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  1. Hospitalizations in patients with atrial fibrillation: an analysis from ROCKET AF

    PubMed Central

    DeVore, Adam D.; Hellkamp, Anne S.; Becker, Richard C.; Berkowitz, Scott D.; Breithardt, Guenter; Hacke, Werner; Halperin, Jonathan L.; Hankey, Graeme J.; Mahaffey, Kenneth W.; Nessel, Christopher C.; Singer, Daniel E.; Fox, Keith A. A.; Patel, Manesh R.; Piccini, Jonathan P.

    2016-01-01

    Aims The high costs associated with treatment for atrial fibrillation (AF) are primarily due to hospital care, but there are limited data to understand the reasons for and predictors of hospitalization in patients with AF. Methods and results The ROCKET AF trial compared rivaroxaban with warfarin for stroke prophylaxis in AF. We described the frequency of and reasons for hospitalization during study follow-up and utilized Cox proportional hazards models to assess for baseline characteristics associated with all-cause hospitalization. Of 14 171 patients, 14% were hospitalized at least once. Of 2614 total hospitalizations, 41% were cardiovascular including 4% for AF; of the remaining, 12% were for bleeding. Compared with patients not hospitalized, hospitalized patients were older (74 vs. 72 years), and more frequently had diabetes (46 vs. 39%), prior MI (23 vs. 16%), and paroxysmal AF (19 vs. 17%), but less frequently had prior transient ischaemic attack/stroke (49 vs. 56%). After multivariable adjustment, lung disease [hazard ratio (HR) 1.46, 95% confidence interval (CI) 1.29–1.66], diabetes [1.22, (1.11–1.34)], prior MI [1.27, (1.13–1.42)], and renal dysfunction [HR 1.07 per 5 unit GFR < 65 mL/min, (1.04–1.10)] were associated with increased hospitalization risk. Treatment assignment was not associated with differential rates of hospitalization. Conclusion Nearly 1 in 7 of the moderate-to-high-risk patients with AF enrolled in this trial was hospitalized within 2 years, and both AF and bleeding were rare causes of hospitalization. Further research is needed to determine whether care pathways directed at comorbid conditions among AF patients could reduce the need for and costs associated with hospitalization. PMID:27174904

  2. Validation of the Risk Estimator Decision aid for Atrial Fibrillation (RED-AF) for Predicting 30-Day Adverse Events in Emergency Department Patients With Atrial Fibrillation

    PubMed Central

    Barrett, Tyler W.; Jenkins, Cathy A.; Self, Wesley H.

    2014-01-01

    Objective Nearly 70% of emergency departments (ED) visits for atrial fibrillation (AF) result in hospitalization. The incidence of serious 30-day adverse events following an ED evaluation for AF remains low. This study’s goal was to prospectively validate our previously reported Risk Estimator Decision aid for AF (RED-AF) model for estimating a patient’s risk of experiencing a 30-day adverse event. Methods This was a prospective cohort study, which enrolled a convenience sample of ED patients presenting with AF. RED-AF, previously derived from a retrospective cohort of 832 patients, assigns points based on age, sex, coexisting disease (heart failure, hypertension, chronic obstructive pulmonary disease), smoking, home medications (beta blocker, diuretic), physical examination findings (dyspnea, palpitations, peripheral edema), and adequacy of ED ventricular rate control. Primary outcome was occurrence of ≥1 AF-related adverse outcome (ED visits, rehospitalization, cardiovascular complications, death) within 30 days. We identified a clinically relevant threshold and measured RED-AF’s performance in this prospective cohort, assessing its calibration, discrimination, and diagnostic accuracy. Results The study enrolled 497 patients between June 2010 and February 2013. Of these, 120 (24%) had ≥1 adverse event within 30 days. A RED-AF score of 87 was identified as an optimal threshold, resulting in sensitivity (95% CI) and specificity (95%CI) of 96% (91–98) and 19% (15–23), respectively. Positive and negative predictive values were 27% (23–32) and 93% (85–97), respectively. The c-statistic for RED-AF was 0.65 (95% CI, 0.59 to 0.71). Conclusion In this separate validation cohort, RED-AF performed moderately well and similar to the original derivation cohort for identifying the risk of short-term AF-related adverse events in ED patients diagnosed with AF. PMID:25245277

  3. Comparison of international normalized ratio audit parameters in patients enrolled in GARFIELD-AF and treated with vitamin K antagonists.

    PubMed

    Fitzmaurice, David A; Accetta, Gabriele; Haas, Sylvia; Kayani, Gloria; Lucas Luciardi, Hector; Misselwitz, Frank; Pieper, Karen; Ten Cate, Hugo; Turpie, Alexander G G; Kakkar, Ajay K

    2016-08-01

    Vitamin K antagonist (VKA) therapy for stroke prevention in atrial fibrillation (AF) requires monitoring of the international normalized ratio (INR). We evaluated the agreement between two INR audit parameters, frequency in range (FIR) and proportion of time in the therapeutic range (TTR), using data from a global population of patients with newly diagnosed non-valvular AF, the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF). Among 17 168 patients with 1-year follow-up data available at the time of the analysis, 8445 received VKA therapy (±antiplatelet therapy) at enrolment, and of these patients, 5066 with ≥3 INR readings and for whom both FIR and TTR could be calculated were included in the analysis. In total, 70 905 INRs were analysed. At the patient level, TTR showed higher values than FIR (mean, 56·0% vs 49·8%; median, 59·7% vs 50·0%). Although patient-level FIR and TTR values were highly correlated (Pearson correlation coefficient [95% confidence interval; CI], 0·860 [0·852-0·867]), estimates from individuals showed widespread disagreement and variability (Lin's concordance coefficient [95% CI], 0·829 [0·821-0·837]). The difference between FIR and TTR explained 17·4% of the total variability of measurements. These results suggest that FIR and TTR are not equivalent and cannot be used interchangeably. PMID:27071942

  4. Increased Mortality Associated with Digoxin in Contemporary Patients with Atrial Fibrillation: Findings from the TREAT-AF Study

    PubMed Central

    Turakhia, Mintu P.; Santangeli, Pasquale; Winkelmayer, Wolfgang C.; Xu, Xiangyan; Ullal, Aditya J.; Than, Claire T.; Schmitt, Susan; Holmes, Tyson H.; Frayne, Susan M.; Phibbs, Ciaran S.; Yang, Felix; Hoang, Donald D.; Ho, P. Michael; Heidenreich, Paul A.

    2014-01-01

    Objectives To evaluate the association of digoxin with mortality in atrial fibrillation. Background Despite endorsement of digoxin in clinical practice guidelines, there exist limited data on its safety in atrial fibrillation and flutter (AF). Methods Using complete data from the US Department of Veterans Administration (VA) Health Care System, we identified patients with newly-diagnosed, non-valvular AF seen within 90 days in an outpatient setting between VA fiscal years 2004-2008. We used multivariate and propensity-matched Cox proportional hazards to evaluate the association of digoxin use to death. Residual confounding was assessed by sensitivity analysis. Results Of 122,465 patients with 353,168 person-years of follow-up (age 72.1±10.3 years, 98.4% males), 28,679 (23.4%) patients received digoxin. Cumulative mortality rates were higher for digoxin-treated patients than for untreated patients (95 vs. 67 per 1,000 person-years; P<0.001). Digoxin use was independently associated with mortality after multivariate adjustment (HR: 1.26, 95%CI: 1.23-1.29, P<0.001) and propensity matching (HR: 1.21, 95%CI: 1.17-1.25, P<0.001), even after adjustment for drug adherence. The risk of death was not modified by age, sex, heart failure, kidney function, or concomitant use of beta blockers, amiodarone, or warfarin. Conclusion Digoxin was associated with increased risk of death in patients with newly-diagnosed AF, independent of drug adherence, kidney function, cardiovascular comorbidities, and concomitant therapies. These findings challenge current cardiovascular society recommendations on use of digoxin in AF. PMID:25125296

  5. Predictors for Stroke and Death in Non-Anticoagulated Asian Patients with Atrial Fibrillation: The Fushimi AF Registry

    PubMed Central

    Hamatani, Yasuhiro; Yamashita, Yugo; Esato, Masahiro; Chun, Yeong-Hwa; Tsuji, Hikari; Wada, Hiromichi; Hasegawa, Koji; Abe, Mitsuru

    2015-01-01

    Background Atrial fibrillation (AF) increases the risk of stroke and death. Data on the predictors for stroke and death in ‘real-world’ AF patients are limited, especially from large prospective Asian cohorts. Methods The Fushimi AF Registry is a community-based prospective survey designed to enroll all AF patients who visited the participating medical institutions in Fushimi-ku, Kyoto, Japan. Follow-up data were available for 3,304 patients (median follow-up period 741 days). We explored the predictors for ‘death, stroke, and systemic embolism (SE)’ during follow-up in 1,541 patients not receiving oral anticoagulants (OAC) at baseline. Results The mean age was 73.1 ± 12.5 years, and 673 (44%) patients were female. The mean CHADS2 and CHA2DS2-VASc scores were 1.76 and 3.08, respectively. Cumulative events were as follows: stroke/SE in 61 (4%) and death in 230 (15%), respectively. On multivariate analysis, advanced age (hazard ratio (HR): 1.68, 95% confidence interval (CI): 1.24–2.29), underweight (body mass index <18.5 kg/m2) (HR: 1.71, 95% CI: 1.25–2.32), previous stroke/SE/transient ischemic attack (HR: 1.70, 95% CI: 1.25–2.30), heart failure (HR: 1.59, 95% CI: 1.17–2.15), chronic kidney disease (HR: 1.53, 95% CI: 1.16–2.02), and anemia (HR: 2.41, 95% CI: 1.78–3.28) were independent predictors for death/stroke/SE. Cumulative numbers of these 6 risk predictors could stratify the incidence of death/stroke/SE in patients without OAC, as well as those with OAC in our registry. Conclusions Advanced age, underweight, previous stroke/SE/transient ischemic attack, heart failure, chronic kidney disease, and anemia were independently associated with the risk of death/stroke/SE in non-anticoagulated Japanese AF patients. PMID:26540107

  6. A clustered randomized trial to IMProve treatment with AntiCoagulanTs in patients with Atrial Fibrillation (IMPACT-AF): design and rationale.

    PubMed

    Rao, Meena P; Ciobanu, Andrea O; Lopes, Renato D; Fox, Kathleen A; Xian, Ying; Pokorney, Sean D; Al-Khalidi, Hussein R; Jiang, Jei; Kamath, Deepak Y; Berwanger, Otavio; Xavier, Denis; Bahit, Cecilia M; Tajer, Carlos; Vinereanu, Dragos; Huo, Yong; Granger, Christopher B

    2016-06-01

    Atrial fibrillation (AF) is common, increasing as the population ages, and a major cause of embolic stroke. While oral anticoagulation (OAC) is highly effective at preventing stroke in patients with AF, it continues to be underused in eligible patients worldwide. The objective of this prospective, cluster randomized controlled trial (IMPACT-AF; ClinicalTrials.gov #NCT02082548) is to determine whether a comprehensive customized intervention will increase the rate and persistence of use of OAC in patients with AF. IMPACT-AF will be conducted in approximately 50 centers in 5 low- to middle-income countries. Before randomization, sites within countries will be paired to match in size, practice type and baseline rate of OAC use. Site pairs will be randomized to intervention versus control. In total, 40 to 70 patients with AF and at least 2 CHA2DS2-VASc risk factors will be enrolled at each site using a consecutive enrollment strategy, with the goal of capturing actual practice patterns. We aim for patients with a new diagnosis of AF to comprise at least 30% of the study cohort. Assuming an average baseline OAC use of 60% and a post-intervention use of 70% with a post-control rate of 60%, there will be roughly 94-98% power with 25 clusters per group (intracluster correlation coefficient of 0.02). While this trial focuses on improving treatment use and reducing preventable strokes, we also aim to better understand the reasons for OAC underuse. This will improve the intervention with the goal of creating educational recommendations to improve care for patients with AF. PMID:27264227

  7. Alternative Calculations of Individual Patient Time in Therapeutic Range While Taking Warfarin: Results From the ROCKET AF Trial

    PubMed Central

    Singer, Daniel E.; Hellkamp, Anne S.; Yuan, Zhong; Lokhnygina, Yuliya; Patel, Manesh R.; Piccini, Jonathan P.; Hankey, Graeme J.; Breithardt, Günter; Halperin, Jonathan L.; Becker, Richard C.; Hacke, Werner; Nessel, Christopher C.; Mahaffey, Kenneth W.; Fox, Keith A. A.; Califf, Robert M.

    2015-01-01

    Background In the ROCKET AF (Rivaroxaban–Once‐daily, oral, direct Factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation) trial, marked regional differences in control of warfarin anticoagulation, measured as the average individual patient time in the therapeutic range (iTTR) of the international normalized ratio (INR), were associated with longer inter‐INR test intervals. The standard Rosendaal approach can produce biased low estimates of TTR after an appropriate dose change if the follow‐up INR test interval is prolonged. We explored the effect of alternative calculations of TTR that more immediately account for dose changes on regional differences in mean iTTR in the ROCKET AF trial. Methods and Results We used an INR imputation method that accounts for dose change. We compared group mean iTTR values between our dose change–based method with the standard Rosendaal method and determined that the differences between approaches depended on the balance of dose changes that produced in‐range INRs (“corrections”) versus INRs that were out of range in the opposite direction (“overshoots”). In ROCKET AF, the overall mean iTTR of 55.2% (Rosendaal) increased up to 3.1% by using the dose change–based approach, depending on assumptions. However, large inter‐regional differences in anticoagulation control persisted. Conclusions TTR, the standard measure of control of warfarin anticoagulation, depends on imputing daily INR values for the vast majority of follow‐up days. Our TTR calculation method may better reflect the impact of warfarin dose changes than the Rosendaal approach. In the ROCKET AF trial, this dose change–based approach led to a modest increase in overall mean iTTR but did not materially affect the large inter‐regional differences previously reported. Clinical Trial Registration URL: ClinicalTrials.gov. Unique identifier: NCT00403767. PMID:25736441

  8. NOACs versus warfarin for stroke prevention in patients with AF: a systematic review and meta-analysis

    PubMed Central

    Stewart, Fiona; Eisinga, Anne

    2016-01-01

    Background Warfarin has been the anticoagulant of choice for the prevention of ischaemic stroke in patients with atrial fibrillation (AF). Novel oral anticoagulants (NOACs) are increasingly used as an alternative. Objectives The objective of this review was to evaluate the efficacy and safety of the NOACs versus warfarin in patients with AF. Search methods Medline, EMBASE and grey literature search for all phase II and III randomised control trials. Data collection/analysis Two authors independently reviewed abstracts and performed data extraction of eligible full-text articles. Revman V.5 was used for meta-analysis. Main results 12 studies were identified with a total study population of 77 011. NOACs demonstrated a reduction in the composite of stroke or systemic embolic events OR 0.85 (95% CI 0.75 to 0.98), a 52% reduction in intracranial haemorrhage OR 0.48 (95% CI 0.40 to 0.57) and a 14% reduction in mortality OR 0.86 (0.82 to 0.91). The 30-day end of study switch to warfarin demonstrated an in increase in stroke or systemic embolic events OR 2.60 (95% CI 1.61 to 4.18) and an increase in major bleeding OR 2.19 (95% CI 1.42 to 3.36). Conclusions NOACs are superior to warfarin for the prevention of the composite of stroke and systemic embolism in patients with AF and an additional risk factor for stroke. There is a significant reduction in intracranial haemorrhage, which drives the finding of significantly lower mortality. During the poststudy switch from NOACs to warfarin there is an excess of the composite of stroke and systemic embolism as well as major bleeding events, which may be of significance in clinical practice. PMID:26848392

  9. Rivaroxaban in the Prevention of Stroke and Systemic Embolism in Patients with Non-Valvular Atrial Fibrillation: Clinical Implications of the ROCKET AF Trial and Its Subanalyses.

    PubMed

    Spencer, Ryan J; Amerena, John V

    2015-12-01

    Atrial fibrillation (AF) is an increasingly common cause of stroke and systemic embolism. While warfarin has been the mainstay of stroke prevention in patients with AF, newer novel oral anticoagulant medications are now available. Rivaroxaban, a direct factor Xa inhibitor with a rapid onset and offset after oral administration, offers potential advantages over warfarin, predominantly due to its predictable pharmacokinetics across wide patient populations. It requires no coagulation monitoring, and only two different doses are needed (20 mg daily for patients with normal renal function and 15 mg daily in those with reduced renal function). A large randomized trial (ROCKET AF) has shown non-inferiority to warfarin for preventing stroke or systemic embolism in the per-protocol population and superiority to warfarin in the on-treatment safety population. Several subanalyses confirm that the treatment effect of rivaroxaban is consistent across different patient subgroups, including those with reduced renal function. The tolerability of rivaroxaban appears similar to that of warfarin, with comparable overall bleeding rates in clinical trials. In ROCKET AF, significantly lower rates of fatal and intracranial bleeding were seen with rivaroxaban, while lower rates of gastrointestinal bleeding were seen with warfarin. Important contraindications to rivaroxaban include valvular AF, the presence of a prosthetic valve (mechanical or bioprosthetic) or valve repair, the need for concurrent dual antiplatelet therapy, and creatinine clearance <30 ml/min. Once-daily dosing and the lack of coagulation monitoring may increase utilization and adherence compared with warfarin, potentially decreasing the large burden of care associated with stroke secondary to AF. Overall, rivaroxaban offers a useful alternative to warfarin for stroke prevention in patients with AF. PMID:26062914

  10. Device-detected atrial fibrillation and risk for stroke: an analysis of >10 000 patients from the SOS AF project (Stroke preventiOn Strategies based on Atrial Fibrillation information from implanted devices)

    PubMed Central

    Boriani, Giuseppe; Glotzer, Taya V.; Santini, Massimo; West, Teena M.; De Melis, Mirko; Sepsi, Milan; Gasparini, Maurizio; Lewalter, Thorsten; Camm, John A.; Singer, Daniel E.

    2014-01-01

    Objective The aim of this study was to assess the association between maximum daily atrial fibrillation (AF) burden and risk of ischaemic stroke. Background Cardiac implanted electronic devices (CIEDs) enhance detection of AF, providing a comprehensive measure of AF burden. Design, setting, and patients A pooled analysis of individual patient data from five prospective studies was performed. Patients without permanent AF, previously implanted with CIEDs, were included if they had at least 3 months of follow-up. A total of 10 016 patients (median age 70 years) met these criteria. The risk of ischaemic stroke associated with pre-specified cut-off points of AF burden (5 min, 1, 6, 12, and 23 h, respectively) was assessed. Results During a median follow-up of 24 months, 43% of 10 016 patients experienced at least 1 day with at least 5 min of AF burden and for them the median time to the maximum AF burden was 6 months (inter-quartile range: 1.3–14). A Cox regression analysis adjusted for the CHADS2 score and anticoagulants at baseline demonstrated that AF burden was an independent predictor of ischaemic stroke. Among the thresholds of AF burden that we evaluated, 1 h was associated with the highest hazard ratio (HR) for ischaemic stroke, i.e. 2.11 (95% CI: 1.22–3.64, P = 0.008). Conclusions Device-detected AF burden is associated with an increased risk of ischaemic stroke in a relatively unselected population of CIEDs patients. This finding may add to the basis for timely and clinically appropriate decision-making on anticoagulation treatment. PMID:24334432

  11. [Reducing the side effects of aggressive chemotherapy (cisplatin and epirubicin) with xenogenic peptides (factor AF2) in patients with hormone refractory metastatic prostate cancer. A prospective, randomized study].

    PubMed

    Papadopoulos, I; Wand, H

    1989-06-01

    The indication of a chemotherapy is advisable with patients who are suffering from a progressively metastasised, secondarily hormone refractory carcinoma of the prostate. In search of efficient chemotherapy protocols we combined cisplatin with epirubicin (PE scheme) in our clinic. Massive side effects of that aggressive chemotherapy scheme like gastro-intestinal trouble and myelotoxicity are the limiting factors of the scheme. With measures like reducing the dosage, delaying the next cycle, or breaking off the therapy the effective dosage can often not be achieved. The anti-emetics which are usually used today exclusively give anti-emetic protection. The additional administration of xenogenic peptides (Factor AF2) had additionally myeloprotective effect in former studies. In this study we examined whether, by additionally giving Factor AF2, the patients' subjective condition, and above all their hemogram, could be stabilised in order to achieve the effective dosage or dosage intensity. For that, the patients were prospectively randomised in two groups by means of a random selection board. The analysis of the data gained in the protocol showed that the additional administration of Factor AF2 improves the patients' subjective conditions significantly. Apart from that, we noticed a considerable reduction of the vomiting frequency. Concerning the objective measured parameters of the leukocytes, thrombocytes, erythrocytes, and the hemoglobin level, the significantly myeloprotective effect of Factor AF2 could be proved. Due to the fact that in the verum group there were considerably fewer cases of breaking off or delays of the treatment than in the control group, the effective dosage intensity could be achieved with a higher number of patients in that group. PMID:2691943

  12. Antithrombotic therapy use in patients with atrial fibrillation before the era of non-vitamin K antagonist oral anticoagulants: the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) Phase I cohort

    PubMed Central

    Huisman, Menno V.; Ma, Chang Sheng; Diener, Hans-Christoph; Dubner, Sergio J.; Halperin, Jonathan L.; Rothman, Kenneth J.; Teutsch, Christine; Schoof, Nils; Kleine, Eva; Bartels, Dorothee B.; Lip, Gregory Y.H.

    2016-01-01

    Aims The introduction of non-VKA oral anticoagulants (NOACs), which differ from the earlier vitamin K antagonist (VKA) treatments, has changed the approach to stroke prevention in atrial fibrillation (AF). GLORIA-AF is a prospective, global registry programme describing the selection of antithrombotic treatment in newly diagnosed AF patients at risk of stroke. It comprises three phases: Phase I, before the introduction of NOACs; Phase II, during the time of the introduction of dabigatran, the first NOAC; and Phase III, once NOACs have been established in clinical practice. Methods and results In Phase I, 1063 patients were eligible from the 1100 enrolled (54.3% male; median age 70 years); patients were from China (67.1%), Europe (EU; 27.4%), and the Middle East (ME; 5.6%). The majority of patients using VKAs had high stroke risk (CHA2DS2-VASc ≥ 2; 86.5%); 13.5% had moderate risk (CHA2DS2-VASc = 1). Vitamin K antagonist use was higher for persistent/permanent AF (47.7%) than that for paroxysmal (23.9%). Most patients in China were treated with antiplatelet agents (53.7%) vs. 27.1% in EU and 28.8% in ME. In China, 25.9% of patients had no antithrombotic therapy, vs. 8.6% in EU and 8.5% in ME. Conclusion Phase I of GLORIA-AF shows that VKAs were mostly used in patients with persistent/permanent (vs. paroxysmal) AF and in those with high stroke risk. Furthermore, there were meaningful geographical differences in the use of VKA therapy in the era before the availability of NOACs, including a much lower use of VKAs in China, where most patients either received antiplatelet agents or no antithrombotic treatment. PMID:27335063

  13. Improvement of impaired mitogen-induced interferon-gamma release of peripheral blood mononuclear cells derived from tumor patients by Factor AF2.

    PubMed

    Baier, J E; Neumann, H A; Gallati, H; Ricken, D

    1991-01-01

    Factor AF2, a now standardized extract from liver and spleen of newborn lambs, showed myeloprotective capacity on platelet- and erythrocyte-count as well as on hemoglobinconcentration in patients undergoing aggressive chemotherapy. In addition, a possible influence on prolonged remission duration in patients with mammary carcinoma had been claimed. In this study, the effect of Factor AF2 on mitogen-induced interferon-gamma release by PBMC was tested in 23 healthy humans and in 23 tumor patients. All patients were prior to surgery and had not yet received radio- or chemotherapy at the time of examination. The interferon-gamma concentration of the supernatants was measured using an enzyme-linked immunosorbent assay (ELISA). The cells were stimulated with PHA at 7.5 micrograms/ml. In the reference group, interferon-gamma concentration rose to 26 units/ml and to 15.5 units/ml in the tumor patients. In the reference persons, an addition of Factor AF2 at concentrations from 10(1) micrograms/ml to 10(3) micrograms/ml resulted in a small non-significant decrease of interferon-gamma release. At 10(4) micrograms/ml, neither test group showed measurable interferon-gamma concentration. In the tumor patients, cocultivation with Factor AF2 until concentration of 10(2) micrograms/ml resulted in a dose-dependent increase of interferon-gamma release, where 20.5 units/ml interferon-gamma were reached. At 10(3) micrograms/ml, Factor AF2 showed no effect on interferon-gamma release compared with the stimulation with mitogen alone. Flow-cytometry analysis of CD3, CD4, CD8, CD16, CD19, CD56, and HLA-DR expression of the PBMC deriving either from reference persons or from patients revealed an almost identical distribution. A slight difference in CD16-positive and HLA-DR positive cells, respectively, was not significant. PMID:1788474

  14. A cohort study of relationship between serum calcium levels and cerebral microbleeds (CMBs) in ischemic stroke patients with AF and/or RHD.

    PubMed

    Liu, Junfeng; Wang, Deren; Xiong, Yao; Liu, Bian; Wei, Chenchen; Ma, Zhenxing; Wu, Bo; Yuan, Ruozhen; Tang, Hehan; Liu, Ming

    2016-06-01

    Calcium is an essential element for life and has cerebroprotective property in stroke patients. Low serum calcium levels were found to be related to large hematoma volumes in intracerebral hemorrhagic patients and hemorrhagic transformation in ischemic stroke patients after thrombolysis. However, their impact on hemorrhage-prone small vessel disease represented by cerebral microbleeds (CMBs) is uncertain. We aim to investigate whether low serum calcium levels are associated with presence and location of CMBs.Ischemic stroke patients with atrial fibrillation (AF) and/or rheumatic heart disease admitted to our hospital were consecutively and prospectively enrolled. Demographic and clinical information were collected and analyzed according to the occurrence and location of CMBs, and levels of serum calcium. We used logistic regression analysis to estimate the multivariable adjusted relationship between serum calcium levels and the presence or location of CMBs.Among the 67 patients (28 males; mean age, 67.3 years) in the final analysis, 39 (58.2%) were found to have CMBs. After adjustment for age, sex, smoking habits, drinking habits, and renal impairment, the presence of CMBs and deep CMBs was, respectively, 4.96- and 4.83-fold higher in patients with lower serum calcium levels (≤2.15 mmol/L) than in patients with higher serum calcium levels.Lower serum calcium levels (≤2.15 mmol/L) are independently associated with the presence of CMBs and deep CMBs in ischemic stroke patients with AF and/or rheumatic heart disease, which should be verified and extended in large cohorts, with other types of stroke patients and the general population. PMID:27368027

  15. A cohort study of relationship between serum calcium levels and cerebral microbleeds (CMBs) in ischemic stroke patients with AF and/or RHD

    PubMed Central

    Liu, Junfeng; Wang, Deren; Xiong, Yao; Liu, Bian; Wei, Chenchen; Ma, Zhenxing; Wu, Bo; Yuan, Ruozhen; Tang, Hehan; Liu, Ming

    2016-01-01

    Abstract Calcium is an essential element for life and has cerebroprotective property in stroke patients. Low serum calcium levels were found to be related to large hematoma volumes in intracerebral hemorrhagic patients and hemorrhagic transformation in ischemic stroke patients after thrombolysis. However, their impact on hemorrhage-prone small vessel disease represented by cerebral microbleeds (CMBs) is uncertain. We aim to investigate whether low serum calcium levels are associated with presence and location of CMBs. Ischemic stroke patients with atrial fibrillation (AF) and/or rheumatic heart disease admitted to our hospital were consecutively and prospectively enrolled. Demographic and clinical information were collected and analyzed according to the occurrence and location of CMBs, and levels of serum calcium. We used logistic regression analysis to estimate the multivariable adjusted relationship between serum calcium levels and the presence or location of CMBs. Among the 67 patients (28 males; mean age, 67.3 years) in the final analysis, 39 (58.2%) were found to have CMBs. After adjustment for age, sex, smoking habits, drinking habits, and renal impairment, the presence of CMBs and deep CMBs was, respectively, 4.96- and 4.83-fold higher in patients with lower serum calcium levels (≤2.15 mmol/L) than in patients with higher serum calcium levels. Lower serum calcium levels (≤2.15 mmol/L) are independently associated with the presence of CMBs and deep CMBs in ischemic stroke patients with AF and/or rheumatic heart disease, which should be verified and extended in large cohorts, with other types of stroke patients and the general population. PMID:27368027

  16. Assessment of Device-Related Thrombus and Associated Clinical Outcomes With the WATCHMAN Left Atrial Appendage Closure Device for Embolic Protection in Patients With Atrial Fibrillation (from the PROTECT-AF Trial).

    PubMed

    Main, Michael L; Fan, Dali; Reddy, Vivek Y; Holmes, David R; Gordon, Nicole T; Coggins, Tina R; House, John A; Liao, Lawrence; Rabineau, Dawn; Latus, George G; Huber, Kenneth C; Sievert, Horst; Wright, Richard F; Doshi, Shephal K; Douglas, Pamela S

    2016-04-01

    Left atrial appendage closure with the WATCHMAN device is an alternative to anticoagulation for stroke prevention in selected patients with atrial fibrillation (AF). LA device-related thrombus (DRT) is poorly defined and understood. We aimed to (1) develop consensus echocardiographic diagnostic criteria for DRT; (2) estimate the incidence of DRT; and (3) determine clinical event rates in patients with DRT. In phase 1 (training), a training manual was developed and reviewed by 3 echocardiographers with left atrial appendage closure device experience. All available transesophageal (TEE) studies in the WATCHMAN left atrial appendage system for embolic protection in patients with atrial fibrillation (PROTECT-AF) trial patients with suspected DRT were reviewed in 2 subsequent phases. In phase 2 (primary blind read), each reviewer independently scored each study for DRT, and final echo criteria were developed. Unanimously scored studies were considered adjudicated, whereas all others were reevaluated by all reviewers in phase 3 (group adjudication read). DRT was suspected in 35 of 485 patients by the site investigator, the echocardiography core laboratory, or both; 93 of the individual TEE studies were available for review. In phase 2, 3 readers agreed on 67 (72%) of time points. Based on phases 1 and 2, 5 DRT criteria were developed. In phase 3, studies without agreement in phase 2 were adjudicated using these criteria. Overall, at least 1 TEE was DRT positive in 27 (5.7%) PROTECT-AF patients. Stroke, peripheral embolism, or cardiac/unexplained death occurred in subjects with DRT at a rate of 3.4 per 100 patient-years follow-up. In conclusion, DRT were identified on at least 1 TEE in 27 PROTECT-AF patients, indicating a DRT incidence of 5.7%. Primary efficacy events in patients with DRT occurred at a rate of 3.4 per 100 patient-years follow-up, intermediate in frequency between event rates previously reported for the overall device and warfarin arms in PROTECT-AF. PMID

  17. Korean Atrial Fibrillation (AF) Network: Genetic Variants for AF Do Not Predict Ablation Success

    PubMed Central

    Choi, Eue-Keun; Park, Jae Hyung; Lee, Ji-Young; Nam, Chung Mo; Hwang, Min Ki; Uhm, Jae-Sun; Joung, Boyoung; Ko, Young-Guk; Lee, Moon-Hyoung; Lubitz, Steven A; Ellinor, Patrick T; Pak, Hui-Nam

    2015-01-01

    Background Genomewide association studies have identified several loci associated with atrial fibrillation (AF) and have been reportedly associated with response to catheter ablation for AF in patients of European ancestry; however, associations between top susceptibility loci and AF recurrence after ablation have not been examined in Asian populations. We examined whether the top single nucleotide polymorphisms (SNPs) at chromosomes 4q25 (PITX2), 16q22 (ZFHX3), and 1q21 (KCNN3) were associated with AF in a Korean population and whether these SNPs were associated with clinical outcomes after catheter ablation for AF. Methods and Results We determined the association between 4 SNPs and AF in 1068 AF patients who underwent catheter ablation (74.6% male, aged 57.5±10.9 years, 67.9% paroxysmal AF) and 1068 age- and sex-matched controls. The SNPs at the PITX2 and ZFHX3 loci, but not the KCNN3 locus, were significantly associated with AF (PITX2/rs6843082_G: odds ratio 3.41, 95% CI 2.55 to 4.55, P=1.32×10−16; PITX2/rs2200733_T: odds ratio 2.05, 95% CI 1.66 to 2.53, P=2.20×10−11; ZFHX3/rs2106261_A: odds ratio 2.33, 95% CI 1.87 to 2.91, P=3.75×10−14; KCNN3/rs13376333_T: odds ratio 1.74, 95% CI 0.93 to 3.25, P=0.085). Among those patients who underwent catheter ablation for AF, none of the top AF-associated SNPs were associated with long-term clinical recurrence of AF after catheter ablation. Conclusions SNPs at the PITX2 and ZFHX3 loci were strongly associated with AF in Korean patients. In contrast to prior reports, none of the 4 top AF-susceptibility SNPs predicted clinical recurrence after catheter ablation. PMID:26272656

  18. Nonvitamin K Anticoagulant Agents in Patients With Advanced Chronic Kidney Disease or on Dialysis With AF.

    PubMed

    Chan, Kevin E; Giugliano, Robert P; Patel, Manesh R; Abramson, Stuart; Jardine, Meg; Zhao, Sophia; Perkovic, Vlado; Maddux, Franklin W; Piccini, Jonathan P

    2016-06-21

    Nonvitamin K-dependent oral anticoagulant agents (NOACs) are currently recommended for patients with atrial fibrillation at risk for stroke. As a group, NOACs significantly reduce stroke, intracranial hemorrhage, and mortality, with lower to similar major bleeding rates compared with warfarin. All NOACs are dependent on the kidney for elimination, such that patients with creatinine clearance <25 ml/min were excluded from all the pivotal phase 3 NOAC trials. It therefore remains unclear how or if NOACs should be prescribed to patients with advanced chronic kidney disease and those on dialysis. The authors review the current pharmacokinetic, observational, and prospective data on NOACs in patients with advanced chronic kidney disease (creatinine clearance <30 ml/min) and those on dialysis. The authors frame the evidence in terms of risk versus benefit to bring greater clarity to NOAC-related major bleeding and efficacy at preventing stroke specifically in patients with creatinine clearance <30 ml/min. PMID:27311528

  19. AFS controlling algorithm

    NASA Astrophysics Data System (ADS)

    Liu, Hong; Jiang, Lanfang; Wang, Gengjie; Wang, Li

    2008-12-01

    Adaptive front lighting system (i.e., AFS) is the development trend of lighting system of motor vehicles. AFS means that headlamp can adjust beam direction to get best illumination according to road condition and its bodywork. The paper discusses the AFS key techniques: establishing calculation formulae of vehicle body state concerned road condition and steering state. Because of sensor technology limitations, it only can deal with inclination and turn of vehicle body state by means of sensor's signals. This paper studies the relationship between inclination and turn of the body and lamp lighting on the base of relative standards, and gives out the calculation formulae for the body and lamp lighting adjustment, also discusses its dynamical properties. The study is basic work for lighting adjustment automatically.

