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Purpose: This study aimed to determine blood pressure characteristics and long-term progress in patients with white coat hypertension (WCH) and obstructive sleep apnea (OSA)., Methods: Systolic blood pressure (SBP) and diastolic blood pressure (DBP) and sleep test results over a period of 26 months were analyzed from WCH patients with OSA (n = 28), WCH patients (n = 23), and healthy control subjects (n = 27)., Results: At the end of observation, WCH patients with OSA presented significantly increased daytime and nighttime BP and lower diurnal difference of SBP (all Ps < 0.05) and the increased rate of "non-dipper" status (SBP 28.6 %, DBP 32.1 %) was significantly higher when compared with WCH and control groups (all Ps < 0.01). Sustained hypertension was observed in 42.8 % of the WCH patients with OSA, which was significantly higher than that in the WCH and control groups (Ps < 0.01) and was predicted by non-dipper status via 24-h ambulatory SBP/DBP monitoring (Ps < 0.05)., Conclusion: WCH may represent a prehypertension status, which could develop into sustained hypertension with OSA.

The frequency and duration of periods with high temperatures are expected to increase under global warming. Thus, even short-lived organisms are increasingly likely to experience periods of hot temperatures at some point of their life-cycle. Despite recent progress, it remains unclear how various temperature experiences during the life-cycle of organisms affect demographic traits. We simulated hot days (daily mean temperature of 30 °C) increasingly experienced under field conditions and investigated how the timing and duration of such hot days during the life cycle of Plutella xylostella affects adult traits. We show that hot days experienced during some life stages (but not all) altered adult lifespan, fecundity, and oviposition patterns. Importantly, the effects of hot days were contingent on which stage was affected, and these stage-specific effects were not always additive. Thus, adults that experience different temporal patterns of hot periods (i.e., changes in timing and duration) during their life-cycle often had different demographic rates and reproductive patterns. These results indicate that we cannot predict the effects of current and future climate on natural populations by simply focusing on changes in the mean temperature. Instead, we need to incorporate the temporal patterns of heat events relative to the life-cycle of organisms to describe population dynamics and how they will respond to future climate change.

Aims: This prospective clinical trial was designed to evaluate the efficacy of an ablation strategy, namely '2C3L', in the treatment of persistent atrial fibrillation (AF); and to compare its efficacy with that of the 'stepwise' approach, which has been acknowledged as a promising ablation technique for persistent AF., Methods and Results: The '2C3L' technique is a fixed ablation approach consisting of bilateral circumferential pulmonary vein antrum isolation (PVAI) and three linear ablation lesion sets across the mitral isthmus, left atrial roof, and cavo-tricuspid isthmus. One hundred and forty-six patients with persistent AF were randomized to undergo ablation by using the '2C3L' or the 'stepwise' technique (n = 73, respectively). The primary endpoint was freedom from any atrial tachyarrhythmia off antiarrhythmic drug (AAD) after a single procedure at follow-up. Twelve months after a single procedure, there was no difference in sinus rhythm (SR) maintenance rate between the two groups (67% for '2C3L' vs. 60% for 'stepwise', P = 0.394; 95% confidence interval of between-group difference -8.7 to 22.4%). The procedure (222 ± 42 vs. 263 ± 41 min), fluoroscopy (41 ± 9 vs. 55 ± 8 min), and radiofrequency (RF) (107 ± 32 vs. 128 ± 38 min) time were significantly shorter in the '2C3L' group (all P < 0.001). At 25 ± 5 months after the first procedure, 57.5 and 52.1% of patients from the '2C3L' group and the 'stepwise' group were in SR off AAD (P = 0.494), respectively., Conclusions: For catheter ablation of persistent AF, the '2C3L' strategy is a fixed approach associated with clinical efficacy similar to that of the 'stepwise' approach but with less RF delivery, fewer X-ray exposure, and shorter procedural time., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Aims: This study sought to explore the relationship between plasma galectin-3 (Gal-3) and persistent atrial fibrillation (PsAF), and investigate whether Gal-3 predicts clinical outcomes in patients with PsAF undergoing catheter ablation., Methods: Fifty consecutive PsAF patients without coexisting structural heart disease undergoing first-time catheter ablation and 46 healthy controls were included. Blood samples were collected on admission for analysis of plasma Gal-3. Pre-ablation clinical and laboratory data were also recorded. Persistent atrial fibrillations patients were followed after ablation and AF recurrence was defined as episodes of AF or atrial tachycardia lasting >30 s after the blanking period., Results: Plasma Gal-3 concentrations were higher in PsAF patients than in healthy controls (P < 0.001). In PsAF group, those with AF recurrence had higher plasma Gal-3 than did those without recurrence (P = 0.007). Both Gal-3 (hazard ratio 1.28, P = 0.006) and left atrial diameter (LAD) (hazard ratio 1.1, P = 0.025) were independent predictors of AF recurrence after ablation. Moreover, adding Gal-3 to LAD had an incremental predictive value for ablation outcomes (global χ(2) of LAD alone: 8.2; LAD and Gal-3 concentrations: 15.7; P = 0.006)., Conclusion: Plasma Gal-3 concentrations are elevated in PsAF patients without structural heart disease and independently predict AF recurrence after ablation. Plasma Gal-3 concentration may be helpful in identifying appropriate candidates for AF ablation., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Background: Follicular helper T (TFH) cells underpin T cell-dependent humoral immunity and the success of most vaccines. TFH cells also contribute to human immune disorders, such as autoimmunity, immunodeficiency, and malignancy. Understanding the molecular requirements for the generation and function of TFH cells will provide strategies for targeting these cells to modulate their behavior in the setting of these immunologic abnormalities., Objective: We sought to determine the signaling pathways and cellular interactions required for the development and function of TFH cells in human subjects., Methods: Human primary immunodeficiencies (PIDs) resulting from monogenic mutations provide a unique opportunity to assess the requirement for particular molecules in regulating human lymphocyte function. Circulating follicular helper T (cTFH) cell subsets, memory B cells, and serum immunoglobulin levels were quantified and functionally assessed in healthy control subjects, as well as in patients with PIDs resulting from mutations in STAT3, STAT1, TYK2, IL21, IL21R, IL10R, IFNGR1/2, IL12RB1, CD40LG, NEMO, ICOS, or BTK., Results: Loss-of-function (LOF) mutations in STAT3, IL10R, CD40LG, NEMO, ICOS, or BTK reduced cTFH cell frequencies. STAT3 and IL21/R LOF and STAT1 gain-of-function mutations skewed cTFH cell differentiation toward a phenotype characterized by overexpression of IFN-γ and programmed death 1. IFN-γ inhibited cTFH cell function in vitro and in vivo, as corroborated by hypergammaglobulinemia in patients with IFNGR1/2, STAT1, and IL12RB1 LOF mutations., Conclusion: Specific mutations affect the quantity and quality of cTFH cells, highlighting the need to assess TFH cells in patients by using multiple criteria, including phenotype and function. Furthermore, IFN-γ functions in vivo to restrain TFH cell-induced B-cell differentiation. These findings shed new light on TFH cell biology and the integrated signaling pathways required for their generation, maintenance, and effector function and explain the compromised humoral immunity seen in patients with some PIDs., Competing Interests: The authors declare no conflicts of interest, (Copyright © 2015 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Background: Rheumatoid arthritis (RA) is associated with an increased incidence of atrial fibrillation (AF). This study evaluated the safety and efficacy of catheter ablation (CA) in the treatment of AF in patients with RA, which has not been previously reported., Methods: A total of 15 RA patients with AF who underwent CA were enrolled. For each RA patient, we selected 4 individuals (control group, 60 patients in total) who presented for AF ablation in the absence of structural heart or systemic disease and matched the RA patients with same gender, age (±2 years), type of AF, and procedure date., Results: Patients with RA had a significantly higher C-reactive protein level (1.81 ± 2.35 mg/dl vs. 4.14 ± 2.30 mg/dl, p=0.0320), white blood cell count (5632 ± 1200 mm(3) vs. 6361 ± 1567 mm(3), p=0.0482), and neutrophil count (3308 ± 973 mm(3) vs. 3949 ± 1461 mm(3), p=0.0441). At 2-year follow-up, atrial tachyarrhythmia (ATa) recurrence rate in the RA group (33.3%, 5/15) was similar to that in the control group (31.7%, 19/60; p=0.579) after single procedure. In all the five patients from the RA group who developed recurrence, ATa relapsed within 90 days following index procedure (median recurrence time 18 days vs. 92 days in control group; p=0.0373). Multivariate Cox regression analysis showed that hypertension and left atrial diameter but not RA, C-reactive protein, white blood cell count, and neutrophil count were independent predictors of ATa recurrence., Conclusions: Catheter ablation of AF can be safely performed in patients with RA, with a success rate comparable to that of patients without RA. RA patients tend to develop early ATa recurrence after AF ablation., (Copyright © 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Autosomal recessive, complete TYK2 deficiency was previously described in a patient (P1) with intracellular bacterial and viral infections and features of hyper-IgE syndrome (HIES), including atopic dermatitis, high serum IgE levels, and staphylococcal abscesses. We identified seven other TYK2-deficient patients from five families and four different ethnic groups. These patients were homozygous for one of five null mutations, different from that seen in P1. They displayed mycobacterial and/or viral infections, but no HIES. All eight TYK2-deficient patients displayed impaired but not abolished cellular responses to (a) IL-12 and IFN-α/β, accounting for mycobacterial and viral infections, respectively; (b) IL-23, with normal proportions of circulating IL-17(+) T cells, accounting for their apparent lack of mucocutaneous candidiasis; and (c) IL-10, with no overt clinical consequences, including a lack of inflammatory bowel disease. Cellular responses to IL-21, IL-27, IFN-γ, IL-28/29 (IFN-λ), and leukemia inhibitory factor (LIF) were normal. The leukocytes and fibroblasts of all seven newly identified TYK2-deficient patients, unlike those of P1, responded normally to IL-6, possibly accounting for the lack of HIES in these patients. The expression of exogenous wild-type TYK2 or the silencing of endogenous TYK2 did not rescue IL-6 hyporesponsiveness, suggesting that this phenotype was not a consequence of the TYK2 genotype. The core clinical phenotype of TYK2 deficiency is mycobacterial and/or viral infections, caused by impaired responses to IL-12 and IFN-α/β. Moreover, impaired IL-6 responses and HIES do not appear to be intrinsic features of TYK2 deficiency in humans., (© 2015 Kreins et al.)

