Ischemic patterns assessed by positron emission tomography predict adverse outcome in patients with idiopathic dilated cardiomyopathy

Although patients with idiopathic dilated cardiomyopathy (DCM) have no coronary artery disease, regional impairment of myocardial perfusion combined with preserved metabolism has been found using positron emission tomography (PET). Our aim was to assess the prognostic relevance of PET-mismatch between stress myocardial perfusion and glucose uptake on clinical outcome in DCM. In 24 patients with DCM who underwent both myocardial perfusion and metabolism PET scanning, "mismatch" was assessed and the association with clinical outcome (hospitalization, mortality, and heart transplantation) was investigated. Mismatch was found in 16 patients (66.7%). Univariate analysis showed that the presence of mismatch was associated with adverse outcome (P = 0.03). After adjustment for sex and age, the association remained significant with an adjusted relative risk of 10.4 (95% CI 1.1-103; P = 0.04) for death, heart transplant, or hospitalization. Univariate analysis also showed that a higher extent of mismatch was significantly associated with adverse outcome (P = 0.02). After adjusting for sex and age, the association remained significant with an adjusted relative risk of 6.5 [95% CI 1.2-36; P = 0.03] for death, heart transplantation, or hospitalization. PET stress perfusion-metabolism mismatch, indicative for ischemia, is frequently found in DCM patients and related to a poorer outcome

Environmental enrichment reduces signs of boredom in caged mink

Animals housed in impoverished cages are often labelled 'bored'. They have also been called 'apathetic' or 'depressed', particularly when profoundly inactive. However, these terms are rarely operationally defined and validated. As a negative state caused by under-stimulation, boredom should increase interest in stimuli of all kinds. Apathy (lack of interest), by contrast, should manifest as decreased interest in all stimuli, while anhedonia (loss of pleasure, a depressive symptom) should specifically decrease interest in normally rewarding stimuli. We tested the hypotheses that mink, a model carnivore, experience more boredom, depression-like apathy, or anhedonia in non-enriched (NE) cages than in complex, enriched (E) cages. We exposed 29 subjects (13 E, 16 NE) to ten stimuli categorized a priori as aversive (e.g. air puffs), rewarding (e.g. evoking chasing) or ambiguous/neutral (e.g. candles). Interest in stimuli was assessed via latencies to contact, contact durations, and durations oriented to stimuli. NE mink contacted all stimuli faster (P = 0.003) than E mink, and spent longer oriented to/in contact with them, albeit only significantly so for ambiguous ones (treatment*type P<0.013). With stimulus category removed from statistical models, interest in all stimuli was consistently higher among NE mink (P<0.0001 for all measures). NE mink also consumed more food rewards (P = 0.037). Finally, we investigated whether lying down while awake and stereotypic behaviour (both increased by NE housing) predicted these responses. Lying awake positively co-varied with certain measures of increased exploration. In contrast, stereotypic 'scrabbling' or locomotion (e.g. pacing) did not. Overall, NE mink showed no evidence of apathy or depression, but instead a heightened investigation of diverse stimuli consistent with boredom. This state was potentially indicated by spending much time lying still but awake (although this result requires replication). Boredom can thus be operationalized and assessed empirically in non-human animals. It can also be reduced by environmental enrichment

Physical Fitness and Telomere Length in Patients with Coronary Heart Disease: Findings from the Heart and Soul Study

Background: Short telomere length (TL) is an independent predictor of mortality in patients with coronary heart disease (CHD). However, the relationship between physical fitness and TL has not been explored in these patients. Methods: In a cross sectional study of 944 outpatients with stable CHD, we performed exercise treadmill testing, assessed self-reported physical activity, and measured leukocyte TL using a quantitative PCR assay. We used generalized linear models to calculate mean TL (T/S ratio), and logistic regression models to compare the proportion of patients with short TL (defined as the lowest quartile), among participants with low, medium and high physical fitness, based on metabolic equivalent tasks achieved (METs). Results: 229 participants had low physical fitness (,5 METS), 334 had moderate physical fitness (5–7 METS), and 381 had high physical fitness (.7 METS). Mean6 T/S ratio ranged from 0.8660.21 (534963781 base pairs) in those with low physical fitness to 0.9560.23 (556663829 base pairs) in those with high physical fitness (p,.001). This association remained strong after adjustment for numerous patient characteristics, including measures of cardiac disease severity and physical inactivity (p = 0.005). Compared with participants with high physical fitness, those with low physical fitness had 2-fold greater odds o

