Search

Genetic testing has advanced significantly since the publication of the 2011 HRS/EHRA Expert Consensus Statement on the State of Genetic Testing for the Channelopathies and Cardiomyopathies.1 In addition to single-gene testing, there is now the ability to perform whole-exome sequencing (WES) and whole-genome sequencing (WGS). There is growing appreciation of oligogenic disorders,2,3 the role of modifier genes,2 and the use of genetic testing for risk stratification, even in common cardiac diseases such as coronary artery disease or atrial fibrillation (AFib), including a proposal for a score awaiting validation.4 This document reviews the state of genetic testing at the present time, and addresses the questions of what tests to perform and when to perform them. It should be noted that, as articulated in a 1999 Task Force Document by the European Society of Cardiology (ESC) on the legal value of medical guidelines,5 ‘The guidelines from an international organization, such as the ESC, have no specific legal territory and have no legally enforcing character. Nonetheless, in so far as they represent the state-of-the-art, they may be used as indicating deviation from evidence-based medicine in cases of questioned liability’. In the case of potentially lethal and treatable conditions such as catecholaminergic polymorphic ventricular tachycardia (CPVT) or long QT syndrome (LQTS), it is the responsibility of the physician, preferably in conjunction with an expert genetics team, to communicate to the patient/family the critical importance of family screening, whether this be facilitated by cascade genetic testing or by broader clinical family screening

Several Peronospora species are carried by wind over short and long distances, from warmer climates where they survive on living plants to cooler climates. In eastern Canada, this annual flow of sporangia was thought to be the main source of Peronospora destructor responsible for onion downy mildew. However, the results of a recent study showed that the increasing frequency of onion downy mildew epidemics in eastern Canada is associated with warmer autumns, milder winters, and previous year disease severity, suggesting overwintering of the inoculum in an area where the pathogen is not known to be endogenous. In this study, genotyping by sequencing was used to investigate the population structure of P. destructor at the landscape scale. The study focused on a particular region of southwestern Québec-Les Jardins de Napierville-to determine if the populations were clonal and regionally differentiated. The data were characterized by a high level of linkage disequilibrium, characteristic of clonal organisms. Consequently, the null hypothesis of random mating was rejected when tested on predefined or nonpredefined populations, indicating that linkage disequilibrium was not a function of population structure and suggesting a mixed reproduction mode. Discriminant analysis of principal components performed with predefined population assignment allowed grouping P. destructor isolates by geographical regions, while analysis of molecular variance confirmed that this genetic differentiation was significant at the regional level. Without using a priori population assignment, isolates were clustered into four genetic clusters. These results represent a baseline estimate of the genetic diversity and population structure of P. destructor.

Objective The aim of this retrospective study was to review the clinical data and outcomes of patients that suffered ectopic cilium (EC). Animals studied One hundred and twelve dogs from multiple private practices in France, with a clinical diagnosis of EC were included in the study. Results The mean age of affected dogs was 2.3 years. There were 64 females and 48 males. The most represented breeds were the Shi Tzu, the French Bulldog, the English Bulldog and the Chihuahua. Eleven dogs were affected bilaterally. The upper eyelid was implicated in 93.5% of the cases, with the median portion being the most affected. No statistical difference was observed between the right and the left eye. EC were associated with distichiasis in 50% of the cases. Pigmentation of the conjunctiva at the point of exit of the EC was present in 58% of the cases. EC were short in 75% and long in 25% of the cases. Corneal complications were statistically associated with short EC. The corneal lesions associated with EC were keratitis (94%), corneal granuloma (0.8%), corneal fibrosis (2.7%), corneal degeneration (0.8%), superficial corneal ulcer (68.7%), deep corneal ulcer (8%) and perforating corneal ulcer (0.8%). The surgeries which consisted of the removal of the hair follicle was successful in 88.4% of the cases. Conclusion EC is a rare condition which can be treated successfully by the removal of the hair follicles. It must be suspected in cases of corneal lesions unresponsive to medical treatment.