  20. Totally thorascopic surgical ablation of persistent AF and long-standing persistent atrial fibrillation using the "Dallas" lesion set.

    PubMed

    Edgerton, James R; Jackman, Warren M; Mahoney, Cecile; Mack, Michael J

    2009-12-01

    Minimally invasive surgery consisting of bipolar radiofrequency pulmonary vein (PV) isolation and limited ganglionated plexus ablation is effective in eliminating atrial fibrillation (AF) in patients with paroxysmal AF but is less effective in those with persistent AF or long-standing persistent AF. The purpose of this study was examine the results of minimally invasive surgery incorporating an additional set of radiofrequency ablation lines replicating a left-sided Cox maze III procedure. Thirty patients with persistent AF (n = 10) or long-standing persistent AF (n = 20) underwent minimally invasive surgery with an extended lesion set and PV isolation for a minimum follow-up of 6 months. Linear lesions were created at the roof line, at the anterior line, and between the roof line and the left atrial appendage. All patients underwent limited ganglionated plexus ablation and left atrial appendage excision as well as PV isolation verification. Block across the roof and anterior lines was confirmed in 29 (96.6%) of the 30 patients. Follow-up included 2-week event monitoring with auto-trigger in 21 patients, pacemaker interrogation in 8, and ECG in 1 who was in AF and refused longer-term monitoring. No operative mortality or major morbidity occurred. At 6 months, 24 (80%) of the 30 patients were free of AF: 15 (75%) with long-standing persistent AF and 9 (90%) with persistent AF. Among the six failures, burden of AF was low: one had 1 episode >15 seconds, two had 4 episodes, one had 6 episodes, one had >50 episodes, and one had AF on ECG and refused further monitoring. Early results of minimally invasive surgery with a new extended linear lesion set suggest increased efficacy over PV isolation and limited ganglionated plexus ablation in patients with persistent AF or long-standing persistent AF. PMID:19959146

  1. Atrial Fibrillation Management Strategies in Routine Clinical Practice: Insights from the International RealiseAF Survey

    PubMed Central

    Chiang, Chern-En; Naditch-Brûlé, Lisa; Brette, Sandrine; Silva-Cardoso, José; Gamra, Habib; Murin, Jan; Zharinov, Oleg J.; Steg, Philippe Gabriel

    2016-01-01

    Background Atrial fibrillation (AF) can be managed with rhythm- or rate-control strategies. There are few data from routine clinical practice on the frequency with which each strategy is used and their correlates in terms of patients’ clinical characteristics, AF control, and symptom burden. Methods RealiseAF was an international, cross-sectional, observational survey of 11,198 patients with AF. The aim of this analysis was to describe patient profiles and symptoms according to the AF management strategy used. A multivariate logistic regression identified factors associated with AF management strategy at the end of the visit. Results Among 10,497 eligible patients, 53.7% used a rate-control strategy, compared with 34.5% who used a rhythm-control strategy. In 11.8% of patients, no clear strategy was stated. The proportion of patients with AF-related symptoms (EHRA Class > = II) was 78.1% (n = 4396/5630) for those using a rate-control strategy vs. 67.8% for those using a rhythm-control strategy (p<0.001). Multivariate logistic regression analysis revealed that age <75 years or the paroxysmal or persistent form of AF favored the choice of a rhythm-control strategy. A change in strategy was infrequent, even in patients with European Heart Rhythm Association (EHRA) Class > = II. Conclusions In the RealiseAF routine clinical practice survey, rate control was more commonly used than rhythm control, and a change in strategy was uncommon, even in symptomatic patients. In almost 12% of patients, no clear strategy was stated. Physician awareness regarding optimal management strategies for AF may be improved. PMID:26800084

  2. Atrial Fibrillation (AF or AFib)

    MedlinePlus

    ... Pressure High Blood Pressure Tools & Resources Stroke More Atrial Fibrillation (AF or AFib) Updated:Feb 10,2016 What ... to the Terms and Conditions and Privacy Policy Atrial Fibrillation • Introduction • What is Atrial Fibrillation? • Why AFib Matters • ...

  3. Pathogenesis of AF: Impact on intracardiac signals

    PubMed Central

    Shah, Ashok J; Dubois, Rémi; Miyazaki, Shinsuke; Jadidi, Amir S; Scherr, Daniel; Wilton, Stephen B; Roten, Laurent; Pascale, Patrizio; Pedersen, Michala; Derval, Nicolas; Knecht, Sebastien; Sacher, Frederic; Jais, Pierre; Narayan, Sanjiv; Hocini, Mélèze; Haïssaguerre, Michel

    2014-01-01

    Atrial fibrillation (AF) is the most common cardiac arrhythmia, and is responsible for the highest number of rhythm-related disorders and cardioembolic strokes worldwide. Intracardiac signal analysis during the onset of paroxysmal AF led to the discovery of pulmonary vein as a triggering source of AF, which has led to the development of pulmonary vein ablation—an established curative therapy for drug-resistant AF. Complex, multicomponent and rapid electrical activity widely involving the atrial substrate characterizes persistent/permanent AF. Widespread nature of the problem and complexity of signals in persistent AF reduce the success rate of ablation therapy. Although signal processing applied to extraction of relevant features from these complex electrograms has helped to improve the efficacy of ablation therapy in persistent/permanent AF, improved understanding of complex signals should help to identify sources of AF and further increase the success rate of ablation therapy. PMID:22255589

  4. Effects of Iron Depletion on CALM-AF10 Leukemias

    PubMed Central

    Heath, Jessica L.; Weiss, Joshua M.

    2014-01-01

    Iron, an essential nutrient for cellular growth and proliferation, enters cells via clathrin-mediated endocytosis (CME). The clathrin assembly lymphoid myeloid (CALM) protein plays an essential role in the cellular import of iron by CME. CALM-AF10 leukemias harbor a single copy of the normal CALM gene, and may therefore be more sensitive to the growth inhibitory effect of iron restriction compared with normal hematopoietic cells. We found that Calm heterozygous (CalmHET) murine fibroblasts exhibit signs of iron deficiency, with increased surface transferrin receptor (sTfR) levels and reduced growth rates. CalmHET hematopoietic cells are more sensitive in vitro to iron chelators than their wild type counterparts. Iron chelation also displayed toxicity towards cultured CalmHET CALM-AF10 leukemia cells and this effect was additive to that of chemotherapy. In mice transplanted with CalmHET CALM-AF10 leukemia, we found that dietary iron restriction reduces tumor burden in the spleen. However, dietary iron restriction, used alone or in conjunction with chemotherapy, did not increase survival of mice with CalmHET CALM-AF10 leukemia. In summary, while Calm heterozygosity results in iron deficiency and increased sensitivity to iron chelation in vitro, our data in mice do not suggest that iron depletion strategies would be beneficial for the therapy of CALM-AF10 leukemia patients. PMID:25193880

  5. Mutant U2AF1 Expression Alters Hematopoiesis and Pre-mRNA Splicing In Vivo

    PubMed Central

    Shirai, Cara Lunn; Ley, James N.; White, Brian S.; Kim, Sanghyun; Tibbitts, Justin; Shao, Jin; Ndonwi, Matthew; Wadugu, Brian; Duncavage, Eric J.; Okeyo-Owuor, Theresa; Liu, Tuoen; Griffith, Malachi; McGrath, Sean; Magrini, Vincent; Fulton, Robert S.; Fronick, Catrina; O’Laughlin, Michelle; Graubert, Timothy A.; Walter, Matthew J.

    2015-01-01

    SUMMARY Heterozygous somatic mutations in the spliceosome gene U2AF1 occur in ~11% of patients with myelodysplastic syndromes (MDS), the most common adult myeloid malignancy. It is unclear how these mutations contribute to disease. We examined in vivo hematopoietic consequences of the most common U2AF1 mutation using a doxycycline-inducible transgenic mouse model. Mice expressing mutant U2AF1(S34F) display altered hematopoiesis and changes in pre-mRNA splicing in hematopoietic progenitor cells by whole transcriptome analysis (RNA-seq). Integration with human RNA-seq datasets determined that common mutant U2AF1-induced splicing alterations are enriched in RNA processing genes, ribosomal genes, and recurrently-mutated MDS and acute myeloid leukemia-associated genes. These findings support the hypothesis that mutant U2AF1 alters downstream gene isoform expression, thereby contributing to abnormal hematopoiesis in MDS patients. PMID:25965570

  6. Pharmacokinetics of cefaclor AF: effects of age, antacids and H2-receptor antagonists.

    PubMed

    Satterwhite, J H; Cerimele, B J; Coleman, D L; Hatcher, B L; Kisicki, J; DeSante, K A

    1992-01-01

    The pharmacokinetics and bioavailability of cefaclor advanced formulation (cefaclor AF) were investigated in two studies, one comparing healthy elderly and younger volunteers and the other assessing the effects of an antacid and H2-receptor antagonist on cefaclor AF bioavailability. The pharmacokinetics of a 750 mg dose of cefaclor AF were studied in 30 subjects ranging in age from 65 to 84 years and 10 control subjects 21-45 years of age. Compared with controls, elderly subjects exhibited higher plasma concentrations of cefaclor which were attributed to lower plasma clearance. There was a strong association between age and renal function, and the plasma clearance of cefaclor was highly dependent upon renal function. Thus, elderly patients with impaired renal function had a reduced ability to eliminate cefaclor. Due to a short elimination half-life and wide therapeutic index, dosage adjustments are not necessary in patients exhibiting moderate renal dysfunction. The 15 healthy men in the second trial were crossed over to receive five treatments, including cefaclor AF (500 mg) alone, cefaclor AF with or preceded by cimetidine, cefaclor AF followed by Maalox TC and cefaclor immediate release (500 mg) alone. Cefaclor AF and immediate release cefaclor had similar bioavailability, but plasma concentrations were maintained for a longer period of time when cefaclor AF was administered. Cimetidine did not alter the bioavailability of cefaclor AF but Maalox TC, coadministered with cefaclor AF, reduced the extent of absorption. This suggests that cefaclor AF bioavailability is influenced by the antacid Maalox TC but not by H2-receptor antagonist cimetidine. PMID:1287615

  7. Outcomes registry for better informed treatment of atrial fibrillation II: Rationale and design of the ORBIT-AF II registry

    PubMed Central

    Steinberg, Benjamin A.; Blanco, Rosalia G.; Ollis, Donna; Kim, Sunghee; Holmes, DaJuanicia N.; Kowey, Peter R.; Fonarow, Gregg C.; Ansell, Jack; Gersh, Bernard; Go, Alan S.; Hylek, Elaine; Mahaffey, Kenneth W.; Thomas, Laine; Chang, Paul; Peterson, Eric D.; Piccini, Jonathan P.

    2014-01-01

    Background Recent clinical trials have demonstrated the safety and efficacy of several non–vitamin K oral anticoagulants (NOACs) for the treatment of atrial fibrillation (AF). However, there are limited data on their use and outcomes in routine clinical practice, particularly among patients newly diagnosed as having AF and patients with AF recently transitioned to a NOAC. Methods/Design ORBIT-AF II is a multicenter, national registry of patients with AF that is enrolling up to 15,000 newly diagnosed patients with AF and/or those with AF recently transitioned to a NOAC from 300 US outpatient practices. These patients will be followed for up to 2 years, including clinical status, outcomes (major adverse cardiovascular events, bleeding), and management of anticoagulation surrounding bleeding events. In addition, detailed data regarding the use of these agents in and around cardiac procedures, their complications, and management of such complications will be collected. Conclusions The ORBIT-AF II registry will provide valuable insights into the safety and effectiveness of NOACs used in AF in community practice settings. PMID:25066554

  8. AF1q is a novel TCF7 co-factor which activates CD44 and promotes breast cancer metastasis.

    PubMed

    Park, Jino; Schlederer, Michaela; Schreiber, Martin; Ice, Ryan; Merkel, Olaf; Bilban, Martin; Hofbauer, Sebastian; Kim, Soojin; Addison, Joseph; Zou, Jie; Ji, Chunyan; Bunting, Silvia T; Wang, Zhengqi; Shoham, Menachem; Huang, Gang; Bago-Horvath, Zsuzsanna; Gibson, Laura F; Rojanasakul, Yon; Remick, Scot; Ivanov, Alexey; Pugacheva, Elena; Bunting, Kevin D; Moriggl, Richard; Kenner, Lukas; Tse, William

    2015-08-21

    AF1q is an MLL fusion partner that was identified from acute myeloid leukemia (AML) patients with t (1; 11) (q21; q23) chromosomal abnormality. The function of AF1q is not yet fully known, however, elevated AF1q expression is associated with poor clinical outcomes in various malignancies. Here, we show that AF1q specifically binds to T-cell-factor-7 (TCF7) in the Wnt signaling pathway and results in transcriptional activation of CD44 as well as multiple downstream targets of the TCF7/LEF1. In addition, enhanced AF1q expression promotes breast cancer cell proliferation, migration, mammosphere formation, and chemo-resistance. In xenograft models, enforced AF1q expression in breast cancer cells also promotes liver metastasis and lung colonization. In a cohort of 63 breast cancer patients, higher percentages of AF1q-positive cancer cells in primary sites were associated with significantly poorer overall survival (OS), disease-free survival (DFS), and brain metastasis-free survival (b-MFS). Using paired primary/metastatic samples from the same patients, we demonstrate that AF1q-positive breast cancer cells become dynamically dominant in the metastatic sites compared to the primary sites. Our findings indicate that breast cancer cells with a hyperactive AF1q/TCF7/CD44 regulatory axis in the primary sites may represent "metastatic founder cells" which have invasive properties. PMID:26079538

  9. AF1q is a novel TCF7 co-factor which activates CD44 and promotes breast cancer metastasis

    PubMed Central

    Park, Jino; Schlederer, Michaela; Schreiber, Martin; Ice, Ryan; Merkel, Olaf; Bilban, Martin; Hofbauer, Sebastian; Kim, Soojin; Addison, Joseph; Zou, Jie; Ji, Chunyan; Bunting, Silvia T.; Wang, Zhengqi; Shoham, Menachem; Huang, Gang; Bago-Horvath, Zsuzsanna; Gibson, Laura F.; Rojanasakul, Yon; Remick, Scot; Ivanov, Alexey; Pugacheva, Elena; Bunting, Kevin D.; Moriggl, Richard

    2015-01-01

    AF1q is an MLL fusion partner that was identified from acute myeloid leukemia (AML) patients with t (1; 11) (q21; q23) chromosomal abnormality. The function of AF1q is not yet fully known, however, elevated AF1q expression is associated with poor clinical outcomes in various malignancies. Here, we show that AF1q specifically binds to T-cell-factor-7 (TCF7) in the Wnt signaling pathway and results in transcriptional activation of CD44 as well as multiple downstream targets of the TCF7/LEF1. In addition, enhanced AF1q expression promotes breast cancer cell proliferation, migration, mammosphere formation, and chemo-resistance. In xenograft models, enforced AF1q expression in breast cancer cells also promotes liver metastasis and lung colonization. In a cohort of 63 breast cancer patients, higher percentages of AF1q-positive cancer cells in primary sites were associated with significantly poorer overall survival (OS), disease-free survival (DFS), and brain metastasis-free survival (b-MFS). Using paired primary/metastatic samples from the same patients, we demonstrate that AF1q-positive breast cancer cells become dynamically dominant in the metastatic sites compared to the primary sites. Our findings indicate that breast cancer cells with a hyperactive AF1q/TCF7/CD44 regulatory axis in the primary sites may represent “metastatic founder cells” which have invasive properties. PMID:26079538

  10. Natalizumab-induced POU2AF1/Spi-B upregulation

    PubMed Central

    Meira, Maria; Sievers, Claudia; Hoffmann, Francine; Haghikia, Aiden; Rasenack, Maria; Décard, Bernhard F.; Kuhle, Jens; Derfuss, Tobias; Kappos, Ludwig

    2016-01-01

    Objectives: To assess messenger RNA (mRNA) expression of POU2AF1 and Spi-B and their potential regulatory microRNAs (miRNAs) in natalizumab-treated patients with multiple sclerosis and in therapy-associated progressive multifocal leukoencephalopathy (PML). Methods: Expression of POU2AF1/Spi-B was analyzed by using real-time reverse transcription PCR assays on isolated B/CD8+ T lymphocytes and peripheral blood mononuclear cells (PBMCs) from cohorts of untreated and natalizumab-treated patients with and without PML. Longitudinal expression analysis was performed on CD4+, CD8+ T and B cells from 14 patients who interrupted natalizumab therapy for 8 weeks. The miRNA profiling was conducted in PBMCs from 5 untreated and 5 natalizumab-treated patients using low-density arrays followed by validation with single miRNAs assays in untreated and natalizumab-treated patients. Results: POU2AF1 and Spi-B mRNAs were upregulated in B and CD8+ T cells from natalizumab-treated patients, which was validated in PBMCs from different cohorts of natalizumab-treated patients with and without PML, with a noteworthy higher expression of Spi-B in patients with PML. In contrast, downregulation of POU2AF1/Spi-B expression was measured in B and CD8+ T cells after natalizumab discontinuation. Seventeen differentially expressed miRNAs including miR-10b, a regulator of POU2AF1 mRNA, were identified in long-term natalizumab-treated patients compared with untreated ones. Conclusions: Upregulation of POU2AF1 and Spi-B, known transactivators of the JC virus, the causative agent for PML, and its association with occurrence of PML in natalizumab-treated patients, corroborates POU2AF1/Spi-B as potential biomarkers for PML risk, which merits further evaluation. PMID:27088119

  11. Study about AFS swerve mode

    NASA Astrophysics Data System (ADS)

    Liu, Hong; Jiang, Lanfang; Zhao, Qin; Wang, Li

    2009-11-01

    A swerving mathematical model was established after stating the shortage of the present AFS swerving algorithm. The conception of 'expected lighting distance' was extended to 'expected lighting bound' and approximate treatment of geometry of light beam falling to ground of headlamp was processed. The expected lighting bound was ascertained and the lighting range of turning angle of headlamp was calculated. The calculation formula of turning angle of headlamp was worked out. It was indicated that the turning angle of inside and outside of headlamp calculated by revised algorithm was reasonable by comparing calculation. Finally the control strategy about the turning angle of inside and outside headlamp when turning was worked out. It is of practical significance in promoting the active safety, reducing the traffic accidents caused by insufficient angle and range of irradiation of headlamp.

  12. Eaton AF5000+Genesis Communication Driver

    Energy Science and Technology Software Center (ESTSC)

    1995-05-25

    Communication driver allows the Genesis Control Series software to interact with Eaton AF5000+ frequency drives via RS-232 communications. All Eaton AF5000+ parameters that support communications are supported by the Genesis driver. Multidrop addressing to multiple units is available with the Genesis communication driver.

  13. U2AF1 Mutations Alter Sequence Specificity of pre-mRNA Binding and Splicing

    PubMed Central

    Okeyo-Owuor, Theresa; White, Brian S.; Chatrikhi, Rakesh; Mohan, Dipika R.; Kim, Sanghyun; Griffith, Malachi; Ding, Li; Ketkar-Kulkarni, Shamika; Hundal, Jasreet; Laird, Kholiswa M.; Kielkopf, Clara L.; Ley, Timothy J.; Walter, Matthew J.; Graubert, Timothy A.

    2014-01-01

    We previously identified missense mutations in the U2AF1 splicing factor affecting codons S34 (S34F and S34Y) or Q157 (Q157R and Q157P) in 11% of patients with de novo myelodysplastic syndromes (MDS). Although the role of U2AF1 as an accessory factor in the U2 snRNP is well established, it is not yet clear how mutations affect splicing or contribute to MDS pathophysiology. We analyzed splice junctions in RNA-seq data generated from transfected CD34+ hematopoietic cells and found significant differences in the abundance of known and novel junctions in samples expressing mutant U2AF1 (S34F). For selected transcripts, splicing alterations detected by RNA-seq were confirmed by analysis of primary de novo MDS patient samples. These effects were not due to impaired U2AF1 (S34F) localization as it co-localized normally with U2AF2 within nuclear speckles. We further found evidence in the RNA-seq data for decreased affinity of U2AF1 (S34F) for uridine (relative to cytidine) at the e-3 position immediately upstream of the splice acceptor site and corroborated this finding using affinity binding assays. These data suggest that the S34F mutation alters U2AF1 function in the context of specific RNA sequences, leading to aberrant alternative splicing of target genes, some of which may be relevant for MDS pathogenesis. PMID:25311244

  14. A Critical Role for CRM1 in Regulating HOXA Gene Transcription in CALM-AF10 Leukemias

    PubMed Central

    Conway, Amanda E.; Haldeman, Jonathan M.; Wechsler, Daniel S.; Lavau, Catherine P.

    2014-01-01

    The leukemogenic CALM-AF10 fusion protein is found in patients with immature acute myeloid and T-lymphoid malignancies. CALM-AF10 leukemias display abnormal H3K79 methylation and increased HOXA cluster gene transcription. Elevated expression of HOXA genes is critical for leukemia maintenance and progression; however, the precise mechanism by which CALM-AF10 alters HOXA gene expression is unclear. We previously determined that CALM contains a CRM1-dependent nuclear export signal (NES), which is both necessary and sufficient for CALM-AF10-mediated leukemogenesis. Here, we find that interaction of CALM-AF10 with the nuclear export receptor CRM1 is necessary for activating HOXA gene expression. We show that CRM1 localizes to HOXA loci where it recruits CALM-AF10, leading to transcriptional and epigenetic activation of HOXA genes. Genetic and pharmacological inhibition of the CALM-CRM1 interaction prevents CALM-AF10 enrichment at HOXA chromatin, resulting in immediate loss of transcription. These results provide a comprehensive mechanism by which the CALM-AF10 translocation activates the critical HOXA cluster genes. Furthermore, this report identifies a novel function of CRM1: the ability to bind chromatin and recruit the NES-containing CALM-AF10 transcription factor. PMID:25027513

  15. STBC AF relay for unmanned aircraft system

    NASA Astrophysics Data System (ADS)

    Adachi, Fumiyuki; Miyazaki, Hiroyuki; Endo, Chikara

    2015-01-01

    If a large scale disaster similar to the Great East Japan Earthquake 2011 happens, some areas may be isolated from the communications network. Recently, unmanned aircraft system (UAS) based wireless relay communication has been attracting much attention since it is able to quickly re-establish the connection between isolated areas and the network. However, the channel between ground station (GS) and unmanned aircraft (UA) is unreliable due to UA's swing motion and as consequence, the relay communication quality degrades. In this paper, we introduce space-time block coded (STBC) amplify-and-forward (AF) relay for UAS based wireless relay communication to improve relay communication quality. A group of UAs forms single frequency network (SFN) to perform STBC-AF cooperative relay. In STBC-AF relay, only conjugate operation, block exchange and amplifying are required at UAs. Therefore, STBC-AF relay improves the relay communication quality while alleviating the complexity problem at UAs. It is shown by computer simulation that STBC-AF relay can achieve better throughput performance than conventional AF relay.

  16. A CALM-derived nuclear export signal is essential for CALM-AF10–mediated leukemogenesis

    PubMed Central

    Conway, Amanda E.; Scotland, Paula B.; Lavau, Catherine P.

    2013-01-01

    The t(10;11) chromosomal translocation gives rise to the CALM-AF10 fusion gene and is found in patients with aggressive and difficult-to-treat hematopoietic malignancies. CALM-AF10–driven leukemias are characterized by HOXA gene up-regulation and a global reduction in H3K79 methylation. DOT1L, the H3K79 methyltransferase, interacts with the octapeptide/leucine zipper domain of AF10, and this region has been shown to be necessary and sufficient for CALM-AF10–mediated transformation. However, the precise role of CALM in leukemogenesis remains unclear. Here, we show that CALM contains a nuclear export signal (NES) that mediates cytoplasmic localization of CALM-AF10 and is necessary for CALM-AF10–dependent transformation. Fusions of the CALM NES (NESCALM-AF10) or NES motifs from heterologous proteins (ABL1, Rev, PKIA, APC) in-frame with AF10 are sufficient to immortalize murine hematopoietic progenitors in vitro. The CALM NES is essential for CALM-AF10–dependent Hoxa gene up-regulation and aberrant H3K79 methylation, possibly by mislocalization of DOT1L. Finally, we observed that CALM-AF10 leukemia cells are selectively sensitive to inhibition of nuclear export by Leptomycin B. These findings uncover a novel mechanism of leukemogenesis mediated by the nuclear export pathway and support further investigation of the utility of nuclear export inhibitors as therapeutic agents for patients with CALM-AF10 leukemias. PMID:23487024

  17. Stroke prevention in atrial fibrillation and 'real world' adherence to guidelines in the Balkan Region: The BALKAN-AF Survey.

    PubMed

    Potpara, Tatjana S; Dan, Gheorghe-Andrei; Trendafilova, Elina; Goda, Artan; Kusljugic, Zumreta; Manola, Sime; Music, Ljilja; Musetescu, Rodica; Badila, Elisabeta; Mitic, Gorana; Paparisto, Vilma; Dimitrova, Elena S; Polovina, Marija M; Petranov, Stanislav L; Djergo, Hortensia; Loncar, Daniela; Bijedic, Amira; Brusich, Sandro; Lip, Gregory Y H

    2016-01-01

    Data on the management of atrial fibrillation (AF) in the Balkan Region are limited. The Serbian AF Association (SAFA) prospectively investigated contemporary 'real-world' AF management in clinical practice in Albania, Bosnia&Herzegovina, Bulgaria, Croatia, Montenegro, Romania and Serbia through a 14-week (December 2014-February 2015) prospective, multicentre survey of consecutive AF patients. We report the results pertinent to stroke prevention strategies. Of 2712 enrolled patients, 2663 (98.2%) with complete data were included in this analysis (mean age 69.1 ± 10.9 years, female 44.6%). Overall, 1960 patients (73.6%) received oral anticoagulants (OAC) and 762 (28.6%) received antiplatelet drugs. Of patients given OAC, 17.2% received non-vitamin K antagonist oral anticoagulants (NOACs). CHA2DS2-VASc score was not significantly associated with OAC use. Of the 'truly low-risk' patients (CHA2DS2-VASc = 0 [males], or 1 [females]) 56.5% received OAC. Time in Therapeutic Range (TTR) was available in only 18.7% of patients (mean TTR: 49.5% ± 22.3%). Age ≥ 80 years, prior myocardial infarction and paroxysmal AF were independent predictors of OAC non-use. Our survey shows a relatively high overall use of OAC in AF patients, but with low quality of vitamin K antagonist therapy and insufficient adherence to AF guidelines. Additional efforts are needed to improve AF-related thromboprophylaxis in clinical practice in the Balkan Region. PMID:26869284

  18. Degradation of AF1Q by chaperone-mediated autophagy

    SciTech Connect

    Li, Peng; Ji, Min; Lu, Fei; Zhang, Jingru; Li, Huanjie; Cui, Taixing; Li Wang, Xing; Tang, Dongqi; Ji, Chunyan

    2014-09-10

    AF1Q, a mixed lineage leukemia gene fusion partner, is identified as a poor prognostic biomarker for pediatric acute myeloid leukemia (AML), adult AML with normal cytogenetic and adult myelodysplastic syndrome. AF1Q is highly regulated during hematopoietic progenitor differentiation and development but its regulatory mechanism has not been defined clearly. In the present study, we used pharmacological and genetic approaches to influence chaperone-mediated autophagy (CMA) and explored the degradation mechanism of AF1Q. Pharmacological inhibitors of lysosomal degradation, such as chloroquine, increased AF1Q levels, whereas activators of CMA, including 6-aminonicotinamide and nutrient starvation, decreased AF1Q levels. AF1Q interacts with HSPA8 and LAMP-2A, which are core components of the CMA machinery. Knockdown of HSPA8 or LAMP-2A increased AF1Q protein levels, whereas overexpression showed the opposite effect. Using an amino acid deletion AF1Q mutation plasmid, we identified that AF1Q had a KFERQ-like motif which was recognized by HSPA8 for CMA-dependent proteolysis. In conclusion, we demonstrate for the first time that AF1Q can be degraded in lysosomes by CMA. - Highlights: • Chaperone-mediated autophagy (CMA) is involved in the degradation of AF1Q. • Macroautophagy does not contribute to the AF1Q degradation. • AF1Q has a KFERQ-like motif that is recognized by CMA core components.

  19. AFS Estuaries Section - A Successful Partnership

    EPA Science Inventory

    The Estuaries Section of the American Fisheries Society offers travel awards to students in support of their attendance and presentations at the AFS meeting. Since 2007, the Southern Association of Marine Laboratories has partnered with the Estuaries Section to sponsor two stude...

  20. Health Information in Somali (af Soomaali): MedlinePlus

    MedlinePlus

    ... af Soomaali (Somali) Bilingual PDF Health Information Translations Animal Bites Animal Bites and Scratches Qaniinyada iyo Xagashada Xayawaanka - af ... Soomaali (Somali) Bilingual PDF Health Information Translations Radiation Therapy Preventing Infections When Your White Blood Cell Count ...

  1. Health Information in Somali (af Soomaali): MedlinePlus

    MedlinePlus

    ... Bilingual PDF Health Information Translations Appendectomy for a Child Qabsin-saarid ilmo - af Soomaali (Somali) Bilingual PDF ... Somali) Bilingual PDF Health Information Translations Asthma in Children Nebulizer Treatments Daawenta wal in Xaqiiqsanaan - af Soomaali ( ...

  2. Statin Therapy for the Prevention of Atrial Fibrillation Trial (SToP AF trial)

    PubMed Central

    Negi, Smita; Shukrullah, Irfan; Veledar, Emir; Bloom, Heather L.; Jones, Dean P.; Dudley, Samuel C.

