Precancerous Pyloric Gland Metaplasia in the Biliary Epithelium Associated with Congenital Biliary Dilatation in a Three-Month-Old Infant

Pyloric gland metaplasia in the biliary epithelium is a precancerous lesion and has been confirmed in patients with congenital biliary dilatation presenting with overt biliary tract cancer. A patient was found to have an intra-abdominal cyst on fetal ultrasonography and was born at 37 weeks of gestation with a body weight of 2,636 g. Abdominal distension and repeated vomiting appeared 2 days after birth. Congenital biliary dilatation was diagnosed by imaging, wherein the common bile duct was enlarged to 9–10 cm in size, and the surrounding organs were extensively compressed; however, there was no sign of pancreatitis or cholangitis. Biliary drainage was performed through the gallbladder at 6 days of age, but it was insufficient because of the narrow and twisted cystic duct and changed to common bile duct at 18 days to relieve the compression. Because the body weight gain was poor due to loss of large amount of bile, the dilated bile duct and gallbladder were resected and hepatic duct Roux-Y jejunostomy was performed at 115 days of age with 4,500 g of body weight. Intraoperative imaging showed a pancreaticobiliary maljunction, and the pancreatic enzyme activities of the bile in the biliary system were remarkably elevated. Histopathological examination revealed pyloric gland metaplasia in the gallbladder epithelium and cystic duct. The patient is now over 2 years old and has been doing well without any complications. Based on our experience, precancerous pyloric gland metaplasia of the biliary epithelium may already occur even in a 3-month-old infant presenting with congenital biliary dilatation

Non-missense variants of KCNH2 show better outcomes in type 2 long QT syndrome

AIMS: More than one-third of type 2 long QT syndrome (LQT2) patients carry KCNH2 non-missense variants that can result in haploinsufficiency (HI), leading to mechanistic loss-of-function. However, their clinical phenotypes have not been fully investigated. The remaining two-thirds of patients harbour missense variants, and past studies uncovered that most of these variants cause trafficking deficiency, resulting in different functional changes: either HI or dominant-negative (DN) effects. In this study, we examined the impact of altered molecular mechanisms on clinical outcomes in LQT2 patients. METHODS AND RESULTS: We included 429 LQT2 patients (234 probands) carrying a rare KCNH2 variant from our patient cohort undergoing genetic testing. Non-missense variants showed shorter corrected QT (QTc) and less arrhythmic events (AEs) than missense variants. We found that 40% of missense variants in this study were previously reported as HI or DN. Non-missense and HI-groups had similar phenotypes, while both exhibited shorter QTc and less AEs than the DN-group. Based on previous work, we predicted the functional change of the unreported variants-whether they cause HI or DN via altered functional domains-and stratified them as predicted HI (pHI)- or pDN-group. The pHI-group including non-missense variants exhibited milder phenotypes compared to the pDN-group. Multivariable Cox model showed that the functional change was an independent risk of AEs (P = 0.005). CONCLUSION: Stratification based on molecular biological studies enables us to better predict clinical outcomes in the patients with LQT2

Electrical Storm in Idiopathic Ventricular Fibrillation Is Associated With Early Repolarization