OBJECTIVES Little is known about cardiac hemodynamics in the fetus with transposition of the great arteries and intact ventricular septum (TGA-IVS). Better understanding of the fetal physiology in TGA-IVS would help to provide insights into specific clinical complications observed after birth, in particular neonatal hypoxia and pulmonary hypertension. The aim of this study was to assess cardiac hemodynamics in fetuses with TGA-IVS by performing systematic longitudinal echocardiographic follow-up from diagnosis to delivery. METHODS This was a longitudinal retrospective study of fetuses referred between 2010 and 2018 to the Sainte-Justine University Hospital Centre. Complete assessment of cardiac hemodynamics was performed in fetuses with TGA-IVS at 18-22, 28-32 and 35-38 weeks' gestation, which were compared with normal fetuses matched for gestational age. The maximum diameter of the foramen ovale was measured using two-dimensional echocardiography under the guidance of color Doppler echocardiography. Fetal cardiac hemodynamics were analyzed according to postnatal preductal transcutaneous oxygen saturation (TcSO2 )

INTRODUCTION While wideband segmented, breath-hold late gadolinium-enhancement (LGE) cardiovascular magnetic resonance (CMR) has been shown to suppress image artifacts associated with cardiac-implanted electronic devices (CIEDs), it may produce image artifacts in patients with arrhythmia and/or dyspnea. Single-shot LGE is capable of suppressing said artifacts. We sought to compare the performance of wideband single-shot free-breathing LGE against the standard and wideband-segmented LGEs in CIED patients. METHODS AND RESULTS We retrospectively identified all 54 consecutive patients (mean age: 61 ± 15 years; 31% females) with CIED who had undergone CMR with standard segmented, wideband segmented, and/or wideband single-shot LGE sequences as part of quality assurance for determining best clinical practice at 1.5 T. Two raters independently graded the conspicuity of myocardial scar or normal myocardium and the presence of device artifact level on a 5-point Likert scale (1: worst; 3: acceptable; 5: best). Summed visual score (SVS) was calculated as the sum of conspicuity and artifact scores (SVS ≥ 6 defined as diagnostically interpretable). Median conspicuity and artifact scores were significantly better for wideband single-shot LGE (F = 24.2, p

Summary Plants that successfully acclimate to stress can resume growth under stressful conditions. The grass Brachypodium distachyon can grow a cold‐adaptive morphology during cold acclimation. Studies on transcriptional memory (TM) have revealed that plants can be primed for stress by adjusting their transcriptional responses, but the function of TM in stress acclimation is not well understood. We investigated the function of TM during cold acclimation in B. distachyon.Quantitative polymerase chain reaction (qPCR), RNA‐seq and chromatin immunoprecipitation qPCR analyses were performed on plants exposed to repeated episodes of cold to characterize the presence and stability of TM during the stress and growth responses of cold acclimation.Transcriptional memory mainly dampened stress responses as growth resumed and as B. distachyon became habituated to cold stress. Although permanent on vernalization gene VRN1, TMs were short‐term and reversible on cold‐stress genes. Growing under cold conditions also coincided with the acquisition of new and targeted cold‐induced transcriptional responses.Overall, TM provided plasticity to cold stress responses during cold acclimation in B. distachyon, leading to stress habituation, acquired stress responses, and resumed growth. Our study shows that chromatin‐associated TMs are involved in tuning plant responses to environmental change and, as such, regulate both stress and developmental components that characterize cold‐climate adaptation in B. distachyon.

Several recent studies show that citizens' identification with Europe is one of the most important determinants of support for EU integration, that may also hold the key to greater economic solidarity and support for international redistribution. This article proposes a multidimensional conception of European identity, and that citizens' support for redistribution within the EU is highly contingent not only on the level of identification with Europe but also on the nature of their feeling of belonging to the community. In particular, we suggest that citizens who feel European, based on civic ties, are more likely to support redistribution than those who instead identify with Europe on the basis of religion and in particular, Christianity. Using unique and newly collected regional‐level data, we found support for these claims. Thus, not only if, or how much, but also why citizens identify with Europe matters for the level of social solidarity across borders.

