naohiro ichino

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.

INTRODUCTION: 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.

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.

BACKGROUND: There is limited evidence regarding the relationship between Diabetes mellitus (DM) in middle age and mild cognitive impairment after a follow-up. Therefore, we investigated the relationship between fasting blood glucose (FBG) levels in middle age and cognitive function (assessed using the Japanese version of the Montreal Cognitive Assessment (MoCA-J) in later life, following over 15 years of follow-up in the Aichi Workers' Cohort Study in Japan. METHODS: Participants were 253 former local government employees aged 60-79 years in 2018 who participated in a baseline survey conducted in 2002. Using baseline FBG levels and self-reported history, participants were classified into the normal, impaired fasting glucose (IFG) and, and DM groups. Total MoCA-J score ranges from 0 to 30, and cognitive impairment was defined as MoCA-J score ≤25 in this study. A general linear model was used to estimate the mean MoCA-J scores in the FBG groups, adjusted for age, sex, educational year, smoking status, alcohol consumption, physical activity, body mass index, systolic blood pressure, total cholesterol, and estimated glomerular filtration rate. RESULTS: The mean MoCA-J score in the total population was 25.0, and the prevalence of MoCA-J score ≤25 was 49.0%. Multivariable-adjusted total MoCA-J scores were 25.2, 24.8, and 23.4 in the normal, IFG, and DM groups, respectively. The odds ratio of MoCA-J score ≤25 in the DM group was 3.29. CONCLUSIONS: FBG level in middle age was negatively associated with total MoCA-J scores assessed later in life, independent of confounding variables.

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.

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.

北海道八雲町の検診受診者526名(男性219名、女性307名、39歳以上)を対象に、喫煙状況と各種microRNA(miRNA)発現との関連について検討した。定量的リアルタイムPCR法により血清miRNA発現を調べた。非喫煙者を基準として、元喫煙者と喫煙者の血清miRNAのオッズ比を算出した。lethal(let)-7d、miRNA(miR)-150、miR-192、miR-320の発現は喫煙者が非喫煙者よりも有意に多かった。多変量ロジスティック回帰分析により、喫煙者はmiRNA let-7d、miR-21、miR-122、miR-146、miR-150、miR-192、miR-197、miR-320の血清レベルが非喫煙者よりも有意に上昇しているのに対して、元喫煙者はmiR-1、miR-146、miR-150、miR-195、miR-320の血清レベルのオッズ比が有意に高かった。喫煙は各種血清miRNAの発現亢進と関連していることが示された。