    2010-01-01

    Background Inflammation and oxidative stress are associated with atrial fibrillation (AF). Statins have antioxidant and anti-inflammatory properties. We tested if atorvastatin reduced AF recurrence after DC cardioversion (CV) by modifying systemic oxidative stress and inflammation. (NCT00252967) Methods and Results In a randomized, double-blinded, placebo-controlled trial, patients with atrial fibrillation/flutter (AF) were randomized to receive either atorvastatin 80 mg (n=33) or placebo (n=31) before CV. Treatment was continued for 12 months or until AF recurred. Serum oxidative stress markers (ratios of oxidized to reduced glutathione and cysteine, derivatives of reactive oxygen species, isoprostanes) and inflammatory markers [ high sensitivity C- reactive protein (hs-CRP), interleukin-6 (IL-6), interleukin-1β(IL-1β), tumor necrosis factor-α (TNFα)] were measured at baseline and on follow-up. AF recurred in 22 (66.7%) of atorvastatin and 26 (83.9%) of placebo group (p=0.2). The adjusted hazard ratio of having recurrence on atorvastatin versus on placebo was 0.99 (95% CI: 0.98-1.01, p=0.3). There was no significant difference in the time to recurrence using Kaplan-Meier survival estimates (median (IR): 29 (2-145) days vs. 22 (7-70) days, p=0.9). While no significant effect was seen on oxidative stress, 2 of 4 inflammatory markers, IL-6 (adjusted OR: 0.59, 95% CI: 0.35-0.97, p= 0.04) and hs-CRP (adjusted OR: 0.59, 95% CI: 0.37-0.95, p=0.03) were significantly lowered with atorvastatin. Cholesterol levels significantly decreased with atorvastatin (p=0.03). Conclusions High dose atorvastatin did not reduce the recurrence of AF after CV. It reduced selective markers of inflammation without affecting systemic oxidative stress. Failure of atorvastatin to prevent AF recurrence may be due to its failure to affect oxidative stress. PMID:20946227

  3. Validation of the Framingham Heart Study and CHARGE-AF Risk Scores for Atrial Fibrillation in Hispanics, African-Americans, and Non-Hispanic Whites.

    PubMed

    Shulman, Eric; Kargoli, Faraj; Aagaard, Philip; Hoch, Ethan; Di Biase, Luigi; Fisher, John; Gross, Jay; Kim, Soo; Krumerman, Andrew; Ferrick, Kevin J

    2016-01-01

    A risk score for atrial fibrillation (AF) has been developed by the Framingham Heart Study and Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE)-AF consortium. However, validation of these risk scores in an inner-city population is uncertain. Thus, a validation model was built using the Framingham Risk Score for AF and CHARGE-AF covariates. An in and outpatient electrocardiographic database was interrogated from 2000 to 2013 for the development of AF. Patients were included if their age was >45 and <95 years, had <10-year follow-up, if their initial electrocardiogram was without AF, had ≥ 2 electrocardiograms, and declared a race and/or ethnicity as non-Hispanic white, African-American, or Hispanic. For the Framingham Heart Study, 49,599 patients met inclusion criteria, of which 4,860 developed AF. Discrimination analysis using area under the curve (AUC) for original risk equations: non-Hispanic white AUC = 0.712 (95% confidence interval [CI] 0.694 to 0.731), African-American AUC = 0.733 (95% CI 0.716 to 0.751), and Hispanic AUC = 0.740 (95% CI 0.723 to 0.757). For the CHARGE-AF, 45,571 patients met inclusion criteria, of which 4,512 developed AF. Non-Hispanic white AUC = 0.673 (95% CI 0.652 to 0.694), African-American AUC = 0.706 (95% CI 0.685 to 0.727), and Hispanic AUC = 0.711 (95% CI 0.691 to 0.732). Calibration analysis showed qualitative similarities between cohorts. In conclusion, this is the first study to validate both the Framingham Heart Study and CHARGE-AF risk scores in both a Hispanic and African-American cohort. All models predicted AF well across all race and ethnic cohorts. PMID:26589820

  4. Microfluidic Pumps Containing Teflon [Trademark] AF Diaphragms

    NASA Technical Reports Server (NTRS)

    Willis, Peter; White, Victor; Grunthaner, Frank; Ikeda, Mike; Mathies, Richard A.

    2009-01-01

    Microfluidic pumps and valves based on pneumatically actuated diaphragms made of Teflon AF polymers are being developed for incorporation into laboratory-on-a-chip devices that must perform well over temperature ranges wider than those of prior diaphragm-based microfluidic pumps and valves. Other potential applications include implanted biomedical microfluidic devices, wherein the biocompatability of Teflon AF polymers would be highly advantageous. These pumps and valves have been demonstrated to function stably after cycling through temperatures from -125 to 120 C. These pumps and valves are intended to be successors to similar prior pumps and valves containing diaphragms made of polydimethylsiloxane (PDMS) [commonly known as silicone rubber]. The PDMS-containing valves ae designed to function stably only within the temperature range from 5 to 80 C. Undesirably, PDMS membranes are somwehat porous and retain water. PDMS is especially unsuitable for use at temperatures below 0 C because the formation of ice crystals increases porosity and introduces microshear.

  5. Anticoagulation for the prevention of stroke in non-valvular AF in general practice: room for improvement

    PubMed Central

    Ioannou, Adam; Metaxa, Sofia; Kassianos, George; Missouris, Constantinos G.

    2016-01-01

    Objective: Our aim was to assess whether the recommendations and guidelines for thromboprophylaxis in patients with atrial fibrillation (AF) have been adopted in general practice (GP). Methods: We conducted a retrospective study using the GP computer database (Hatfield, UK) on all 9400 patients to assess the quality of anticoagulation in patients with a recorded diagnosis of AF. Results: Of the 180 patients with a diagnosis of AF, 107 (59.4%) were treated with warfarin, 19 (10.6%) with a novel oral anticoagulant (NOAC), 31 (17.2%) with aspirin or clopidogrel, and 23 (12.8%) received none. Thirty-seven patients (34.6%) who were taking warfarin had a time in the therapeutic range (TTR) of less than 65%. Forty-five (27.6%) of the 163 patients who had a CHA2DS2VASc score of two or more were not prescribed a vitamin K antagonist (VKA) or a NOAC. None had a HAS-BLED greater than the CHA2DS2VASc score. Conclusion: Our study demonstrates that one in four patients with non-valvular AF, at risk of a stroke, is not being adequately treated with an oral anticoagulant in primary care. The majority were treated with warfarin, a third of which had a low TTR. A high proportion of patients are prescribed antiplatelet therapy instead. This is despite overwhelming evidence that VKAs and NOACs, and not aspirin or clopidogrel, improve outcome in patients with non-valvular AF. We suggest that a review of GP practice databases should be considered to identify patients with non-valvular AF, at risk of a disabling or fatal event, and measures taken to initiate anticoagulant therapy. PMID:27403193

  6. [Evaluation of the complementary drug Factor AF2 as a supportive agent in management of advanced urothelial carcinoma. Prospective randomized multicenter study].

    PubMed

    Krege, S; Hinke, A; Otto, T; Rübben, H

    2002-03-01

    This is a prospective randomized multicenter trial for evaluation of the biological response modifier Factor AF2 in advanced urothelial cancer treated with chemotherapy. Main aim of the study was the analysis of supportive effects. Additionally patients were examined with regard to tumor response, time to progression and survival. 106 patients with advanced urothelial cancer received chemotherapy with cisplatin and methotrexate. They were randomized for additional Factor AF2 (500 mg i.v., given at days 0-3, 7-10 and 11-14). Myelotoxicity was more common and severe in the group without Factor AF2 reaching statistical significance. Gastrointestinal side effects occurred in both groups, though grade III to IV toxicity was more common without Factor AF2. Overall remission rate was 38%, median survival 33 weeks, mean time to progression 20 weeks. There was no significant difference between the two groups with or without Factor AF2. PMID:11993095

  7. Helicobacter pylori infection in Chinese patients with atrial fibrillation

    PubMed Central

    Wang, De-Zhao; Chen, Wei; Yang, Song; Wang, Jun; Li, Qun; Fu, Qiang; Li, Shi-Jing; Chen, Bu-Xing

    2015-01-01

    Objective To explore the relationship between Helicobacter pylori (Hp) infection and atrial fibrillation (AF) in Chinese patients. Methods A total of 285 hospitalized patients with AF and 300 patients from Health Screening Center who matched age and sex with AF group were enrolled. AF patients were divided into two groups: the short-standing AF category (less than a year) and the long-standing AF category (more than a year). All patients had laboratory testing of 13C urea breath test, high-sensitive C-reactive protein (hs-CRP) and left atrial diameter (LAD). We analyzed the difference of these factors in all groups and explored the correlation between Hp infection and AF using logistic regression analysis. Results Both AF groups had more hypertension, diabetes, and Hp infection than the control group. The Hp value and the hs-CRP level in patients with long-standing AF were higher than those in the short-standing AF and the control groups (for Hp value: P<0.001 for both and for hs-CRP level: P=0.003, 0.002, respectively). The LAD of patients in the long-standing AF group was significantly larger than those in the short-standing AF group and control group (P=0.001 and P<0.001, respectively). The values of Hp, hs-CRP, and LAD in the long-standing AF category were significantly higher than those in the short-standing AF category (all P<0.05). After controlling the potential confounders, Hp value ≥4‰, hs-CRP >5 mg/L, and LAD >36 mm were significantly related to long-standing AF. Conclusion The values of Hp in patients with long-standing AF were significantly higher than those in short-standing AF and control groups. Hp δ value ≥4‰ is an independent predictor for long-standing AF. PMID:25960645

  8. An insertional mutagenesis screen identifies genes that cooperate with Mll-AF9 in a murine leukemogenesis model

    PubMed Central

    Bergerson, Rachel J.; Collier, Lara S.; Sarver, Aaron L.; Been, Raha A.; Lugthart, Sanne; Diers, Miechaleen D.; Zuber, Johannes; Rappaport, Amy R.; Nixon, Molly J.; Silverstein, Kevin A. T.; Fan, Danhua; Lamblin, Anne-Francoise J.; Wolff, Linda; Kersey, John H.; Delwel, Ruud; Lowe, Scott W.; O'Sullivan, M. Gerard; Kogan, Scott C.; Adams, David J.

    2012-01-01

    Patients with a t(9;11) translocation (MLL-AF9) develop acute myeloid leukemia (AML), and while in mice the expression of this fusion oncogene also results in the development of myeloid leukemia, it is with long latency. To identify mutations that cooperate with Mll-AF9, we infected neonatal wild-type (WT) or Mll-AF9 mice with a murine leukemia virus (MuLV). MuLV-infected Mll-AF9 mice succumbed to disease significantly faster than controls presenting predominantly with myeloid leukemia while infected WT animals developed predominantly lymphoid leukemia. We identified 88 candidate cancer genes near common sites of proviral insertion. Analysis of transcript levels revealed significantly elevated expression of Mn1, and a trend toward increased expression of Bcl11a and Fosb in Mll-AF9 murine leukemia samples with proviral insertions proximal to these genes. Accordingly, FOSB and BCL11A were also overexpressed in human AML harboring MLL gene translocations. FOSB was revealed to be essential for growth in mouse and human myeloid leukemia cells using shRNA lentiviral vectors in vitro. Importantly, MN1 cooperated with Mll-AF9 in leukemogenesis in an in vivo BM viral transduction and transplantation assay. Together, our data identified genes that define transcription factor networks and important genetic pathways acting during progression of leukemia induced by MLL fusion oncogenes. PMID:22427200

  9. 4:2:1 conduction of an AF initiating trigger

    PubMed Central

    Kojodjojo, Pipin; Chong, Eric; Lim, Toon Wei; Seow, Swee Chong

    2015-01-01

    A 44 year old male with idiopathic dilated cardiomyopathy was undergoing persistent atrial fibrillation (AF) ablation. Following antral ablation, AF terminated into a regular narrow complex rhythm. Earliest activation was mapped to a focus in the superior vena cava (SVC) which was conducted in a 2:1 ratio to the atria which in turn was conducted with 2:1 ratio to the ventricles, resulting in an unusual 4:2:1 conduction of the SVC tachycardia. 1:1 conduction of the SVC tachycardia to the atrium preceded initiation of AF. During AF, SVC tachycardia continued unperturbed. Sinus rhythm was restored following catheter ablation of the focus. PMID:27134438

  10. Stroke prevention in atrial fibrillation and ‘real world’ adherence to guidelines in the Balkan Region: The BALKAN-AF Survey

    PubMed Central

    Potpara, Tatjana S.; Dan, Gheorghe-Andrei; Trendafilova, Elina; Goda, Artan; Kusljugic, Zumreta; Manola, Sime; Music, Ljilja; Musetescu, Rodica; Badila, Elisabeta; Mitic, Gorana; Paparisto, Vilma; Dimitrova, Elena S.; Polovina, Marija M.; Petranov, Stanislav L.; Djergo, Hortensia; Loncar, Daniela; Bijedic, Amira; Brusich, Sandro; Lip, Gregory Y. H.; Potpara, Tatjana S.; Polovina, Marija; Milanov, Srdjan; Pavlovic, Marija; Petrovic, Marijana; Simovic, Stefan; Mitic, Gorana; Milanov, Marko; Savic, Jelena; Gnip, Sanja; Radovic, Pavica; Markovic, Snezana; Koncarevic, Ivana; Gavrilovic, Jelena; Acimovic, Tijana; Djikic, Dijana; Malic, Semir; Hodzic, Jusuf; Stojanovic, Milovan; Ilic, Marina Deljanin; Zlatar, Milan; Matic, Dragan; Lazic, Snezana; Peric, Vladan; Markovic, Sanja; Kovacevic, Snezana; Arandjelovic, Aleksandra; Asanin, Milika; Zdravkovic, Marija; Dan, Gheorghe-Andrei; Breha, Anca; Dan, Anca Rodica; Musetescu, Rodica; Popescu, Mircea Ioachim; Badila, Elisabeta; Georgescu, Catalina Arsenescu; Pop, Sorina; Popescu, Raluca; Neamtu, Simina; Oancea, Floriana; Trendafilova, Elina; Dimitrova, Elena; Goshev, Evgenii; Velichkova, Anna; Petranov, Stanislav; Kamenova, Delyana; Kamenova, Penka; Elefterova, Svetoslava; Shterev, Valentin; Zekova, Maria; Diukiandzhieva, Stela; Dimitrov, Boiko; Sotirov, Tihomir; Simeonova, Valentina; Drianovska, Dimitrina; Boiadzhieva, Liliya Ivanova Vasileva; Buchukova, Darina; Goda, Artan; Paparisto, Vilma; Gjergo, Hortensia; Mijo, Alma; Shirka, Ervina; Gjini, Viktor; Ekmekciu, Uliks; Refatllari, Ina; Kusljugic, Zumreta; Loncar, Daniela; Mrsic, Denis; Tulumovic, Hazim; Pojskic, Belma; Sijamija, Alma; Bijedic, Amira; Karamujic, Indira; Bijedic, Irma; Halilovic, Sanela; Sokolovic, Sekib; Manola, Sime; Zeljkovic, Ivan; Pavlovic, Nikola; Radeljic, Vjekoslav; Brusich, Sandro; Anic, Ante; Jeric, Melita; Pekic, Petar; Milas, Kresimir; Music, Ljilja; Bulatovic, Nebojsa; Nenezic, Ana; Asanovic, Dijana

    2016-01-01

    Data on the management of atrial fibrillation (AF) in the Balkan Region are limited. The Serbian AF Association (SAFA) prospectively investigated contemporary ‘real-world’ AF management in clinical practice in Albania, Bosnia&Herzegovina, Bulgaria, Croatia, Montenegro, Romania and Serbia through a 14-week (December 2014-February 2015) prospective, multicentre survey of consecutive AF patients. We report the results pertinent to stroke prevention strategies. Of 2712 enrolled patients, 2663 (98.2%) with complete data were included in this analysis (mean age 69.1 ± 10.9 years, female 44.6%). Overall, 1960 patients (73.6%) received oral anticoagulants (OAC) and 762 (28.6%) received antiplatelet drugs. Of patients given OAC, 17.2% received non-vitamin K antagonist oral anticoagulants (NOACs). CHA2DS2-VASc score was not significantly associated with OAC use. Of the ‘truly low-risk’ patients (CHA2DS2-VASc = 0 [males], or 1 [females]) 56.5% received OAC. Time in Therapeutic Range (TTR) was available in only 18.7% of patients (mean TTR: 49.5% ± 22.3%). Age ≥ 80 years, prior myocardial infarction and paroxysmal AF were independent predictors of OAC non-use. Our survey shows a relatively high overall use of OAC in AF patients, but with low quality of vitamin K antagonist therapy and insufficient adherence to AF guidelines. Additional efforts are needed to improve AF-related thromboprophylaxis in clinical practice in the Balkan Region. PMID:26869284

  11. AF4 and AF4N protein complexes: recruitment of P-TEFb kinase, their interactome and potential functions

    PubMed Central

    Scholz, Bastian; Kowarz, Eric; Rössler, Tanja; Ahmad, Khalil; Steinhilber, Dieter; Marschalek, Rolf

    2015-01-01

    AF4/AFF1 and AF5/AFF4 are the molecular backbone to assemble “super-elongation complexes” (SECs) that have two main functions: (1) control of transcriptional elongation by recruiting the positive transcription elongation factor b (P-TEFb = CyclinT1/CDK9) that is usually stored in inhibitory 7SK RNPs; (2) binding of different histone methyltransferases, like DOT1L, NSD1 and CARM1. This way, transcribed genes obtain specific histone signatures (e.g. H3K79me2/3, H3K36me2) to generate a transcriptional memory system. Here we addressed several questions: how is P-TEFb recruited into SEC, how is the AF4 interactome composed, and what is the function of the naturally occuring AF4N protein variant which exhibits only the first 360 amino acids of the AF4 full-length protein. Noteworthy, shorter protein variants are a specific feature of all AFF protein family members. Here, we demonstrate that full-length AF4 and AF4N are both catalyzing the transition of P-TEFb from 7SK RNP to their N-terminal domain. We have also mapped the protein-protein interaction network within both complexes. In addition, we have first evidence that the AF4N protein also recruits TFIIH and the tumor suppressor MEN1. This indicate that AF4N may have additional functions in transcriptional initiation and in MEN1-dependend transcriptional processes. PMID:26171280

  12. Racial Differences in Quality of Anticoagulation Therapy for Atrial Fibrillation (from the TREAT-AF Study).

    PubMed

    Yong, Celina; Azarbal, Farnaz; Abnousi, Freddy; Heidenreich, Paul A; Schmitt, Susan; Fan, Jun; Than, Claire T; Ullal, Aditya J; Yang, Felix; Phibbs, Ciaran S; Frayne, Susan M; Ho, P Michael; Shore, Supriya; Mahaffey, Kenneth W; Turakhia, Mintu P

    2016-01-01

    The influence of race on quality of anticoagulation control is not well described. We examined the association between race, international normalized ratio (INR) monitoring intensity, and INR control in warfarin-treated patients with atrial fibrillation (AF). Using data from the Veterans Health Administration (VHA), we performed a retrospective cohort study of 184,161 patients with a new diagnosis of AF/flutter from 2004 to 2012 who received any VHA prescription within 90 days of diagnosis. The primary predictor was race, ascertained from multiple VHA and linked Medicare demographic files. The primary outcome was first-year and long-term time in therapeutic range (TTR) of INR 2.0 to 3.0. Secondary outcomes were INR monitoring intensity and warfarin persistence. Of the 116,021 patients who received warfarin in the cohort, INR monitoring intensity was similar across racial groups. However, TTR was lowest in blacks and highest in whites (first year 0.49 ± 0.23 vs 0.57 ± 0.21, p <0.001; long term 0.52 ± 0.20 vs 0.59 ± 0.18, p <0.001); 64% of whites and 49% of blacks had long-term TTR >55% (p <0.001). After adjusting for site and patient-level covariates, black race was associated with lower first-year and long-term TTRs (4.2% and 4.1% below the conditional mean, relative to whites; p <0.0001 for both). One-year warfarin persistence was slightly lower in blacks compared to whites (58% vs 60%, p <0.0001). In conclusion, in patients with AF anticoagulated with warfarin, differences in INR control are most evident among blacks, underscoring the need to determine if other types of intensive management or warfarin alternatives may be necessary to improve anticoagulation among vulnerable AF populations. PMID:26552504

  13. 7 CFR Exhibits A-F to Subpart A... - [Reserved

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 14 2013-01-01 2013-01-01 false A Exhibits A-F to Subpart A of Part 1955 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS-COOPERATIVE... Real and Chattel Property Exhibits A-F to Subpart A of Part 1955...

  14. 7 CFR Exhibits A-F to Subpart A... - [Reserved

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 14 2012-01-01 2012-01-01 false A Exhibits A-F to Subpart A of Part 1955 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS-COOPERATIVE... Real and Chattel Property Exhibits A-F to Subpart A of Part 1955...

  15. 7 CFR Exhibits A-F to Subpart A... - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 14 2010-01-01 2009-01-01 true A Exhibits A-F to Subpart A of Part 1955 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS-COOPERATIVE... Real and Chattel Property Exhibits A-F to Subpart A of Part 1955...

  16. 7 CFR Exhibits A-F to Subpart A... - [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 14 2011-01-01 2011-01-01 false A Exhibits A-F to Subpart A of Part 1955 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS-COOPERATIVE... Real and Chattel Property Exhibits A-F to Subpart A of Part 1955...

  17. 7 CFR Exhibits A-F to Subpart A... - [Reserved

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 14 2014-01-01 2014-01-01 false A Exhibits A-F to Subpart A of Part 1955 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS-COOPERATIVE... Real and Chattel Property Exhibits A-F to Subpart A of Part 1955...

  18. Part III: AFS - A Secure Distributed File System

    SciTech Connect

    Wachsmann, A.; /SLAC

    2005-06-29

    AFS is a secure distributed global file system providing location independence, scalability and transparent migration capabilities for data. AFS works across a multitude of Unix and non-Unix operating systems and is used at many large sites in production for many years. AFS still provides unique features that are not available with other distributed file systems even though AFS is almost 20 years old. This age might make it less appealing to some but with IBM making AFS available as open-source in 2000, new interest in use and development was sparked. When talking about AFS, people often mention other file systems as potential alternatives. Coda (http://www.coda.cs.cmu.edu/) with its disconnected mode will always be a research project and never have production quality. Intermezzo (http://www.inter-mezzo.org/) is now in the Linux kernel but not available for any other operating systems. NFSv4 (http://www.nfsv4.org/) which picked up many ideas from AFS and Coda is not mature enough yet to be used in serious production mode. This article presents the rich features of AFS and invites readers to play with it.

  19. Toward a petabyte-scale AFS service at CERN

    NASA Astrophysics Data System (ADS)

    van der Ster, Daniel; Moscicki, Jakub T.; Wiebalck, Arne

    2014-06-01

    AFS is a mature and reliable storage service at CERN, having worked for more than 20 years as the provider of Unix home directories and project areas. Recently, the AFS service has grown at unprecedented rates (200% in the past year); this growth was unlocked thanks to innovations in both the hardware and software components of our file servers. This work presents how AFS is used at CERN and how the service offering is evolving with the increasing storage needs of its local and remote user communities. In particular, we demonstrate the usage patterns for home directories, workspaces and project spaces, as well as show the daily work which is required to rebalance data and maintaining stability and performance. Finally, we highlight some recent changes and optimisations made to the AFS Service, thereby revealing how AFS can possibly operate at all while being subjected to frequent-almost DDOS-like-attacks from its users.

  20. An Implicit LU/AF FDTD Method

    NASA Technical Reports Server (NTRS)

    Beggs, John H.; Briley, W. Roger

    2001-01-01

    There has been some recent work to develop two and three-dimensional alternating direction implicit (ADI) FDTD schemes. These ADI schemes are based upon the original ADI concept developed by Peaceman and Rachford and Douglas and Gunn, which is a popular solution method in Computational Fluid Dynamics (CFD). These ADI schemes work well and they require solution of a tridiagonal system of equations. A new approach proposed in this paper applies a LU/AF approximate factorization technique from CFD to Maxwell s equations in flux conservative form for one space dimension. The result is a scheme that will retain its unconditional stability in three space dimensions, but does not require the solution of tridiagonal systems. The theory for this new algorithm is outlined in a one-dimensional context for clarity. An extension to two and threedimensional cases is discussed. Results of Fourier analysis are discussed for both stability and dispersion/damping properties of the algorithm. Results are presented for a one-dimensional model problem, and the explicit FDTD algorithm is chosen as a convenient reference for comparison.

  1. The AF4-mimetic peptide, PFWT, induces necrotic cell death in MV4-11 leukemia cells

    PubMed Central

    Palermo, Christine M.; Bennett, Cecily A.; Winters, Amanda C.; Hemenway, Charles S.

    2008-01-01

    Despite ongoing success in the treatment of childhood acute lymphoblastic leukemia, patients harboring translocations involving the MLL gene at chromosome 11q23 remain resistant to treatment. To improve outcomes, novel therapeutics designed to target the unusual biology of these leukemias need to be developed. Previously, we identified an interaction between the two most common MLL fusion proteins, AF4 and AF9, and designed a synthetic peptide (PFWT) capable of disrupting this interaction. PFWT induced cell death in leukemia cells expressing MLL-AF4 with little effect on the colony forming potential of hematopoietic progenitor cells, suggesting the AF4–AF9 complex is an important pharmacological target for leukemia therapy and PFWT is a promising chemotherapeutic prototype. In these studies, we demonstrate that PFWT induces death by necrosis in MV4-11 cells. Cell death is characterized by rapid loss of plasma membrane integrity with maintenance of nuclear membrane integrity, and is independent of caspase activation, DNA fragmentation, and mitochondrial membrane depolarization. PFWT-mediated necrosis is inhibited by the serine protease inhibitor TLCK, suggesting this death pathway is regulated. Given the resistance of t(4;11) leukemias to conventional chemotherapeutic agents that induce apoptosis, further identification of the molecular events mediating this death process should uncover new avenues for therapeutic intervention. PMID:17875318

  2. Prevention of Obesity and Insulin Resistance by Estrogens Requires ERα Activation Function-2 (ERαAF-2), Whereas ERαAF-1 Is Dispensable

    PubMed Central

    Handgraaf, Sandra; Riant, Elodie; Fabre, Aurélie; Waget, Aurélie; Burcelin, Rémy; Lière, Philippe; Krust, Andrée; Chambon, Pierre; Arnal, Jean-François; Gourdy, Pierre

    2013-01-01

    The beneficial metabolic actions of estrogen-based therapies are mainly mediated by estrogen receptor α (ERα), a nuclear receptor that regulates gene transcription through two activation functions (AFs): AF-1 and AF-2. Using mouse models deleted electively for ERαAF-1 (ERαAF-1°) or ERαAF-2 (ERαAF-2°), we determined their respective roles in the actions of estrogens on body composition and glucose homeostasis in response to either a normal diet or a high-fat diet (HFD). ERαAF-2° males and females developed accelerated weight gain, massive adiposity, severe insulin resistance, and glucose intolerance—quite reminiscent of the phenotype observed in mice deleted for the entire ERα protein (ERα−/−). In striking contrast, ERαAF-1° and wild-type (wt) mice shared a similar metabolic phenotype. Accordingly, 17β-estradiol administration regulated key metabolic genes in insulin-sensitive tissues and conferred a strong protection against HFD-induced metabolic disturbances in wt and ERαAF-1° ovariectomized mice, whereas these actions were totally abrogated in ERαAF-2° and ERα−/− mice. Thus, whereas both AFs have been previously shown to contribute to endometrial and breast cancer cell proliferation, the protective effect of estrogens against obesity and insulin resistance depends on ERαAF-2 but not ERαAF-1, thereby delineating new options for selective modulation of ERα. PMID:23903353

  3. A Comparison of Atrial Fibrillation Monitoring Strategies After Cryptogenic Stroke (from the Cryptogenic Stroke and Underlying AF Trial).

    PubMed

    Choe, William C; Passman, Rod S; Brachmann, Johannes; Morillo, Carlos A; Sanna, Tommaso; Bernstein, Richard A; Di Lazzaro, Vincenzo; Diener, Hans-Christoph; Rymer, Marilyn M; Beckers, Frank; Koehler, Jodi; Ziegler, Paul D

    2015-09-15

    Ischemic stroke cause remains undetermined in 30% of cases, leading to a diagnosis of cryptogenic stroke. Paroxysmal atrial fibrillation (AF) is a major cause of ischemic stroke but may go undetected with short periods of ECG monitoring. The Cryptogenic Stroke and Underlying Atrial Fibrillation trial (CRYSTAL AF) demonstrated that long-term electrocardiographic monitoring with insertable cardiac monitors (ICM) is superior to conventional follow-up in detecting AF in the population with cryptogenic stroke. We evaluated the sensitivity and negative predictive value (NPV) of various external monitoring techniques within a cryptogenic stroke cohort. Simulated intermittent monitoring strategies were compared to continuous rhythm monitoring in 168 ICM patients of the CRYSTAL AF trial. Short-term monitoring included a single 24-hour, 48-hour, and 7-day Holter and 21-day and 30-day event recorders. Periodic monitoring consisted of quarterly monitoring through 24-hour, 48-hour, and 7-day Holters and monthly 24-hour Holters. For a single monitoring period, the sensitivity for AF diagnosis was lowest with a 24-hour Holter (1.3%) and highest with a 30-day event recorder (22.8%). The NPV ranged from 82.3% to 85.6% for all single external monitoring strategies. Quarterly monitoring with 24-hour Holters had a sensitivity of 3.1%, whereas quarterly 7-day monitors increased the sensitivity to 20.8%. The NPVs for repetitive periodic monitoring strategies were similar at 82.6% to 85.3%. Long-term continuous monitoring was superior in detecting AF compared to all intermittent monitoring strategies evaluated (p <0.001). Long-term continuous electrocardiographic monitoring with ICMs is significantly more effective than any of the simulated intermittent monitoring strategies for identifying AF in patients with previous cryptogenic stroke. PMID:26183793

  4. Predictors of Atrial Fibrillation Recurrence in Hyperthyroid and Euthyroid Patients

    PubMed Central

    Gürdoğan, Muhammet; Ari, Hasan; Tenekecioğlu, Erhan; Arı, Selma; Bozat, Tahsin; Koca, Vedat; Melek, Mehmet

    2016-01-01

    Background Atrial fibrillation (AF) is the most common arrhythmia in adults, and is encountered in 10-15% of the patients with hyperthyroidism. Unless euthyroidism is restored, pharmacological or electrical cardioversion is controversial in patients with AF who remain hyperthyroid. Objective The aim of this study was to assess the efficacy of electrical cardioversion and predictors of AF recurrence in hyperthyroid and euthyroid patients. Methods The study included 33 hyperthyroid (21 males) and 48 euthyroid (17 males) patients with persistent AF. The patients were sedated with intravenous midazolam before undergoing electrical cardioversion delivered by synchronized biphasic shocks. Rates of AF recurrence were recorded. Results Mean follow-up was 23.63 ± 3.74 months in the hyperthyroid group and 22.78 ± 3.15 months in the euthyroid group (p = 0.51). AF recurred in 14 (43.8%) and 21 (44.7%) patients in each group, respectively (p = 0.93). Multivariate regression analysis in each group showed that AF duration was the only predictor of AF recurrence, with odds ratios of 1.38 (95% confidence interval [CI] = 1.05 - 1.82, p = 0.02) in the hyperthyroid group and 1.42 (95% CI = 1.05 - 1.91, p= 0.02) in the euthyroid group. Conclusion Rates of long-term AF recurrence were similar in successfully cardioverted hyperthyroid and euthyroid patients. The only predictor of AF recurrence in both groups was AF duration. PMID:26815460

  5. Tuning the Music: Acoustic Force Spectroscopy (AFS) 2.0.

    PubMed

    Kamsma, Douwe; Creyghton, Ramon; Sitters, Gerrit; Wuite, Gijs J L; Peterman, Erwin J G

    2016-08-01

    AFS is a recently introduced high-throughput single-molecule technique that allows studying structural and mechanochemical properties of many biomolecules in parallel. To further improve the method, we developed a modelling tool to optimize the layer thicknesses, and a calibration method to experimentally validate the modelled force profiles. After optimization, we are able to apply 350pN on 4.5μm polystyrene beads, without the use of an amplifier, at the coverslip side of the AFS chip. Furthermore, we present the use of a transparent piezo to generate the acoustic force and we show that AFS can be combined with high-NA oil or water-immersion objectives. With this set of developments AFS will be applicable to a broad range of single-molecule experiments. PMID:27163865

  6. Quantification of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL) using amplicon-fusion-site polymerase chain reaction (AFS-PCR)

    PubMed Central

    2012-01-01

    The amplification of putative oncogenes is a common finding within the genome of various cancer types. Identification and further targeting of specific junction sites within the sequence of genomic amplicons (amplicon fusion sites, AFS) by PCR (AFS-PCR) is suitable for quantification of minimal residual disease (MRD). This approach has recently been developed and described for MYCN amplified neuroblastomas. To compare AFS-PCR directly to routinely used MRD diagnostic strategies, we mapped the amplified genomic regions (ampGR) of an iAMP21-amplicon in high resolution of a patient with acute lymphoblastic leukemia (ALL). Successfully, we established AFS-PCR covering junction sites between ampGR within the iAMP21-amplicon. Quantification of MRD by AFS-PCR was directly comparable to IgH/TCR based real time quantitative PCR and fluorescence activated cell sorting (FACS) analysis in consecutive bone marrow (BM) specimens. Our data give an additional proof of concept of AFS-PCR for quantification of MRD. The method could be taken into account for ALL patients with genomic amplifications as alternative MRD diagnostic, if no or qualitatively poor Ig/TCR-PCRs are available. PMID:23210797

  7. Prognosis in patients hospitalized with permanent and nonpermanent atrial fibrillation in heart failure.

    PubMed

    Taillandier, Sophie; Brunet Bernard, Anne; Lallemand, Benedicte; Simeon, Edouard; Pericart, Lauriane; Clementy, Nicolas; Babuty, Dominique; Fauchier, Laurent

    2014-04-01

    Atrial fibrillation (AF) and heart failure (HF) frequently coexist and are associated with an increased mortality. This study evaluated the prognosis of permanent and nonpermanent AF in patients with both AF and HF. All AF patients seen in our institution were identified and followed up. We included 1,906 patients suffering from AF and HF: 839 patients (44%) had preserved left ventricular ejection fraction (LVEF) and 1,067 patients (56%) had decreased LVEF; 1,056 patients (55%) had nonpermanent AF and 850 patients (45%) had permanent AF. During a median follow-up of 1.9 years (interquartile range 0.3 to 5.0), 377 patients died, 462 were readmitted for HF, and 200 had stroke or thromboembolic events. In patients with decreased LVEF, the rate of death was similar in patients with permanent or nonpermanent AF. In patients with preserved LVEF, permanent AF was associated with a higher risk of death and a higher risk of HF hospitalization. Stroke risk did not differ with permanent AF whatever the LVEF. NYHA functional class was an independent predictor of death (risk ratio [RR]=1.33, 95% confidence interval [CI] 1.12 to 1.59, p=0.001), as was permanent AF (RR=1.79, 95%CI 1.32 to 2.42, p=0.0002). Permanent AF (RR=1.52, 95% CI 1.20 to 1.93, p=0.0006) was also an independent predictor of readmission for HF. In conclusion, in patients with AF and HF, the risk of admission for HF and risk of death were higher when AF was permanent, particularly in patients with preserved LVEF. Stroke risk did not differ according to the pattern of AF, whatever the LVEF. PMID:24507167

  8. Dual-chamber implantable cardioverter-defibrillator. Is it useful in patient with permanent atrial fibrillation?

    PubMed

    Porres-Aracama, José M; Cerezuela, José Luis; García-Urra, Francisco; Luque-Lezcano, Oscar; Herrero, Vicente

    2016-08-01

    In patients with permanent atrial fibrillation (AF) and implantable cardioverter-defibrillator (ICD) implant indication, a single-chamber device is the choice because AF does not provide interesting information for the treatment. It is very unusual to find patients with permanent AF that coexist with atrial tachycardia with various degree of Atrioventricular block. PMID:27525075

  9. Feasibility and cost-effectiveness of stroke prevention through community screening for atrial fibrillation using iPhone ECG in pharmacies. The SEARCH-AF study.