Background: Impacts of a single radiofrequency ablation (RFA) on quality of life (QoL) were not well investigated in atrial fibrillation (AF) patients with low stroke risk., Methods and Results: Nine hundred AF patients with low CHADS2 score (ie, CHADS2 ≤1) who completed both a baseline and 6-month Atrial Fibrillation Effect on QualiTy-of-life (AFEQT) questionnaire were selected from The Chinese Atrial Fibrillation Registry between 2011 and 2013. A final cohort of 222 patients was constructed after a propensity score matching with 74 in the RFA group and 148 in the non-RFA group. Domains of AFEQT were balanced at baseline between the 2 groups. No statistically significant differences were noted in QoL (all P>0.05) when AFEQT at 6 months was compared between groups, except for the symptoms domain (83.07±12.37 units in the RFA group vs. 77.68±17.14 units in the non-RFA group; P=0.008) and treatment satisfaction domain (76.34±14.92 units in the RFA group vs. 70.38±16.81 units in the non-RFA group; P=0.01). Within-group changes in all domains and the global score of the questionnaire were moderate to large, whereas between-group comparisons in baseline to 6-month changes and QoL at 6 months were small to moderate according to Cohen effect sizes., Conclusions: QoL was balanced at baseline and improved at 6 months in both groups from this observational propensity-matched cohort based on the AFEQT questionnaire. However, RFA treatment was only associated with small-to-moderate superiorities over non-RFA treatment. The role of RFA in QoL improvement among AF patients with low stroke risk requires further research., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: Premature ventricular contractions (PVCs) originating from aortic sinus cusps (ASCs) can exhibit preferential conduction to right ventricular outflow tract (RVOT)., Objectives: This study aimed to examine the electrophysiological characteristics for guiding catheter ablation in patients with two morphological types of PVCs that originate from ASCs or the great cardiac vein (GCV)., Methods: We analyzed electrocardiogram from 10 patients with PVCs of two QRS morphologies. The patients who exhibited dominant left bundle branch block (LBBB) QRS morphology and less right bundle branch block (RBBB) morphology were designated as group 1 (n = 7), and those with dominant RBBB QRS morphology were designated as group 2 (n = 3). During PVCs, electroanatomical mapping was performed in both RVOT and ASC in group 1 and only performed in ASC or GCV in group 2., Results: In group 1, the earliest ventricular activation preceding the onset of the QRS complex (V-QRS) was recorded for 27 ± 6 ms (range 18-36 ms) in RVOT and 25 ± 6 ms (range 18-34 ms) in the ASC, while V-QRS was recorded for 28 ms, 42 ms, 40 ms in the ASC or GCV in group 2. All patients were successfully ablated at one site finally, including left coronary cusp in seven, left-right coronary cusp commissure in two, and GCV in one. None of the patients experienced recurrence or complications during the 18.4 ± 5.1 (range 6-24 months) months of follow-up., Conclusions: Two QRS morphologies (LBBB and RBBB with inferior axis) in PVCs could be a predictor of PVCs originating from ASC or GCV., (© 2015 Wiley Periodicals, Inc.)

Metastases are tumors that develop at a distance from their primary origin and are responsible for the death of 90% of cancer patients. For over a century the notion of seed (migrating cells) and soil (the locus where those cells anchor) provided an accurate account of which were the protagonists in their genesis. Despite aggressive efforts to unravel the dynamics involving migrating cells and the niche in which they anchor, explanations of this process remain ill-defined and controversial. The controversy is generated by the different premises that researchers adopt to integrate the vast amount of data collected at different levels of biological organization. The so-far hegemonic theory of cancer and its metastases has been the somatic mutation theory (SMT) and a number of its variants: They consider that cancers and their metastases represent a cell-based, genetic and molecular disease. This interpretation has been challenged by the tissue organization field theory (TOFT), which considers instead that cancer is a tissue-based disease, akin to development gone awry. In this Commentary, the merits of both theories are compared now in the context of metastases. Based on the epistemological shortcomings of the SMT and the acknowledged failure of therapeutic approaches based on this theory, we conclude that TOFT explains comprehensibly carcinogenesis and the appearance of metastases., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Human inborn errors of immunity mediated by the cytokines interleukin-17A and interleukin-17F (IL-17A/F) underlie mucocutaneous candidiasis, whereas inborn errors of interferon-γ (IFN-γ) immunity underlie mycobacterial disease. We report the discovery of bi-allelic RORC loss-of-function mutations in seven individuals from three kindreds of different ethnic origins with both candidiasis and mycobacteriosis. The lack of functional RORγ and RORγT isoforms resulted in the absence of IL-17A/F-producing T cells in these individuals, probably accounting for their chronic candidiasis. Unexpectedly, leukocytes from RORγ- and RORγT-deficient individuals also displayed an impaired IFN-γ response to Mycobacterium. This principally reflected profoundly defective IFN-γ production by circulating γδ T cells and CD4(+)CCR6(+)CXCR3(+) αβ T cells. In humans, both mucocutaneous immunity to Candida and systemic immunity to Mycobacterium require RORγ, RORγT, or both., (Copyright © 2015, American Association for the Advancement of Science.)

For some insect groups, wing outline is an important character for species identification. We have constructed a program as the integral part of an automated system to identify insects based on wing outlines (DAIIS). This program includes two main functions: (1) outline digitization and Elliptic Fourier transformation and (2) classifier model training by pattern recognition of support vector machines and model validation. To demonstrate the utility of this program, a sample of 120 owlflies (Neuroptera: Ascalaphidae) was split into training and validation sets. After training, the sample was sorted into seven species using this tool. In five repeated experiments, the mean accuracy for identification of each species ranged from 90% to 98%. The accuracy increased to 99% when the samples were first divided into two groups based on features of their compound eyes. DAIIS can therefore be a useful tool for developing a system of automated insect identification.

