Genetic Study in Left Ventricular Noncompaction

Background—Left ventricular noncompaction (LVNC) has since been classified as a primary genetic cardiomyopathy, but the genetic basis is not fully evaluated. The aim of the present study was to identify the genetic spectrum using next-generation sequencing and to evaluate genotype–phenotype correlations in LVNC patients. Methods and Results—Using next-generation sequencing, we targeted and sequenced 73 genes related to cardiomyopathy in 102 unrelated LVNC patients. We identified 43 pathogenic variants in 16 genes in 39 patients (38%); 28 were novel variants. Sarcomere gene variants accounted for 63%, and variants in genes associated with channelopathies accounted for 12%. MYH7 and TAZ pathogenic variants were the most common, and rare variant collapsing analysis showed variants in these genes contributed to the risk of LVNC, although patients carrying MYH7 and TAZ pathogenic variants displayed different phenotypes. Patients with pathogenic variants had early age of onset and more severely decreased left ventricular ejection fractions. Survival analysis showed poorer prognosis in patients with pathogenic variants, especially those with multiple variants: All died before their first birthdays. Adverse events were noted in 17 patients, including 13 deaths, 3 heart transplants, and 1 implantable cardioverter-defibrillator insertion. Congestive heart failure at diagnosis and pathogenic variants were independent risk factors for these adverse events. Conclusions—Next-generation sequencing revealed a wide spectrum of genetic variations and a high incidence of pathogenic variants in LVNC patients. These pathogenic variants were independent risk factors for adverse events. Patients harboring pathogenic variants showed poor prognosis and should be followed closely

Effectiveness of switching endoscopists for repeat surveillance colonoscopy: a retrospective study

Abstract Background Surveillance colonoscopy decreases colorectal cancer mortality; however, lesions are occasionally missed. Although an appropriate surveillance interval is indicated, variations may occur in the methods used, such as scope manipulation or observation. Therefore, individual endoscopists may miss certain areas. This study aimed to verify the effectiveness of performing repeat colonoscopies with a different endoscopist from the initial procedure. Methods We retrospectively reviewed a database of 8093 consecutive colonoscopies performed in the Omori Red Cross Hospital from January 1st 2018 to June 30th 2021. Data from repeat total colonoscopies performed within three months were collected to assess missed lesions. The patients were divided into two groups according to whether the two examinations were performed by different endoscopists (group D) or the same endoscopist (group S). The primary outcome in both groups was the missed lesion detection rate (MLDR). Results Overall, 205 eligible patients were analyzed. In total, 102 and 103 patients were enrolled in groups D and S, respectively. The MLDR was significantly higher in group D (61.8% vs. 31.1%, P  6 min) (odds ratio, 3.10; 95% CI, 1.12–8.61) as significant variables. Conclusions Overall, our study showed a significant improvement in the detection of missed lesions when performed by different endoscopists. When performing repeat colonoscopy, it is desirable that a different endoscopist perform the second colonoscopy. Trial registration This study was approved by the Institutional Review Board of the Omori Red Cross Hospital on November 28, 2022 (approval number:22–43)

Left Ventricular Noncompaction and Congenital Heart Disease Increases the Risk of Congestive Heart Failure

Background: Left ventricular noncompaction (LVNC) is a hereditary cardiomyopathy that is associated with high morbidity and mortality rates. Recently, LVNC was classified into several phenotypes including congenital heart disease (CHD). However, although LVNC and CHD are frequently observed, the role and clinical significance of genetics in these cardiomyopathies has not been fully evaluated. Therefore, we aimed to evaluate the impact on the perioperative outcomes of children with concomitant LVNC and CHD using next-generation sequencing (NGS). Methods: From May 2000 to August 2018, 53 Japanese probands with LVNC (25 males and 28 females) were enrolled and we screened 182 cardiomyopathy-associated genes in these patients using NGS. Results: The age at diagnosis of the enrolled patients ranged from 0 to 14 years (median: 0.3 months). A total of 23 patients (43.4%) were diagnosed with heart failure, 14 with heart murmur (26.4%), and 6 with cyanosis (11.3%). During the observation period, 31 patients (58.5%) experienced heart failure and 13 (24.5%) developed arrhythmias such as ventricular tachycardia, supraventricular tachycardia, and atrioventricular block. Moreover, 29 patients (54.7%) had ventricular septal defects (VSDs), 17 (32.1%) had atrial septal defects, 10 had patent ductus arteriosus (PDA), and 7 (13.2%) had Ebstein’s anomaly and double outlet right ventricle. Among the included patients, 30 underwent surgery, 19 underwent biventricular repair, and 2 underwent pulmonary artery banding, bilateral pulmonary artery banding, and PDA ligation. Overall, 30 genetic variants were identified in 28 patients with LVNC and CHD. Eight variants were detected in MYH7 and two in TPM1. Echocardiography showed lower ejection fractions and more thickened trabeculations in the left ventricle in patients with LVNC and CHD than in age-matched patients with VSDs. During follow-up, 4 patients died and the condition of 8 worsened postoperatively. The multivariable proportional hazards model showed that heart failure, LV ejection fraction of < 24%, LV end-diastolic diameter z-score of > 8.56, and noncompacted-to-compacted ratio of the left ventricular apex of > 8.33 at the last visit were risk factors for survival. Conclusions: LVNC and CHD are frequently associated with genetic abnormalities. Knowledge of the association between CHD and LVNC is important for the awareness of clinical implications during the preoperative and postoperative periods to identify the populations who are at an increased risk of additional morbidity

TBX5 R264K acts as a modifier to develop dilated cardiomyopathy in mice independently of T-box pathway.