    PubMed

    Lowres, Nicole; Neubeck, Lis; Salkeld, Glenn; Krass, Ines; McLachlan, Andrew J; Redfern, Julie; Bennett, Alexandra A; Briffa, Tom; Bauman, Adrian; Martinez, Carlos; Wallenhorst, Christopher; Lau, Jerrett K; Brieger, David B; Sy, Raymond W; Freedman, S Ben

    2014-06-01

    Atrial fibrillation (AF) causes a third of all strokes, but often goes undetected before stroke. Identification of unknown AF in the community and subsequent anti-thrombotic treatment could reduce stroke burden. We investigated community screening for unknown AF using an iPhone electrocardiogram (iECG) in pharmacies, and determined the cost-effectiveness of this strategy.Pharmacists performedpulse palpation and iECG recordings, with cardiologist iECG over-reading. General practitioner review/12-lead ECG was facilitated for suspected new AF. An automated AF algorithm was retrospectively applied to collected iECGs. Cost-effectiveness analysis incorporated costs of iECG screening, and treatment/outcome data from a United Kingdom cohort of 5,555 patients with incidentally detected asymptomatic AF. A total of 1,000 pharmacy customers aged ≥65 years (mean 76 ± 7 years; 44% male) were screened. Newly identified AF was found in 1.5% (95% CI, 0.8-2.5%); mean age 79 ± 6 years; all had CHA2DS2-VASc score ≥2. AF prevalence was 6.7% (67/1,000). The automated iECG algorithm showed 98.5% (CI, 92-100%) sensitivity for AF detection and 91.4% (CI, 89-93%) specificity. The incremental cost-effectiveness ratio of extending iECG screening into the community, based on 55% warfarin prescription adherence, would be $AUD5,988 (€3,142; $USD4,066) per Quality Adjusted Life Year gained and $AUD30,481 (€15,993; $USD20,695) for preventing one stroke. Sensitivity analysis indicated cost-effectiveness improved with increased treatment adherence.Screening with iECG in pharmacies with an automated algorithm is both feasible and cost-effective. The high and largely preventable stroke/thromboembolism risk of those with newly identified AF highlights the likely benefits of community AF screening. Guideline recommendation of community iECG AF screening should be considered. PMID:24687081

  10. AF-GEOSpace Version 2.5: Space Environment Software

    NASA Astrophysics Data System (ADS)

    Hilmer, R. V.; Hall, T.; Roth, C.; Ling, A.; Ginet, G. P.; Madden, D.

    2010-12-01

    AF-GEOSpace is a graphics-intensive software program with space environment models and applications developed by the Space Weather Center of Excellence at AFRL. The software addresses a wide range of physical domains, e.g., solar disturbance propagation, geomagnetic field and radiation belt configurations, auroral particle precipitation, and ionospheric scintillation. AF-GEOSpace has become a platform for developing and prototyping space weather visualization products. The new AF-GEOSpace Version 2.5 (release scheduled for 2010) expands on the content of Version 2.1 by including modules addressing the following new topics: (1) energetic proton maps for the South Atlantic Anomaly (from Ginet et al. [2007]), (2) GPS scintillation outage simulation tools, (3) magnetopause location determination (Shue et al. [1998]), (4) a plasmasphere model (Global Core Plasma Model, 2009 version based on Gallagher et al. [2000]), (5) a standard ionospheric model (International Reference Ionosphere 2007), (6) the CAMMICE/MICS model of inner magnetosphere plasma population (based on Roeder et al. [2005]), (7) magnetic field models (e.g., Tsyganenko and Sitnov [2005]), and (8) loading and displaying externally-produced 3D gridded data sets within AF-GEOSpace. Improvements to existing Version 2.1 capabilities include: (1) a 2005 update to the geomagnetic cutoff rigidity model of Smart and Shea [2003], (2) a 2005 update to the ionospheric scintillation Wide-Band Model (WBMOD) of Secan and Bussey [1994], and (3) improved magnetic field flux mapping options for the existing set of AF-GEOSpace radiation belt models. A basic review of these new AF-GEOSpace capabilities will be provided. To obtain a copy of the software, please contact the first author.

  11. AF-GEOSpace Version 2.1 Release

    NASA Astrophysics Data System (ADS)

    Hilmer, R. V.; Ginet, G. P.; Hall, T.; Holeman, E.; Madden, D.; Perry, K. L.; Tautz, M.; Roth, C.

    2006-05-01

    AF-GEOSpace Version 2.1 is a graphics-intensive software program with space environment models and applications developed recently by the Space Weather Center of Excellence at AFRL. A review of new and planned AF-GEOSpace capabilities will be given. The software addresses a wide range of physical domains and addresses such topics as solar disturbance propagation, geomagnetic field and radiation belt configurations, auroral particle precipitation, and ionospheric scintillation. Building on the success of previous releases, AF-GEOSpace has become a platform for the rapid prototyping of automated operational and simulation space weather visualization products and helps with a variety of tasks, including: orbit specification for radiation hazard avoidance; satellite design assessment and post-event anomaly analysis; solar disturbance effects forecasting; determination of link outage regions for active ionospheric conditions; satellite magnetic conjugate studies, scientific model validation and comparison, physics research, and education. Previously, Version 2.0 provided a simplified graphical user interface, improved science and application modules, significantly enhanced graphical performance, common input data archive sets, and 1-D, 2-D, and 3- D visualization tools for all models. Dynamic capabilities permit multiple environments to be generated at user- specified time intervals while animation tools enable the display of satellite orbits and environment data together as a function of time. Building on the Version 2.0 software architecture, AF-GEOSpace Version 2.1 includes a host of new modules providing, for example, plasma sheet charged particle fluxes, neutral atmosphere densities, 3-D cosmic ray cutoff maps, low-altitude trapped proton belt flux specification, DMSP particle data displays, satellite magnetic field footprint mapping determination, and meteor sky maps and shower/storm fluxes with spacecraft impact probabilities. AF-GEOSpace Version 2.1 was

  12. GPIM AF-M315E Propulsion System

    NASA Technical Reports Server (NTRS)

    Spores, Ronald A.; Masse, Robert; Kimbrel, Scott; McLean, Chris

    2014-01-01

    The NASA Space Technology mission Directorate's (STMD) Green Propellant Infusion Mission (GPIM) Technology Demonstration Mission (TDM) will demonstrate an operational AF-M315E green propellant propulsion system. Aerojet-Rocketdyne is responsible for the development of the propulsion system payload. This paper statuses the propulsion system module development, including thruster design and system design; Initial test results for the 1N engineering model thruster are presented. The culmination of this program will be high-performance, green AF-M315E propulsion system technology at TRL 7+, with components demonstrated to TRL 9, ready for direct infusion to a wide range of applications for the space user community.

  13. Molecular and functional identification of three interleukin-17A/F (IL-17A/F) homologues in large yellow croaker (Larimichthys crocea).

    PubMed

    Ding, Yang; Ao, Jingqun; Ai, Chunxiang; Chen, Xinhua

    2016-02-01

    The interleukin-17 (IL-17) cytokine family plays a central role in the coordination of inflammatory responses. In fish species, three genes that have a similar homology to both IL-17A and IL-17F were designated IL-17A/F1, 2, and 3. In this study, we identified three IL-17A/F homologues (LycIL-17A/F1, 2, and 3) from large yellow croaker (Larimichthys crocea). The deduced LycIL-17A/F1 and 3 had four cysteine residues conserved in teleost IL-17A/F1 and 3 homologues and shared a domain similar to the B chain of human IL-17F. The deduced LycIL-17A/F2 possessed the unique arrangement of six cysteine residues as teleost IL-17A/F2 (except Fugu IL-17A/F2) and higher vertebrate IL-17A and F, and shared a domain similar to the D/E chain of human IL-17A. Phylogenetic analysis showed that teleost IL-17A/F1 and 3 fall into a major clade, whereas IL-17A/F2 forms a separated clade and is clustered with IL-17N. Based on structural and phylogenetic analyses, we suggest that teleost IL-17A/Fs may be classified into two subgroups: one consisting of IL-17A/F1 and 3, and the other composed of IL-17A/F2. The three LycIL-17A/Fs were constitutively expressed in all tissues examined although at a different level. Following challenge with Aeromonas hydrophila, expression of these three LycIL-17A/Fs was rapidly increased in head kidney and gills. The in vivo assays showed that recombinant LycIL-17A/F1, 2, and 3 all were able to enhance the expression of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α2), chemokines (CXCL8 and CXCL13), and antimicrobial peptide hepcidin in head kidney. Furthermore, LycIL-17A/Fs appeared to mediate pro-inflammatory responses via NF-κB signalling. These results therefore reveal similar functions between the two subgroup members,LycIL-17A/F1 and 3 and LycIL-17A/F2, in promoting inflammation and host defences. PMID:26429410

  14. An Empirical Test of Oklahoma's A-F School Grades

    ERIC Educational Resources Information Center

    Adams, Curt M.; Forsyth, Patrick B.; Ware, Jordan; Mwavita, Mwarumba; Barnes, Laura L.; Khojasteb, Jam

    2016-01-01

    Oklahoma is one of 16 states electing to use an A-F letter grade as an indicator of school quality. On the surface, letter grades are an attractive policy instrument for school improvement; they are seemingly clear, simple, and easy to interpret. Evidence, however, on the use of letter grades as an instrument to rank and improve schools is scant…

  15. R2 AIRS/AFS FACILITY GIS LAYER

    EPA Science Inventory

    The AFS subsystem contains emissions, compliance, and permit data for stationary sources regulated by the U.S. EPA and state and local air pollution agencies. This information is used by states in preparation of State Implementation Plans (SIPs), to track the compliance status ...

  16. R2 AIRS/AFS PERMITS GIS LAYER

    EPA Science Inventory

    The Region 2 AIRS/AFS Permits Regulated Facility GIS layer contains identification (name, address, ID), and location (latitude, longitude, and locational metadata), attributes of stationary source(s) of air pollution associated with facilities that are regulated by the U. S. EPA....

  17. Treatment Guidelines of Atrial Fibrillation (AFib or AF)

    MedlinePlus

    ... Pressure Tools & Resources Stroke More Treatment Guidelines of Atrial Fibrillation (AFib or AF) Updated:Jun 23,2016 What ... content was last reviewed on 04/16/14. Atrial Fibrillation • Introduction • What is Atrial Fibrillation? • Why AFib Matters • ...

  18. Extracting uranium from seawater: Promising AF series adsorbents

    SciTech Connect

    Das, Sadananda; Oyola, Y.; Mayes, Richard T.; Janke, Christopher James; Kuo, Li-Jung; Gill, Gary; Wood, Jordana; Dai, Sheng

    2015-11-02

    Here, a new family of high surface area polyethylene fiber adsorbents (AF series) was recently developed at the Oak Ridge National Laboratory (ORNL). The AF series of were synthesized by radiation-induced graft polymerization of acrylonitrile and itaconic acid (at different monomer/co-monomer mol ratios) onto high surface area polyethylene fibers. The degree of grafting (%DOG) of AF series adsorbents was found to be 154 354%. The grafted nitrile groups were converted to amidoxime groups by treating with hydroxylamine. The amidoximated adsorbents were then conditioned with 0.44M KOH at 80 C followed by screening at ORNL with simulated seawater spiked with 8 ppm uranium. Uranium adsorption capacity in simulated seawater screening ranged from 170-200 g-U/kg-ads irrespective of %DOG. A monomer/co-monomer mol ratio in the range of 7.57-10.14 seemed to be optimum for highest uranium loading capacity. Subsequently, the adsorbents were also tested with natural seawater at Pacific Northwest National Laboratory (PNNL) using flow-through exposure uptake experiments to determine uranium loading capacity with varying KOH conditioning time at 80 C. The highest adsorption capacity of AF1 measured after 56 days of marine testing was demonstrated as 3.9 g-U/kg-adsorbent and 3.2 g-U/kg-adsorbent for 1hr and 3hrs of KOH conditioning at 80 C, respectively. Based on capacity values of several AF1 samples, it was observed that changing KOH conditioning from 3hrs to 1hr at 80 C resulted in 22-27% increase in uranium loading capacity in seawater.

  19. Extracting uranium from seawater: Promising AF series adsorbents

    DOE PAGESBeta

    Das, Sadananda; Oyola, Y.; Mayes, Richard T.; Janke, Christopher James; Kuo, Li-Jung; Gill, Gary; Wood, Jordana; Dai, Sheng

    2015-11-02

    Here, a new family of high surface area polyethylene fiber adsorbents (AF series) was recently developed at the Oak Ridge National Laboratory (ORNL). The AF series of were synthesized by radiation-induced graft polymerization of acrylonitrile and itaconic acid (at different monomer/co-monomer mol ratios) onto high surface area polyethylene fibers. The degree of grafting (%DOG) of AF series adsorbents was found to be 154 354%. The grafted nitrile groups were converted to amidoxime groups by treating with hydroxylamine. The amidoximated adsorbents were then conditioned with 0.44M KOH at 80 C followed by screening at ORNL with simulated seawater spiked with 8more » ppm uranium. Uranium adsorption capacity in simulated seawater screening ranged from 170-200 g-U/kg-ads irrespective of %DOG. A monomer/co-monomer mol ratio in the range of 7.57-10.14 seemed to be optimum for highest uranium loading capacity. Subsequently, the adsorbents were also tested with natural seawater at Pacific Northwest National Laboratory (PNNL) using flow-through exposure uptake experiments to determine uranium loading capacity with varying KOH conditioning time at 80 C. The highest adsorption capacity of AF1 measured after 56 days of marine testing was demonstrated as 3.9 g-U/kg-adsorbent and 3.2 g-U/kg-adsorbent for 1hr and 3hrs of KOH conditioning at 80 C, respectively. Based on capacity values of several AF1 samples, it was observed that changing KOH conditioning from 3hrs to 1hr at 80 C resulted in 22-27% increase in uranium loading capacity in seawater.« less

  20. 32 CFR 989.12 - AF Form 813, Request for Environmental Impact Analysis.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... record the focusing of environmental issues. ... 32 National Defense 6 2010-07-01 2010-07-01 false AF Form 813, Request for Environmental Impact... FORCE ENVIRONMENTAL PROTECTION ENVIRONMENTAL IMPACT ANALYSIS PROCESS (EIAP) § 989.12 AF Form...

  1. 32 CFR 989.12 - AF Form 813, Request for Environmental Impact Analysis.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... record the focusing of environmental issues. ... 32 National Defense 6 2011-07-01 2011-07-01 false AF Form 813, Request for Environmental Impact... FORCE ENVIRONMENTAL PROTECTION ENVIRONMENTAL IMPACT ANALYSIS PROCESS (EIAP) § 989.12 AF Form...

  2. 32 CFR 989.12 - AF Form 813, Request for Environmental Impact Analysis.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... record the focusing of environmental issues. ... 32 National Defense 6 2013-07-01 2013-07-01 false AF Form 813, Request for Environmental Impact... FORCE ENVIRONMENTAL PROTECTION ENVIRONMENTAL IMPACT ANALYSIS PROCESS (EIAP) § 989.12 AF Form...

  3. Embossed Teflon AF Laminate Membrane Microfluidic Diaphragm Valves

    NASA Technical Reports Server (NTRS)

    Willis, Peter; Hunt, Brian; White,Victor; Grunthaner, Frank

    2008-01-01

    A microfluidic system has been designed to survive spaceflight and to function autonomously on the Martian surface. It manipulates microscopic quantities of liquid water and performs chemical analyses on these samples to assay for the presence of molecules associated with past or present living processes. This technology lies at the core of the Urey Instrument, which is scheduled for inclusion on the Pasteur Payload of the ESA ExoMars rover mission in 2013. Fabrication processes have been developed to make the microfabricated Teflon-AF microfluidic diaphragm pumps capable of surviving extreme temperature excursions before and after exposure to liquid water. Two glass wafers are etched with features and a continuous Teflon membrane is sandwiched between them (see figure). Single valves are constructed using this geometry. The microfabricated devices are then post processed by heating the assembled device while applying pneumatic pressure to force the Teflon diaphragm against the valve seat while it is softened. After cooling the device, the embossed membrane retains this new shape. This solves previous problems with bubble introduction into the fluid flow where deformations of the membrane at the valve seat occurred during device bonding at elevated temperatures (100-150 C). The use of laminated membranes containing commercial Teflon AF 2400 sheet sandwiched between spun Teflon AF 1600 layers performed best, and were less gas permeable than Teflon AF 1600 membranes on their own. Spinning Teflon AF 1600 solution (6 percent in FLOURINERT(Registered TradeMark) FC40 solvent, 3M Company) at 500 rpm for 1.5 seconds, followed by 1,000 rpm for 3 seconds onto Borofloat glass wafers, results in a 10-micron-thick film of extremely smooth Teflon AF. This spinning process is repeated several times on flat, blank, glass wafers in order to gradually build a thick, smooth membrane. After running this process at least five times, the wafer and Teflon coating are heated under vacuum

  4. Cox-Maze IV Results for Patients With Lone Atrial Fibrillation Versus Concomitant Mitral Disease

    PubMed Central

    Saint, Lindsey L.; Bailey, Marci S.; Prasad, Sunil; Guthrie, Tracey J.; Bell, Jennifer; Moon, Marc R.; Lawton, Jennifer S.; Munfakh, Nabil A.; Schuessler, Richard B.; Damiano, Ralph J.; Maniar, Hersh S.

    2012-01-01

    Background This study compared Cox-Maze IV (CMIV) outcomes for the treatment of atrial fibrillation (AF) in patients with lone AF vs those with AF and mitral valve (MV) disease. Methods Since 2002, 200 patients have undergone a CMIV procedure for lone AF (n = 101) or concomitantly with MV operations (n = 99). Preoperative, perioperative, and late outcomes between these groups were compared. Data were collected prospectively and reported at 3, 6, and 12 months. Results Lone AF patients had AF of longer duration; patients with AF and MV disease were older, with larger left atria and worse New York Heart Association classification (p < 0.05). Operative mortality (1% vs 4%, p > 0.05, respectively) was similar between both groups. Perioperative atrial tachyarrhythmias were more prevalent in patients with concomitant MV operations (57% vs 41%, p = 0.03); however, freedom from AF and antiar-rhythmics was similar for both groups at 12 months (76% and 77%). The only predictor for atrial tachyarrhythmia recurrence or arrhythmic drug dependence was failure to isolate the posterior left atrium (p < 0.01). Conclusions Patients with AF and MV disease have distinct comorbidities compared with patients with lone AF. However, the CMIV is safe and effective in both groups and should be considered for patients with AF undergoing MV operations. Patients with MV disease had more atrial tachyarrhythmias at 3 months, but freedom from AF and antiarrhythmics was similar to patients with lone AF at 1 year. The posterior left atrium should be isolated in every patient, because this was the only predictor for failure of the CMIV for either group. PMID:22305055

  5. Differential role of Id1 in MLL-AF9-driven leukemia based on cell of origin.

    PubMed

    Man, Na; Sun, Xiao-Jian; Tan, Yurong; García-Cao, Marta; Liu, Fan; Cheng, Guoyan; Hatlen, Megan; Xu, Haiming; Shah, Ronit; Chastain, Nolan; Liu, Na; Huang, Gang; Zhou, Yuan; Sheng, Mengyao; Song, Junhong; Yang, Feng-Chun; Benezra, Robert; Nimer, Stephen D; Wang, Lan

    2016-05-12

    Inhibitor of DNA binding 1 (Id1) functions as an E protein inhibitor, and overexpression of Id1 is seen in acute myeloid leukemia (AML) patients. To define the effects of Id1 on leukemogenesis, we expressed MLL-AF9 in fetal liver (FL) cells or bone marrow (BM) cells isolated from wild-type, Id1(-/-), p21(-/-), or Id1(-/-)p21(-/-) mice, and transplanted them into syngeneic recipient mice. We found that although mice receiving MLL-AF9-transduced FL or BM cells develop AML, loss of Id1 significantly prolonged the median survival of mice receiving FL cells but accelerated leukemogenesis in recipients of BM cells. Deletion of Cdkn1a (p21), an Id1 target gene, can rescue the effect of Id1 loss in both models, suggesting that Cdkn1a is a critical target of Id1 in leukemogenesis. It has been suggested that the FL transplant model mimics human fetal-origin (infant) MLL fusion protein (FP)-driven leukemia, whereas the BM transplantation model resembles postnatal MLL leukemia; in fact, the analysis of clinical samples from patients with MLL-FP(+) leukemia showed that Id1 expression is elevated in the former and reduced in the latter type of MLL-FP(+) AML. Our findings suggest that Id1 could be a potential therapeutic target for infant MLL-AF9-driven leukemia. PMID:26944543

  6. Characterization of physically vapor deposited AF2400 thin films

    SciTech Connect

    Chow, R.; Spragge, M.K.; Loomis, G.E.; Rainer, F.; Ward, R.; Thomas, I.M.; Kozlowski, M.R.

    1993-11-01

    Anti-reflective coatings made with Teflon AF2400 had the highest damage thresholds recorded for physical vapor deposited coatings at the Lawrence Livermore National Laboratory damage facility. Physical vapor deposited layers of Teflon AF2400, a perfluorinated amorphous polymer, maintained the bulk optical properties of a high transmittance from 200 nm to 1600 nm, and a low refractive index. In addition, the refractive index can be intentionally reduced by control of two common deposition parameters, deposition rate and substrate temperature. Scanning electron microscopy and nuclear magnetic resonance observations indicated that morphological changes caused the variations in the refractive index rather than compositional changes. The coatings adhered to fused silica and silicon wafers under normal laboratory handling conditions.

  7. Sinuladiterpenes A-F, new cembrane diterpenes from Sinularia flexibilis.

    PubMed

    Lo, Kuang-Liang; Khalil, Ashraf Taha; Kuo, Yao-Haur; Shen, Ya-Ching

    2009-12-01

    Chromatographic investigation of the octocoral Sinularia flexibilis afforded six new cembrane diterpenes, sinuladiterpenes A-F (1-6, resp.), in addition to four known cembranolides, 11-episinulariolide acetate, 11-dehydrosinulariolide, 11-episinulariolide, and sinulariolide. Their structures were elucidated by spectroscopic analysis, especially 2D-NMR and HR-ESI-MS. Compound 2 exhibited significant in vitro cytotoxic activity against human colon adenocarcinoma (WiDr) cell line. PMID:20020460

  8. Durable Superhydrophobic Surfaces via Spontaneous Wrinkling of Teflon AF.

    PubMed

    Scarratt, Liam R J; Hoatson, Ben S; Wood, Elliot S; Hawkett, Brian S; Neto, Chiara

    2016-03-16

    We report the fabrication of both single-scale and hierarchical superhydrophobic surfaces, created by exploiting the spontaneous wrinkling of a rigid Teflon AF film on two types of shrinkable plastic substrates. Sub-100 nm to micrometric wrinkles were reproducibly generated by this simple process, with remarkable control over the size and hierarchy. Hierarchical Teflon AF wrinkled surfaces showed extremely high water repellence (contact angle 172°) and very low contact angle hysteresis (2°), resulting in droplets rolling off the surface at tilt angles lower than 5°. The wrinkling process intimately binds the Teflon AF layer with its substrate, making these surfaces mechanically robust, as revealed by macroscale and nanoscale wear tests: hardness values were close to that of commercial optical lenses and aluminum films, resistance to scratch was comparable to commercial hydrophobic coatings, and damage by extensive sonication did not significantly affect water repellence. By this fabrication method the size of the wrinkles can be reproducibly tuned from the nanoscale to the microscale, across the whole surface in one step; the fabrication procedure is extremely rapid, requiring only 2 min of thermal annealing to produce the desired topography, and uses inexpensive materials. The very low roll-off angles achieved in the hierarchical surfaces offer a potentially up-scalable alternative as self-cleaning and drag-reducing coatings. PMID:26910574

  9. Genomic functions of U2AF in constitutive and regulated splicing

    PubMed Central

    Wu, Tongbin; Fu, Xiang-Dong

    2015-01-01

    The U2AF heterodimer is generally accepted to play a vital role in defining functional 3′ splice sites in pre-mRNA splicing. Given prevalent mutations in U2AF, particularly in the U2AF1 gene (which encodes for the U2AF35 subunit) in blood disorders and other human cancers, there are renewed interests in these classic splicing factors to further understand their regulatory functions in RNA metabolism in both physiological and disease settings. We recently reported that U2AF has a maximal capacity to directly bind ˜88% of functional 3′ splice sites in the human genome and that numerous U2AF binding events also occur in various exonic and intronic locations, thus providing additional mechanisms for the regulation of alternative splicing besides their traditional role in titrating weak splice sites in the cell. These findings, coupled with the existence of multiple related proteins to both U2AF65 and U2AF35, beg a series of questions on the universal role of U2AF in functional 3′ splice site definition, their binding specificities in vivo, potential mechanisms to bypass their requirement for certain intron removal events, contribution of splicing-independent functions of U2AF to important cellular functions, and the mechanism for U2AF mutations to invoke specific diseases in humans. PMID:25901584

  10. Screening Education And Recognition in Community pHarmacies of Atrial Fibrillation to prevent stroke in an ambulant population aged ≥65 years (SEARCH-AF stroke prevention study): a cross-sectional study protocol

    PubMed Central

    Freedman, Saul Benedict; Redfern, Julie; McLachlan, Andrew; Krass, Ines; Bennett, Alexandra; Briffa, Thomas; Bauman, Adrian; Neubeck, Lis

    2012-01-01

    Background Atrial fibrillation (AF) is associated with a high risk of stroke and may often be asymptomatic. AF is commonly undiagnosed until patients present with sequelae, such as heart failure and stroke. Stroke secondary to AF is highly preventable with the use of appropriate thromboprophylaxis. Therefore, early identification and appropriate evidence-based management of AF could lead to subsequent stroke prevention. This study aims to determine the feasibility and impact of a community pharmacy-based screening programme focused on identifying undiagnosed AF in people aged 65 years and older. Methods and analysis This cross-sectional study of community-based screening to identify undiagnosed AF will evaluate the feasibility of screening for AF using a pulse palpation and handheld single-lead electrocardiograph (ECG) device. 10 community pharmacies will be recruited and trained to implement the screening protocol, targeting a total of 1000 participants. The primary outcome is the proportion of people newly identified with AF at the completion of the screening programme. Secondary outcomes include level of agreement between the pharmacist's and the cardiologist's interpretation of the single-lead ECG; level of agreement between irregular rhythm identified with pulse palpation and with the single-lead ECG. Process outcomes related to sustainability of the screening programme beyond the trial setting, pharmacist knowledge of AF and rate of uptake of referral to full ECG evaluation and cardiology review will also be collected. Ethics and dissemination Primary ethics approval was received on 26 March 2012 from Sydney Local Health District Human Research Ethics Committee—Concord Repatriation General Hospital zone. Results will be disseminated via forums including, but not limited to, peer-reviewed publication and presentation at national and international conferences. Clinical trials registration number ACTRN12612000406808. PMID:22734120

  11. Identification and functional characterization of grass carp IL-17A/F1: An evaluation of the immunoregulatory role of teleost IL-17A/F1.

    PubMed

    Du, Linyong; Feng, Shiyu; Yin, Licheng; Wang, Xinyan; Zhang, Anying; Yang, Kun; Zhou, Hong

    2015-07-01

    In mammals, IL-17A and IL-17F are hallmark cytokines of Th17 cells which act significant roles in eradicating extracellular pathogens. IL-17A and IL-17F homologs nominated as IL-17A/F1-3 have been revealed in fish and their functions remain largely undefined. Here we identified and characterized grass carp IL-17A/F1 (gcIL-17A/F1) in fish immune system. In this regard, both tissue distribution and inductive expression of gcIL-17A/F1 indicated its possible involvement in immune response. Moreover, recombinant gcIL-17A/F1 (rgcIL-17A/F1) was prepared and displayed an ability to enhance pro-inflammatory cytokines (IL-1β, TNF-α and IL-6) mRNA expression in head kidney leukocytes. It is suggestive of that gcIL-17A/F1 may act as a proinflammatory cytokine in fish immunity. Besides, rgcIL-17A/F1 induced gene expression and protein release of grass carp chemokine CXCL-8 (gcCXCL-8) in head kidney cells (HKCs), probably via NF-κB, p38 and Erk1/2 pathways. In particular, culture medium from the HKCs treated by rgcIL-17A/F1 could stimulate peripheral blood leukocytes migration and immunoneutralization of endogenous gcCXCL-8 could partially attenuate this stimulation, suggesting that rgcIL-17A/F1 could recruit immune cells through producing gcCXCL-8 as mammalian IL-17 A and F. Taken together, we not only identified the pro-inflammatory role of gcIL-17A/F1 in host defense, but also provided the basis for clarifying Th17 cells in teleost. PMID:25847875

  12. A Systematic Review of Depression and Anxiety in Patients with Atrial Fibrillation: The Mind-Heart Link

    PubMed Central

    Patel, Dimpi; Mc Conkey, Nathaniel D.; Sohaney, Ryann; Mc Neil, Ashley; Jedrzejczyk, Andy

    2013-01-01

    Atrial fibrillation (AF) is the most commonly seen arrhythmia in clinical practice. At present, few studies have been conducted centering on depression and anxiety in AF patients. Our aim in this systematic review is to use the relevant literature to (1) describe the prevalence of depression and anxiety in AF patients, (2) assess the impact that depression and anxiety have on illness perception in patients with AF, (3) provide evidence to support a hypothetical connection between the pathophysiology of AF and depression and anxiety, (4) evaluate the benefit of treatment of AF on depression and anxiety, and (5) give insight on medically managing a patient with AF and concomitant depression and anxiety. PMID:23710335

  13. Binding sites for two novel phosphoproteins, 3AF5 and 3AF3, are required for rbcS-3A expression.

    PubMed Central

    Sarokin, L P; Chua, N H

    1992-01-01

    Previous studies of boxes II (-151 to -138) and III (-125 to -114), binding sites for the nuclear factor GT-1 within the -166 deleted promoter of the ribulose-1,5-bisphosphate carboxylase-3A (rbcS-3A) gene, suggested that GT-1 might act in concert with an additional protein to confer light-responsive rbcS-3A expression. In this work, S1 analysis of RNA isolated from transgenic tobacco plants carrying mutant rbcS-3A constructs led to the identification of two short sequences located at the 5' and 3' ends of box III that are required for expression. These two sequences serve as binding sites for two novel proteins, 3AF5 and 3AF3. Gel shift studies using tetramerized binding sites for both 3AF5 and 3AF3 showed that complexes with faster mobilities were formed using nuclear extracts prepared from dark-adapted plants compared with those from light-grown tobacco plants. Phosphatase treatment of extracts from light-grown plants resulted in the formation of complexes with faster mobility. Although the binding of 3AF3 to its target site is dependent upon phosphorylation, the binding of 3AF5 does not appear to be affected by its phosphorylation state. These results suggest that the phosphorylated forms of both 3AF5 and 3AF3 are required for -166 rbcS-3A expression but that the mechanisms differ by which phosphorylation regulates the activities of 3AF5 and 3AF3. PMID:1498605

  14. The Advancing State of AF-M315E Technology

    NASA Technical Reports Server (NTRS)

    Masse, Robert; Spores, Ronald A.; McLean, Chris

    2014-01-01

    The culmination of twenty years of applied research in hydroxyl ammonium nitrate (HAN)-based monopropellants, the NASA Space Technology mission Directorate's (STMD) Green Propellant Infusion Mission (GPIM) will achieve the first on-orbit demonstration of an operational AF-M315E green propellant propulsion system by the end of 2015. Following an contextual overview of the completed flight design of the GPIM propellant storage and feed system, results of first operation of a flight-representative heavyweight 20-N engineering model thruster (to be conducted in mid-2014) are presented with performance comparisons to prior lab model (heavyweight) test articles.