In this article, we describe a comprehensive management program for hypertension (HTN), based on the experience of leading cardiovascular centers in China. This comprehensive approach, adhering to a number of core principles, includes diagnosis and therapeutic interventions. Therapeutic management includes lifestyle changes, risk factor management and pharmacological intervention and should allow reliable lowering blood pressure (BP). Additional paragraphs discuss the relationship between paroxysmal atrial fibrillation (PAF), and HTN.

The small heat shock protein (sHsp) family is thought to play an important role in protein refolding and signal transduction, and thereby protect organisms from stress. However little is known about sHsp function and conservation across phylogenies. In the current study, we provide a comprehensive assessment of small Hsp genes and their stress responses in the oriental fruit moth (OFM), Grapholita molesta. Fourteen small heat shock proteins of OFM clustered with related Hsps in other Lepidoptera despite a high level of variability among them, and in contrast to the highly conserved Hsp11.1. The only known lepidopteran sHsp ortholog (Hsp21.3) was consistently unaffected under thermal stress in Lepidoptera where it has been characterized. However the phylogenetic position of the sHsps within the Lepidoptera was not associated with conservation of induction patterns under thermal extremes or diapause. These findings suggest that the sHsps have evolved rapidly to develop new functions within the Lepidoptera.

Aims: VENTURE-AF is the first prospective randomized trial of uninterrupted rivaroxaban and vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation (NVAF) undergoing catheter ablation (CA)., Methods and Results: Trial size was administratively set at 250, the protocol-specified target. Events were independently and blindly adjudicated. We randomly assigned 248 NVAF patients to uninterrupted rivaroxaban (20 mg once-daily) or to an uninterrupted VKA prior to CA and for 4 weeks afterwards. The primary endpoint was major bleeding events after CA. Secondary endpoints included thromboembolic events (composite of stroke, systemic embolism, myocardial infarction, and vascular death) and other bleeding or procedure-attributable events. Patients were 59.5 ± 10 years of age, 71% male, 74% paroxysmal AF, and had a CHA2DS2-VASc score of 1.6. The average total heparin dose used to manage activated clotting time (ACT) was slightly higher (13 871 vs. 10 964 units; P < 0.001) and the mean ACT level attained slightly lower (302 vs. 332 s; P < 0.001) in rivaroxaban and VKA arms, respectively. The incidence of major bleeding was low (0.4%; 1 major bleeding event). Similarly, thromboembolic events were low (0.8%; 1 ischemic stroke and 1 vascular death). All events occurred in the VKA arm and all after CA. The number of any adjudicated events (26 vs. 25), any bleeding events (21 vs. 18), and any other procedure-attributable events (5 vs. 5) were similar., Conclusion: In patients undergoing CA for AF, the use of uninterrupted oral rivaroxaban was feasible and event rates were similar to those for uninterrupted VKA therapy., Name of the Trial Registry: Clinicaltrials.gov trial registration number is NCT01729871., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Organisms in natural environments experience diel temperature fluctuations, including sporadic extreme conditions, rather than constant temperatures. Studies based mainly on model organisms have tended to focus on responses to average temperatures or short-term heat stress, which overlooks the potential impact of daily fluctuations, including stressful daytime periods and milder night-time periods. Here, we focus on daily maximum temperatures, while holding night-time temperatures constant, to specifically investigate the effects of high temperature on demographic parameters and fitness in the English grain aphid Sitobion avenae. We then compared the observed effects of different daily maximum temperatures with predictions from constant temperature-performance expectations. Moderate daily maximum temperatures depressed aphid performance while extreme conditions had dramatic effects, even when mean temperatures were below the critical maximum. Predictions based on daily average temperature underestimated negative effects of temperature on performance by ignoring daily maximum temperature, while predictions based on daytime maximum temperatures overestimated detrimental impacts by ignoring recovery under mild night-time temperatures. Our findings suggest that daily maximum temperature will play an important role in regulating natural population dynamics and should be considered in predictions. These findings have implications for natural population dynamics, particularly when considering the expected increase in extreme temperature events under climate change., (© 2015. Published by The Company of Biologists Ltd.)

Unconventional T cells such as γδ T cells, natural killer T cells (NKT cells) and mucosal-associated invariant T cells (MAIT cells) are a major component of the immune system; however, the cytokine signaling pathways that control their development and function in humans are unknown. Primary immunodeficiencies caused by single gene mutations provide a unique opportunity to investigate the role of specific molecules in regulating human lymphocyte development and function. We found that individuals with loss-of-function mutations in STAT3 had reduced numbers of peripheral blood MAIT and NKT but not γδ T cells. Analysis of STAT3 mosaic individuals revealed that this effect was cell intrinsic. Surprisingly, the residual STAT3-deficient MAIT cells expressed normal levels of the transcription factor RORγt. Despite this, they displayed a deficiency in secretion of IL-17A and IL-17F, but were able to secrete normal levels of cytokines such as IFNγ and TNF. The deficiency in MAIT and NKT cells in STAT3-deficient patients was mirrored by loss-of-function mutations in IL12RB1 and IL21R, respectively. Thus, these results reveal for the first time the essential role of STAT3 signaling downstream of IL-23R and IL-21R in controlling human MAIT and NKT cell numbers., (© 2015 Wilson et al.)

Hot days in summer (involving a few hours at particularly high temperatures) are expected to become more common under climate change. How such events at different life stages affect survival and reproduction remains unclear in most organisms. Here, we investigated how an exposure to 40 °C at different life stages in the global insect pest, Plutella xylostella, affects immediate survival, subsequent survival and reproductive output. First-instar larvae showed the lowest survival under heat stress, whereas 3rd-instar larvae were relatively heat resistant. Heat exposure at the 1(st)-instar or egg stage did not influence subsequent maturation success, while exposure at the 3rd-instar larval stage did have an effect. We found that heat stress at developmental stages closer to adult stage caused greater detrimental effects on reproduction than heat stress experienced at earlier life stages. The effects of hot events on insect populations can therefore depend critically on the timing of the event relative to an organism's life-cycle.

The mechanistic links between genetic variation and autoantibody production in autoimmune disease remain obscure. Autoimmune lymphoproliferative syndrome (ALPS) is caused by inactivating mutations in FAS or FASL, with autoantibodies thought to arise through failure of FAS-mediated removal of self-reactive germinal center (GC) B cells. Here we show that FAS is in fact not required for this process. Instead, FAS inactivation led to accumulation of a population of unconventional GC B cells that underwent somatic hypermutation, survived despite losing antigen reactivity, and differentiated into a large population of plasma cells that included autoantibody-secreting clones. IgE(+) plasma cell numbers, in particular, increased after FAS inactivation and a major cohort of ALPS-affected patients were found to have hyper-IgE. We propose that these previously unidentified cells, designated "rogue GC B cells," are a major driver of autoantibody production and provide a mechanistic explanation for the linked production of IgE and autoantibodies in autoimmune disease., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To explore the impact of a "one-week" staged multivessel percutaneous coronary intervention (PCI) versus culprit-only PCI on deaths and major adverse cardiac events (MACE)., Methods: We retrospectively analyzed 447 patients with multivessel disease who experienced a ST-segment elevation myocardial infarction (STEMI) within 12 h before undergoing PCI between July 26, 2008 and September 25, 2011. After completion of PCI in the infarct artery, 201 patients still in the hospital agreed to undergo PCI in non-infarct arteries with more than 70% stenosis for a "one-week" staged multivessel PCI. A total of 246 patients only received intervention for the culprit vessel. Follow-up ended on September 9, 2014. This study examined the differences in deaths from any cause (i.e., cardiac and noncardiac) and MACE between the two treatment groups., Results: Compared to a culprit-only PCI treatment approach, the "one-week" staged multivessel PCI was strongly associated with greater benefits for 55-month all cause death [41 (16.7%) vs.13 (6.5%), P = 0.004] and MACE [82 (33.3%) vs. 40 (19.9%), P = 0.002] rates. In addition, there were significant differences in the number of myocardial infarctions [43 (17.5%) vs. 20 (10.0%), P = 0.023], coronary-artery bypass grafting [CABG; 20 (8.1%) vs. 6 (3.0%), P = 0.021], and PCI [31 (12.6%) vs. 12 (6.0%), P = 0.018]. Patients undergoing culprit-only PCI compared to "one-week" PCI had the same number of stent thrombosis events [7 (2.8%) vs. 3 (1.5%), P = 0.522]., Conclusions: Compared to a culprit-only PCI treatment approach, "one-week" staged multi-vessel PCI was a safe and effective selection for STEMI and multi-vessel PCI.