ObjectivesThis study sought to characterize patients with idiopathic ventricular fibrillation (IVF) who develop electrical storms.BackgroundSome IVF patients develop ventricular fibrillation (VF) storms, but the characteristics of these patients are poorly known.MethodsNinety-one IVF patients (86% male) were selected after the exclusion of structural heart diseases, primary electrical diseases, and coronary spasm. Electrocardiogram features were compared between the patients with and without electrical storms. A VF storm was defined as VF occurring ≥3 times in 24 h and J waves >0.1 mV above the isoelectric line in contiguous leads.ResultsFourteen (15.4%) patients had VF storms occurring out-of-hospital at night or in the early morning. J waves were more closely associated with VF storms compared to patients without VF storms: 92.9% versus 36.4% (p < 0.0001). VF storms were controlled by intravenous isoproterenol, which attenuated the J-wave amplitude. After the subsidence of VF storms, the J waves decreased to the nondiagnostic level during the entire follow-up period. Implantable cardioverter-defibrillator therapy was administered to all patients during follow-up. Quinidine therapy was limited, but the patients on disopyramide (n = 3), bepridil (n = 1), or isoprenaline (n = 1) were free from VF recurrence, while VF recurred in 5 of the 9 patients who were not given antiarrhythmic drugs.ConclusionsThe VF storms in the IVF patients were highly associated with J waves that showed augmentation prior to the VF onset. Isoproterenol was effective in controlling VF and attenuated the J waves, which diminished to below the diagnostic level during follow-up. VF recurred in patients followed up without antiarrhythmic agents

Adult phenology of two species of tiger beetles (Carabidae, Cicindelinae) and estimates of population size of Cylindela elisae , in Tottori Sand Dunes, Honshu, Japan in 2016.

2015年の調査に引き続き，2016年の夏季にも鳥取砂丘オアシス周辺で標識再捕により，当地で絶滅が心配されるエリザハンミョウの生息数を推定した。マークできた個体はエリザハンミョウが270（昨年は304），カワラハンミョウが170（昨年は77），コハンミョウが4（昨年は1：昨年調査の報告書である鶴崎ら2016では「コニワハンミョウ」と誤記）であった。Jolly-Seber法によるエリザハンミョウの個体数推定値はもっとも多かった調査日（6月28日と7月16日）でともに約1,460で，2015年の2,300個体よりも少なかった。おそらく2016年の夏季の高気温のため，成虫の出現期は2015年よりも早く推移し，6 月中旬には成虫が出現し，8月下旬には終息した。エリザハンミョウの幼虫の営巣地はオアシス周辺の尻無川右岸の裸地であるが，成虫は左岸のコウボウシバ群落でも見つかった。カワラハンミョウの成虫は6月下旬から10月上旬まで見られ，170個体をマークしたが再捕獲できた個体は皆無であった。コハンミョウは尻無川の近くで4個体マークしたが本種も再捕獲にいたらなかった。昨年の2個体（マークしたのは1個体）に続けての確認で，細々ではあるが，本種は当地で世代を繰り返している可能性が高い。 / Following a survey of the population size of a tiger beetle species, Cylindera elisae(Motschulsky,1859) in the Tottori Sand Dunes, Tottori City, in 2015 (Tsurusaki et al.2016), we estimated population size of　the same population of the same species also in 2016 by using mark-recapture experiments. A total of　270 adults of Cy. elisae , 170 adults of Chaetodera laetescripta (Motschulsky, 1860) and 4 adults of Myriochila　speculifera (Chevrolat, 1865) (This species was　erroneously recorded as Cicindela　transbaicalica japanensis　Chaudoir, 1863 in Tsurusaki et al. 2016) were individually marked during the summer in 2016.　None of　those　adults marked were recaptured for the　two latter species. The highest number of　adults of Cy. elisae estimated　by the Jolly-Seber method was ca. 1,460 recorded on both　28 June and 16 July

大学生の「具体的殺生行動」に対する認識構造の分析 : 「殺生行動」に対する賛否判断理由の水準分け

In this study, in order to clarify ideas on the human life destroying behaviors, 188 university students were required to state their opinions for and against and give reasons for 4 different situations, namely shooting bears, eating chicken that they had raised, cutting down a big tree and hunting rabbit. There was most approval for shooting bears, and there were many objections to cutting down a big tree. Their reasons were classified into 7 types: labeled "emotional reaction", "the human center", "respect of the life support", "the human center while the life is respected", "the conflict condition", "concession" and "integration". According to the situation, different reasons were given, and, the for and against opinions rate were different by the judgment type. The "respect of the life support" type tended not to support life destroying behavior, but on the other hand, "the human center" type tended to support it