A nanoemulsion with a porphyrin shell (NewPS) was created by the self-assembly of porphyrin salt around an oil core. The NewPS system has excellent colloidal stability, is amenable to different porphyrin salts and oils, and is capable of co-loading with chemotherapeutics. The porphyrin salt shell enables porphyrin-dependent optical tunability. The NewPS consisting of pyropheophorbide a mono-salt has a porphyrin shell of ordered J-aggregates, which produced a narrow, red-shifted Q-band with increased absorbance. Upon nanostructure dissociation, the fluorescence and photodynamic reactivity of the porphyrin monomers are restored. The spectrally distinct photoacoustic imaging (at 715 nm by intact NewPS) and fluorescence increase (at 671 nm by disrupted NewPS) allow the monitoring of NewPS accumulation and disruption in mice bearing KB tumors to guide effective photodynamic therapy. Substituting the oil core with Lipiodol affords additional CT contrast, whereas loading paclitaxel into NewPS facilitates drug delivery.

International audience; Pathogenic variants in FLNC encoding filamin C have been firstly reported to cause myopathies, and were recently linked to isolated cardiac phenotypes. Our aim was to estimate the prevalence of FLNC pathogenic variants in subtypes of cardiomyopathies and to study the relations between phenotype and genotype. DNAs from a cohort of 1150 unrelated index-patients with isolated cardiomyopathy (700 hypertrophic, 300 dilated, 50 restrictive cardiomyopathies, and 100 left ventricle non-compactions) have been sequenced on a custom panel of 51 cardiomyopathy disease-causing genes. An FLNC pathogenic variant was identified in 28 patients corresponding to a prevalence ranging from 1% to 8% depending on the cardiomyopathy subtype. Truncating variants were always identified in patients with dilated cardiomyopathy, while missense or in-frame indel variants were found in other phenotypes. A personal or family history of sudden cardiac death (SCD) was significantly higher in patients with truncating variants than in patients carrying missense variants (P = .01). This work reported the first observation of a left ventricular non-compaction associated with a unique probably causal variant in FLNC which highlights the role of FLNC in cardiomyopathies. A correlation between the nature of the variant and the cardiomyopathy subtype was observed as well as with SCD risk.

