTE) acute coronary syndrome (ACS). METHODS: We studied 212 patients with ACS. All patients underwent electrocardiography, echocardiography and measurement of plasma B-type natriuretic peptide (BNP) level on admission. The study endpoints were hospitalisation and mortality because of heart failure (HF). RESULTS: There was a significant, moderate positive correlation between LAVI/A' and natural logarithm (Ln) BNP level among the participants (r=0.48, p<0.0001). During a mean follow-up of 17 months, eight patients died and nine patients were hospitalised because of HF. The receiver operating characteristics curve indicated that LAVI/A'≥3.0 predicted these events (log-rank, p=0.0021). A significant and moderate positive correlation existed between LAVI/A' and Ln BNP level in the NSTE-ACS group (n=128; r=0.58, p<0.0001). However, the correlation between LAVI/A' and Ln BNP level was weaker in the STE-ACS group (n=84; r=0.33, p=0.0017). CONCLUSION: LAVI/A' was related to plasma BNP levels in patients with ACS, particularly in those with NSTE-ACS. This index was useful for predicting cardiac events in patients with ACS.

BACKGROUND: Both Takotsubo cardiomyopathy (TTC) and reverse TTC (r-TTC) are characterized by reversible regional wall motion abnormalities of the heart unrelated to coronary artery pathology. It remains unclear whether and/or how r-TTC differs from TTC. Subarachnoid hemorrhage (SAH) is occasionally causative of TTC/r-TTC, and this study was conducted to detect possible differences between TTC and r-TTC associated with SAH. METHODS: A single-center retrospective study was conducted on 328 consecutive SAH patients. They routinely underwent transthoracic echocardiography (TTE), ECG, and measurements of plasma catecholamines and other cardiac biomarkers within 24 h of admission. Demographic, echocardiographic, electrocardiographic and neurochemical profiles were compared between patients with TTC and r-TTC. The diagnosis of TTC/r-TTC was based on the revised Mayo Clinic Criteria. RESULTS: Data of 21 SAH-induced TTC and 10 SAH-induced r-TTC patients admitted between January 2009 and December 2014 were analyzed. The patients with r-TTC were significantly younger than those with TTC (51.8 ± 10.9 vs. 63.5 ± 14.4 years, p = 0.04). The former exhibited significantly higher plasma epinephrine levels than the latter (809 ± 710 vs. 380 ± 391 pg/mL, p = 0.04). Plasma norepinephrine levels did not differ significantly (2421 ± 1374 vs. 1724 ± 1591 pg/mL, p = 0.25). No significant differences were observed in other demographic/physiologic variables, echocardiographic parameters, frequency of ECG abnormalities, and 90-day mortality. Moreover, none of the patients who underwent a follow-up TTE exhibited morphologic change from one type to the other. CONCLUSIONS: The pathomechanisms in TTC and r-TTC may not be identical: however, distinguishing the two conditions may not have great importance from the standpoint of clinical management and prognostication.

Objectives: Circulating micro (mi)RNA profiles are influenced by various medical conditions, and miRNAs have been examined as potential biomarkers for cancer, cardiovascular disease, and diabetes. However, few studieshave investigated whether circulating miRNAs and cigarette smoking are correlated. Our aim was to determine theassociation between smoking status and expression of various miRNAs in a Japanese population sample.Methods: We conducted a cross-sectional analysis of 526 subjects (219 men and 307 women) aged 39 years and older who had undergone a health examination at a clinic in Yakumo, Hokkaido in August 2012. We used quantitative real-time polymerase chain reaction to determine serum miRNA expression. We then calculated the odds ratios for elevated serum miRNA levels according to smoking status using never-smokers as the reference group.Results: Expression of lethal (let)-7d, miRNA(miR)-150, miR-192, miR-197 and miR320 was significantly higher in current smokers than in never-smokers. Multivariate logistic regression analyses showed that while current smokers were significantly more likely to have elevated serum levels of miRNA let-7d, miR-21, miR-122, miR-146, miR-150, miR-192, miR-197, and miR320 than never-smokers, former smokers had significantly higher odds of having elevated miR-1, miR-146, miR-150, miR-195, and miR-320 levels in their sera.Conclusions: We found that cigarette smoking is associated with elevated expression of various serum miRNAs. Our results suggest that it is necessary to consider the confounding effect caused by smoking when evaluating expression of serum miRNAs for diagnosing pathological conditions.