Transethnic Genome-Wide Association Study Provides Insights in the Genetic Architecture and Heritability of Long QT Syndrome

BACKGROUND: Long QT syndrome (LQTS) is a rare genetic disorder and a major preventable cause of sudden cardiac death in the young. A causal rare genetic variant with large effect size is identified in up to 80% of probands (genotype positive) and cascade family screening shows incomplete penetrance of genetic variants. Furthermore, a proportion of cases meeting diagnostic criteria for LQTS remain genetically elusive despite genetic testing of established genes (genotype negative). These observations raise the possibility that common genetic variants with small effect size contribute to the clinical picture of LQTS. This study aimed to characterize and quantify the contribution of common genetic variation to LQTS disease susceptibility. METHODS: We conducted genome-wide association studies followed by transethnic meta-analysis in 1656 unrelated patients with LQTS of European or Japanese ancestry and 9890 controls to identify susceptibility single nucleotide polymorphisms. We estimated the common variant heritability of LQTS and tested the genetic correlation between LQTS susceptibility and other cardiac traits. Furthermore, we tested the aggregate effect of the 68 single nucleotide polymorphisms previously associated with the QT-interval in the general population using a polygenic risk score. RESULTS: Genome-wide association analysis identified 3 loci associated with LQTS at genome-wide statistical significance (P&lt;5×10-8) near NOS1AP, KCNQ1, and KLF12, and 1 missense variant in KCNE1(p.Asp85Asn) at the suggestive threshold (P&lt;10-6). Heritability analyses showed that ≈15% of variance in overall LQTS susceptibility was attributable to common genetic variation (h2SNP 0.148; standard error 0.019). LQTS susceptibility showed a strong genome-wide genetic correlation with the QT-interval in the general population (rg=0.40; P=3.2×10-3). The polygenic risk score comprising common variants previously associated with the QT-interval in the general population was greater in LQTS cases compared with controls (P&lt;10-13), and it is notable that, among patients with LQTS, this polygenic risk score was greater in patients who were genotype negative compared with those who were genotype positive (P&lt;0.005). CONCLUSIONS: This work establishes an important role for common genetic variation in susceptibility to LQTS. We demonstrate overlap between genetic control of the QT-interval in the general population and genetic factors contributing to LQTS susceptibility. Using polygenic risk score analyses aggregating common genetic variants that modulate the QT-interval in the general population, we provide evidence for a polygenic architecture in genotype negative LQTS.</p

Correction: Gender Differences in the Inheritance Mode of RYR2 Mutations in Catecholaminergic Polymorphic Ventricular Tachycardia Patients.

[This corrects the article DOI: 10.1371/journal.pone.0131517.]

Gender Differences in the Inheritance Mode of RYR2 Mutations in Catecholaminergic Polymorphic Ventricular Tachycardia Patients.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is one of the causes of sudden cardiac death in young people and results from RYR2 mutations in ~60% of CPVT patients. The inheritance of the RYR2 mutations follows an autosomal dominant trait, however, de novo mutations are often identified during familial analysis. In 36 symptomatic CPVT probands with RYR2 mutations, we genotyped their parents and confirmed the origin of the respective mutation. In 26 sets of proband and both parents (trio), we identified 17 de novo mutations (65.4%), seven from their mothers and only two mutations were inherited from their fathers. Among nine sets of proband and mother, five mutations were inherited from mothers. Four other mutations were of unknown origin. The inheritance of RYR2 mutations was significantly more frequent from mothers (n = 12, 34.3%) than fathers (n = 2, 5.7%) (P = 0.013). The mean ages of onset were not significantly different in probands between de novo mutations and those from mothers. Thus, half of the RYR2 mutations in our cohort were de novo, and most of the remaining mutations were inherited from mothers. These data would be useful for family analysis and risk stratification of the disease