  15. RX-26-AY/AF rifle bullet tests

    SciTech Connect

    Sharp, D.D.

    1980-11-01

    A series of rifle bullet tests was performed on two explosives, RX-26-AY and RX-26-AF, using the Pantex version of the Picatinny Arsenal Test (PA-2). With the exception of one test, both explosives displayed a relatively low sensitivity to bullet impact. However, a marked difference was noted in the average burn time duration between the two types of explosives being tested. A minor modification was made on the rifle barrel used at the test site in order to improve the sighting procedure.

  16. Is Dabigatran As Effective As Warfarin on Cardiac Thrombus in a Patient With Atrial Fibrillation? A Challenging Question.

    PubMed

    Sunbul, Murat; Cincin, Altug; Mammadov, Ceyhun; Mutlu, Bulent

    2016-01-01

    Atrial fibrillation (AF) is an important risk factor for cardioembolic stroke. Warfarin is an effective treatment in reducing the risk of cardioembolic stroke in patients with AF. New anticoagulants have been widely using for stroke prophylaxis in patients with nonvalvular AF. Previous studies have suggested that thrombolytic therapy is effective treatment choice in patients with pulmonary embolisms. Warfarin therapy is also effective on prevention or treatment of cardiac thrombus in patients with AF. However, there are no evidence-based data on treatment of cardiac thrombus with new oral anticoagulants in patients with AF. In our case report, we reported an AF patient with cardiac thrombus and pulmonary embolism under dabigatran therapy. PMID:25415546

  17. Monocyte Toll-Like Receptor Expression in Patients With Atrial Fibrillation.

    PubMed

    Gurses, Kadri Murat; Kocyigit, Duygu; Yalcin, Muhammed Ulvi; Canpinar, Hande; Yorgun, Hikmet; Sahiner, Mehmet Levent; Kaya, Ergun Baris; Oto, Mehmet Ali; Ozer, Necla; Guc, Dicle; Aytemir, Kudret

    2016-05-01

    Atrial fibrillation (AF) is the most common sustained arrhythmia. Inflammation has been suggested to play a vital role in the pathogenesis. Previous studies have investigated expression of inflammatory markers in AF. Several studies have focused on the effects of toll-like receptors (TLRs) on heart in terms of capability of modulating inflammation. In this study, we aimed to investigate whether peripheral monocyte TLR expression was associated with the AF presence, and recurrence of AF after cryoablation, as a reflection of inflammatory status. Patients with AF who were scheduled for cryoballoon-based ablation for AF and age- and gender-matched subjects in sinus rhythm were included. Peripheral monocyte TLR-2 and TLR-4 expressions were evaluated by flow cytometric analysis in peripheral venous blood samples obtained during evaluation in outpatient clinics: 172 patients (56.5 ± 6.6 years, 52.3% men) were included in the study. Peripheral monocyte TLR-2 and TLR-4 expression levels were significantly higher in patients with AF (p <0.05). Among patients with AF, 12 patients (14.0%) developed AF recurrence at a follow- up of 17 months. Multivariate Cox regression analysis showed that left atrial volume index (hazard ratio 2.040, 95% CI 1.197 to 3.477, p = 0.009) and monocyte TLR-4 expression (hazard ratio 1.226, 95% CI 1.042 to 1.443, p = 0.014) were independent predictors of AF recurrence after blanking period following second-generation cryoballoon-based pulmonary vein isolation for paroxysmal AF. In conclusion, our study highlights the role of TLR-mediated inflammation in the pathogenesis of AF. This link may also constitute a therapeutic target in patients with AF. PMID:26988292

  18. Prevalence and Predictors of Atrial Fibrillation among Patients Undergoing Bariatric Surgery

    PubMed Central

    Shoemaker, M. Benjamin; Gidfar, Sanaz; Pipilas, Daniel C.; Tamboli, Robyn A.; Galimberti, Eleonora Savio; Williams, D. Brandon; Clements, Ronald H.; Darbar, Dawood

    2013-01-01

    Introduction/Purpose While AF is a disease of the elderly, it can occur earlier in the presence of risk factors such as obesity. Bariatric surgery patients are significantly younger and more obese than previously described populations with AF. Therefore, it remains to be determined whether current estimates of the prevalence and predictors for AF remain true in the bariatric surgery population. Materials and Methods We performed a cross-sectional analysis of 1341 consecutive patients who underwent bariatric surgery from 1/2008 to 10/2012. Baseline characteristics were compared between patients with and without AF. For additional comparison, 176 patients with AF and body mass index (BMI) >40 kg/m2 were identified from the Vanderbilt AF Registry. A multivariable logistic regression was performed to identify predictors of AF within the bariatric surgery cohort. Results The prevalence of AF in the bariatric surgery cohort was 1.9% (25/1341). Patients with AF were older (median 56 years (Interquartile range [52-64) vs.46 [38-56] years, p<0.001), were more often male (48% vs. 23%, p=0.004), had more comorbidities, but had no difference in BMI (50 kg/m2 [44-58] vs. 48 [43-54], p=0.4). In multivariable analysis, the odds of AF increased 2.2-fold by age per decade (95% CI: 1.4-3.5, p<0.001) and 2.4-fold by male gender (1.1-5.4, p=0.03) when adjusted for BMI. BMI was not independently associated with AF (OR 1.15 [95% CI: 0.98-1.41], p=0.09). Conclusions The prevalence of AF is 1.9% among patients undergoing bariatric surgery. Risk of AF was found to increase with age and male gender, but not with higher BMI. PMID:24214203

  19. NMR study of the AF-SC-SC-AF phased transition in a pnictide superconductor LaFeAsO1-xHx

    NASA Astrophysics Data System (ADS)

    Fujiwara, Naoki; Sakurai, Ryosuke; Iimura, Soushi; Matsuishi, Satoru; Hosono, Hideo; Yamakawa, Youichi; Kontani, Hiroshi

    2014-03-01

    We have performed 75As and 1H NMR measurements in LaFeAsO1xHx, an isomorphic compound of LaFeAsO1xFx. LaFeAsO1xHx is an electron doped system, and O2- can be replaced with H- up to x = 0.5. LaFeAsO1xHx is known for having double superconducting (SC) domes on H doping. Recently, we discovered that a new antiferromagnetic (AF) phase follows the double SC domes on further H doping, forming a symmetric AF-SC-SC-AF phase alignment in the electronic phase diagram Unlike the AF ordering in the lightly H-doped regime, the AF ordering in the highly H-doped regime is attributed to the nesting between electron pockets. In the conference, we will show the data of both NMR spectra and the relaxation rate 1/T1 in the whole doping region. We will discuss the difference of electronic states between the lightly H-doped AF-SC phases and highly H-doped SC-AF phases. This work is supported by a Grant-in-Aid (Grant No. KAKENHI 23340101) from the Ministry of Education, Science, and Culture, Japan.

  20. AFS men and women differ most in their lifestyle choices

    USGS Publications Warehouse

    Connelly, N.A.; Brown, T.L.; Hardiman, J.M.

    2006-01-01

    The American Fisheries Society sponsored a survey to examine the career development choices of men and women and how they might differ by gender. A random sample of 700 men and 700 women was selected from the AFS membership database. The survey was mailed out in October 2004 and 991 questionnaires were returned for an adjusted response rate of 71%. Some differences exist between men and women in the areas of interest development, education, and employment, but the substantive differences occur in lifestyle choices. Women with a fisheries career are less likely to be married than men, even when age is controlled for, and women who are married are more likely to have dual-career considerations than their male counterparts. Among respondents without dependents in their home during their professional career, twice as many women as men think having children will adversely affect their career. For those with dependents, more than twice as many women as men said they had to put their career "on hold" because of their dependents. While AFS members do not represent all members of the fisheries profession, their experiences shed substantial light on the lifestyle choices likely faced by most members of the profession.

  1. Identification and characterization of the afsR homologue regulatory gene from Streptomyces peucetius ATCC 27952.

    PubMed

    Parajuli, Niranjan; Viet, Hung Trinh; Ishida, Kenji; Tong, Hang Thi; Lee, Hei Chan; Liou, Kwangkyoung; Sohng, Jae Kyung

    2005-01-01

    We have isolated an afsR homologue, called afsR-p, through genome analysis of Streptomyces peucetius ATCC 27952. AfsR-p shares 60% sequence identity with AfsR from Streptomyces coelicolor A3 (2). afsR-p was expressed under the control of the ermE* promoter in its hosts S. peucetius, Streptomyces lividans TK 24, Streptomyces clavuligerus and Streptomyces griseus. We observed overproduction of doxorubicin (4-fold) in S. peucetius, gamma-actinorhodin (2.6-fold) in S. lividans, clavulanic acid (1.5-fold) in S. clavuligerus and streptomycin (slight) in S. griseus. Overproduction was due to expression of the gene in these strains as compared to the wild-type strains harboring the vector only. Comparative study of the expression of afsR-p revealed that regulatory networking in Streptomyces is not uniform. We speculate that phosphorylated AfsR-p becomes bound to the promoter region of afsS. The latter activates other regulatory genes, including pathway regulatory genes, and induces the production of secondary metabolites including antibiotics. We identified specific conserved amino acids and exploited them for the isolation of the partial sequence of the afsR homologue from S. clavuligerus and Streptomyces achromogens (rubradirin producer). Such findings provide additional evidence for the presence of a serine/threonine and tyrosine kinase-dependent global regulatory network in Streptomyces. PMID:15921897

  2. Dual Function for U2AF35 in AG-Dependent Pre-mRNA Splicing

    PubMed Central

    Guth, Sabine; Tange, Thomas O/.; Kellenberger, Esther; Valcárcel, Juan

    2001-01-01

    The splicing factor U2AF is required for the recruitment of U2 small nuclear RNP to pre-mRNAs in higher eukaryotes. The 65-kDa subunit of U2AF (U2AF65) binds to the polypyrimidine (Py) tract preceding the 3′ splice site, while the 35-kDa subunit (U2AF35) contacts the conserved AG dinucleotide at the 3′ end of the intron. It has been shown that the interaction between U2AF35 and the 3′ splice site AG can stabilize U2AF65 binding to weak Py tracts characteristic of so-called AG-dependent pre-mRNAs. U2AF35 has also been implicated in arginine-serine (RS) domain-mediated bridging interactions with splicing factors of the SR protein family bound to exonic splicing enhancers (ESE), and these interactions can also stabilize U2AF65 binding. Complementation of the splicing activity of nuclear extracts depleted of U2AF by chromatography in oligo(dT)-cellulose requires, for some pre-mRNAs, only the presence of U2AF65. In contrast, splicing of a mouse immunoglobulin M (IgM) M1-M2 pre-mRNA requires both U2AF subunits. In this report we have investigated the sequence elements (e.g., Py tract strength, 3′ splice site AG, ESE) responsible for the U2AF35 dependence of IgM. The results indicate that (i) the IgM substrate is an AG-dependent pre-mRNA, (ii) U2AF35 dependence correlates with AG dependence, and (iii) the identity of the first nucleotide of exon 2 is important for U2AF35 function. In contrast, RS domain-mediated interactions with SR proteins bound to the ESE appear to be dispensable, because the purine-rich ESE present in exon M2 is not essential for U2AF35 activity and because a truncation mutant of U2AF35 consisting only of the pseudo-RNA recognition motif domain and lacking the RS domain is active in our complementation assays. While some of the effects of U2AF35 can be explained in terms of enhanced U2AF65 binding, other activities of U2AF35 do not correlate with increased cross-linking of U2AF65 to the Py tract. Collectively, the results argue that

  3. Racial Differences in the Prevalence and Outcomes of Atrial Fibrillation in Patients Hospitalized With Heart Failure.

    PubMed

    Bhatia, Subir; Qazi, Mohammad; Erande, Ashwini; Shah, Kunjan; Amin, Alpesh; Patel, Pranav; Malik, Shaista

    2016-05-01

    Previous research has shown that roughly 15% to 30% of those with heart failure (HF) develop atrial fibrillation (AF). Although studies have shown variations in the incidence of AF in patients with HF, there has been no evidence of mortality differences by race. The purpose of this study was to assess AF prevalence and inhospital mortality in patients with HF among different racial groups in the United States. Using the National Inpatient Sample registry, the largest publicly available all-payer inpatient care database representing >95% of the US inpatient population, we analyzed subjects hospitalized with a primary diagnosis of HF from 2001 to 2011 (n = 11,485,673) using the International Classification of Diseases, Ninth Edition (ICD 9) codes 428.0-0.1, 428.20-0.23, 428.30-0.33, 428.40-0.43, and 428.9; patients with AF were identified using the ICD 9 code 427.31. We assessed prevalence and mortality among racial groups. Using logistic regression, we examined odds of mortality adjusted for demographics and co-morbidity using Elixhauser co-morbidity index. We also examined utilization of procedures by race. Of the 11,485,673 patients hospitalized with HF in our study, 3,939,129 (34%) had AF. Patients with HF and AF had greater inhospital mortality compared with those without AF (4.6% vs 3.3% respectively, p <0.0001). Additionally, black, Hispanic, Asian, and white patients with HF and AF had a 24%, 17%, 13%, and 6% higher mortality, respectively, than if they did not have AF. Among patients with HF and AF, minority racial groups had underutilization of catheter ablation and cardioversion compared with white patients. In conclusion, minority patients with HF and AF had a disproportionately higher risk of inpatient death compared with white patients with HF. We also found a significant underutilization of cardioversion and catheter ablation in minority racial groups compared with white patients. PMID:26970814

  4. Recurrence of atrial fibrillation within three months after pulmonary vein isolation for patients with paroxysmal atrial fibrillation: Analysis using external loop recorder with auto-trigger function

    PubMed Central

    Kawasaki, Shiro; Tanno, Kaoru; Ochi, Akinori; Inokuchi, Koichiro; Chiba, Yuta; Onishi, Yoshimi; Onuma, Yoshimasa; Munetsugu, Yumi; Kikuchi, Miwa; Ito, Hiroyuki; Onuki, Tatsuya; Miyoshi, Fumito; Minoura, Yoshino; Watanabe, Norikazu; Adachi, Taro; Asano, Taku; Kobayashi, Youichi

    2014-01-01

    Background Pulmonary vein isolation (PVI) via catheter ablation has been shown to be a highly effective treatment option for patients with symptomatic paroxysmal atrial fibrillation (AF). The recurrence of AF within 3 months after PVI is not considered to be the result of ablation procedure failure, because early recurrence of AF is not always associated with late recurrence. We examined the usefulness of an external loop recorder with an auto-trigger function (ELR-AUTO) for the detection of atrial fibrillation following PVI to characterize early recurrence and to determine the implications of AF occurrence within 3 months after PVI. Methods Fifty-three consecutive symptomatic patients with paroxysmal AF (age 61.6±12.6 years, 77% male) who underwent PVI and were fitted with ELR-AUTO for 7±2.0 days within 3 months after PVI were enrolled in this study. Results Of the 33 (62.2%) patients who did not have AF recurrence within 3 months after PVI, only 1 patient experienced AF recurrence at 12 months. Seven (35%) of the 20 patients who experienced AF within 3 months of PVI experienced symptomatic AF recurrence at 12 months. The sensitivity, specificity, positive predictive value, and negative predictive value of early AF recurrence for late recurrence were 87.5%, 71.1%, 35.0%, and 96.9%, respectively. Conclusions AF recurrence measured by ELR-AUTO within 3 months after PVI can predict the late recurrence of AF. Freedom from AF in the first 3 months following ablation significantly predicts long-term AF freedom. ELR-AUTO is useful for the detection of symptomatic and asymptomatic AF. PMID:26336538

  5. Comprehensive risk reduction in patients with atrial fibrillation: emerging diagnostic and therapeutic options--a report from the 3rd Atrial Fibrillation Competence NETwork/European Heart Rhythm Association consensus conference.

    PubMed

    Kirchhof, Paulus; Lip, Gregory Y H; Van Gelder, Isabelle C; Bax, Jeroen; Hylek, Elaine; Kaab, Stefan; Schotten, Ulrich; Wegscheider, Karl; Boriani, Giuseppe; Brandes, Axel; Ezekowitz, Michael; Diener, Hans; Haegeli, Laurent; Heidbuchel, Hein; Lane, Deirdre; Mont, Luis; Willems, Stephan; Dorian, Paul; Aunes-Jansson, Maria; Blomstrom-Lundqvist, Carina; Borentain, Maria; Breitenstein, Stefanie; Brueckmann, Martina; Cater, Nilo; Clemens, Andreas; Dobrev, Dobromir; Dubner, Sergio; Edvardsson, Nils G; Friberg, Leif; Goette, Andreas; Gulizia, Michele; Hatala, Robert; Horwood, Jenny; Szumowski, Lukas; Kappenberger, Lukas; Kautzner, Josef; Leute, Angelika; Lobban, Trudie; Meyer, Ralf; Millerhagen, Jay; Morgan, John; Muenzel, Felix; Nabauer, Michael; Baertels, Christoph; Oeff, Michael; Paar, Dieter; Polifka, Juergen; Ravens, Ursula; Rosin, Ludger; Stegink, W; Steinbeck, Gerhard; Vardas, Panos; Vincent, Alphons; Walter, Maureen; Breithardt, Günter; Camm, A John

    2012-01-01

    While management of atrial fibrillation (AF) patients is improved by guideline-conform application of anticoagulant therapy, rate control, rhythm control, and therapy of accompanying heart disease, the morbidity and mortality associated with AF remain unacceptably high. This paper describes the proceedings of the 3rd Atrial Fibrillation NETwork (AFNET)/European Heart Rhythm Association (EHRA) consensus conference that convened over 60 scientists and representatives from industry to jointly discuss emerging therapeutic and diagnostic improvements to achieve better management of AF patients. The paper covers four chapters: (i) risk factors and risk markers for AF; (ii) pathophysiological classification of AF; (iii) relevance of monitored AF duration for AF-related outcomes; and (iv) perspectives and needs for implementing better antithrombotic therapy. Relevant published literature for each section is covered, and suggestions for the improvement of management in each area are put forward. Combined, the propositions formulate a perspective to implement comprehensive management in AF. PMID:21791573

  6. Comprehensive risk reduction in patients with atrial fibrillation: emerging diagnostic and therapeutic options—a report from the 3rd Atrial Fibrillation Competence NETwork/European Heart Rhythm Association consensus conference

    PubMed Central

    Kirchhof, Paulus; Lip, Gregory Y.H.; Van Gelder, Isabelle C.; Bax, Jeroen; Hylek, Elaine; Kaab, Stefan; Schotten, Ulrich; Wegscheider, Karl; Boriani, Giuseppe; Brandes, Axel; Ezekowitz, Michael; Diener, Hans; Haegeli, Laurent; Heidbuchel, Hein; Lane, Deirdre; Mont, Luis; Willems, Stephan; Dorian, Paul; Aunes-Jansson, Maria; Blomstrom-Lundqvist, Carina; Borentain, Maria; Breitenstein, Stefanie; Brueckmann, Martina; Cater, Nilo; Clemens, Andreas; Dobrev, Dobromir; Dubner, Sergio; Edvardsson, Nils G.; Friberg, Leif; Goette, Andreas; Gulizia, Michele; Hatala, Robert; Horwood, Jenny; Szumowski, Lukas; Kappenberger, Lukas; Kautzner, Josef; Leute, Angelika; Lobban, Trudie; Meyer, Ralf; Millerhagen, Jay; Morgan, John; Muenzel, Felix; Nabauer, Michael; Baertels, Christoph; Oeff, Michael; Paar, Dieter; Polifka, Juergen; Ravens, Ursula; Rosin, Ludger; Stegink, W.; Steinbeck, Gerhard; Vardas, Panos; Vincent, Alphons; Walter, Maureen; Breithardt, Günter; Camm, A. John

    2012-01-01

    While management of atrial fibrillation (AF) patients is improved by guideline-conform application of anticoagulant therapy, rate control, rhythm control, and therapy of accompanying heart disease, the morbidity and mortality associated with AF remain unacceptably high. This paper describes the proceedings of the 3rd Atrial Fibrillation NETwork (AFNET)/European Heart Rhythm Association (EHRA) consensus conference that convened over 60 scientists and representatives from industry to jointly discuss emerging therapeutic and diagnostic improvements to achieve better management of AF patients. The paper covers four chapters: (i) risk factors and risk markers for AF; (ii) pathophysiological classification of AF; (iii) relevance of monitored AF duration for AF-related outcomes; and (iv) perspectives and needs for implementing better antithrombotic therapy. Relevant published literature for each section is covered, and suggestions for the improvement of management in each area are put forward. Combined, the propositions formulate a perspective to implement comprehensive management in AF. PMID:21791573

  7. Penipyridones A-F, Pyridone Alkaloids from Penicillium funiculosum.

    PubMed

    Zhou, Haibo; Li, Liyuan; Wu, Chongming; Kurtán, Tibor; Mándi, Attila; Liu, Yankai; Gu, Qianqun; Zhu, Tianjiao; Guo, Peng; Li, Dehai

    2016-07-22

    Six new pyridone alkaloids, named penipyridones A-F (1-6), were isolated from the fermentation broth of an Antarctic moss-derived fungus, Penicillium funiculosum GWT2-24. Their structures were elucidated from extensive NMR and MS data. Although they possess the same major chromophore and some of them presented almost mirror ECD spectra, their absolute configurations were found to be uniformly S, as evidenced by X-ray single-crystal diffraction analysis, stereocontrolled total synthesis, and chemical conversions. TDDFT-ECD calculations of compounds 3 and 6 revealed that subtle conformational changes are responsible for the significantly different ECD curves. None of the compounds were cytotoxic (IC50 > 50 μM), while compounds 1, 2, 5, and 7 elicited lipid-lowering activity in HepG2 hepatocytes. PMID:27359163

  8. Optimised secure transmission through untrusted AF relays using link adaptation

    NASA Astrophysics Data System (ADS)

    Taki, Mehrdad; Sadeghi, Mohammad

    2016-05-01

    A new transmission scheme is presented for a two-hop relay network including two AF relays, considering physical layer security where relays are not able to detect signal with an acceptable bit error rate (BER) but the combined received signal is detected with an acceptable BER at the final receiver. It is assumed that there is no direct path between the transmitter and the receiver (relay network without diversity). Adaptive modulation and coding is utilised at the transmitter and transmission powers of the transmitter and of the relays are continuously adapted provisioning individual average power constraint for each node. Numerical evaluations show that an acceptable performance degradation is seen by the proposed secure relaying scheme compared to the optimum relay selection scheme without security constraint.

  9. Evaluation of the atoxigenic Aspergillus flavus strain AF36 in pistachio orchards

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The atoxigenic strain Aspergillus flavus AF36, which has been extensively used as a biocontrol agent in commercial corn and cotton fields to reduce aflatoxin contamination, was applied in research pistachio orchards from 2002 to 2005 and in commercial pistachio orchards from 2008 to 2011. AF36 was a...

  10. Assessment of the Framingham risk factors among ED patients with newly diagnosed atrial fibrillation

    PubMed Central

    Barrett, Tyler W.; Storrow, Alan B.; Jenkins, Cathy A.; Harrell, Frank E.; Amdahl, John; Russ, Stephan; Slovis, Corey M.; Darbar, Dawood

    2010-01-01

    Study Objective Atrial fibrillation (AF) is often first diagnosed in the emergency department (ED) and accounts for nearly 1% of all ED visits. Our objective was to assess the Framingham Heart Study risk score for AF development in ED patients with newly diagnosed AF. Methods We systematically reviewed the electronic medical records of ED patients with newly diagnosed AF between August 2005 and July 2008. We measured the frequency of the Framingham Heart Study predictors and calculated each patient's risk score. Results During the 3-year study period, 914 patients had 1228 ED visits. New AF was diagnosed in 296 (32%) patients. Among these patients, 107 (36%) were female, 127 (43%) had prior ED visits since 2003, 189 (64%) were taking hypertension medications and 170 (57.4%) had previous electrocardiograms with measurable PR intervals. The median PR interval was 166 ms (151 to 180) and 60% of available PR intervals were ≥160 ms. The median (Interquartile range) age, body mass index, and systolic blood pressure were 66 years (53 to 77), 27 (23 to 31), and 134 mm Hg (118 to 151), respectively. Median risk score was 7 (3 to 9) indicating high predicted risk. Heart failure and cardiac murmurs were previously diagnosed in 45 (15%) and 32 (11%) of these patients, respectively. Conclusions The Framingham risk factors for AF are commonly encountered among ED patients with newly diagnosed AF. The ED might provide an opportunity to identify patients at high risk for AF and refer them for primary prevention interventions. PMID:21208770

  11. PREVALENCE OF ATRIAL FIBRILLATION AND WARFARIN USE IN OLDER PATIENTS RECEIVING HEMODIALYSIS

    PubMed Central

    Winkelmayer, Wolfgang C.; Liu, Jun; Patrick, Amanda R.; Setoguchi, Soko; Choudhry, Niteesh K.

    2011-01-01

    Background Little is known about the use of warfarin in hemodialysis (HD) patients with atrial fibrillation (AF). We studied temporal trends of AF among older HD patients, and of warfarin use among those with AF. Methods We linked Medicare and prescription claims from older patients undergoing HD in two Eastern states. We established annual cohorts of prevalent HD patients; AF was ascertained from >2 claims (>7 days apart) in the same year with a diagnosis code indicating AF. Among those with AF, we defined current and past warfarin use. Demographic and clinical characteristics were also ascertained for each cohort. We used repeated-measures logistic regression to define the odds of AF and of current or past vs. absence of warfarin use. Results Of 6563 unique patients, 2185 were determined to have AF. The prevalence of AF increased from 26% in 1998 to 32% in 2005. In 2005, current warfarin use was present in 24% of AF patients and past use in 25%; 51% had no evidence of any warfarin use. No significant trends in utilization were observed from 1998-2005. Patients aged ≥85 years and non-whites were less likely to have received warfarin; most comorbidities were not associated with warfarin use except for patients with past pulmonary embolism or deep venous thrombosis who were more likely than those without such history. Conclusion While the prevalence of AF has been increasing among older HD patients, warfarin use was low and unchanged over time, perhaps reflecting the lack of evidence supporting such use. PMID:22180223

  12. Ablation of Atrial Fibrillation: Patient Selection, Periprocedural Anticoagulation, Techniques, and Preventive Measures After Ablation.

    PubMed

    Link, Mark S; Haïssaguerre, Michel; Natale, Andrea

    2016-07-26

    Atrial fibrillation (AF) is the most common arrhythmia encountered by cardiologists and is a major cause of morbidity and mortality. Risk factors for AF include age, male sex, genetic predisposition, hypertension, diabetes mellitus, sleep apnea, obesity, excessive alcohol, smoking, hyperthyroidism, pulmonary disease, air pollution, heart failure, and possibly excessive exercise. The management of AF involves decisions about rate versus rhythm control. Asymptomatic patients are generally managed with rate control and anticoagulation. Symptomatic patients will desire rhythm control. Rhythm control options are either antiarrhythmic agents or ablation, with each having its own risks and benefits. Ablation of AF has evolved from a rare and complex procedure to a common electrophysiological technique. Selection of patients to undergo ablation is an important aspect of AF care. Patients with the highest success rates of ablation are those with normal structural hearts and paroxysmal AF, although those with congestive heart failure have the greatest potential benefit of the procedure. Although pulmonary vein isolation of any means/energy source is the approach generally agreed on for those with paroxysmal AF, optimal techniques for the ablation of nonparoxysmal AF are not yet clear. Anticoagulation reduces thromboembolic complications; the newer anticoagulants have eased management for both the patient and the cardiologist. Aggressive management of modifiable risk factors (hypertension, diabetes mellitus, sleep apnea, obesity, excessive alcohol, smoking, hyperthyroidism, pulmonary disease, air pollution, and possibly excessive exercise) after ablation reduces the odds of recurrent AF and is an important element of care. PMID:27462054

  13. Lessons from the dissection of the activation functions (AF-1 and AF-2) of the estrogen receptor alpha in vivo.

    PubMed

    Arnal, Jean-François; Fontaine, Coralie; Abot, Anne; Valera, Marie-Cécile; Laurell, Henrik; Gourdy, Pierre; Lenfant, Françoise

    2013-06-01

    Estrogens influence most of the physiological processes in mammals, including but not limited to reproduction, cognition, behavior, vascular system, metabolism and bone integrity. Given this widespread role for estrogen in human physiology, it is not surprising that estrogen influence the pathophysiology of numerous diseases, including cancer (of the reproductive tract as breast, endometrial but also colorectal, prostate,…), as well as neurodegenerative, inflammatory-immune, cardiovascular and metabolic diseases, and osteoporosis. These actions are mediated by the activation of estrogen receptors (ER) alpha (ERα) and beta (ERβ), which regulate target gene transcription (genomic action) through two independent activation functions (AF)-1 and AF-2, but can also elicit rapid membrane initiated steroid signals (MISS). Targeted ER gene inactivation has shown that although ERβ plays an important role in the central nervous system and in the heart, ERα appears to play a prominent role in most of the other tissues. Pharmacological activation or inhibition of ERα and/or ERβ provides already the basis for many therapeutic interventions, from hormone replacement at menopause to prevention of the recurrence of breast cancer. However, the use of these estrogens or selective estrogen receptors modulators (SERMs) have also induced undesired effects. Thus, an important challenge consists now to uncouple the beneficial actions from other deleterious ones. The in vivo molecular "dissection" of ERα represents both a molecular and integrated approach that already allowed to delineate in mouse the role of the main "subfunctions" of the receptor and that could pave the way to an optimization of the ER modulation. PMID:23200732

  14. Feasibility of visualizing higher regions of Shannon entropy in atrial fibrillation patients.

    PubMed

    Arunachalam, Shivaram P; Mulpuru, Siva K; Friedman, Paul A; Tolkacheva, Elena G

    2015-08-01

    Catheter ablation is associated with limited success rates in patients with persistent atrial fibrillation (AF), which is mostly maintained by rotors that are located outside of pulmonary veins (PV) region. None of the currently available commercial mapping systems can accurately predict the rotor location outside of PV in patients with persistent AF. PMID:26737294

  15. Relation of syncope in young patients with Wolff-Parkinson-White syndrome to rapid ventricular response during atrial fibrillation.