BACKGROUND: Albuminuria is a risk factor for not only nephropathy progression but also cardiovascular disease. Oxidative stress may have a role in the positive association between albuminuria and cardiovascular disease. METHODS: This cross-sectional study investigated the associations of serum levels of carotenoids, which are dietary antioxidants, with albuminuria among 501 Japanese adults (198 men, mean age ± SD: 66.4 ± 10.0 years; 303 women, mean age ± SD: 65.4 ± 9.8 years) who attended a health examination. Serum levels of carotenoids were determined by high-performance liquid chromatography. Logistic regression analysis was used to estimate odds ratios (ORs) with 95% CIs for albuminuria after adjustment for age, body mass index, smoking habits, drinking habits, hypertension, diabetes mellitus, and dyslipidemia. RESULTS: Prevalence of albuminuria was 15.4% among men and 18.1% among women. Among women with albuminuria, geometric mean serum levels of canthaxanthin, lycopene, β-carotene, total carotenes, and provitamin A were significantly lower than those of normoalbuminuric women. Adjusted ORs for albuminuria among women in the highest tertiles of serum β-carotene (OR, 0.45; 95% CI, 0.20-0.98) and provitamin A (OR, 0.45; 95% CI, 0.20-0.97) were significantly lower as compared with those for women in the lowest tertile. There were no associations between serum carotenoids and albuminuria in men. CONCLUSIONS: An increased level of serum provitamin A, especially serum β-carotene, was independently associated with lower risk of albuminuria among Japanese women.

学生が腹部超音波検査実習をより効果的かつ効率的に行うことを目的として、情報端末にiPadを用い、各臓器における探蝕子の走査法とその際に得られる超音波画像を同期させた動画にて表示するシステムを開発した。実習内容は、「肝臓、胆嚢、膵臓、脾臓、腎臓の各臓器における指定画像の記録」「その画像に対する口頭試問」「学生自身が模擬患者となり、OSCE形式による実技試験」「異常症例の検討」とした。実技支援システム使用群と未使用群で、実技試験の結果を比較したところ、学生が苦手としている脾臓の観察で、使用群の方が有意に高得点であった。アンケート調査の結果、約75%の学生が本システムが役にたったと回答した。総合的評価では、約90%が高く評価していた。今回開発した実習支援システムは、学生の腹部超音波検査実習における補助的ツールとして有用であることが分かった。

PURPOSE: Assessment of plaque formation in the common carotid artery (CCA) is important for stratification of the risk of subsequent stroke. The stiffness parameter β, which can be assessed using an ultrasonic phase-locked echo-tracking system, was developed to evaluate arterial stiffness. The purpose this study was to examine the relationship of the stiffness parameter β to intima-media thickness (IMT) and plaque formation. METHODS: The stiffness parameter β and mean IMT were measured using an ultrasonic phase-locked echo-tracking system and an automatic IMT measurement system, respectively, and the presence of plaque was assessed by ultrasonography in 347 subjects who took part in a health check-up program for community-dwelling people in Hokkaido. RESULTS: Values of the stiffness parameter β were significantly higher in subjects with plaque formation than in those without plaque (10.60 ± 0.45 vs. 8.88 ± 0.23, P < 0.005) in whom IMT was not thickened; however, it was not different in subjects with increased IMT (>1.0 mm). The percentage of plaque formation was significantly correlated with the value of the stiffness parameter β. Furthermore, the stiffness parameter β was significantly correlated with plaque formation after adjustment for several clinical variables (odds ratio 1.113-1.178, P < 0.001). CONCLUSION: The stiffness parameter β is associated with plaque formation in the CCA, especially in subjects with a normal IMT. This could potentially be used as a predictor for plaque formation.

心エコー検査正常3742例(男1901例,女1841例)の計測値を性別,年齢別にまとめた.BSA及び断層法による各計測値については,BSA,心室中隔拡張末期壁厚(IVS),左室拡張末期径(LVDd),大動脈根部径,左房径は女に比べ男が有意に大であった.年代別では,BSA及びLVDdは加齢に伴い減少傾向を認め,IVSは増大傾向であった.左室駆出率は男女差,加齢変化とも認めなかった.ドプラ法による計測値は,左室流入血流速度E波とA波の比で加齢に伴う有意な負の相関を,E波の減速時間は正の相関を認めた.大動脈及び肺動脈駆出血流速度には加齢変化は認めなかった.弁逆流発生頻度は加齢に伴い増加する傾向で,特に大動脈弁逆流が著明であった