Background: Previous studies have described the impact of mitral isthmus (MI) anatomy on the likelihood of achieving MI linear block in patients with native mitral valves (NMV) who underwent atrial fibrillation (AF) ablation. However, none have investigated that issue in AF patients with mechanical mitral valve replacements (MMVR)., Methods and Results: Twenty-nine consecutive patients who developed symptomatic persistent AF post-MMVR and referred for ablation were enrolled. Twenty-nine patients with NMV who underwent ablation of persistent AF during the same period were matched. With preprocedural cardiac computed tomographic imaging, MI anatomical features of all the participants were analyzed. Pouched MI was observed in 19 (65.5%) MMVR patients versus to 6 (20.7%) controls (P = 0.001). Bidirectional linear block across MI was achieved in 21 (72.4%) MMVR patients and 22 (75.9%) in the controls (P = 0.764). In the multivariable analysis, pouched MI was an independent predictor of incomplete MI block., Conclusions: Pouched MI accounts for the majority of AF patients with MMVR and may be associated with incomplete bidirectional linear block of MI., (© 2015 Wiley Periodicals, Inc.)

Breast cancer represents a heterogeneous group of diseases with varied biological features, behavior, and response to therapy; thus, management of breast cancer relies on the availability of robust predictive and prognostic factors to support therapy decision-making. Traditionally, neoadjuvant treatment for breast cancer was preserved for locally advanced, converting an inoperable to a surgical resectable cancer. Neoadjuvant trials, additionally, offer: 1) the opportunity to evaluate new treatment options in a faster way and with fewer patients than large adjuvant trials; 2) to identify and validate the prognostic and predictive value of a marker with its association with clinical outcome in relation to the administered treatment. In this setting, thanks to new, affordable technologies which help to detail the molecular profiles of tumors, new trial designs based on new target therapies, like window-of-opportunity, are also suggested, as they represent the chance to identify tumor sensitivity or to overcome tumor resistance to the treatment used, based on its interaction with tumor biology in early tumor stages. However, clinicians and researchers should pay particular attention: In this setting, the safety of patients is paramount, given the exposure of potentially curable patients to investigational agents with limited safety experience, the definition of the study population and the study design, such as adaptive strategies, should limit patient exposure to ineffective agents, and intensify safety monitoring in the course of the treatment. Here, issues related to outcome determination in breast cancer, including some critical points of view, are presented., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

The frequency and magnitude of extreme events are predicted to increase under future climate change. Despite recent advancements, we still lack a detailed understanding of how changes in the frequency and amplitude of extreme climate events are linked to the temporal and spatial structure of natural communities. To answer this question, we used a combination of laboratory experiments, field experiments, and analysis of multi-year field observations to reveal the effects of extreme high temperature events on the demographic rates and relative dominance of three co-occurrence aphid species which differ in their transmission efficiency of different agricultural pathogens. We then linked the geographical shift in their relative dominance to frequent extreme high temperatures through a meta-analysis. We found that both frequency and amplitude of extreme high temperatures altered demographic rates of species. However, these effects were species-specific. Increasing the frequency and amplitude of extreme temperature events altered which species had the highest fitness. Importantly, this change in relative fitness of species was consistent with significant changes in the relative dominance of species in natural communities in a 1 year long field heating experiment and 6 year long field survey of natural populations. Finally, at a global spatial scale, we found the same relationship between relative abundance of species and frequency of extreme temperatures. Together, our results indicate that changes in frequency and amplitude of extreme high temperatures can alter the temporal and spatial structure of natural communities, and that these changes are driven by asymmetric effects of high temperatures on the demographic rates and fitness of species. They also highlight the importance of understanding how extreme events affect the life-history of species for predicting the impacts of climate change at the individual and community level, and emphasize the importance of using a broad range of approaches when studying climate change., (© 2014 John Wiley & Sons Ltd.)

Aims: Transient ST-T elevation (STE) is a rare complication that occurs during transseptal catheterization. This study aims to delineate the incidence and characteristics of transient STE during transseptal catheterization for atrial fibrillation (AF) ablation., Methods and Results: Consecutive patients who underwent fluoroscopy-guided transseptal catheterization for circumferential pulmonary vein radiofrequency ablation in Beijing An Zhen Hospital from January 2006 to January 2013 were enrolled in this study. Out of 2965 patients with a total of 3452 transseptal catheterization procedures, 13 patients (0.38%, mean age 57 ± 8, 6 female, 12 paroxysmal AF, mean left atrial diameter 35.4 ± 3.8 mm) had STE. ST-T elevation occurred after transseptal puncture in 10 patients and after pulmonary vein venography in three patients. Systolic blood pressure (129 ± 10 vs. 104 ± 20 mmHg, P < 0.001), diastolic blood pressure (78 ± 6 vs. 64 ± 11 mmHg, P < 0.001), and heart rate (83 ± 19 bpm vs. 64 ± 23 b.p.m., P = 0.022) significantly decreased when STE occurred. Eleven patients complained of chest pain, one patient complained of dizziness, and one patient had no symptoms. Patients recovered in about 4.6 min (2-10 min) with dopamine or fast saline drip. Catheter ablation of AF was completed in all the 13 patients without sequelae or other complications. Four of the 13 patients (30.8%) had recurrence of AF after a mean follow-up of 21.7 months., Conclusion: ST-T elevation is a rare complication associated with transseptal catheterization without sequelae. Catheter ablation of AF could be safely completed in these patients., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Aims: The aim of this study was to evaluate whether the levels of HbA1c could predict the outcome of ablation in patients with type 2 diabetes mellitus (T2DM) and paroxysmal atrial fibrillation (PAF)., Patients and Methods: The study comprised 149 consecutive patients with T2DM and PAF who underwent their first circumferential pulmonary vein isolation. HbA1c levels were measured before ablation. Cox proportional hazards models were constructed to assess the relationship between HbA1c levels and the recurrence of atrial fibrillation (AF)., Results: Of the 149 patients, 60 (40.3 %) developed AF recurrence after a median 12-month follow-up. Multivariate Cox regression analysis revealed that left atrium size and HbA1c were independent predictors of recurrent atrial tachyarrhythmia. Receiver operating characteristic analysis demonstrated that an HbA1c cut-off value of ≥ 6.9 % predicted recurrence with 55.0 % sensitivity and 67.4 % specificity (AUC = 0.634). The success rate of ablation was 69.0 % in patients with an HbA1c value of < 6.9 % compared with 46.8 % in those with an HbA1c value of ≥ 6.9 % (log-rank test, p = 0.004)., Conclusion: High levels of HbA1c were associated with an increased risk of recurrence of atrial tachyarrhythmia in patients with T2DM and PAF undergoing catheter ablation.