A wave of recent cross‐national research has pointed to the positive consequences for countries with high levels of “quality of government” (QoG), broadly defined, such as corruption, impartiality, and quality of public services. Yet the question of how QoG varies at the sub‐national level is still widely overlooked, in particular with measures that are available over time. To address it, we present the third round of data from the regional European Quality of Government Index (EQI) survey corruption (D73), Europe (N44) governance (H11); sub‐national (R50), time series (C22), collected in 2017 and built upon the opinions of 78,000 respondents in 193 regions from 21 European countries. The data provides several contributions to the literature. First, while the majority of QoG‐type indices rely on expert assessments, the EQI relies on the assessments of citizens, who are the on‐the‐ground consumers of public services. Second, the data begins to show trends on QoG variation over time, as well as across European regions. Consequently, this data is the most comprehensive sub‐national data to date; mapping of QoG within and across EU countries over the past decade. Building on previous rounds of data collected in 2010 and 2013, the 2017 EQI, which is published free for scholarly use, builds on both perceptions and experiences of citizens in public service areas such as health care, education, and law enforcement. This paper presents the results of the latest survey, improved with respect to the previous ones, discussion of trends across space and over time, as well as interesting avenues for future research that we detect across European regions. Una serie de investigaciones internacionales recientes ha senalado las consecuencias positivas para los paises con altos niveles de “calidad de gobierno” (CdG), definida en terminos generales como corrupcion, imparcialidad y calidad de los servicios publicos. Sin embargo, la cuestion de como varia la CdG a nivel subnacional aun se suele seguir pasando por alto, en particular respecto a las medidas disponibles a lo largo del tiempo. Para abordarlo, se presenta aqui la tercera ronda de datos de la encuesta regional del Indice Europeo de Calidad de Gobierno (EQI, por sus siglas en ingles) sobre corrupcion (D73), gobernanza (H11) en Europa (N44); subnacional (R50), series temporales (C22), recopilada en 2017 y basada en las opiniones de 78 000 encuestados de 193 regiones de 21 paises europeos. Los datos proporcionan varias contribuciones a la literatura. En primer lugar, mientras que la mayoria de los indices de tipo CdG se basan en evaluaciones expertas, la EQI se basa en las evaluaciones de los ciudadanos, que son los consumidores sobre el terreno de los servicios publicos. En segundo lugar, los datos empiezan a mostrar las tendencias de la variacion de la CdG a lo largo del tiempo, asi como en todas las regiones europeas. Por consiguiente, esta encuesta ofrece los datos subnacionales mas completos hasta la fecha y el cartografiado de la CdG en los paises de la UE y entre paises ,durante la ultima decada. A partir de las rondas anteriores de datos recopilados en 2010 y 2013, la EQI 2017, que se publica gratuitamente para uso academico, se basa tanto en las percepciones como en las experiencias de los ciudadanos en diferentes areas de servicio publico como la atencion de la salud, la educacion y la aplicacion de la ley. Este documento presenta los resultados de la ultima encuesta, mejorada con respecto a las anteriores, un debate sobre las tendencias espaciales y temporales, asi como vias interesantes para la investigacion futura que detectamos en las regiones europeas. 政府の質(quality of government:QoG)は、腐敗、公正性、公共サービスの質など定義は広いが、多数の国際研究が、QoGのレベルの高い国のプラスの結果を相次いで指摘している。地方レベルではQoGがどのように異なるかという疑問は、予てからその解決方法は利用可能であるにもかかわらず、未だに広く見過されている。そこで、2017年に収集された、欧州21カ国における193地域の78,000人の回答者の意見に基づいて構築された、地域のEuropean Quality of Government Index(EQI:欧州における政府の質指数)による調査腐敗(D73)、欧州(N44)統治(H11)、地方レベル(C22)、時系列(R50)からの第三のデータを提示した。データから以下の知見が得られた。1)QoGの分類指標の多くが専門家の評価に依存するものであるが、EQIは、公共サービスの実質的利用者である一般市民の評価に依存している。2)データは、QoGの変化のトレンドを経時的に、かつ欧州全域的にも示すようになってきている。すなわち、このデータは現時点で最も包括的な地方データであり、過去10年におけるEU圏内全域のQoGの分布を示すものである。2017年のEQIは、2010年と2013年に収集されたEQIの既存データに基づいて構築され、これは研究用に無料で公開されているが、医療、教育、法執行機関などの公共サービス領域に従事する市民の理解と経験の両方に基づいて構築されている。本稿では、過去の調査と比較して改善された、最新の調査の結果を提示し、空間と時間を超えたトレンドの考察と、欧州全域で認められた将来の研究に向かう興味深い道を提示する。

Various endocrine factors contribute to cold-induced white adipose tissue (WAT) browning, but glucagon has largely been ignored. The purpose of the current investigation was to determine if glucagon was required for the effects of cold on WAT browning. Utilizing whole-body glucagon receptor knockout (Gcgr-/-) mice and their wild-type (WT) littermate controls, we examined the response of inguinal WAT (iWAT) and interscapular brown adipose tissue (BAT) to an acute (48 h) cold stress or challenge with the β3-adrenergic agonist CL316,243. The effects of glucagon alone on the induction of thermogenic genes in adipose tissue from C57BL6/J mice were also examined. Gcgr-/- mice displayed modest increases in indices of browning at room temperature while displaying a blunted induction of Ucp1, Cidea, and Ffg21 mRNA expression in iWAT following cold exposure. Similarly, cold induced increases in mitochondrial DNA copy number, and the protein content of mitochondrial respiratory chain complexes, UCP1, and PGC1α were attenuated in iWAT from Gcgr-/- mice. In BAT, the induction of thermogenic markers following cold exposure was reduced, but the effect was less pronounced than in iWAT. Glucagon treatment increased the expression of thermogenic genes in both iWAT and BAT of C57BL6/J mice. In response to CL316,243, circulating fatty acids, glycerol, and the phosphorylation of hormone-sensitive lipase were attenuated in iWAT of Gcgr-/- mice. We provide evidence that glucagon is sufficient for the induction of thermogenic genes in iWAT, and the absence of intact glucagon signaling blunts the cold-induced browning of WAT, possibly due, in part, to impaired adrenergic signaling.-Townsend, L. K., Medak, K. D., Knuth, C. M., Peppler, W. T., Charron, M. J., Wright, D. C. Loss of glucagon signaling alters white adipose tissue browning.