    PubMed

    Paul, T; Guccione, P; Garson, A

    1990-02-01

    Syncope in patients due to Wolff-Parkinson-White (WPW) syndrome may be related either to a rapid rate of supraventricular tachycardia or to rapid ventricular response over the accessory pathway during atrial fibrillation (AF). From 1982 to 1987, 74 patients less than or equal to 25 years old (mean age 12.6 years) with WPW syndrome on electrocardiogram underwent electrophysiologic study. Of the 74 patients, 14 (19%) had a history of syncope. During electrophysiologic study 9 of 14 patients with syncope had sustained (greater than 5 minutes or requiring termination due to hypotension) AF. Of the remaining 5 patients, 3 had inducible nonsustained AF and 2 had no AF. None of the 60 patients without syncope developed sustained AF; 34 had nonsustained and 26 had no AF. Occurrence of sustained AF had a sensitivity of 64% and specificity of 100% for history of syncope. All patients with syncope and AF (12) had a short RR interval between 2 consecutive preexcited QRS complexes during AF at less than or equal to 220 ms, in contrast to 9 of 34 patients without syncope (p less than 0.001, sensitivity 100%, specificity 74%). No patient with a short RR interval between 2 consecutive preexcited QRS complexes during AF of greater than 220 ms had a history of syncope. Thus, in these young patients with WPW syndrome, occurrence of AF with a rapid ventricular response during electrophysiologic study correlated well with a history of syncope and may be the cause of syncope in most patients. Electrophysiologic study may be helpful in identification of young patients with WPW at risk for syncope. PMID:2301260

  16. Effectiveness of moxonidine to reduce atrial fibrillation burden in hypertensive patients.

    PubMed

    Deftereos, Spyridon; Giannopoulos, Georgios; Kossyvakis, Charalampos; Efremidis, Michael; Panagopoulou, Vasiliki; Raisakis, Konstantinos; Kaoukis, Andreas; Karageorgiou, Sofia; Bouras, Georgios; Katsivas, Apostolos; Pyrgakis, Vlasios; Stefanadis, Christodoulos

    2013-09-01

    There is substantial evidence that the autonomic system plays an important part in the pathogenesis of atrial fibrillation (AF). It appears that, although some patients have a preponderantly sympathetic or vagal overactivation leading to AF, a combined sympathovagal drive is most commonly responsible for AF triggering. The purpose of this hypothesis-generating study was to test whether moxonidine, a centrally acting sympathoinhibitory agent, on top of optimal antihypertensive treatment, can lead to a decrease in AF burden in hypertensive patients with paroxysmal AF. This was a prospective, double-blind, 1-group, crossover study. Hypertensive patients with paroxysmal AF sequentially received treatment with placebo and moxonidine for two 6-week periods, respectively. The change in AF burden (measured as minutes of AF per day in three 48-hour Holter recordings) between the 2 treatment periods was the primary outcome measure. Fifty-six patients (median age 63.5 years, 35 men) were included. During moxonidine treatment, AF burden was reduced from 28.0 min/day (interquartile range [IQR] 15.0 to 57.8) to 16.5 min/day (IQR 4.0 to 36.3; p <0.01). European Heart Rhythm Association symptom severity class decreased from a median of 2.0 (IQR 1.0 to 2.0) to 1.0 (IQR 1.0 to 2.0; p = 0.01). Systolic blood pressure levels were similar in the 2 treatment periods, whereas diastolic blood pressure was lower (p <0.01) during moxonidine treatment. The most frequent complaint was dry mouth (28.6%). No serious adverse events were recorded. In conclusion, treatment with moxonidine, a centrally acting sympathoinhibitory agent, results in reduction of AF burden and alleviation of AF-related symptoms in hypertensive patients with paroxysmal AF. PMID:23726175

  17. One year follow-up after cryoballoon isolation of the pulmonary veins in patients with paroxysmal atrial fibrillation

    PubMed Central

    Van Belle, Yves; Janse, Petter; Theuns, Dominic; Szili-Torok, Tamas; Jordaens, Luc

    2008-01-01

    Aims Pulmonary vein isolation (PVI) with cryoenergy delivered through a balloon is a new approach in the treatment of atrial fibrillation (AF), but long-term follow-up is lacking. The aim of this study was to provide insight in the success rate and the incidence of recurrences. Methods and results Patients with symptomatic AF despite anti-arrhythmic drugs (AADs) were treated with cryoballoon PVI. Daily transtelephonic ECG monitoring, 24 h Holter-ECG, and an arrhythmia-focused questionnaire were used to document AF. One hundred and forty-one patients completed a follow-up of 457 ± 252 days. Before ablation, Holter-ECG showed AF in 45%, including 16% continuous AF throughout the recording. Event recording revealed a median AF burden of 26%. The questionnaire showed a median of weekly AF complaints lasting for hours. All but one patient had successful PVI with a single procedure. After ablation, AF (defined as lasting for more than 30 s) was seen in 11% of Holter-ECGs, with 1% continuous AF. The event recording showed an AF burden of 9%. The median patient reported no more AF-related symptoms. Recurrence during the first 3 months was predictive for later recurrence. A second procedure was performed in 24 patients. The freedom of AF was 59% without AADs after 1,2 procedures. Four right phrenic nerve paralyses occurred, all resolving within 6 months. No PV stenoses were observed. Conclusion Pulmonary vein isolation with a cryothermal balloon is an effective treatment for paroxysmal AF, resulting in a clinical success rate comparable to studies involving radiofrequency ablation. Temporary right phrenic nerve paralysis is the most important complication. PMID:18955409

  18. Hsp90 Directly Modulates the Spatial Distribution of AF9/MLLT3 and Affects Target Gene Expression*

    PubMed Central

    Lin, Jeffrey J.; Hemenway, Charles S.

    2010-01-01

    AF9/MLLT3 contributes to the regulation of the gene encoding the epithelial sodium channel α, ENaCα, in renal tubular cells. Specifically, increases in AF9 protein lead to a reduction in ENaCα expression and changes in AF9 activity appear to be an important component of aldosterone signaling in the kidney. Whereas AF9 is found in the nucleus where it interacts with the histone H3 lysine 79 methyltransferase, Dot1, AF9 is also present in the cytoplasm. Data presented in this report indicate that the heat shock protein Hsp90 directly and specifically interacts with AF9 as part of an Hsp90-Hsp70-p60/Hop chaperone complex. Experimental manipulation of Hsp90 function by the inhibitor novobiocin, but not 17-AAG, results in redistribution of AF9 from a primarily nuclear to cytoplasmic location. Knockdown of Hsp90 with siRNA mimics the effect elicited by novobiocin. As expected, a shift in AF9 from the nucleus to the cytoplasm in response to Hsp90 interference leads to increased ENaCα expression. This is accompanied by a decrease in AF9 occupancy at the ENaCα promoter. Our data suggest that the interaction of Hsp90, Hsp70, and p60/Hop with AF9 is necessary for the proper subnuclear localization and activity of AF9. AF9 is among a growing number of nuclear proteins recognized to rely on the Hsp90 complex for nuclear targeting. PMID:20159978

  19. Prognostic significance of prevalent and incident atrial fibrillation among patients hospitalized with acute coronary syndrome: findings from the Gulf RACE-2 Registry.

    PubMed

    Hersi, Ahmad; Alhabib, Khalid F; Alsheikh-Ali, Alawi A; Sulaiman, Kadhim; Alfaleh, Hussam F; Alsaif, Shukri; Al-Mahmeed, Wael; Asaad, Nidal; Haitham, Amin; Al-Motarreb, Ahmed; Suwaidi, Jassim; Shehab, Abdullah

    2012-08-01

    There is a paucity of data on atrial fibrillation (AF) complicating acute coronary syndrome (ACS) in Arabian Gulf countries. Thus, we assessed the incidence of AF in patients with ACS in these countries and examined the associated in-hospital, 30-day, and 1-year adverse outcomes. The population comprised 7930 patients enrolled in the second Gulf Registry of Acute Coronary Events (Gulf RACE-2). Of 7930 patients with ACS, 217 (2.7%) had AF. Compared with patients without AF, patients with AF were less likely to be male (65.9 vs 79.1%) and were older (mean age 64.6 vs 56.6 years). Compared with patients without AF, in-hospital, 30-day, and 1-year mortality were significantly higher in patients with any AF (odds ratio [OR]: 2.7, 2.2, 1.9, respectively; P < .001) and in patients with new-onset AF (OR: 5.2, 3.9, 3.1, respectively; P < .001. In conclusion, AF in patients with ACS was associated with significantly higher short- and long-term mortality. PMID:22144666

  20. Association between Postoperatively Developed Atrial Fibrillation and Long-Term Mortality after Esophagectomy in Esophageal Cancer Patients: An Observational Study

    PubMed Central

    Chin, Ji-Hyun; Moon, Young-Jin; Jo, Jun-Young; Han, Yun A.; Kim, Hyeong Ryul; Choi, In-Cheol

    2016-01-01

    Background Newly developed atrial fibrillation (AF) in patients who have undergone an esophagectomy increases the incidence of postoperative complications. However, the clinical implications of AF have not been fully elucidated in these patients. This retrospective observational study investigated the predictors for AF and the effect of AF on the mortality in esophageal cancer patients undergoing esophagectomy. Methods This study evaluated 583 patients undergoing esophagectomy, from January 2005 to April 2012. AF was defined as newly developed postoperative AF requiring treatment. The risk factors for AF and the association between AF and mortality were evaluated. The long-term mortality was the all-cause mortality, for which the cutoff date was May 31, 2014. Results AF developed in 63 patients (10.8%). Advanced age (odds ratio [OR] 1.099, 95% confidence interval [CI] 1.056–1.144, P < 0.001), preoperative calcium channel blocker (CCB) (OR 2.339, 95% CI 1.143–4.786, P = 0.020), and angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) (OR 0.206, 95% CI 0.067–0.635, P = 0.006) were associated with the incidence of AF. The Kaplan-Meier curve showed a significantly lower survival rate in the AF group compared to the non-AF group (P = 0.045), during a median follow-up of 50.7 months. The multivariable analysis revealed associations between AF and the 1-year mortality (hazard ratio [HR] 2.556, 95% CI 1.430–4.570, P = 0.002) and between AF and the long-term mortality (HR 1.507, 95% CI 1.003–2.266, P = 0.049). Conclusions In esophageal cancer patients, the advanced age and the preoperative medications (CCB, ACEI or ARB) were associated with the incidence of AF. Furthermore, postoperatively developed AF was associated with mortality in esophageal cancer patients after esophagectomy, suggesting that a close surveillance might be required in patients who showed AF during postoperative period. PMID:27148877

  1. [Factor AF2--the 4th column in tumor therapy. Documentation No.22].

    PubMed

    Kast, A; Hauser, S P

    1990-04-17

    Factor AF2 is an extract from the spleen and liver of sheep embryos and lambs. The product contains biotechnologically produced, chromatographically uniform, molecularly standardized polypeptides, glycopeptides, glycolipids and nucleotides, deproteinized and free of pyrogens'. Factor AF2 is intended mainly for use in 'supportive antitumour therapy', as a 'biological antiemetic and analgesic'. The proposed duration of treatment is usually more than six months. The dosage varies considerably according to the indication. The average daily costs are, therefore, between DM 4.- (prevention of recurrence) and DM 107.- (adjuvant to chemotherapy). Allergic reactions have been reported in 'rare cases'. Factor AF2 was developed in the forties by Guarnieri in Rome. Since 1984, Factor AF2 is 'biotechnologically' produced and as a 'biological response modifier' (BRM) in the oncotherapy distributed by Biosyn Arzneimittel GmbH, Stuttgart. Dr. rer. nat. T. Stiefel and Dr. rer. nat. H. Porcher are the representatives of Biosyn Arzneimittel GmbH. In the past, both worked with Vitorgan Arzneimittel GmbH (cytoplasmatic therapy according to Theurer). It is claimed that Factor AF2 contains 'immunomodulating and immunorestorative biomolecules' assignable to the BRM group. Terms and investigations from current immunological research are applied to Factor AF2. No preclinical investigations are available which demonstrate any cytostatic effect of Factor AF2. In vivo, no effects were observed on the transplanted meth-A-sarcoma in mice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2349412

  2. The Ras Target AF-6 is a Substrate of the Fam Deubiquitinating Enzyme

    PubMed Central

    Taya, Shinichiro; Yamamoto, Takaharu; Kano, Kyoko; Kawano, Yoji; Iwamatsu, Akihiro; Tsuchiya, Tomoko; Tanaka, Keiji; Kanai-Azuma, Masami; Wood, Stephen A.; Mattick, John S.; Kaibuchi, Kozo

    1998-01-01

    The Ras target AF-6 has been shown to serve as one of the peripheral components of cell–cell adhesions, and is thought to participate in cell–cell adhesion regulation downstream of Ras. We here purified an AF-6-interacting protein with a molecular mass of ∼220 kD (p220) to investigate the function of AF-6 at cell–cell adhesions. The peptide sequences of p220 were identical to the amino acid sequences of mouse Fam. Fam is homologous to a deubiquitinating enzyme in Drosophila, the product of the fat facets gene. Recent genetic analyses indicate that the deubiquitinating activity of the fat facets product plays a critical role in controlling the cell fate. We found that Fam accumulated at the cell–cell contact sites of MDCKII cells, but not at free ends of plasma membranes. Fam was partially colocalized with AF-6 and interacted with AF-6 in vivo and in vitro. We also showed that AF-6 was ubiquitinated in intact cells, and that Fam prevented the ubiquitination of AF-6. PMID:9722616

  3. Critical behavior of a triangular lattice Ising AF/FM bilayer

    NASA Astrophysics Data System (ADS)

    Žukovič, M.; Bobák, A.

    2016-03-01

    We study a bilayer Ising spin system consisting of antiferromagnetic (AF) and ferromagnetic (FM) triangular planes, coupled by ferromagnetic exchange interaction, by standard Monte Carlo and parallel tempering methods. The AF/FM bilayer is found to display the critical behavior completely different from both the single FM and AF constituents as well as the FM/FM and AF/AF bilayers. Namely, by finite-size scaling (FSS) analysis we identify at the same temperature a standard Ising transition from the paramagnetic to FM state in the FM plane that induces a ferrimagnetic state with a finite net magnetic moment in the AF plane. At lower temperatures there is another phase transition, that takes place only in the AF plane, to different ferrimagnetic state with spins on two sublattices pointing parallel and on one sublattice antiparallel to the spins on the FM plane. FSS indicates that the corresponding critical exponents are close to the two-dimensional three-state ferromagnetic Potts model values.

  4. Atrial Fibrillation is Associated With Morphine Treatment in Female Breast Cancer Patients

    PubMed Central

    Lee, Cynthia Wei-Sheng; Muo, Chih-Hsin; Liang, Ji-An; Lin, Ming-Chia; Kao, Chia-Hung

    2016-01-01

    Abstract We investigated the relationship between morphine treatment and the risk of atrial fibrillation (AF) in female patients with breast cancer. We identified a malignancy cohort of 73,917 female breast cancer patients without an AF history before the date of breast cancer diagnosis between 2000 and 2010 by using the Longitudinal Health Insurance Database for Catastrophic Illness Patients in Taiwan. This malignancy cohort was divided into morphine and comparison cohorts comprising 18,671 and 55,246 patients, respectively, and the incidences of newly diagnosed AF were calculated. We used the Cox proportional hazard model with time-dependent exposure covariates to estimate the risk of AF. The effect of morphine was assessed through multivariable Cox proportional hazard regression controlling for age, the Charlson comorbidity index (CCI) score, and the use of bisphosphonates and paclitaxel. Compared with nonmorphine users, patients who received morphine exhibited a 4.37-fold (95% CI = 3.56–5.36) increase in the risk of developing AF. The risk of AF increased as the CCI score increased, but decreased in patients with tamoxifen treatment. This risk is especially significant in current morphine users of all ages and with low CCI score. AF risk increased as the duration of morphine use lengthened (P for trend <0.0001). The incidence of AF in female breast cancer patients in Taiwan is associated with morphine, but prevented by tamoxifen treatment. PMID:26986153

  5. Ternary complex formation and competition quench fluorescence of ZnAF family zinc sensors.

    PubMed

    Staszewska, Anna; Kurowska, Ewa; Bal, Wojciech

    2013-11-01

    Our current understanding of the intracellular thermodynamics and kinetics of Zn(ii) ions is largely based on the application of fluorescent sensor molecules, used to study and visualize the concentration, distribution and transport of Zn(ii) ions in real time. Such agents are designed for high selectivity for zinc in respect to other biological metal ions. However, the issue of their sensitivity to physiological levels of low molecular weight Zn(ii) ligands (LMWLs) has not been addressed. We followed the effects of eight such compounds on the fluorescence of ZnAF-1 and ZnAF-2F, two representatives of the ZnAF family of fluorescein-based zinc sensors containing the N,N-bis(2-pyridylmethyl)ethylenediamine chelating unit. Fluorescence titrations of equimolar Zn(ii)-ZnAF-1 and Zn(ii)-ZnAF-2F solutions with acetate, phosphate, citrate, glycine, glutamic acid, histidine, ATP and GSH demonstrated strong fluorescence quenching. These results are interpreted in terms of an interplay of the formation of the [ZnAF-Zn(ii)-LMWL] ternary complexes and the competition for Zn(ii) between ZnAF and LMWLs. UV-vis spectroscopic titrations revealed the existence of supramolecular interactions between the fluorescein moiety of ZnAF-1 and ATP and His, which, however, did not contribute to fluorescence quenching. Therefore, the obtained results show that the ZnAF sensors, other currently used zinc sensors containing the N,N-bis(2-pyridylmethyl)ethylenediamine unit, and, in general, all sensors that do not saturate the Zn(ii) coordination sphere may co-report cellular metabolites and Zn(ii) ions, leading to misrepresentations of the concentrations and fluxes of biological zinc. PMID:23939683

  6. Effect of early direct current cardioversion on the recurrence of atrial fibrillation in patients with persistent atrial fibrillation.

    PubMed

    Osmanagic, Armin; Möller, Sören; Osmanagic, Azra; Sheta, Hussam M; Vinther, Kristina H; Egstrup, Kenneth

    2015-07-15

    In patients with persistent atrial fibrillation (AF), the sinus rhythm (SR) can be restored by direct current cardioversion (DCC), although the recurrence of AF after successful DCC is common. We examined whether transesophageal echocardiography (TEE)-guided early DCC, compared with the conventional approach of DCC after 3 weeks of anticoagulation with dabigatran-etexilat, reduces the recurrence of AF. A total of 126 consecutive patients with persistent AF were randomly assigned to a TEE followed by early DCC (n = 65) or to a conventional treatment with dabigatran-etexilat for 3 weeks followed by DCC (n = 61). None of the patients received any antiarrhythmic treatment other than β blockers, and all the DCCs were successful. Forty-eight-hour Holter monitoring was performed at 28 days and at 3, 6, and 12 months after the DCC. The primary outcome was AF recurrence lasting ≥30 seconds. The analysis was stratified by AF duration <60 (n = 62) or >60 days (n = 64) before DCC. We observed a significant reduction in the AF recurrence risk (p = 0.003) in patients with persistent AF <60 days who received early DCC, but there was no significant benefit of early DCC (p = 0.456) in patients with persistent AF lasting >60 days. The recurrence-free survival probability at 28 days in patients with persistent AF <60 days was 0.27 (95% confidence interval 0.14 to 0.51) in the conventional treatment group compared with 0.69 (95% confidence interval 0.54 to 0.87; p = 0.006) in the early DCC group. A benefit of early DCC persisted throughout 12 months of follow-up. In conclusion, TEE-guided early DCC in patients with persistent AF <60 days results in a significant reduction of AF recurrence. PMID:25972054

  7. Incremental Value of Left Atrial Global Longitudinal Strain for Prediction of Post Stroke Atrial Fibrillation in Patients with Acute Ischemic Stroke

    PubMed Central

    Kim, Darae; Cho, In Jeong; Kim, Young Dae; Nam, Hyo Suk; Chang, Hyuk-Jae; Hong, Geu-Ru; Ha, Jong-Won; Heo, Ji Hoe; Chung, Namsik

    2016-01-01

    Background Atrial fibrillation (AF) is a well-established risk factor for stroke. Interestingly, ischemic stroke increases risk of incident AF in patients without prior diagnosed AF. For better risk stratification for post-stroke AF, we studied left atrial (LA) size and mechanical function using two-dimensional (2D) speckle tracking imaging in patients with acute ischemic stroke. Methods A total of 227 patients (132 males, age 67 ± 12) with acute ischemic stroke without a history of AF underwent 2D transthoracic echocardiography and speckle tracking imaging for the assessment of LA volume index and global LA longitudinal strain (LALS). From clinical variables, the CHA2DS2-VASc score and National Institute of Health Stroke Scale (NIHSS) were calculated in each patient. Post-stroke AF was defined as newly diagnosed AF during the course after ischemic stroke. Results Post-stroke AF occurred in 25 patients (11%). Patients with post-stroke AF were older and showed a higher tendency of CHA2DS2-VASc score, significantly higher log NIHSS, larger LA volume index and lower global LALS than those without. In multivariate analysis, global LALS was an independent predictor for post-stroke AF (hazard ratio 0.90, 95% confidence interval 0.83.0.97, p < 0.01) after controlling for confounding factors. Furthermore, global LALS provided incremental predictive value for post-stroke AF over the CHA2DS2-VASc score, NIHSS, and LA volume index. The global LALS < 14.5% better distinguished post-stroke AF (area under the curve 0.837, sensitivity 60%, specificity 95%, p < 0.01) than CHA2DS2-VASc score. Conclusion Global LALS as a marker of LA mechanical function has incremental predictive value for post-stroke AF in patients with acute ischemic stroke. PMID:27081440

  8. Relaxin Level in Patients With Atrial Fibrillation and Association with Heart Failure Occurrence

    PubMed Central

    Zhou, Hao; Qu, Xiang; Gao, Zhan; Zheng, Gaoshu; Lin, Jie; Su, Lan; Huang, Zhouqing; Li, Haiying; Huang, Weijian

    2016-01-01

    Abstract Atrial fibrillation (AF) is the most common arrhythmia requiring medical treatment and has been associated with enhanced atrial fibrosis and heart failure (HF). Relaxin (RLX), an antifibrosis and antiinflammatory peptide hormone, may be used to evaluate atrial fibrosis and is associated with HF occurrence in AF. We aimed to clarify the clinical significance of RLX level in patients with AF. We measured circulating levels of RLX and other fibrosis-related factors in 311 patients with sinus rhythm (SR; n = 116) or AF (n = 195). All discharged AF patients were followed up for the occurrence of HF for a mean of 6 months. Circulating levels of RLX were significantly different in patients with AF as compared with SR (P < 0.001), and in the subgroup analysis of AF. RLX level was correlated with left atrial diameter (LAD; R = 0.358, P < 0.001). Among followed up AF patients, on Kaplan–Meier curve analysis, patients with the third RLX tertile (T3) had a significantly higher HF rate than those with the 1st tertile (T1) (P = 0.002) and the cut-off value was 294.8 ng/L (area under the ROC curve [AUC] = 0.723). On multivariable analysis, HF occurrence with AF was associated with increased tertile of serum RLX level (odds ratio [OR] 2.659; confidence interval [95% CI] 1.434–4.930; P = 0.002). RLX is associated with fibrosis-related biomarkers and significantly elevated in AF. RLX was related to the HF occurrence in patients with AF. PMID:27227926

  9. Injury of the Arcuate Fasciculus in the Dominant Hemisphere in Patients With Mild Traumatic Brain Injury

    PubMed Central

    Jang, Sung Ho; Lee, Ah Young; Shin, So Min

    2016-01-01

    Abstract Little is known about injury of the arcuate fasciculus (AF) in patients with mild traumatic brain injury (TBI). We investigated injury of the AF in the dominant hemisphere in patients with mild TBI, using diffusion tensor tractography (DTT). We recruited 25 patients with injury of the left AF among 64 right-handed consecutive patients with mild TBI and 20 normal control subjects. DTTs of the left AF were reconstructed, and fractional anisotropy (FA), apparent diffusion coefficient (ADC), and fiber number of the AF were measured. Among 64 consecutive patients, 25 (39%) patients showed injury of the left AF. The patient group showed lower FA value and fiber number with higher ADC value than the control group (P < 0.05). On K-WAB evaluation, aphasia quotient and language quotient were 95.9 ± 4.1 (range 85–100) and 95.0 ± 5.4 (range 80–100), respectively. However, 23 (92.0%) of 25 patients complained of language-related symptoms after TBI; paraphasia in 12 (48.0%) patients, deficits of comprehension in 4 (16.0%) patients, deficits of speech production in 1 (4.0%) patient, and >2 language symptoms in 6 (24.0%) patients. We found that a significant number (39%) of patients with mild TBI had injury of the AF in the dominant hemisphere and these patients had mild language deficit. These results suggest that DTT could provide useful information in detecting injury of the AF and evaluation of the AF using DTT would be necessary even in the case of a patient with mild TBI who complains of mild language deficit. PMID:26945425

  10. The Inhibition of Inflammasome by Brazilian Propolis (EPP-AF)

    PubMed Central

    Hori, Juliana I.; Zamboni, Dario S.; Carrão, Daniel B.; Goldman, Gustavo Henrique; Berretta, Andresa A.

    2013-01-01

    Propolis extracts have gained the attention of consumers and researchers due to their unique chemical compositions and functional properties such as its anti-inflammatory activity. Recently, it was described a complex that is also important in inflammatory processes, named inflammasome. The inflammasomes are a large molecular platform formed in the cell cytosol in response to stress signals, toxins, and microbial infections. Once activated, the inflammasome induces caspase-1, which in turn induces the processing of inflammatory cytokines such as IL-1β and IL-18. So, to understand inflammasomes regulation becomes crucial to treat several disorders including autoinflammatory diseases. Since green propolis extracts are able to regulate inflammatory pathways, this work purpose was to investigate if this extract could also act on inflammasomes regulation. First, the extract was characterized and it demonstrated the presence of important compounds, especially Artepillin C. This extract was effective in reducing the IL-1β secretion in mouse macrophages and this reduction was correlated with a decrease in activation of the protease caspase-1. Furthermore, we found that the extract at a concentration of 30 μg/mL was not toxic to the cells even after a 18-hour treatment. Altogether, these data indicate that Brazilian green propolis (EPP-AF) extract has a role in regulating the inflammasomes. PMID:23690844

  11. Flacourtosides A-F, phenolic glycosides isolated from Flacourtia ramontchi.

    PubMed

    Bourjot, Mélanie; Leyssen, Pieter; Eydoux, Cécilia; Guillemot, Jean-Claude; Canard, Bruno; Rasoanaivo, Philippe; Guéritte, Françoise; Litaudon, Marc

    2012-04-27

    In an effort to identify novel inhibitors of chikungunya (CHIKV) and dengue (DENV) virus replication, a systematic study with 820 ethyl acetate extracts of madagascan plants was performed in a virus-cell-based assay for CHIKV, and a DENV NS5 RNA-dependent RNA polymerase (RdRp) assay. The extract obtained from the stem bark of Flacourtia ramontchi was selected for its significant activity in both assays. Six new phenolic glycosides, named flacourtosides A-F (1-6), phenolic glycosides itoside H, xylosmin, scolochinenoside D, and poliothrysoside, and betulinic acid 3β-caffeate were obtained using the bioassay-guided isolation process. Their structures were elucidated by comprehensive analyses of NMR spectroscopic and mass spectrometric data. Even though several extracts and fractions showed significant selective antiviral activity in the CHIKV virus-cell-based assay, none of the purified compounds did. However, in the DENV RNA polymerase assay, significant inhibition was observed with betulinic acid 3β-caffeate (IC(50) = 0.85 ± 0.1 μM) and to a lesser extent for the flacourtosides A and E (1 and 5, respectively), and scolochinenoside D (IC(50) values ~10 μM). PMID:22439591

  12. The gene for human U2 snRNP auxiliary factor small 35-kDa subunit (U2AF1) maps to the progressive myoclonus epilepsy (EPM1) critical region on chromosome 21q22.3

    SciTech Connect

    Lalioti, M.D.; Rossier, C.; Antonarakis, S.E.

    1996-04-15

    We used targeted exon trapping to clone portions of genes from human chromosome 21q22.3. One trapped sequence showed complete homology with the cDNA of human U2AF{sup 35} (M96982; HGM-approved nomenclature U2AF1), which encodes for the small 35-kDa subunit of the U2 snRNP auxiliary factor. Using the U2AF1 cDNA as a probe, we mapped this gene to cosmid Q15D2, a P1, and YAC 350F7 of the Chumakov et al. contig, close to the cystathionine-{beta}-synthase gene (CBS) on 21q22.3. This localization was confirmed by PCR using oligonucleotides from the 3{prime} UTR and by FISH. As U2AF1 associated with a number of different factors during mRNA splicing, overexpression in trisomy 21 individuals could contribute to some Down syndrome phenotypes by interfering with the splicing process. Furthermore, because this gene maps in the critical region for the progressive myoclonus epilepsy I locus (EPM1), mutation analysis will be carried out in patients to evaluate the potential role of U2AF1 as a candidate for EPM1. 24 refs., 1 fig.

  13. MLL-AF9 Expression in Hematopoietic Stem Cells Drives a Highly Invasive AML Expressing EMT-Related Genes Linked to Poor Outcome.

    PubMed

    Stavropoulou, Vaia; Kaspar, Susanne; Brault, Laurent; Sanders, Mathijs A; Juge, Sabine; Morettini, Stefano; Tzankov, Alexandar; Iacovino, Michelina; Lau, I-Jun; Milne, Thomas A; Royo, Hélène; Kyba, Michael; Valk, Peter J M; Peters, Antoine H F M; Schwaller, Juerg

    2016-07-11

    To address the impact of cellular origin on acute myeloid leukemia (AML), we generated an inducible transgenic mouse model for MLL-AF9-driven leukemia. MLL-AF9 expression in long-term hematopoietic stem cells (LT-HSC) in vitro resulted in dispersed clonogenic growth and expression of genes involved in migration and invasion. In vivo, 20% LT-HSC-derived AML were particularly aggressive with extensive tissue infiltration, chemoresistance, and expressed genes related to epithelial-mesenchymal transition (EMT) in solid cancers. Knockdown of the EMT regulator ZEB1 significantly reduced leukemic blast invasion. By classifying mouse and human leukemias according to Evi1/EVI1 and Erg/ERG expression, reflecting aggressiveness and cell of origin, and performing comparative transcriptomics, we identified several EMT-related genes that were significantly associated with poor overall survival of AML patients. PMID:27344946

  14. Right Ventricular and Right Atrial Involvement Can Predict Atrial Fibrillation in Patients with Hypertrophic Cardiomyopathy?

    PubMed Central

    Doesch, Christina; Lossnitzer, Dirk; Rudic, Boris; Tueluemen, Erol; Budjan, Johannes; Haubenreisser, Holger; Henzler, Thomas; Schoenberg, Stefan O.; Borggrefe, Martin; Papavassiliu, Theano

    2016-01-01

    Objectives and Background: Atrial fibrillation (AF) is associated with clinical deterioration, stroke and disability in patients with hypertrophic cardiomyopathy (HCM). Therefore, the objective of this study was to evaluated cardiac magnetic resonance (CMR)-derived determinants for the occurrence of AF in patients with HCM. Methods: 98 Patients with HCM and 30 healthy controls underwent CMR and were followed-up for 6±3 years. Results: 19 (19.4%) patients presented with AF at initial diagnosis, 19 (19.4%) developed AF during follow-up and 60 (61.2%) remained in sinus rhythm (SR). Compared to healthy controls, patients with HCM who remained in SR presented with significantly increased left ventricular mass, an elevated left ventricular remodeling index, enlarged left atrial volumes and reduced septal mitral annular plane systolic excursion (MAPSE) compared to healthy controls. Whereas HCM patients who presented with AF at initial diagnosis and those who developed AF during follow-up additionally presented with reduced tricuspid annular plane systolic excursion (TAPSE) and right atrial (RA) dilatation. Receiver-operator curve analysis indicated good predictive performance of TAPSE, RA diameter and septal MAPSE (AUC 0.73, 0.69 and 0.71, respectively) to detect patients at risk of developing AF. Conclusion: Reduced MAPSE measurements and enlarged LA volumes seems to be a common feature in patients with HCM, whereas reduced TAPSE and RA dilatation only seem to be altered in patients with history of AF and those developing AF. Therefore, they could serve as easy determinable markers of AF in patients with HCM. PMID:26812947

  15. Antithrombotic Treatments for Stroke Prevention in Elderly Patients With Nonvalvular Atrial Fibrillation: Drugs and Doses.