In partnership with the Hawai'i Journal of Medicine & Public Health, the Daniel K. Inouye College of Pharmacy (DKICP) is pleased to provide Scripts on a regular basis. In the inaugural "Script," a brief history of the profession in Hawai'i was presented up to the founding of the DKICP, Hawai'i's only academic pharmacy program. In this second part of the inaugural article, we describe some key accomplishments to date. The mission of the College is to educate pharmacy practitioners and leaders to serve as a catalyst for innovations and discoveries in pharmaceutical sciences and practice for promoting health and well-being, and to provide community service, including quality patient care. Examples are given to support the stated goals of the mission. With 341 graduates to date, and a 96% pass rate on the national licensing board exams, the college has played a significant role in improving healthcare in Hawai'i and throughout the Pacific Region. Additionally, a PhD program with substantial research programs in both pharmacy practice and the pharmaceutical science has been launched. Considerable extramural funding has been garnered from organizations such as the National Institutes of Health and Centers for Medicare and Medicaid Services. The economic impact of the College is estimated to be over $50 million each year. With over 200 signed clinical affiliation agreements within the state as well as nationally and internationally, the DKICP has helped to ameliorate the shortage of pharmacists in the state, and has enhanced the profile and practice standard of the pharmacist's role on interprofessional health care teams.

A partnership was formed between the University of Hawai'i at Hilo Daniel K. Inouye College of Pharmacy (DKICP) and the Department of Health to carry out the Hawai'i Asthma Friendly Pharmacy Project (HAFPP), which utilizes pharmacy students as a workforce to administer Asthma Control Tests™ (ACT), and provide Asthma Action Plans (AAP) and inhaler technique education. Evaluation of data from a pilot project in 2008 with first and second year students prompted more intensive training in therapeutics, inhaler medication training, and communication techniques. Data collection began when two classes of students were first and second year students and continued until the students became fourth year students in their advanced experiential ambulatory care clinic and retail community pharmacy rotations. Patients seen included pediatric (32%) and adult (68%) aged individuals. Hawai'i County was the most common geographic site (50%) and most sites were retail pharmacies (72%). Administered ACT surveys (N=96) yielded a mean score of 19.64 (SD +/-3.89). In addition, 12% of patients had received previous ACT, and 47% had previous AAPs. Approximately 83% of patients received an additional intervention of AAP and inhaler education with 73% of these patients able to demonstrate back proper inhaler technique. Project challenges included timing of student training, revising curriculum and logistics of scheduling students to ensure consistent access to patients.

Introduction: Atrial fibrillation (AF) is commonly found in patients with structural heart disease (SHD), including atrial septal defect (ASD). The feasibility and safety of ablation for AF in patients with unrepaired ASD is seldom reported., Objectives: This study aims to evaluate and compare the long-term efficacy of AF ablation in patients with and without ASD., Methods: From January 2008 to December 2012, 18 consecutive patients were identified with medically refractory AF and an unrepaired ASD under catheter ablation. For each ASD patient, four control subjects were matched from our database., Results: There were no significant differences between groups in terms of age, sex, type of AF, LA diameter, LVIDD, and EF. The mean procedural and fluoroscopy times were not different between the groups (p = NS). After a median follow-up of 20 months, the patients in the ASD group had 44.4 % AF recurrence after a single procedure compared with 34.7 % in the control group (p = 0.11). The mean LA diameter in non-recurrent patients was smaller than in recurrent patients (p = 0.03). In univariate Cox proportional hazards analyses, the factor found to have a significant association with arrhythmia recurrences was left atrial diameter (hazard ratio 1.059, 95 % confidence interval 1.002 to 1.120, p = 0.03)., Conclusions: These results indicate that in patients with AF and an ASD amenable to percutaneous closure, a staged approach with radiofrequency ablation of AF preceding closure is a rational strategy.

Background: Large-scale clinical research on the relationship between red blood cell distribution width (RDW) and intermediate-term prognosis in elderly patients with coronary artery disease (CAD) is lacking. Thus, this study investigated the effects of RDW on the intermediate-term mortality of elderly patients who underwent elective percutaneous coronary intervention (PCI)., Methods: Data from 1891 patients ≥ 65 years old underwent elective PCI from July 2009 to September 2011 were collected. Based on preoperative median RDW (12.3%), the patients were divided into two groups. The low RDW group (RDW < 12.3%) had 899 cases; the high RDW group (RDW ≥ 12.3%) had 992 cases. The all-cause mortality rates of the two groups were compared., Results: Patients in the high RDW group were more likely to be female and accompanied with diabetes, had lower hemoglobin level. The mean follow-up period was 527 days. During follow-up, 61 patients died (3.2%). The postoperative mortality of the high RDW group was significantly higher than that of the low RDW group (4.3% vs. 2.0%, P = 0.004). After adjusting other factors, multivariate Cox regression analysis revealed that preoperative high RDW was significantly associated with postoperative all-cause mortality (hazard ratio: 2.301, 95% confidence interval: 1.106-4.785, P = 0.026)., Conclusions: Increased RDW was an independent predictor of the increased intermediate-term all-cause mortality in elderly CAD patients after elective PCI.

Background: In hypertrophic cardiomyopathy (HCM) patients complicated with atrial fibrillation (AF), catheter ablation has been recommended as a treatment option. Meanwhile, prolongation of QTc interval has been linked to an increased AF incidence in the general population and to poor outcomes in HCM patients. However, whether QTc prolongation predicts arrhythmia recurrence after AF ablation in the HCM population remains unknown., Methods and Results: Thirty-nine HCM patients undergoing primary AF ablation were enrolled. The ablation strategy included bilateral pulmonary vein isolation (PVI) for paroxysmal AF (n=27) and PVI plus left atrial roof, mitral isthmus and tricuspid isthmus linear ablations for persistent AF (n=12). Pre-procedural QTc was corrected by using the Bazett's formula. At a 14.8-month follow up, 23 patients experienced atrial tachyarrhythmia recurrence. Recurrent patients had longer QTc than non-recurrent patients (461.0±28.8 ms vs. 434.3±18.2 ms, P=0.002). QTc and left atrial diameter (LAD) were independent predictors of recurrence. The cut-off value of QTc 448 ms predicted arrhythmia recurrence with a sensitivity of 73.9% and a specificity of 81.2%. A combination of LAD and QTc (global chi-squared=13.209) was better than LAD alone (global chi-squared=6.888) or QTc alone (global chi-squared=8.977) in predicting arrhythmia recurrence after AF ablation in HCM patients., Conclusions: QTc prolongation is an independent predictor of arrhythmia recurrence in HCM patients undergoing AF ablation, and might be useful for identifying those patients likely to have a better outcome following the procedure.

Background: A few recent studies have suggested that regulated on activation, normal T cell expressed and secreted (RANTES) polymorphisms (-403 G/A, -28C/G) are associated with rheumatoid arthritis (RA) and atopic dermatitis (AD). However, there still existed studies that did not confirm this correlation., Objective: The objective of this study was to evaluate the relationships of RANTES and RA and AD using a meta-analysis., Methods: Pubmed, Embase, and Cochrane library databases were systemically searched. Data were extracted by two independent reviewers, and pooled odds ratio (OR) with 95% confidence interval (CI) were calculated., Results: Eight studies were enrolled, including a total of 548 RA cases and 493 controls of -403G/A, 305 RA cases and 303 controls of -28C/G, and 705 AD cases and 578 controls of -403G/A in this meta-analysis. In RA, the overall OR and 95% CI of -403A were 1.41, 1.10-1.82 (p = 0.391) and 2.18, 1.30-3.66 (p = 0.335) in dominant and recessive models, respectively. The overall OR and 95% CI of -28G in RA were 1.35, 0.91-2.01 (p = 0.707) and 3.32, 1.29-8.52 (p = 0.559) in dominant and recessive models, respectively. Moreover, the overall OR and 95% CI of -403A in AD were 1.38, 1.08-1.76 (p = 0.421) and 1.06 and 0.65-1.72 (p = 0.361) in dominant and recessive models, respectively., Conclusions: This meta-analysis showed that RANTES -403G/A and -28C/G were not associated with RA and AD.