バレイショ近縁種における種の分化 XIII. S.acaule X S.demissumより得た7倍雑種の染色体行動と両親ゲノムの類縁関係

中央アンデス産Acaulia群4倍種S. acaule (acl, 2n=48)とメキシコ産Demissa群6倍種S. demissum (dms, 2n=72)のゲノムの類縁関係を明らかにするために, 前者を母本として得た7倍雑種(2n=84)の還元分裂における染色体行動と稔性を調べた。以下その結果を要約する。両種間の交雑は極めて困難で, aclを母とした時のみ受粉花数当り0.02の低率で雑種が得られたにすぎない。得られた雑種は, 両親との形態的比較から, aclの非還元性卵とdmsの還元性花粉の受精に起因するものと推定された。この雑種の第1中期における染色体対合行動は甚だしく多様であったが, その対合型のモードは(12)_+(20)_+8_I, その平均対合頻度は(0.18)_V+(1.11)_+(11.73)_+(18.11)_+(7.26)_Iで, 著しく高頻度の3価形成を示す点が特徴的であった。このような対合行動はその後の染色体行動にも反映し, 第1後期では観察細胞のすべてに平均4.8の遅滞染色体がみられ, 第2中期では94%の細胞が分散染色体を示し, 数的平衡核板頻度は0.6%にすぎなかった。稔性は極めて低く, 調査花粉粒数の27%が一見正常であったが, 自殖及び戻交配のいずれにおいても全く種子を生じなかった。上記の観察結果, 特に高頻度で出現した3価染色体の成因を考察して次の知見を得た。すでにaclはAAA^aA^a, dmsはA^dA^dC_1C_1C_2C_2のゲノム型をもつことが知られているので, 当雑種のゲノム型はAAA^aA^aA^dC_1C_2となる。A^dゲノムは若干の構造的差異はもつもののAゲノム群に属することも知られている。したがって, 当雑種にみられる3価形成は, 主に, aclからのAAとdmsからのA^dの3ゲノム間の染色体対合に由来すると推論でき, 両種はこれらのゲノムの相同性によって相互に関係づけられているものと考えられる。 / Meiotic behavior and fertility were studied in a heptaploid F_1 hybrid (2n=84) obtained from crossing S. acaule (acl, 2n=48) with S. demissum (dms, 2n=72), with the aim of assessing a genomic relationship between the parent species. Crossability between the two species was very low, the number of hybrid plants per pollination being only 0.02. Morphological evidence indicated that the hybrid arose through the union of an unreduced egg of acl and a reduced pollen grain of dms. The hybrid had the mean pairing frequency of (0.18)_V+(1.11)_+(11.73)_+(18.11)_+(7.26)_I per cell at metaphase I, with (12)_+(20)_+8_I as the modal configuration. Its subsequent behaviors were extremely irregular, showing several laggards in all the cells and chromatid bridges in occasional cells at anaphase I and also scattered chromosomes in 94% of the cells at metaphase II. The hybrid gave only 27% stainable pollen and no seed either on selfing or on backcrossing with both parents. The pattern of chromosome pairing found in the hybrid was interpreted in terms of genomic relationship between both parent species. From this, it was suggested that one (A) of the two genomes (designated AA^a) which acl possess in its gametes seems to be closely similar to, but not identical with, one (A^d) of the three genomes (A^dC_1C_2) which dms possess in its gemetes

Meta-analysis of 49 549 individuals imputed with the 1000 Genomes Project reveals an exonic damaging variant in ANGPTL4 determining fasting TG levels

Background So far, more than 170 loci have been associated with circulating lipid levels through genome-wide association studies (GWAS). These associations are largely driven by common variants, their function is often not known, and many are likely to be markers for the causal variants. In this study we aimed to identify more new rare and low-frequency functional variants associated with circulating lipid levels.Methods We used the 1000 Genomes Project as a reference panel for the imputations of GWAS data from similar to 60 000 individuals in the discovery stage and similar to 90 000 samples in the replication stage.Results Our study resulted in the identification of five new associations with circulating lipid levels at four loci. All four loci are within genes that can be linked biologically to lipid metabolism. One of the variants, rs116843064, is a damaging missense variant within the ANGPTL4 gene.Conclusions This study illustrates that GWAS with high-scale imputation may still help us unravel the biological mechanism behind circulating lipid levels

A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure

Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals. Stage 1 analysis examined similar to 18.8 million SNPs and small insertion/deletion variants in 129,913 individuals from four ancestries (European, African, Asian, and Hispanic) with follow-up analysis of promising variants in 480,178 additional individuals from five ancestries. We identified 15 loci that were genome-wide significant (p <5 x 10(-8)) in stage 1 and formally replicated in stage 2. A combined stage 1 and 2 meta-analysis identified 66 additional genome-wide significant loci (13, 35, and 18 loci in European, African, and trans-ancestry, respectively). A total of 56 known BP loci were also identified by our results (p <5 x 10(-8)). Of the newly identified loci, ten showed significant interaction with smoking status, but none of them were replicated in stage 2. Several loci were identified in African ancestry, highlighting the importance of genetic studies in diverse populations. The identified loci show strong evidence for regulatory features and support shared pathophysiology with cardiometabolic and addiction traits. They also highlight a role in BP regulation for biological candidates such as modulators of vascular structure and function (CDKN1B, BCAR1-CFDP1, PXDN, EEA1), ciliopathies (SDCCAG8, RPGRIP1L), telomere maintenance (TNKS, PINX1, AKTIP), and central dopaminergic signaling MSRA, EBF2).Peer reviewe