    PubMed

    Kilickap, Mustafa; Bosch, Jackie; Eikelboom, John W; Hart, Robert G

    2016-09-01

    Atrial fibrillation (AF) is a common cardiac rhythm disturbance and is associated with a 5-fold increased risk of stroke. The most important risk factors for stroke in patients with AF are previous stroke and age ≥ 75 years. Canadian guidelines recommend anticoagulant therapy for patients with AF who are older than the age of 65 years, but the elderly often remain undertreated, primarily because of concerns regarding bleeding. Non-vitamin K oral anticoagulants appear to be safer, at least as efficacious, and more convenient than warfarin, and are a cost-effective alternative for elderly patients with AF. We review the evidence for the use of antithrombotic agents for stroke prevention in elderly patients (age ≥ 75 years) with nonvalvular AF. PMID:27568871

  16. Validation of a simple method for atrial fibrillation screening in patients with stroke.

    PubMed

    Gandolfo, C; Balestrino, M; Bruno, C; Finocchi, C; Reale, N

    2015-09-01

    Atrial fibrillation (AF) is the most common cardiac arrhythmia in adult and old people and represents a risk factor for stroke. Correct AF individuation bears strong relevance in primary and secondary stroke prevention. Our goal was to evaluate the reliability of a low-cost, non-invasive technology in detecting AF in acute stroke patients. AFib model BP3MQ1-2D (Microlife USA, Dunedin, FL) showed good accuracy in diagnosing AF in a general cardiologic outpatient population. We carried out an observational study in patients with recent stroke. We studied 207 subjects, 103 men, 104 women, mean age (±SD) 77.7 ± 11.34 years, who underwent a test by AFib device with indication of AF or lack of it. The golden standard was a 12-lead EKG done immediately and evaluated by a certified cardiologist. We computed estimates of Sensitivity and Specificity and their 95 % confidence intervals (CI). AF was present in 38 subjects from the sample of 207 (18.4 %). AFib correctly demonstrated AF in 34 and failed diagnosing AF in 4 cases; on the other hand, AFib correctly excluded AF in 167 and caused an erroneous diagnosis of AF in 2 cases. The Sensitivity was 0.895 (95 % CI 0.7597-0.958) and the Specificity was 0.988 (95 % CI 0.958-0.997). The AFib device global accuracy was 0.971 (95 % CI 0.938-0.987). This device was able to detect AF with high specificity and a good sensitivity. This device may be considered as an accurate tool in detecting AF in stroke patients. PMID:25926072

  17. Anaerobic treatment of strong sewage by a two stage system of AF and UASB reactors.

    PubMed

    Sawajneh, Z; Al-Omari, A; Halalsheh, M

    2010-01-01

    An anaerobic treatment system that consists of an Anaerobic Filter (AF) and an Upflow Anaerobic Sludge Blanket (UASB) in series was built and operated to investigate its performance in treating strong domestic wastewater with high suspended solids fraction under Jordan's ambient temperatures of 25 degrees C for summer and 18 degrees C for winter. The system was operated from September 2003 until early April 2004. The system was operated at a Hydraulic Retention Time (HRT) of 4 hours for the first stage AF and 8 hours for the second stage UASB. Average COD(t) and COD(ss) removal efficiencies of the AF/UASB were 58% and 81% respectively for the operation period. The results showed that the first stage AF was effective in removing suspended solids. In addition, hydrolysis, acidification and methanogenesis took place in the first stage AF which was advantageous to the second stage UASB. It was concluded that the AF/UASB system is effective in treating strong domestic wastewater with high suspended solids content under Jordan's ambient temperatures. PMID:20418638

  18. PUF60: a novel U2AF65-related splicing activity.

    PubMed Central

    Page-McCaw, P S; Amonlirdviman, K; Sharp, P A

    1999-01-01

    We have identified a new pyrimidine-tract binding factor, PUF, that is required, together with U2AF, for efficient reconstitution of RNA splicing in vitro. The activity has been purified and consists of two proteins, PUF60 and the previously described splicing factor p54. p54 and PUF60 form a stable complex in vitro when cotranslated in a reaction mixture. PUF activity, in conjunction with U2AF, facilitates the association of U2 snRNP with the pre-mRNA. This reaction is dependent upon the presence of the large subunit of U2AF, U2AF65, but not the small subunit U2AF35. PUF60 is homologous to both U2AF65 and the yeast splicing factor Mud2p. The C-terminal domain of PUF60, the PUMP domain, is distantly related to the RNA-recognition motif domain, and is probably important in protein-protein interactions. PMID:10606266

  19. Oxygen tolerance capacity of upflow anaerobic solid-state (UASS) with anaerobic filter (AF) system.

    PubMed

    Meng, Yao; Jost, Carsten; Mumme, Jan; Wang, Kaijun; Linke, Bernd

    2016-07-01

    In order to investigate the oxygen tolerance capacity of upflow anaerobic solid-state (UASS) with anaerobic filter (AF) system, the effect of microaeration on thermophilic anaerobic digestion of maize straw was investigated under batch conditions and in the UASS with AF system. Aeration intensities of 0-431mL O2/gvs were conducted as pretreatment under batch conditions. Aeration pretreatment obviously enhanced anaerobic digestion and an aeration intensity of 431mL O2/gvs increased the methane yield by 82.2%. Aeration intensities of 0-355mL O2/gvs were conducted in the process liquor circulation of the UASS with AF system. Dissolved oxygen (DO) of UASS and AF reactors kept around 1.39±0.27 and 0.99±0.38mg/L, respectively. pH was relatively stable around 7.11±0.04. Volatile fatty acids and soluble chemical oxygen demand concentration in UASS reactor were higher than those in AF reactor. Methane yield of the whole system was almost stable at 85±7mL/gvs as aeration intensity increased step by step. The UASS with AF system showed good oxygen tolerance capacity. PMID:27372134

  20. Lower preoperative fluctuation of heart rate variability is an independent risk factor for postoperative atrial fibrillation in patients undergoing major pulmonary resection

    PubMed Central

    Ciszewski, Pawel; Tyczka, Joanna; Nadolski, Jacek; Roszak, Magdalena; Dyszkiewicz, Wojciech

    2013-01-01

    OBJECTIVES The following study presents a special independent atrial fibrillation (AF) risk factor—preoperative fluctuation of heart rate variability (HRV), as well as other perioperative AF risk factors in patients qualified for pneumonectomy and undergoing pneumonectomy or lobectomy for lung cancer. METHODS The prospective study was performed in patients who had undergone anatomical resection for non-small-cell lung cancer. A total of 117 patients (92 men and 25 women) qualified for statistical research. In order to determine the risk factors, all patients were divided into two groups: Group A—98 patients without AF and Group B—19 patients with AF during the perioperative time. A number of different risk factors of AF have been analysed and further divided into preoperative, operative and postoperative. RESULTS Postoperative AF occurred in 19 patients (16%), all of them were male. The patients with higher short-term HRV parameters (SD1, RMSSD), slower mean heart rate and those with a lower fluctuation of HRV-related parameters (HRV Afternoon, Night, Day (A/N/D)) before the operation, were more prone to AF. Postoperative risk of AF was higher in patients with a higher number of ventricular ectopic beats before the operation, a higher number of supraventricular and ventricular ectopic beats and a higher maximal heart rate after the operation. Statistical analysis revealed that male gender and the extent of pulmonary resection, particularly left pneumonectomy, constituted significant risk factors. AF was more often observed in patients who had ASA physical status score of III, in comparison with ASAI and ASAII patients. CONCLUSIONS Along with other concomitant AF risk factors presented in this work, the evaluation of the fluctuation tendencies of HRV parameters should be taken into consideration before any major lung resection. The balance disturbance between the sympathetic and parasympathetic nervous systems is responsible for AF. PMID:23832838

  1. Primary prevention of atrial fibrillation with beta-blockers in patients with end-stage renal disease undergoing dialysis

    PubMed Central

    Lin, Ting-Tse; Chiang, Jiun-Yang; Liao, Min-Tsun; Tsai, Chia-Ti; Hwang, Juey Jen; Chiang, Fu-Tien; Lin, Jiunn-Lee; Lin, Lian-Yu

    2015-01-01

    Current evidence suggests that beta-blocker lower the risk of development of atrial fibrillation (AF) and in-hospital stroke after cardiac surgery. This study was to assess whether beta-blockers could decrease incidence of new-onset AF in patients with end stage renal disease (ESRD). We identified patients from a nation-wide database called Registry for Catastrophic Illness, which encompassed almost 100% of the patients receiving dialysis therapy in Taiwan from 1995 to 2008. Propensity score matching and Cox’s proportional hazards regression model were used to estimate hazard ratios (HRs) for new-onset AF. Among 100066 patients, 41.7% received beta-blockers. After a median follow-up of 1500 days, the incidence of new-onset AF significantly decreased in patients treated with beta-blockers (HR = 0.483, 95% confidence interval = 0.437-0.534). The prevention of new-onset AF was significantly better in patients taking longer duration of beta-blockers therapy (P for time trend <0.001). The AF prevention effect remains robust in subgroup analyses. In conclusion, beta-blockers seem effective in the primary prevention of AF in ESRD patients. Hence, beta-blockers may be the target about upstream treatment of AF. PMID:26643783

  2. Anticoagulation Management in Patients with Pacemaker-Detected Atrial Fibrillation

    PubMed Central

    Poposka, Lidija; Boskov, Vladimir; Risteski, Dejan; Taleski, Jane; Georgievska-Ismail, Ljubica

    2016-01-01

    INTRODUCTION: In patients with an implanted pacemaker, asymptomatic atrial fibrillation (AF) is associated with an increased risk of thrombo-embolic complications. There is still no consensus which duration of episodes of atrial fibrillation should be taken as an indicator for inclusion of oral anticoagulation therapy (OAC). MATERIAL AND METHODS: A total of 104 patients who had no AF episodes in the past and have an indication for permanent pacing were included in the study. RESULTS: During an average follow-up of 18 months, 33 of the patients developed episodes of AF. Inclusion of OAC was performed in 17 patients, in whom AF was recorded, although in all patients CHA2DS2-VASc score was ≥ 1. The inclusion of OAC showed a statistically significant correlation with increasing duration of episodes of AF (r = 0.502, p = 0.003). During the follow-up period none of the patients developed thrombo-embolic complication. CONCLUSION: Considering that our group of patients had no thrombo-embolic events, we could conclude that dividing the AF episodes in less than 1% in 24 hours and longer than 1% within 24 hours could be an indicator for decision-making to include OAK if the CHA2DS2-VASc score is ≥ 1. PMID:27335594

  3. The Prevalence and Incidence of Atrial Fibrillation in Patients with Acute Pulmonary Embolism

    PubMed Central

    Lau, Jerrett K.; Yong, Andy Sze Chiang; Chow, Vincent; Kritharides, Leonard

    2016-01-01

    Background Symptomatic pulmonary embolism (PE) is a major cause of cardiovascular death and morbidity. Estimated prevalence and incidence of atrial fibrillation (AF) in developed countries are between 388–661 per 100,000, and 90–123 per 100,000 person-years respectively. However, the prevalence and incidence of AF in patients presenting with an acute PE and its predictors are not clear. Methods Individual patient clinical details were retrieved from a database containing all confirmed acute PE presentations to a tertiary institution from 2001–2012. Prevalence and incidence of AF was tracked from a population registry by systematically searching for AF during any hospital admission (2000–2013) based on International Classification of Disease (ICD-10) code. Results Of the 1,142 patients included in this study, 935 (81.9%) had no AF during index PE admission whilst 207 patients had documented baseline AF (prevalence rate 18,126 per 100,000; age-adjusted 4,672 per 100,000). Of the 935 patients without AF, 126 developed AF post-PE (incidence rate 2,778 per 100,000 person-years; age-adjusted 984 per 100,000 person-years). Mean time from PE to subsequent AF was 3.4 ± 2.9 years. Total mortality (mean follow-up 5.0 ± 3.7 years) was 42% (n = 478): 35% (n = 283), 59% (n = 119) and 60% (n = 76) in the no AF, baseline AF and subsequent AF cohorts respectively. Independent predictors for subsequent AF after acute PE include age (hazard ratio [HR] 1.06, 95% confidence interval [CI] 1.04–1.08, p<0.001), history of congestive cardiac failure (HR 1.88, 95% CI 1.12–3.16, p = 0.02), diabetes (HR 1.72, 95% CI 1.07–2.77, p = 0.02), obstructive sleep apnea (HR 4.83, 1.48–15.8, p = 0.009) and day-1 serum sodium level during index PE admission (HR 0.94, 95% CI 0.90–0.98, p = 0.002). Conclusions Patients presenting with acute PE have a markedly increased age-adjusted prevalence and subsequent incidence of AF. Screening for AF may be of importance post-PE. PMID:26930405

  4. The Registry of the German Competence NETwork on Atrial Fibrillation: patient characteristics and initial management

    PubMed Central

    Nabauer, Michael; Gerth, Andrea; Limbourg, Tobias; Schneider, Steffen; Oeff, Michael; Kirchhof, Paulus; Goette, Andreas; Lewalter, Thorsten; Ravens, Ursula; Meinertz, Thomas; Breithardt, Günter; Steinbeck, Gerhard

    2009-01-01

    Aims The aim of this study was to describe the characteristics of patients with atrial fibrillation (AF) enrolled in the Central Registry of the German Competence NETwork on Atrial Fibrillation (AFNET) and to assess current medical practice in patients treated at various levels of medical care in Germany. Methods and results From February 2004 to March 2006, 9582 ambulatory and hospitalized patients with ECG-documented AF were enrolled by 194 participating study centres from all levels of medical care in Germany. Clinical type of AF was reported as paroxysmal in 2893, persistent in 1873, and permanent in 3134 patients or classified as a first episode in 1035 patients. Predisposing conditions were common and present in 87.6% of the patients. Most patients were symptomatic with AF (75.1%). Rhythm control in persistent AF was provided to 53.4% of the symptomatic patients and to 47.8% of the patients without symptoms. Anticoagulation for stroke prevention was given to 71.4% of the patients considered eligible by applicable guidelines and to 48.4% of patients with low risk where guidelines do not recommend anticoagulation. Conclusion This registry provides insight into current medical care of patients with AF in Germany. The use of oral anticoagulation in eligible patients was among the highest reported, whereas decisions on rate and rhythm control often do not follow current recommendations. PMID:19153087

  5. Standardized Prevalence Ratios for Atrial Fibrillation in Adult Dialysis Patients in Japan

    PubMed Central

    Ohsawa, Masaki; Tanno, Kozo; Okamura, Tomonori; Yonekura, Yuki; Kato, Karen; Fujishima, Yosuke; Obara, Wataru; Abe, Takaya; Itai, Kazuyoshi; Ogasawara, Kuniaki; Omama, Shinichi; Turin, Tanvir Chowdhury; Miyamatsu, Naomi; Ishibashi, Yasuhiro; Morino, Yoshihiro; Itoh, Tomonori; Onoda, Toshiyuki; Kuribayashi, Toru; Makita, Shinji; Yoshida, Yuki; Nakamura, Motoyuki; Tanaka, Fumitaka; Ohta, Mutsuko; Sakata, Kiyomi; Okayama, Akira

    2016-01-01

    Background While it is assumed that dialysis patients in Japan have a higher prevalence of atrial fibrillation (AF) than the general population, the magnitude of this difference is not known. Methods Standardized prevalence ratios (SPRs) for AF in dialysis patients (n = 1510) were calculated compared to data from the general population (n = 26 454) living in the same area. Results The prevalences of AF were 3.8% and 1.6% in dialysis patients and the general population, respectively. In male subjects, these respective values were 4.9% and 3.3%, and in female subjects they were 1.6% and 0.6%. The SPRs for AF were 2.53 (95% confidence interval [CI], 1.88–3.19) in all dialysis patients, 1.80 (95% CI, 1.30–2.29) in male dialysis patients, and 2.13 (95% CI, 0.66–3.61) in female dialysis patients. Conclusions The prevalence of AF in dialysis patients was twice that in the population-based controls. Since AF strongly contributes to a higher risk of cardiovascular mortality and morbidity in the general population, further longitudinal studies should be conducted regarding the risk of several outcomes attributable to AF among Japanese dialysis patients. PMID:26804038

  6. Relaxin Level in Patients With Atrial Fibrillation and Association with Heart Failure Occurrence: A STROBE Compliant Article.

    PubMed

    Zhou, Hao; Qu, Xiang; Gao, Zhan; Zheng, Gaoshu; Lin, Jie; Su, Lan; Huang, Zhouqing; Li, Haiying; Huang, Weijian

    2016-05-01

    Atrial fibrillation (AF) is the most common arrhythmia requiring medical treatment and has been associated with enhanced atrial fibrosis and heart failure (HF). Relaxin (RLX), an antifibrosis and antiinflammatory peptide hormone, may be used to evaluate atrial fibrosis and is associated with HF occurrence in AF. We aimed to clarify the clinical significance of RLX level in patients with AF.We measured circulating levels of RLX and other fibrosis-related factors in 311 patients with sinus rhythm (SR; n = 116) or AF (n = 195). All discharged AF patients were followed up for the occurrence of HF for a mean of 6 months.Circulating levels of RLX were significantly different in patients with AF as compared with SR (P < 0.001), and in the subgroup analysis of AF. RLX level was correlated with left atrial diameter (LAD; R = 0.358, P < 0.001). Among followed up AF patients, on Kaplan-Meier curve analysis, patients with the third RLX tertile (T3) had a significantly higher HF rate than those with the 1st tertile (T1) (P = 0.002) and the cut-off value was 294.8 ng/L (area under the ROC curve [AUC] = 0.723). On multivariable analysis, HF occurrence with AF was associated with increased tertile of serum RLX level (odds ratio [OR] 2.659; confidence interval [95% CI] 1.434-4.930; P = 0.002).RLX is associated with fibrosis-related biomarkers and significantly elevated in AF. RLX was related to the HF occurrence in patients with AF. PMID:27227926

  7. AF9 promotes hESC neural differentiation through recruiting TET2 to neurodevelopmental gene loci for methylcytosine hydroxylation

    PubMed Central

    Qiao, Yunbo; Wang, Xiongjun; Wang, Ran; Li, Yuanyuan; Yu, Fang; Yang, Xianfa; Song, Lu; Xu, Guoliang; Chin, Y Eugene; Jing, Naihe

    2015-01-01

    AF9 mutations have been implicated in human neurodevelopmental diseases and murine Af9 mediates histone methylation during cortical neuron generation. However, AF9 function and related mechanisms in human neurodevelopment remain unknown. Here we show that AF9 is necessary and sufficient for human embryonic stem cell (hESC) neural differentiation and neurodevelopmental gene activation. The 5-methylcytosine (5mC) dioxygenase TET2, which was identified in an AF9-associated protein complex, physically interacted with AF9. Both AF9 and TET2 co-localized in 5-hydroxymethylcytosine (5hmC)-positive hESC-derived neurons and were required for appropriate hESC neural differentiation. Upon binding to AAC-containing motifs, AF9 recruited TET2 to occupy the common neurodevelopmental gene loci to direct 5mC-to-5hmC conversion, which was followed by sequential activation of neural target genes and hESC neural commitment. These findings define an AF9–TET2 regulatory complex for modulating human neural development and reveal a novel mechanism by which the AF9 recognition specificity and TET2 hydroxylation activity cooperate to control neurodevelopmental gene activation. PMID:27462416

  8. Direct oral anticoagulants: key considerations for use to prevent stroke in patients with nonvalvular atrial fibrillation

    PubMed Central

    Ment, Jerome

    2015-01-01

    Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide. Strokes that occur as a complication of AF are usually more severe and associated with a higher disability or morbidity and mortality rate compared with non-AF-related strokes. The risk of stroke in AF is dependent on several risk factors; AF itself acts as an independent risk factor for stroke. The combination of effective anticoagulation therapy, risk stratification (based on stroke risk scores, such as CHADS2 and CHA2DS2-VASc), and recommendations provided by guidelines is essential for decreasing the risk of stroke in patients with AF. Although effective in preventing the occurrence of stroke, vitamin K antagonists (VKAs; eg, warfarin) are associated with several limitations. Therefore, direct oral anticoagulants, such as apixaban, dabigatran etexilate, edoxaban, and rivaroxaban, have emerged as an alternative to the VKAs for stroke prevention in patients with nonvalvular AF. Compared with the VKAs, these agents have more favorable pharmacological characteristics and, unlike the VKAs, they are given at fixed doses without the need for routine coagulation monitoring. It remains important that physicians use these direct oral anticoagulants responsibly to ensure optimal safety and effectiveness. This article provides an overview of the existing data on the direct oral anticoagulants, focusing on management protocols for aiding physicians to optimize anticoagulant therapy in patients with nonvalvular AF, particularly in special patient populations (eg, those with renal impairment) and other specific clinical situations. PMID:26089678

  9. Characterization of patients with atrial fibrillation not treated with oral anticoagulants

    PubMed Central

    Hägg, Lovisa; Johansson, Lars; Jansson, Jan-Håkan

    2014-01-01

    Abstract Objective. An underuse of oral anticoagulants (OAC) in patients with atrial fibrillation (AF) has been suggested, as only 50% of all patients with AF receive OAC treatment. Whether this is due to contraindications, lack of an indication to treat, or an expression of underuse is sparsely investigated. This study therefore aimed to characterize individuals without OAC treatment in a real-life population of patients with AF. Design. Retrospective cross-sectional study. The medical records were scrutinized in order to identify the type of AF, risk factors for embolism and bleeding, and other factors of importance for OAC treatment. Setting. The municipalities of Skellefteå and Norsjö, northern Sweden. Subjects. A total of 2274 living residents with at least one verified episode of AF on or before December 31, 2010. Main outcome measures. Prevalence of treatment with OAC and documented reasons to withhold OAC treatment. Results. Among all 2274 patients with AF, 1187 (52%) were not treated with OAC. Of the untreated patients, 19% had no indication or had declined or had experienced adverse effects other than bleeding on warfarin treatment. The most common reason to withhold OAC was presence of risk factors for bleeding, found in 38% of all untreated patients. Furthermore, a documented reason could be identified to withhold OAC in 75%. Conclusions. Among patients with AF without OAC treatment a reason could be identified to withhold OAC in 75%. The underuse of OAC is estimated to be 25%. PMID:25464863

  10. Low strain, long life creep fatigue of AF2-1DA and INCO 718

    SciTech Connect

    Thakker, A.B.; Cowles, B.A.

    1983-04-01

    Two aircraft turbine disk alloys, GATORIZED AF2-DA and INCO 718 were evaluated for their low strain long life creep-fatigue behavior. Static (tensile and creep rupture) and cyclic properties of both alloys were characterized. The cntrolled strain LCF tests were conducted at 760 C (1400 F) and 649 C (1200 F) for AF2-1DA and INCO 718, respectively. Hold times were varied for tensile, compressive and tensile/compressive strain dwell (relaxation) tests. Stress (creep) hold behavior of AF2-1DA was also evaluated. Generally, INCO 718 exhibited more pronounced reduction in cyclic life due to hold than AF2-1DA. The percent reduction in life for both alloys for strain dwell tests was greater at low strain ranges (longer life regime). Changing hold time from 0 to 0.5, 2.0 and 15.0 min. resulted in corresponding reductions in life. The continuous cycle and cyclic/dwell initiation failure mechanism was predominantly transgranular for AF2-1DA and intergranular for INCO 718.

  11. A simple web-based tool to compare freshwater fish data collected using AFS standard methods

    USGS Publications Warehouse

    Bonar, Scott A.; Mercado-Silva, Norman; Rahr, Matt; Torrey, Yuta T.; Cate, Averill, Jr.

    2016-01-01

    The American Fisheries Society (AFS) recently published Standard Methods for Sampling North American Freshwater Fishes. Enlisting the expertise of 284 scientists from 107 organizations throughout Canada, Mexico, and the United States, this text was developed to facilitate comparisons of fish data across regions or time. Here we describe a user-friendly web tool that automates among-sample comparisons in individual fish condition, population length-frequency distributions, and catch per unit effort (CPUE) data collected using AFS standard methods. Currently, the web tool (1) provides instantaneous summaries of almost 4,000 data sets of condition, length frequency, and CPUE of common freshwater fishes collected using standard gears in 43 states and provinces; (2) is easily appended with new standardized field data to update subsequent queries and summaries; (3) compares fish data from a particular water body with continent, ecoregion, and state data summaries; and (4) provides additional information about AFS standard fish sampling including benefits, ongoing validation studies, and opportunities to comment on specific methods. The web tool—programmed in a PHP-based Drupal framework—was supported by several AFS Sections, agencies, and universities and is freely available from the AFS website and fisheriesstandardsampling.org. With widespread use, the online tool could become an important resource for fisheries biologists.

  12. GLA-AF, an emulsion-free vaccine adjuvant for pandemic influenza.

    PubMed

    Clegg, Christopher H; Roque, Richard; Perrone, Lucy A; Rininger, Joseph A; Bowen, Richard; Reed, Steven G

    2014-01-01

    The ongoing threat from Influenza necessitates the development of new vaccine and adjuvant technologies that can maximize vaccine immunogenicity, shorten production cycles, and increase global vaccine supply. Currently, the most successful adjuvants for Influenza vaccines are squalene-based oil-in-water emulsions. These adjuvants enhance seroprotective antibody titers to homologous and heterologous strains of virus, and augment a significant dose sparing activity that could improve vaccine manufacturing capacity. As an alternative to an emulsion, we tested a simple lipid-based aqueous formulation containing a synthetic TLR4 ligand (GLA-AF) for its ability to enhance protection against H5N1 infection. GLA-AF was very effective in adjuvanting recombinant H5 hemagglutinin antigen (rH5) in mice and was as potent as the stable emulsion, SE. Both adjuvants induced similar antibody titers using a sub-microgram dose of rH5, and both conferred complete protection against a highly pathogenic H5N1 challenge. However, GLA-AF was the superior adjuvant in ferrets. GLA-AF stimulated a broader antibody response than SE after both the prime and boost immunization with rH5, and ferrets were better protected against homologous and heterologous strains of H5N1 virus. Thus, GLA-AF is a potent emulsion-free adjuvant that warrants consideration for pandemic influenza vaccine development. PMID:24551202

  13. Low strain, long life creep fatigue of AF2-1DA and INCO 718

    NASA Technical Reports Server (NTRS)

    Thakker, A. B.; Cowles, B. A.

    1983-01-01

    Two aircraft turbine disk alloys, GATORIZED AF2-DA and INCO 718 were evaluated for their low strain long life creep-fatigue behavior. Static (tensile and creep rupture) and cyclic properties of both alloys were characterized. The cntrolled strain LCF tests were conducted at 760 C (1400 F) and 649 C (1200 F) for AF2-1DA and INCO 718, respectively. Hold times were varied for tensile, compressive and tensile/compressive strain dwell (relaxation) tests. Stress (creep) hold behavior of AF2-1DA was also evaluated. Generally, INCO 718 exhibited more pronounced reduction in cyclic life due to hold than AF2-1DA. The percent reduction in life for both alloys for strain dwell tests was greater at low strain ranges (longer life regime). Changing hold time from 0 to 0.5, 2.0 and 15.0 min. resulted in corresponding reductions in life. The continuous cycle and cyclic/dwell initiation failure mechanism was predominantly transgranular for AF2-1DA and intergranular for INCO 718.

  14. Effect of X irradiation on optical properties of Teflon-AF

    NASA Astrophysics Data System (ADS)

    Jahan, M. S.; Ermer, D. R.; Cooke, D. W.

    1993-03-01

    Radiation effects in optical-grade amorphous fluoropolymer, Teflon-AF, is investigated by UV-visible absorption and electron spin resonance (ESR) measurements. When irradiated with low-energy (40 kVp) X-rays at room temperature in air, Teflon-AF is found to develop a broad, structureless UV-absorption band in the wavelength interval 200-350 nm. While the UV absorption increases as a function of X-ray dose, with relative rates of approx 2 × 10 -5 Gy -1 (1 × 10 -5 Gy -1) in Teflon-AF 1600 (Teflon-AF 2400), its optical transparency for a given dose of 67.5 kGy, however, remains unaffected. Additional measurements conducted using electron spin resonance (ESR) technique reveal that the observed UV absorption is caused by the X-ray induced peroxy radical (POO .˙). The results also suggest that the inclusion of dioxole monomer in the PTFE chain not only improves the optical clarity of Teflon-AF, as reported, but also increases its radiation tolerance. During a post-irradiation storage in air at RT for about 30 days the peroxy radical is observed to decay, with a concomitant decrease in UV absorption. A tentative model is proposed to explain the radiation damage and recovery mechanisms.

  15. Pseudomonas syringae type III effector HopAF1 suppresses plant immunity by targeting methionine recycling to block ethylene induction

    PubMed Central

    Washington, Erica J.; Mukhtar, M. Shahid; Finkel, Omri M.; Wan, Li; Kieber, Joseph J.; Dangl, Jeffery L.

    2016-01-01

    HopAF1 is a type III effector protein of unknown function encoded in the genomes of several strains of Pseudomonas syringae and other plant pathogens. Structural modeling predicted that HopAF1 is closely related to deamidase proteins. Deamidation is the irreversible substitution of an amide group with a carboxylate group. Several bacterial virulence factors are deamidases that manipulate the activity of specific host protein substrates. We identified Arabidopsis methylthioadenosine nucleosidase proteins MTN1 and MTN2 as putative targets of HopAF1 deamidation. MTNs are enzymes in the Yang cycle, which is essential for the high levels of ethylene biosynthesis in Arabidopsis. We hypothesized that HopAF1 inhibits the host defense response by manipulating MTN activity and consequently ethylene levels. We determined that bacterially delivered HopAF1 inhibits ethylene biosynthesis induced by pathogen-associated molecular patterns and that Arabidopsis mtn1 mtn2 mutant plants phenocopy the effect of HopAF1. Furthermore, we identified two conserved asparagines in MTN1 and MTN2 from Arabidopsis that confer loss of function phenotypes when deamidated via site-specific mutation. These residues are potential targets of HopAF1 deamidation. HopAF1-mediated manipulation of Yang cycle MTN proteins is likely an evolutionarily conserved mechanism whereby HopAF1 orthologs from multiple plant pathogens contribute to disease in a large variety of plant hosts. PMID:27274076

  16. An Evaluation of the Impacts of AF-M315E Propulsion Systems for Varied Mission Applications

    NASA Technical Reports Server (NTRS)

    Deans, Matthew C.; Oleson, Steven R.; Fittje, James; Colozza, Anthony; Packard, Tom; Gyekenyesi, John; McLean, Christopher H.; Spores, Ronald A.

    2015-01-01

    The purpose of the AF-M315E COMPASS study is to identify near-term (3-5 years) and long term (5 years +) opportunities for infusion, specifically the thruster and associated component technologies being developed as part of the GPIM project. Develop design reference missions which show the advantages of the AF-M315E green propulsion system. Utilize a combination of past COMPASS designs and selected new designs to demonstrate AF-M315E advantages. Use the COMPASS process to show the puts and takes of using AF-M315E at the integrated system level.

  17. Developing a New Computer-Aided Clinical Decision Support System for Prediction of Successful Postcardioversion Patients with Persistent Atrial Fibrillation.