Background: Recent reports have shown that miR-145 concentration correlates with infarct size. In this paper, we attempt to predict heart failure and cardiovascular death after acute myocardial infarction using circulating miR-145 concentration., Methods: We assessed 246 patients with first ST-segment-elevation myocardial infarction who underwent successful percutaneous coronary intervention. We measured circulating miR-145, N-terminal fragment of the precursor B-type natriuretic peptide, myocardial-band creatine kinase, and cardiac troponin-I concentrations on day 5 after primary percutaneous coronary intervention and assessed their correlations with long-term clinical outcome., Results: During the one-year follow-up period, 72 patients experienced primary composite cardiac events (cardiac death or hospitalization for worsening heart failure). Multivariable Cox proportional hazards analysis indicated that circulating miR-145 (hazard ratio 7.174, 95% confidence interval 4.208-12.229); p < 0.0001) was a significant independent predictor of cardiac events after adjustment for multiple confounders., Conclusion: Circulating miR-145 may be a novel biomarker for predicting long-term outcome after acute myocardial infarction.

Anticoagulation of patients with cardiac tamponade (CT) complicating catheter ablation of atrial fibrillation (AF) is an ongoing problem. The aim of this study was to survey the clinical practice of periprocedural anticoagulation in such patients. This study analyzed the periprocedural anticoagulation of 17 patients with CT complicating AF ablation. Emergent pericardiocentesis was performed once CT was confirmed. The mean drained volume was 410.0 ± 194.1 mL. Protamine sulfate was administered to neutralize heparin (1 mg neutralizes 100 units heparin) in 11 patients with persistent pericardial bleeding and vitamin K1 (10 mg) was given to reverse warfarin in 3 patients with supratherapeutic INR (INR > 2.1). Drainage catheters were removed 12 hours after echocardiography confirmed absence of intrapericardial bleeding and anticoagulation therapy was restored 12 hours after removing the catheter. Fifteen patients took oral warfarin and 10 of them were given subcutaneous injection of LMWH (1 mg/kg, twice daily) as a bridge to resumption of systemic anticoagulation with warfarin. Two patients with a small amount of persistent pericardial effusion were given LMWH on days 5 and 13, and warfarin on days 6 and 24. The dosage of warfarin was adjusted to keep the INR within 2-3 in all patients. After 12 months of follow-up, all patients had no neurological events and no occurrence of delayed CT. The results showed that it was effective and safe to resume anticoagulation therapy 12 hours after removal of the drainage catheter. This may help to prevent thromboembolic events following catheter ablation of AF.

Climate warming is expected to increase the exposure of insects to hot events (involving a few hours at extreme high temperatures). These events are unlikely to cause widespread mortality but may modify population dynamics via impacting life history traits such as adult fecundity and egg hatching. These effects and their potential impact on population predictions are still largely unknown. In this study, we simulated a single hot event (maximum of 38°C lasting for 4 h) of a magnitude increasingly found under field conditions and examined its effect in the oriental fruit moth, Grapholitha molesta. This hot event had no impact on the survival of G. molesta adults, copulation periods or male longevity. However, the event increased female lifespan and the length of the oviposition period, leading to a potential increase in lifetime fecundity and suggesting hormesis. In contrast, exposure of males to this event markedly reduced the net reproductive value. Male heat treatment delayed the onset of oviposition in the females they mated with, as well as causing a decrease in the duration of oviposition period and lifetime fecundity. Both male and female stress also reduced egg hatch. Our findings of hormetic effects on female performance but concurrent detrimental effects on egg hatch suggest that hot events have unpredictable consequences on the population dynamics of this pest species with implications for likely effects associated with climate warming.

Aims: X-VeRT is the first prospective randomized trial of a novel oral anticoagulant in patients with atrial fibrillation undergoing elective cardioversion., Methods and Results: We assigned 1504 patients to rivaroxaban (20 mg once daily, 15 mg if creatinine clearance was between 30 and 49 mL/min) or dose-adjusted vitamin K antagonists (VKAs) in a 2:1 ratio. Investigators selected either an early (target period of 1-5 days after randomization) or delayed (3-8 weeks) cardioversion strategy. The primary efficacy outcome was the composite of stroke, transient ischaemic attack, peripheral embolism, myocardial infarction, and cardiovascular death. The primary safety outcome was major bleeding. The primary efficacy outcome occurred in 5 (two strokes) of 978 patients (0.51%) in the rivaroxaban group and in 5 (two strokes) of 492 patients (1.02%) in the VKA group [risk ratio 0.50; 95% confidence interval (CI) 0.15-1.73]. In the rivaroxaban group, four patients experienced primary efficacy events following early cardioversion (0.71%) and one following delayed cardioversion (0.24%). In the VKA group, three patients had primary efficacy events following early cardioversion (1.08%) and two following delayed cardioversion (0.93%). Rivaroxaban was associated with a significantly shorter time to cardioversion compared with VKAs (P < 0.001). Major bleeding occurred in six patients (0.6%) in the rivaroxaban group and four patients (0.8%) in the VKA group (risk ratio 0.76; 95% CI 0.21-2.67)., Conclusion: Oral rivaroxaban appears to be an effective and safe alternative to VKAs and may allow prompt cardioversion., Name of the Trial Registry: Clinicaltrials.gov;, Trial Registration Number: NCT01674647., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Background: Dietary flavonoids have been related to lower risks of various chronic diseases, but it is unclear whether flavonoid intake in midlife helps to maintain good health and wellbeing in aging., Objective: We examined the relation of flavonoid intake in midlife with the prevalence of healthy aging., Design: We included 13,818 women from the Nurses' Health Study with dietary data and no major chronic diseases in 1984-1986 when they were aged in their late 50s (median age: 59 y); all women provided information on multiple aspects of aging an average of 15 y later. Intakes of 6 major flavonoid subclasses in midlife were ascertained on the basis of averaged intakes of flavonoid-rich foods from 2 food-frequency questionnaires (1984-1986). We defined healthy compared with usual aging as of age 70 y; healthy aging was based on survival to ≥70 y with maintenance of 4 health domains (no major chronic diseases or major impairments in cognitive or physical function or mental health)., Results: Of women who survived until ≥70 y of age, 1517 women (11.0%) met our criteria for healthy aging. Compared with women in the lowest quintile of intake, women in the highest quintile of intake of several flavonoid subclasses at midlife had greater odds of healthy aging. After multivariable adjustment, ORs were as follows: flavones, 1.32 (95% CI: 1.10, 1.58); flavanone, 1.28 (95% CI: 1.08, 1.53); anthocyanin, 1.25 (95% CI: 1.04, 1.50); and flavonol, 1.18 (95% CI: 0.98, 1.42) (all P-trend ≤ 0.02). Consistently, greater intakes of major sources of these flavonoids (i.e., oranges, berries, onions, and apples) were associated with increased odds of healthy aging. We showed no association with flavan-3-ol monomers (P-trend = 0.80) or polymers (P-trend = 0.63)., Conclusion: Higher intake of flavonoids at midlife, specifically flavones, flavanones, anthocyanins, and flavonols, is associated with greater likelihood of health and wellbeing in individuals surviving to older ages., (© 2014 American Society for Nutrition.)

Numerous studies have studied the relationships between matrix metalloproteinase (MMP) family gene polymorphisms and ischemic stroke. However, findings remain controversial. The objective of this study was to evaluate the relationships between MMP gene polymorphisms and ischemic stroke by using a meta-analysis. The PubMed, Embase, and Cochrane library databases were systemically searched. Data were extracted by two independent reviewers, and pooled odds ratio (OR) with 95 % confidence interval (CI) were calculated. Eleven studies were enrolled, including a total of 589 cases and 494 controls of MMP-1 -1607 1G/2G; 1,817 cases and 1,731 controls of MMP-3 -1612 5A/6A; and 540 cases and 547 controls of MMP-9 -1562C/T. Under the dominant and recessive models, respectively, the overall ORs and 95 % CIs of -1607 2G were 1.54, 1.16-2.04 (P = 0.005) and 1.25, 0.95-1.65 (P = 0.457); the overall ORs and 95 % CIs of -1612 6A were 1.01, 0.84-1.21 (P = 0.003) and 0.88, 0.75-1.03 (P = 0.057); and the overall ORs and 95 % CIs of -1562T were 0.78, 0.59-1.02 (P = 0.460) and 1.65, 0.73-3.75 (P = 0.340). No publication bias was found in this meta-analysis. This meta-analysis showed that MMP-1 -1607 1G/2G and MMP-3 -1612 5A/6A were risk factors for ischemic stroke, while MMP-9 -1562C/T was not associated with ischemic stroke.