BackgroundTBX5 is a transcription factor that has an important role in development of heart. TBX5 variants in the region encoding the T-box domain have been shown to cause cardiac defects, such as atrial septal defect or ventricular septal defect, while TBX5 variants have also been identified in a few cardiomyopathy patients and considered causative. We identified a TBX5 variant (c.791G>A, p.Arg264Lys), that is over-represented in cardiomyopathy patients. This variant is located outside of the T-box domain, and its pathogenicity has not been confirmed by functional analyses.ObjectiveTo investigate whether the TBX5 R264K is deleterious and could contribute to the pathogenesis of cardiomyopathy.Methods and resultsWe developed mice expressing Tbx5 R264K. Mice homozygous for this variant displayed compensated dilated cardiomyopathy; mild decreased fractional shortening, dilatation of the left ventricle, left ventricular wall thinning and increased heart weight without major heart structural disorders. There was no difference in activation of the ANF promotor, a transcriptional target of Tbx5, compared to wild-type. However, analysis of RNA isolated from left ventricular samples showed significant increases in the expression of Acta1 in left ventricle with concomitant increases in the protein level of ACTA1.ConclusionsMice homozygous for Tbx5 R264K showed compensated dilated cardiomyopathy. Thus, TBX5 R264K may have a significant pathogenic role in some cardiomyopathy patients independently of T-box domain pathway

映像メディア視聴者の情動制御のための物理特徴量の抽出

1. はじめに / 2. アプローチ / 3. 代表的な物理特徴量 / 4. 物理特徴量と情動との相関の解析 / 5. おわりにマルチメディア視聴者の情動生理に影響を与える物理特徴量候補を生理計測なしで抽出する方法を提案し，映像メディアから抽出した．マルチメディア視聴者の生理状態を制御しメディア効果を強調するためには，第１段階として，生理反応に影響を与えるであろう物理特徴量を抽出する必要があるが，考えられる限りの物理特徴量を1つずつ生理計測しながら特定することは現実的ではない．そこで，生理反応に直接対応すると思われる緊張_-_弛緩軸と爽快_-_鬱屈軸からなる情動平面を考え，心理評価によって60の映画シーンを情動平面に割り付ける．76個の物理特徴量を考え，これらの特徴量と2軸との相関係数を求め，危険率1%で有意に相関がある場合，生理反応に影響を与える物理特徴量候補として抽出した．このように時間のかかる生理計測なしで，生理反応に影響を与える物理特徴量候補を26+2個特定したので，今後の生理実験で検証していくWe show a method for extracting physical movie features that may influence movie viewers' physiological responses without physiological measurements and extracted physical features by the method. For our new challenge, emotion control by controlling physical movie features, we need to choose physical movie features that influence human physiological responses, find the relationship between the physical features and the physiological responses, and control the physical features to control the physiological responses indirectly. In this paper, we discuss the first stage

映像ショットの切り替え速度に対する速度感モデルの構築

1. はじめに / ２. モデル概要 / ３. カット周期に対する速度感の印象評価実験 / ４. GA による提案モデルのフィッティング / ５. おわりにマルチメディアコンテンツ制作において，制作者の視聴者に対する意図表現を支援することは重要である．制作者がコンテンツに込める意図の一つとして速度感がある．速度感は一般に，色の変化速度やコンテンツ中のオブジェクトの移動速度などによって変わると考えられる．しかしながら，映像ショットの長さやカット周期の時間配置とこれらが与える速度感との関係は明らかではない．本研究では，カット周期から視聴者が感じる速度感を数値で示すモデルを提案し，コンテンツのカット周期と，そのコンテンツ視聴者が受ける速度の印象との関係を導出する．まず，カット周期を入力変数とする速度感モデルを提案し，主観評価実験で得られた速度感を学習データに提案モデルをフィッティングする．最後に，モデル出力と人間の印象の関係を明らかにして手法の有用性を示す．We propose a model for expressing speed impression caused by switching speed of movie shot. Speed impression is one of the producers' intentions, and realized by changing colors, moving objects, and others. As there are many time-sequential data that make us feel different speed impression, it is difficult to press our speed impress numerically even if we restrict the factor to switching speed of movie shot. We propose a speed impression model that inputs the time-sequential data and outputs one value of our speed impression. First, we evaluate human speed impressions by several movie shot scenes and subjective test. Second, we fit our proposed model to the measured subjective data by tuning the model parameters with GA. Finally, we discuss a relationship between model outputs and human speed impression, and effectiveness