Purpose of Review: To summarize our understanding of the biology of T follicular helper (Tfh) cells and how insights into this are being provided by the study of human monogenic immunological diseases., Recent Findings: Antibody production is a key feature of the vertebrate immune system. Antibodies neutralize and clear pathogens, thereby protecting against infectious diseases. Long-lived humoral immunity depends on help provided by Tfh cells, which support the differentiation of antigen-specific B cells into memory and plasma cells. Tfh cells are generated from naïve CD4 T cells following the receipt of inputs from various cell surface receptors. Although genetically modified mice have provided a great understanding of the requirements for generating Tfh cells, it is critical that the requirements for human Tfh cells are also established. This is being achieved by the systematic analysis of humans with monogenic mutations that cause primary immunodeficiencies characterized by impaired humoral immunity following infection or vaccination., Summary: The elucidation of the mechanisms that regulate Tfh cell generation, differentiation and function should reveal targets for novel therapeutics that may offer opportunities to manipulate these cells to not only improve humoral immunity in the setting of primary immunodeficiencies but also temper their dysregulation in conditions of antibody-mediated autoimmunity.

Background: Serum uric acid (SUA) is a simple and independent marker of morbidity and mortality in a variety of cardiovascular diseases. In this study we aimed to investigate SUA and the risk of left atrial (LA) thrombus in patients with nonvalvular atrial fibrillation (AF)., Methods: In this retrospective study, 1359 consecutive patients undergoing transesophageal echocardiography before catheter ablation of AF were enrolled. Sixty-one of the 1359 patients (4.5%) had LA thrombus., Results: SUA levels in patients with LA thrombus were significantly greater (413.5 ± 98.8 μmol/L vs 366.7 ± 94.3 μmol/L; P < 0.001). Hyperuricemia was defined as SUA ≥ 359.8 μmol/L in women and ≥ 445.6 μmol/L in men determined according to receiver operating characteristic curve. The incidence of LA thrombus was significantly greater in patients with hyperuricemia than in those with a normal SUA level in women (12.1% vs 1.9%; P < 0.001) and in men (8.5% vs 2.8%; P < 0.001). Hyperuricemia had a negative predictive value of 98.1% in women and 97.1% in men for identifying LA thrombus. Hyperuricemia was associated with significantly greater risk of LA thrombus among Congestive Heart Failure, Hypertension, Age ≥ 75 Years, Diabetes Mellitus, Stroke, Vascular Disease, Age 65 to 74 Years, Sex Category (CHA2DS2-VASc) score = 0, 1, and ≥ 2 groups with odds ratios of 7.19, 4.05, and 3.25, respectively. In multivariable analysis, SUA was an independent risk factor of LA thrombus (odds ratio, 1.004; 95% confidence interval, 1.000-1.008; P = 0.028)., Conclusions: Hyperuricemia was a modest risk factor for LA thrombus, which might refine stratification of LA thrombus in patients with nonvalvular AF., (Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Aims: This study sought to explore the predictors of recurrence in patients with paroxysmal atrial fibrillation (AF) undergoing repeat catheter ablation, especially the impact of left atrial (LA) remodelling after the original procedure on the outcome of repeat procedure., Methods and Results: Ninety-five patients undergoing repeat ablation were enrolled in this study. Repeat procedure endpoints were pulmonary vein isolation, linear block when linear ablation is performed, and non-inducibility of atrial tachyarrhythmia by burst pacing. Patients with LA enlargement between the pre-original procedure and pre-repeat procedure were categorized as Group 1 (35 patients), while individuals with no change or decrease of LA diameter were categorized as Group 2 (60 patients). The mean duration from the original procedure to the repeat procedure was 12 months (1-40 months). After 29.6 ± 20.5 (3-73) months follow-up from the repeat procedure, 33 patients experienced recurrence (34.7%). The recurrence rate was significantly higher in Group 1 than in Group 2 (51.4 VS. 25.0%, P = 0.017). In univariate analysis, LA remodelling was the only predictor of recurrence. In multivariate analysis, after adjustment for age and LA diameter, Group 1 had a greater risk of recurrence after the repeat procedure (hazard ratio = 2.22, 95% confidence interval: 1.02-4.81, P = 0.043)., Conclusions: Left atrial enlargement after undergoing the original catheter ablation of paroxysmal AF was an independent risk factor of recurrence after repeat ablation., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Background: Several studies have reported that Connexin37 (Cx37) gene C1019T polymorphism is associated with myocardial infarction (MI) and coronary artery disease (CAD). However, the results remain contradictory., Methods and Results: Pubmed, Embase, and Cochrane library databases were systemically searched. Data were extracted by two independent reviewers and pooled odds ratio (OR) with 95% confidence interval (CI) was calculated. A total of 3498 MI cases and 3986 controls, as well as 1808 CAD cases and 1197 controls were enrolled in this meta-analysis. For MI, the overall ORs and 95% CIs of 1019T were 1.04, 0.95-1.15; and 1.02, 0.85-1.22 in dominant and recessive models, respectively. For CAD, the overall ORs and 95% CIs of 1019T were 0.61, 0.51-0.72; and 0.52, 0.43-0.62 in dominant and recessive models, respectively. No publication bias was found in this meta-analysis., Conclusions: This meta-analysis showed that Cx37 C1019T was a risk factor for MI and a protective factor for CAD., (Copyright © 2014. Published by Elsevier Inc.)

Aims: An association between obstructive sleep apnoea (OSA) and atrial fibrillation (AF) has been established. However, studies on the role of OSA in AF recurrence after catheter ablation have yielded conflicting results, and the effect of OSA treatment by continuous positive airway pressure (CPAP) on the success rate of AF catheter ablation is indeterminate. The aim of this meta-analysis was to investigate the rate of AF recurrence after catheter ablation in patients with AF with or without OSA and to evaluate the relationship between CPAP therapy and AF recurrence., Methods and Results: We performed an online search and identified five studies involving 3743 patients with AF. Patients with OSA had a 31% greater risk of AF recurrence after catheter ablation than did patients without OSA [relative ratio (RR) = 1.31, P = 0.00], and this risk increased by 57% in patients with OSA not undergoing CPAP therapy (RR = 1.57, P = 0.00). However, CPAP users had a risk of AF recurrence similar to that of patients without OSA (RR = 1.25, P = 0.37), and this similarity was maintained even after the removal of study heterogeneity (RR = 0.99, P = 0.39)., Conclusion: Obstructive sleep apnoea was associated with AF recurrence after catheter ablation. The efficacy of catheter ablation for AF was similar between patients without OSA and patients with OSA undergoing CPAP treatment., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Background: The effects of omega-3 polyunsaturated fatty acids (PUFA) on the prevention of postoperative atrial fibrillation (POAF) are inconclusive in current studies. Moreover, the most appropriate composition of PUFA to play the protective role is unclear. The aim of this meta-analysis was to ascertain the protective role of PUFA on POAF and the most appropriate composition., Methods: Studies were identified through PubMed, CENTRAL, EMBASE, reviews and reference lists of relevant papers. The odds ratio (OR) was calculated for POAF. Statistical analyses were performed with Review Manager 5.0., Results: Eleven randomised controlled trials with 3137 patients were included in the analysis. The use of PUFA alone did not reduce the incidence of POAF compared with the control (OR: 0.76; 95% confidence interval [CI]: 0.57-1.03; P=0.08; I(2)=52%). However, combination therapy with PUFA and vitamins C and E reduced the incidence of POAF by 68% (OR: 0.32; 95%CI: 0.17-0.60; P=0.0005; I(2)=38%). Subgroup analysis indicated that the ratio of EPA/DHA 1:2 was effective in preventing POAF (OR: 0.35; 95%CI: 0.24-0.50; P<0.00001; I(2)=0%), while the ratio not 1:2 failed., Conclusions: Combination therapy with PUFA and vitamins C and E is effective in the prevention of POAF while PUFA alone is not. The ratio of EPA/DHA may influence the incidence of POAF, and 1:2 may be most appropriate. Studies about PUFA on the prevention of POAF are still worthwhile to be conducted in the future., (Copyright © 2014 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Purpose: Cerebrovascular accidents (CVAs) frequently coexist with coronary artery disease (CAD) and adversely affect prognosis in patients with CAD; however, fewer studies have investigated the role of prior ischemic stroke on the outcomes of percutaneous coronary intervention (PCI). The aim of this study was to determine the safety and effectiveness of PCI in patients with a prior ischemic stroke., Methods: A review of patients who underwent PCI between June 2003 and September 2005 (n=3893) at the Beijing Anzhen Hospital of Capital University of Medical Science, identified 295 PCI patients with a prior ischemic stroke (≥ 3 months) and 3598 patients without a prior stroke. To investigate whether prior history of an ischemic stroke was independently associated with increased risk of adverse PCI outcomes, prognostic parameters were analyzed using univariate analysis and Cox multivariate regression analysis. Propensity score analysis was then used to match the two subgroups of patients based on multiple factors known to impact cardiac outcome., Results: Patients with a prior ischemic stroke had more frequent high-risk baseline characteristics (diabetes, hypertension, hyperlipidemia and prior myocardial infarction). No significant differences were found in the major adverse cardiac and cerebrovascular event (MACCEs) rates between the two groups (1.7% in the stroke group vs. 1.4% in the non-stroke group; p=0.06). Diabetes mellitus, triple vessel CAD, number of diseased vessels, chronic total occlusion and previous myocardial infarction were independent predictors of MACCE in patients with prior stroke undergoing PCI., Conclusions: This study demonstrates that, in daily clinical practice, PCI can be provided safely and with good results to patients with a prior ischemic stroke (≥ 3 months).

An asymmetric increase in night-time temperatures (NTs) on hot days is one of the main features of global climate change. But the biological effects of an increased night-time temperature combined with high daytime temperature are unclear. We used six thermal regimens to simulate NTs on hot days and investigated the effects of night warming on life-history traits of the English grain aphid Sitobion avenae. Experimental temperatures fluctuated in continuous diurnal cycles, increasing from 27 °C to a maximum 35 °C and then declining to 27 °C gradually before further dropping to different minima (13, 16, 19, 21, 23 or 25 °C) representing NTs. When compared to expectations based on constant temperatures, night warming raised the optimum temperature for development by 3 °C, in contrast to results from experiments where temperature variability was altered symmetrically or in a parallel manner. Night warming also reduced aphid survival under heat from 75% to 37% and depressed adult performance by up to 50%. Overall, night warming exacerbated the detrimental effects of hot days on the intrinsic rate of population increase, which was predicted to drop by 30% when night-time minimum temperatures exceeded 20 °C. Our novel findings on development challenge the 'Kaufmann effect', suggesting this is inapplicable to night warming likely to be encountered in nature. Although many average temperature models predict increasing pest outbreaks, our results suggest that outbreaks of some species might decrease due to the effects of night warming on population dynamics., (© 2013 The Authors. Journal of Animal Ecology © 2013 British Ecological Society.)

Background: A few recent studies have suggested that regulated on activation, normal T cell expressed and secreted (RANTES) polymorphisms (-403 G/A, -28C/G) are associated with asthma. However, there still existed studies which did not confirm these correlations., Objective: The objective of this study was to evaluate the relationship of RANTES and asthma using a meta-analysis., Methods: Pubmed, Embase, and Cochrane library databases were systemically searched. Data were extracted by two independent reviewers and pooled odds ratio (OR) with 95% confidence interval (CI) were calculated., Results: Eighteen studies were enrolled, including a total of 2558 cases and 2630 controls of -403 G/A, as well as 3311 cases and 4031 controls of -28C/G in this meta-analysis. The overall ORs and 95% CIs of -403 G/A were 1.19, 1.06-1.33 (P<0.001) and 1.25, 1.03-1.51 (P = 0.933) in dominant and recessive models, respectively. The overall ORs and 95% CIs of -28G were 1.23, 1.09-1.39 (P = 0.221) and 1.76, 1.32-2.34 (P = 0.356) in dominant and recessive models, respectively. No publication bias among studies was showed., Conclusions: This meta-analysis showed that RANTES -403 G/A polymorphism was a risk factor for asthma, while -28C/G polymorphism were not associated with asthma.

Although effects of thermal stability on eggs have often been considered in vertebrates, there is little data thermal stability in insect eggs even though these eggs are often exposed in nature to widely fluctuating ambient conditions. The modularity of development in invertebrates might lead to compensation across life cycle stages but this remains to be tested particularly within the context of realistic temperature fluctuations encountered in nature. We simulated natural temperate fluctuations on eggs of the worldwide cruciferous insect pest, the diamondback moth (DBM), Plutella xylostella (L.), while maintaining the same mean temperature (25°C±0°C, 25±4°C, 25±6°C, 25±8°C, 25±10°C, 25±12°C) and assessed egg development, survival and life history traits across developmental stages. Moderate fluctuations (25±4°C, 25±6°C) did not influence performance compared to the constant temperature treatment, and none of the treatments influenced egg survival. However the wide fluctuating temperatures (25±10°C, 25±12°C) slowed development time and led to an increase in pre-pupal mass, although these changes did not translate into any effects on longevity or fecundity at the adult stage. These findings indicate that environmental effects can extend across developmental stages despite the modularity of moth development but also highlight that there are few fitness consequences of the most variable thermal conditions likely to be experienced by Plutella xylostella.

Signalling in lymphocytes through cytokine receptors is critical for their development, activation and differentiation into effector cells that mediate protection against pathogens and provide the host with protective immunological memory. The essential role of cytokine signalling has been established not only by the generation and examination of gene-targeted mice, but also 'Experiments of Nature' whereby monogenic mutations cause primary immunodeficient conditions characterised by impaired immunity to infectious diseases due to compromised lymphocyte function. Mutations in STAT3 cause autosomal dominant hyper-IgE syndrome. Here, we will review how the study of STAT3-deficient individuals has revealed non-redundant functions of STAT3 and specific cytokines in human lymphocyte biology, and have delineated mechanisms underlying the distinct clinical features of autosomal dominant hyper-IgE syndrome., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objectives: To address whether menopause affects outcome of catheter ablation (CA) for atrial fibrillation (AF) by comparing the safety and long-term outcome of a single-procedure in pre- and post-menopausal women., Methods: A total of 743 female patients who underwent a single CA procedure of drug-refractory AF were retrospectively analyzed. The differences in clinical presentation and outcomes of CA for AF between the pre-menopausal women (PreM group, 94 patients, 12.7%) and the post-menopausal women (PostM group, 649 patients, 87.3%) were assessed., Results: The patients in the PreM group were younger (P < 0.001) and less likely to have hypertension (P < 0.001) and diabetes (P = 0.005) than those in the PostM group. The two groups were similar with regards to the proportion of concomitant mitral valve regurgitation coronary artery disease, left atrium dimensions, and left ventricular ejection fraction. The overall rate of complications related to AF ablation was similar in both groups (P = 0.385). After 43 (16-108) months of follow-up, the success rate of ablation was 54.3% in the PreM group and 54.2% in the PostM group (P = 0.842). The overall freedom from atrial tachyarrhythmia recurrence was similar in both groups. Menopause was not found to be an independent predictive factor of the recurrence of atrial tachyarrhythmia., Conclusions: The long-term outcomes of single-procedure CA for AF are similar in pre- and post-menopausal women. Results indicated that CA of AF appears to be as safe and effective in pre-menopausal women as in post-menopausal women.

Congenital anomalous coronary sinus ostium is extremely rare. We describe a case of congenital left atrial coronary sinus ostium in a patient scheduled for ablation for atrial fibrillation. The anomalous coronary sinus ostium was found when contrast was injected during the ablation procedure and was confirmed by cardiac computed tomography.