    PubMed

    Sterling, Mark; Huang, David T; Ghoraani, Behnaz

    2015-01-01

    We propose a new algorithm to predict the outcome of direct-current electric (DCE) cardioversion for atrial fibrillation (AF) patients. AF is the most common cardiac arrhythmia and DCE cardioversion is a noninvasive treatment to end AF and return the patient to sinus rhythm (SR). Unfortunately, there is a high risk of AF recurrence in persistent AF patients; hence clinically it is important to predict the DCE outcome in order to avoid the procedure's side effects. This study develops a feature extraction and classification framework to predict AF recurrence patients from the underlying structure of atrial activity (AA). A multiresolution signal decomposition technique, based on matching pursuit (MP), was used to project the AA over a dictionary of wavelets. Seven novel features were derived from the decompositions and were employed in a quadratic discrimination analysis classification to predict the success of post-DCE cardioversion in 40 patients with persistent AF. The proposed algorithm achieved 100% sensitivity and 95% specificity, indicating that the proposed computational approach captures detailed structural information about the underlying AA and could provide reliable information for effective management of AF. PMID:26120354

  18. Developing a New Computer-Aided Clinical Decision Support System for Prediction of Successful Postcardioversion Patients with Persistent Atrial Fibrillation

    PubMed Central

    Sterling, Mark; Huang, David T.; Ghoraani, Behnaz

    2015-01-01

    We propose a new algorithm to predict the outcome of direct-current electric (DCE) cardioversion for atrial fibrillation (AF) patients. AF is the most common cardiac arrhythmia and DCE cardioversion is a noninvasive treatment to end AF and return the patient to sinus rhythm (SR). Unfortunately, there is a high risk of AF recurrence in persistent AF patients; hence clinically it is important to predict the DCE outcome in order to avoid the procedure's side effects. This study develops a feature extraction and classification framework to predict AF recurrence patients from the underlying structure of atrial activity (AA). A multiresolution signal decomposition technique, based on matching pursuit (MP), was used to project the AA over a dictionary of wavelets. Seven novel features were derived from the decompositions and were employed in a quadratic discrimination analysis classification to predict the success of post-DCE cardioversion in 40 patients with persistent AF. The proposed algorithm achieved 100% sensitivity and 95% specificity, indicating that the proposed computational approach captures detailed structural information about the underlying AA and could provide reliable information for effective management of AF. PMID:26120354

  19. The risk of atrial fibrillation in patients with gout: a nationwide population-based study.

    PubMed

    Kuo, Yu-Jui; Tsai, Tzu-Hsien; Chang, Hui-Ping; Chua, Sarah; Chung, Sheng-Ying; Yang, Cheng-Hsu; Lin, Cheng-Jei; Wu, Chiung-Jen; Hang, Chi-Ling

    2016-01-01

    Many studies have found that systemic inflammation plays an important role in the pathogenesis of atrial fibrillation (AF). Gout is a chronic systemic inflammatory disorder, but little evidence exists regarding whether the risk of AF is increased in patients with gout. The National Health Insurance Research Database in Taiwan was used in this study, and gout was defined as the occurrence of at least one episode of an acute gout attack requiring medical treatment. A total of 63264 gout and 63264 age- and gender-matched patients were included as the study population. The Cox model was used to evaluate the risk of AF in patients with gout. Patients with gout experienced a greater frequency of co-morbidities compared to patients without gout. The cumulative incidences of AF were 4.61% and 3.04% in patients with and without gout, respectively (log-rank test, P < 0.001). After adjusting for co-morbidities and prescription medication use, gout was found to be associated with AF [hazard ratio (HR), 1.38]. Moreover, the HR for AF decreased with increasing age in our study. Gout was found to be associated with an increased risk of developing AF after adjusting for potential confounders. PMID:27599578

  20. The risk of atrial fibrillation in patients with gout: a nationwide population-based study

    PubMed Central

    Kuo, Yu-Jui; Tsai, Tzu-Hsien; Chang, Hui-Ping; Chua, Sarah; Chung, Sheng-Ying; Yang, Cheng-Hsu; Lin, Cheng-Jei; Wu, Chiung-Jen; Hang, Chi-Ling

    2016-01-01

    Many studies have found that systemic inflammation plays an important role in the pathogenesis of atrial fibrillation (AF). Gout is a chronic systemic inflammatory disorder, but little evidence exists regarding whether the risk of AF is increased in patients with gout. The National Health Insurance Research Database in Taiwan was used in this study, and gout was defined as the occurrence of at least one episode of an acute gout attack requiring medical treatment. A total of 63264 gout and 63264 age- and gender-matched patients were included as the study population. The Cox model was used to evaluate the risk of AF in patients with gout. Patients with gout experienced a greater frequency of co-morbidities compared to patients without gout. The cumulative incidences of AF were 4.61% and 3.04% in patients with and without gout, respectively (log-rank test, P < 0.001). After adjusting for co-morbidities and prescription medication use, gout was found to be associated with AF [hazard ratio (HR), 1.38]. Moreover, the HR for AF decreased with increasing age in our study. Gout was found to be associated with an increased risk of developing AF after adjusting for potential confounders. PMID:27599578

  1. Polymorphisms of Renin-Angiotensin-Aldosterone System Gene in Chinese Han Patients with Nonfamilial Atrial Fibrillation

    PubMed Central

    Zhao, Li-qun; Wen, Zu-jia; Wei, Yong; Xu, Juan; Chen, Zheng; Qi, Bao-zhen; Wang, Zhi-ming; Shi, Yong-yong; Liu, Shao-wen

    2015-01-01

    Background Atrial fibrillation(AF) is the most common arrhythmia in the adult population. The activated renin-angiotensin-aldosterone system (RAS) has been reported to play an important role in the pathogenesis of atrial fibrillation. The aim of this study was to investigate the association between nonfamilial AF and polymorphisms in RAS gene. Methods A total of 931 patients with nonfamilial AF, 663 non-AF heart disease patients and 727 healthy subjects were selected. 10 tagSNPs (tSNPs) (ACE gene rs8066114, AGT gene rs7539020, rs3789678, rs2478544, rs11568023, rs2478523, rs4762, rs699 and CYP11B2 rs3802230, rs3097) were chosen and genotyped in our study. Single-locus analysis and haplotype analysis were used in this study. Results In single-locus analysis, we found rs11568023 and rs3789678 in AGT gene were associated with nonfamilial AF in Chinese Han population. AF risk was associated with rs3789678 between the AF group and control groups. Under dominant model, the significant AF risk was observed in rs3789678 between the AF group and non AF heart control group; And the protective effect was found in rs11568023, compared with the non-AF heart disease control group. In multilocus haplotype analysis, the association between frequencies of the haplotypes and AF risk was showed in AGT gene (rs7539020-rs3789678), compared ‘TT’ haplotype with the common ‘TC’ haplotype, adjusted for age, gender, LVEF, LVEDD, LAD and frequency of hypertension and diabetes. The diplotype with ‘TC’, carrying rs3789678-C-allele, was associated with reduced risk of AF between the AF group and the healthy control group. The diplotype with ‘TT’ haplotype in the same block, carrying rs3789678-T-allele, was associated with increased risk of AF. Conclusions Via a large-scale case-control study, we found that rs3789678 site was potential susceptible locus of AF whereas rs11568023 was protective factor. PMID:25723521

  2. Design and position control of AF lens actuator for mobile phone using IPMC-EMIM

    NASA Astrophysics Data System (ADS)

    Kim, Sung-Joo; Kim, Chul-Jin; Park, No-Cheol; Yang, Hyun-Seok; Park, Young-Pil; Park, Kang-Ho; Lee, Hyung-Kun; Choi, Nak-Jin

    2008-03-01

    IPMC-EMIM (Ionic Polyer Metal Composites + 1-ethyl-3- methyl imidazolium trifluromethane sulfonate, EMIM-Tfo) is fabricated by substituting ionic liquid for water in Nafion film, which improves water sensitiveness of IPMC and guarantees uniform performance regardless of the surrounding environment. In this paper, we will briefly introduce the procedure of fabrication of IPMC-EMIM and proceed to introduce the Hook-type actuator using IPMC-EMIM and application to AF Lens actuator. Parameters of Hook-type actuator are estimated from experimental data. In the simulation, The proposed AF Lens Actuator is assumed to be a linear system and based on estimated parameters, PID controller will be designed and controlled motion of AF Lens actuator will be shown through simulation.

  3. Cloning and characterization of two duplicated interleukin-17A/F2 genes in common carp (Cyprinus carpio L.): Transcripts expression and bioactivity of recombinant IL-17A/F2.

    PubMed

    Li, Hongxia; Yu, Juhua; Li, Jianlin; Tang, Yongkai; Yu, Fan; Zhou, Jie; Yu, Wenjuan

    2016-04-01

    Interleukin-17 (IL-17) plays an important role in inflammation and host defense in mammals. In this study, we identified two duplicated IL-17A/F2 genes in the common carp (Cyprinus carpio) (ccIL-17A/F2a and ccIL-17A/F2b), putative encoded proteins contain 140 amino acids (aa) with conserved IL-17 family motifs. Expression analysis revealed high constitutive expression of ccIL-17A/F2s in mucosal tissues, including gill, skin and intestine, their expression could be induced by Aeromonas hydrophila, suggesting a potential role in mucosal immunity. Recombinant ccIL-17A/F2a protein (rccIL-17A/F2a) produced in Escherichia coli could induce the expression of proinflammatory cytokines (IL-1β) and the antimicrobial peptides S100A1, S100A10a and S100A10b in the primary kidney in a dose- and time-dependent manner. Above findings suggest that ccIL-17A/F2 plays an important role in both proinflammatory and innate immunity. Two duplicated ccIL-17A/F2s showed different expression level with ccIL-17A/F2a higher than b, comparison of two 5' regulatory regions indicated the length from anticipated promoter to transcriptional start site (TSS) and putative transcription factor binding site (TFBS) were different. Promoter activity of ccIL-17A/F2a was 2.5 times of ccIL-17A/F2b which consistent with expression results of two genes. These suggest mutations in 5'regulatory region contributed to the differentiation of duplicated genes. To our knowledge, this is the first report to analyze 5'regulatory region of piscine IL-17 family genes. PMID:26921542

  4. Patient perspective on the management of atrial fibrillation in five European countries

    PubMed Central

    2013-01-01

    Background Long-term management of chronic conditions, such as atrial fibrillation (AF), require frequent interactions with the healthcare systems. The multinational EUropean Patient Survey in Atrial Fibrillation (EUPS-AF) was conducted to investigate patient satisfaction with AF management in different of five European healthcare systems at a time of changing treatment paradigms for stroke prophylaxis, prior to the advent of newer oral anticoagulants. Methods Adults (>18 years) were recruited at random from the total populations of France, Germany, Italy, Spain and the UK using a randomized telephone dialling system. At least 300 respondents per country reporting to have a diagnosis of AF or receiving oral anticoagulation therapy for suspected AF or to have a heart rhythm disturbance completed a structured telephone interview. Results Most respondents were satisfied with their treatment for AF over the previous 12 months, with 85.5% (n = 1289) rating their care as good or better. Suboptimal clinical practices, however, were identified in several key areas. Coordination of primary and secondary care and a lack of patient engagement and support were particular issues, especially for those patients likely to have extensive contact with their healthcare system. Conclusions In the context of Europe-wide guidelines for management of AF, most patients with AF were satisfied with their care, but for a greater proportion of patients, some aspects are unsatisfactory. Patient-centred surveys, such as the EUPS-AF, are crucial for understanding the factors that contribute to patient satisfaction and compliance with long-term treatment for chronic conditions. PMID:24289181

  5. Effect of Permanent Atrial Fibrillation on Cognitive Function in Patients With Chronic Heart Failure.

    PubMed

    Coma, Maria; González-Moneo, Maria Jesús; Enjuanes, Cristina; Velázquez, Paula Poveda; Espargaró, Deva Bas; Pérez, Bernardo Andrés; Tajes, Marta; Garcia-Elias, Anna; Farré, Núria; Sánchez-Benavides, Gonzalo; Martí-Almor, Julio; Comin-Colet, Josep; Benito, Begoña

    2016-01-15

    In patients with chronic heart failure (HF), cognitive impairment (CI) is associated with poorer treatment adherence and higher readmission and mortality rates. Previous studies suggest that atrial fibrillation (AF) could impair cognitive function. This study sought to assess the association between permanent AF (permAF) and CI in patients with HF. We evaluated cognitive function in 881 patients with stable HF (73 ± 11 years, 44% women, 48% with preserved ejection fraction) using the Mini-Mental State Examination test (n = 876) and the Pfeiffer's Short Portable Mental Status Questionnaire (n = 848). CI was defined as a Mini-Mental State Examination score <24 or Short Portable Mental Status Questionnaire (errors) >2. The independent association between permAF and CI was assessed by binary logistic regression analysis. A total of 295 patients (33.5%) had CI, in 5.1% of cases moderate/severe. Patients with permAF had more frequently any degree of CI (43% vs 31%), and moderate/severe CI (8% vs 5%). In the multivariate analysis, CI was associated with permAF (odds ratio 1.54, 95% C.I. 1.05 to 2.28), an older age, female gender, diabetes mellitus, chronic kidney disease, previous stroke, New York Heart Association class III/IV, and lower systolic blood pressure. No interaction was found for AF and CI between patients with reduced and preserved ejection fraction. In conclusion, the presence of permAF is independently associated with CI in patients with HF, both with reduced and preserved ejection fraction. Given the clinical impact of CI in the HF population, active assessment of cognitive function is particularly warranted in patients with HF with permAF. PMID:26686573

  6. North American Thrombosis Forum, AF Action Initiative Consensus Document.

    PubMed

    Ruff, Christian T; Ansell, Jack E; Becker, Richard C; Benjamin, Emelia J; Deicicchi, David J; Mark Estes, N A; Ezekowitz, Michael D; Fanikos, John; Fareed, Jawed; Garcia, David; Giugliano, Robert P; Goldhaber, Samuel Z; Granger, Christopher; Healey, Jeff S; Hull, Russell; Hylek, Elaine M; Libby, Peter; Lopes, Renato D; Mahaffey, Kenneth W; Mega, Jessica; Piazza, Gregory; Sasahara, Arthur A; Sorond, Farzaneh A; Spyropoulos, Alex C; Walenga, Jeanine M; Weitz, Jeffrey I

    2016-05-01

    The North American Thrombosis Forum Atrial Fibrillation Action Initiative consensus document is a comprehensive yet practical briefing document focusing on stroke and bleeding risk assessment in patients with atrial fibrillation, as well as recommendations regarding anticoagulation options and management. Despite the breadth of clinical trial data and guideline recommendation updates, many clinicians continue to struggle to synthesize the disparate information available. This problem slows the uptake and utilization of updated risk prediction tools and adoption of new oral anticoagulants. This document serves as a practical and educational reference for the entire medical community involved in the care of patients with atrial fibrillation. PMID:27126598

  7. Compliance testing of the Clear AFS Power Plant, coal-fired boiler 1, Clear AFS, Alaska. Final report, 18-23 April 1989

    SciTech Connect

    Scott, P.T.

    1989-10-01

    The 13 MWS/DE through HQ AFSPACECOM/SG requested AFOEHL Quality Function conduct source emission testing of the Clear AFS Power Plant to determine compliance with applicable Alaska Air Quality Control Codes. The Alaska Department of Environmental Conservation required testing of one representative boiler for permit compliance and to determine operating limitations for each boiler. At 80,000 lbs steam/hour particulate emission were within emission limits allowed by the State of Alaska.

  8. 27. "SITE PLAN." Specifications No. OC15775, Drawing No. AF600915, sheet ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    27. "SITE PLAN." Specifications No. OC1-57-75, Drawing No. AF-60-09-15, sheet 1 of 96, D.O. Series No. AF 1394/20, Rev. B. Stamped: RECORD DRAWING - AS CONSTRUCTED. Below stamp: Contract no. 5296 Rev. B, Date: 11/17/59. Site plan of 20,000-foot track, including construction phasing notes. - Edwards Air Force Base, South Base Sled Track, Edwards Air Force Base, North of Avenue B, between 100th & 140th Streets East, Lancaster, Los Angeles County, CA

  9. Multi-object spectroscopy data reduction: the AF2+WYFFOS pipeline

    NASA Astrophysics Data System (ADS)

    Domínquez Palmero, Lilian; Jackson, Richard; Molaeinezhad, Alireza; Fariña, Cecilia; Balcells, Marc; Benn, Chris R.

    2014-08-01

    The scientific productivity of complex instrumentation strongly depends on the availability of data-reduction pipelines. In the case of AF2+WYFFOS, the multi-object one-degree field-of-view fibre-fed spectrograph at the 4.2 m William Herschel Telescope (WHT), the full scientific exploitation of the data has often been slowed down because of the non-availability of a pipeline. A dedicated pipeline has been developed to overcome this. Running in IDL, it performs full reduction of AF2+WYFFOS data: fibre-to-fibre sensitivity corrections, fibre tracing, wavelength calibration, optimal extraction, sky subtraction.

  10. Modeling spall in HY100, HY130, and AF1410 steels

    NASA Astrophysics Data System (ADS)

    Garrett, R. K.; Rajendran, A. M.; Last, H. R.

    1996-05-01

    A comparison spall analysis between three matensitic steels: HY100, HY130, and AF1410 is presented Metallurgical observations on the fracture surfaces of uniaxial tensile specimens as well as the spalled target plates confirmed the nucleation, growth, and coalescence of microvoids in these steels. The threshold stress for void nucleation in these steels were determined from the spall analysis using the EPIC finite element code. According to the model, the spall nucleation occurred at higher stress levels in AF1410 compared to HY100 and HY130. A complete set of material model constants has been determined for these three steels.

  11. Comparison of prognostic value of atrial fibrillation versus sinus rhythm in patients on long-term hemodialysis.

    PubMed

    Vázquez, Eduardo; Sánchez-Perales, Carmen; Lozano, Cristóbal; García-Cortés, Ma José; Borrego, Francisco; Guzmán, Manuel; Pérez, Pilar; Pagola, Carlos; Borrego, Ma José; Pérez, Vicente

    2003-10-01

    The influence of atrial fibrillation (AF) on the clinical pattern of patients with chronic renal insufficiency on hemodialysis remains unknown despite the cardiovascular pathology in these patients being well documented and being the primary cause of death in this patient population. The objective of this study was to compare the long-term outcome in those patients on our dialysis unit in sinus rhythm with those in AF. PMID:14516897

  12. Digoxin Use to Control Ventricular Rate in Patients with Atrial Fibrillation and Heart Failure Is Not Associated with Increased Mortality

    PubMed Central

    Dominic, Paari

    2015-01-01

    Introduction. Digoxin is used to control ventricular rate in atrial fibrillation (AF). There is conflicting evidence regarding safety of digoxin. We aimed to evaluate the risk of mortality with digoxin use in patients with AF using meta-analyses. Methods. PubMed was searched for studies comparing outcomes of patients with AF taking digoxin versus no digoxin, with or without heart failure (HF). Studies were excluded if they reported only a point estimate of mortality, duplicated patient populations, and/or did not report adjusted hazard ratios (HR). The primary endpoint was all-cause mortality. Adjusted HRs were combined using generic inverse variance and log hazard ratios. A multivariate metaregression model was used to explore heterogeneity in studies. Results. Twelve studies with 321,944 patients were included in the meta-analysis. In all AF patients, irrespective of heart failure status, digoxin is associated with increased all-cause mortality (HR [1.23], 95% confidence interval [CI] 1.16–1.31). However, digoxin is not associated with increased mortality in patients with AF and HF (HR [1.08], 95% CI 0.99–1.18). In AF patients without HF digoxin is associated with increased all-cause mortality (HR [1.38], 95% CI 1.12–1.71). Conclusion. In patients with AF and HF, digoxin use is not associated with an increased risk of all-cause mortality when used for rate control. PMID:26788401

  13. Injury of the Arcuate Fasciculus in the Dominant Hemisphere in Patients With Mild Traumatic Brain Injury: A Retrospective Cross-Sectional Study.

    PubMed

    Jang, Sung Ho; Lee, Ah Young; Shin, So Min

    2016-03-01

    Little is known about injury of the arcuate fasciculus (AF) in patients with mild traumatic brain injury (TBI). We investigated injury of the AF in the dominant hemisphere in patients with mild TBI, using diffusion tensor tractography (DTT). We recruited 25 patients with injury of the left AF among 64 right-handed consecutive patients with mild TBI and 20 normal control subjects. DTTs of the left AF were reconstructed, and fractional anisotropy (FA), apparent diffusion coefficient (ADC), and fiber number of the AF were measured. Among 64 consecutive patients, 25 (39%) patients showed injury of the left AF. The patient group showed lower FA value and fiber number with higher ADC value than the control group (P < 0.05). On K-WAB evaluation, aphasia quotient and language quotient were 95.9 ± 4.1 (range 85-100) and 95.0 ± 5.4 (range 80-100), respectively. However, 23 (92.0%) of 25 patients complained of language-related symptoms after TBI; paraphasia in 12 (48.0%) patients, deficits of comprehension in 4 (16.0%) patients, deficits of speech production in 1 (4.0%) patient, and >2 language symptoms in 6 (24.0%) patients. We found that a significant number (39%) of patients with mild TBI had injury of the AF in the dominant hemisphere and these patients had mild language deficit. These results suggest that DTT could provide useful information in detecting injury of the AF and evaluation of the AF using DTT would be necessary even in the case of a patient with mild TBI who complains of mild language deficit. PMID:26945425

  14. The splicing factor U2AF65 stabilizes TRF1 protein by inhibiting its ubiquitin-dependent proteolysis

    SciTech Connect

    Kim, Jeonghee; Chung, In Kwon

    2014-01-17

    Highlights: •Identification of U2AF65 as a novel TRF1-interacting protein. •U2AF65 stabilizes TRF1 protein by inhibiting its ubiquitin-dependent proteolysis. •U2AF65 interferes with the interaction between TRF1 and Fbx4. •U2AF65 represents a new route for modulating TRF1 function at telomeres. -- Abstract: The human telomeric protein TRF1 is a component of the six-subunit protein complex shelterin, which provides telomere protection by organizing the telomere into a high-order structure. TRF1 functions as a negative regulator of telomere length by controlling the access of telomerase to telomeres. Thus, the cellular abundance of TRF1 at telomeres should be maintained and tightly regulated to ensure proper telomere function. Here, we identify U2 small nuclear ribonucleoprotein (snRNP) auxiliary factor 65 (U2AF65), an essential pre-mRNA splicing factor, as a novel TRF1-interacting protein. U2AF65 interacts with TRF1 in vitro and in vivo and is capable of stabilizing TRF1 protein by inhibiting its ubiquitin-dependent proteolysis. We also found that U2AF65 interferes with the interaction between TRF1 and Fbx4, an E3 ubiquitin ligase for TRF1. Depletion of endogenous U2AF65 expression by short interfering RNA (siRNA) reduced the stability of endogenous TRF1 whereas overexpression of U2AF65 significantly extended the half-life of TRF1. These findings demonstrate that U2AF65 plays a critical role in regulating the level of TRF1 through physical interaction and ubiquitin-mediated proteolysis. Hence, U2AF65 represents a new route for modulating TRF1 function at telomeres.

  15. Long-Term Outcomes after Stroke in Elderly Patients with Atrial Fibrillation: A Hospital-Based Follow-Up Study in China

    PubMed Central

    Zhao, Yuguang; Zou, Chunying; Wang, Cui; Zhang, Yongbo; Wang, Shuang

    2016-01-01

    Background: Atrial fibrillation (AF) significantly increases the risk of stroke and disease burden; it is an established predictor of poor outcomes after stroke. However, reported differences in outcomes after stroke among elderly patients between AF and non-AF group are conflicting. We aimed to compare differences in outcomes at 1 year and 3 years after stroke among elderly patients (aged ≥ 75 years old) between AF group and non-AF group. Methods: We recruited 1070 consecutive elderly patients who experienced acute ischemic stroke between January 2008 and December 2013 in Jiamusi University First Hospital, China in this study. Information regarding stroke subtype, severity, risk factors, and outcome (mortality, dependency, and recurrence) at 3 and 12 months after stroke were recorded and assessed between AF group and non-AF group. Results: The prevalence of AF was 16.1% overall, with a similar trend in the prevalence of AF between men and women. The AF group were more likely to experience severe stroke compared to the non-AF group (32.0 vs. 11.9%, respectively; P < 0.001). There were no obvious differences between groups regarding the prevalence of hypertension, dyslipidemia, obesity, current smoking, and alcohol drinking but there was a higher prevalence of diabetes in the non-AF group (20.3 vs. 30.1%, P = 0.010). Mortality and dependency rates were significantly higher in the AF group than in the non-AF group at 1 year after stroke (29.6 vs. 17.8%, P = 0.001 for mortality; and 59.5 vs. 36.1%, P = 0.010 for dependency) and 3 years after stroke (46.1 vs. 33.2%, P = 0.032 for mortality; and 70.7 vs. 49.2%, P = 0.010 for dependency); however, there was no significant between-groups differences in rates of recurrence across the follow-up periods. The results for dependency remained stable after adjustment for sex, stroke severity, and stroke risk factors at 3 years after stroke (OR, 2.26; 95% CI, 1.06–4.81; P = 0.034); however, the relationship between AF and

  16. Fibrillation number based on wavelength and critical mass in patients who underwent radiofrequency catheter ablation for atrial fibrillation.

    PubMed

    Hwang, Minki; Park, Junbeum; Lee, Young-Seon; Park, Jae Hyung; Choi, Sung Hwan; Shim, Eun Bo; Pak, Hui-Nam

    2015-02-01

    The heart characteristic length, the inverse of conduction velocity (CV), and the inverse of the refractory period are known to determine vulnerability to cardiac fibrillation (fibrillation number, FibN) in in silico or ex vivo models. The purpose of this study was to validate the accuracy of FibN through in silico atrial modeling and to evaluate its clinical application in patients with atrial fibrillation (AF) who had undergone radiofrequency catheter ablation. We compared the maintenance duration of AF at various FibNAF values using in silico bidomain atrial modeling. Among 60 patients (72% male, 54±13 years old, 82% with paroxysmal AF) who underwent circumferential pulmonary vein isolation (CPVI) for AF rhythm control, we examined the relationship between FibN AF and postprocedural AF inducibility or induction pacing cycle length (iPCL). Clinical FibNAF was calculated using left atrium (LA) dimension (echocardiogram), the inverse of CV, and the inverse of the atrial effective refractory periods measured at proximal and distal coronary sinus. In silico simulation found a positive correlation between AF maintenance duration and FibNAF ( R = 0.90, ). After clinical CPVI, FibNAF ( 0.296±0.038 versus 0.192±0.028, ) was significantly higher in patients with postprocedural AF inducibility ( n = 41) than in those without ( n = 19 ). Among 41 patients with postprocedural AF inducibility, FibNAF ( P = 0.935, ) had excellent correlations with induction pacing cycle length. FibNAF, based on LA mass and wavelength, correlates well with AF maintenance in computational modeling and clinical AF inducibility after CPVI. PMID:25343755

  17. Simulation of Daily Snapshot Rhythm Monitoring to Identify Atrial Fibrillation in Continuously Monitored Patients with Stroke Risk Factors

    PubMed Central

    Yano, Yuichiro; Greenland, Philip; Lloyd-Jones, Donald M.; Daoud, Emile G.; Koehler, Jodi L.; Ziegler, Paul D.

    2016-01-01

    Background New technologies are diffusing into medical practice swiftly. Hand-held devices such as smartphones can record short-duration (e.g., 1-minute) ECGs, but their effectiveness in identifying patients with paroxysmal atrial fibrillation (AF) is unknown. Methods We used data from the TRENDS study, which included 370 patients (mean age 71 years, 71% men, CHADS2 score≥1 point: mean 2.3 points) who had no documentation of atrial tachycardia (AT)/AF or antiarrhythmic or anticoagulant drug use at baseline. All were subsequently newly diagnosed with AT/AF by a cardiac implantable electronic device (CIED) over one year of follow-up. Using a computer simulation approach (5,000 repetitions), we estimated the detection rate for paroxysmal AT/AF via daily snapshot ECG monitoring over various periods, with the probability of detection equal to the percent AT/AF burden on each day. Results The estimated AT/AF detection rates with snapshot monitoring periods of 14, 28, 56, 112, and 365 days were 10%, 15%, 21%, 28%, and 50% respectively. The detection rate over 365 days of monitoring was higher in those with CHADS2 scores ≥2 than in those with CHADS2 scores of 1 (53% vs. 38%), and was higher in those with AT/AF burden ≥0.044 hours/day compared to those with AT/AF burden <0.044 hours/day (91% vs. 14%; both P<0.05). Conclusions Daily snapshot ECG monitoring over 365 days detects half of patients who developed AT/AF as detected by CIED, and shorter intervals of monitoring detected fewer AT/AF patients. The detection rate was associated with individual CHADS2 score and AT/AF burden. Trial Registration ClinicalTrials.gov NCT00279981 PMID:26882334

  18. Dispersion of refractoriness in patients with paroxysmal atrial fibrillation. Evaluation with simultaneous endocardial recordings from both atria.

    PubMed

    Li, Zhen; Hertervig, Eva; Carlson, Jonas; Johansson, Camilla; Olsson, S Bertil; Yuan, Shiwen

    2002-07-01

    This article studies the role of dispersion of atrial refractoriness (DAR) in the genesis of atrial fibrillation (AF). A 20-polar Halo catheter or a 40-polar basket catheter was placed in the right atrium and a 10-polar catheter in the coronary sinus in 21 patients with paroxysmal AF. Bipolar electrograms during AF were recorded from 7 to 16 sites in both atria. As control, electrograms during AF induced by extra-stimulation or burst pacing were also recorded from 4 to 14 sites in both atria in 12 patients with supraventricular tachycardias but without history of AF. The local atrial fibrillation intervals (AFI) during a period of 10 s or 20 s were measured and the mean, median and the 5th, 10th and 15th percentile AFIs at each site were calculated as estimates of the local effective refractory period (AERP). The maximum dispersion and variance of the estimated AERP among the 7-16/4-14 sites were used as measures of the DAR. The maximum dispersion and variance of the 5th and 10th percentile AFIs were significantly greater in the AF group than those in the control group, which were mainly due to the shortening of the minimum 5th and 10th percentile AFIs. No significant differences in dispersion and variance of the mean and median AFIs were shown between the 2 groups. The dispersion and variance of atrial refractoriness during AF estimated from the measurement of short AFIs were significantly greater in patients with paroxysmal AF than in those without clinical AF. The increased dispersion of refractoriness in patients with AF was mainly due to the shortening of the minimum AFIs. These findings suggest the involvement of an increased dispersion of atrial refractoriness in the genesis of paroxysmal AF. PMID:12122613

  19. Comparisons of Hospitalization Rates Among Younger Atrial Fibrillation Patients Receiving Different Antiarrhythmic Drugs

    PubMed Central

    Allen LaPointe, Nancy M.; Dai, David; Thomas, Laine; Piccini, Jonathan P.; Peterson, Eric D.; Al-Khatib, Sana M.

    2015-01-01

    Background Antiarrhythmic drugs (AADs) are used to reduce the frequency, severity, and duration of atrial fibrillation (AF) events, which should reduce hospitalizations; however, little is known about the associations between different AADs and hospitalization—particularly among younger AF patients without structural heart disease. Methods and Results Using MarketScan® claims data, we identified AF patients without coronary artery disease (CAD) or heart failure who received their first AAD prescription (amiodarone, sotalol, dronedarone, or Class Ic) within 14 days post-first AF encounter. The primary outcome was time from first AAD prescription to AF hospitalization and secondary outcomes included time to cardiovascular and all-cause hospitalizations. We used inverse probability-weighted estimators to adjust for differences in treatment allocation in the Cox proportional hazards model for each outcome. Among 8562 AF patients with a median age of 56 years (IQR 49,61), risk of AF hospitalization was greater with dronedarone than Class Ic (HR 1.59; 95% CI 1.13–2.24), amiodarone (HR 2.63;1.77–3.89), and sotalol (HR 1.72;1.17–2.54), but lower with amiodarone versus Class Ic (HR 0.68;0.57–0.80) and sotalol (HR 0.63;0.53–0.75). Risk of cardiovascular hospitalization was lower with amiodarone than Class Ic (HR 0.80;0.70–0.92), but not non-AF cardiovascular hospitalization (HR 1.26;1.01–1.57). There was no difference in all-cause hospitalization between amiodarone, Class Ic, and sotalol. Conclusions Differences in hospitalization rates were found between AADs in younger AF patients without structural heart disease. Amiodarone had the lowest risk of AF hospitalization and dronedarone had the greatest risk. Additional research is needed to better understand associations between AADs and hospitalization risk. PMID:25829248

  20. Atrial fibrillation and risk of stroke in dialysis patients

    PubMed Central

    Wetmore, James B.; Ellerbeck, Edward F.; Mahnken, Jonathan D.; Phadnis, Milind; Rigler, Sally K.; Mukhopadhyay, Purna; Spertus, John A.; Zhou, Xinhua; Hou, Qingjiang; Shireman, Theresa I.

    2013-01-01

    Purpose Both stroke and chronic atrial fibrillation (AF) are common in dialysis patients, but uncertainty exists in the incidence of new strokes and the risk conferred by chronic AF. Methods A cohort of dually-eligible (Medicare & Medicaid) incident dialysis patients was constructed. Medicare claims were used to determine the onset of chronic AF, which was specifically treated as a time-dependent covariate. Cox proportional hazards models were used to model time to stroke. Results Of 56,734 patients studied, 5629 (9.9%) developed chronic AF. There were 22.8 ischemic and 5.0 hemorrhagic strokes per 1000 patient-years, a ratio of approximately 4.5:1. Chronic AF was independently associated with time to ischemic (HR 1.26, 99% CI’s 1.06 – 1.49, P = 0.0005), but not hemorrhagic, stroke. Race was strongly associated with hemorrhagic stroke: African-Americans (HR 1.46, 99% CI’s 1.08 – 1.96), Hispanics (HR 1.64, 99% CI’s 1.16 – 2.31), and others (HR 1.76, 99% CI’s 1.16 – 2.78) had higher rates than did Caucasians (P < 0.001 for all). Conclusions Chronic AF has a significant, but modest, association with ischemic stroke. Race/ethnicity is strongly associated with hemorrhagic strokes. The proportion of strokes due to hemorrhage is much higher than in the general population. PMID:23332588

  1. 77 FR 14287 - Aspergillus flavus AF36; Amendment to an Exemption From the Requirement of a Tolerance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-09

    ...This regulation amends the existing temporary tolerance exemption for Aspergillus flavus AF36 by establishing a permanent exemption from the requirement of a tolerance for residues of the microbial pesticide, Aspergillus flavus AF36, in or on pistachio when applied as an antifungal agent and used in accordance with good agricultural practices. On behalf of the Arizona Cotton Research and......

  2. Draft Genome Sequence of Komagataeibacter intermedius Strain AF2, a Producer of Cellulose, Isolated from Kombucha Tea.

    PubMed

    Dos Santos, Renato Augusto Corrêa; Berretta, Andresa Aparecida; Barud, Hernane da Silva; Ribeiro, Sidney José Lima; González-García, Laura Natalia; Zucchi, Tiago Domingues; Goldman, Gustavo H; Riaño-Pachón, Diego M

    2015-01-01

    Here, we present the draft genome sequence of Komagataeibacter intermedius strain AF2, which was isolated from Kombucha tea and is capable of producing cellulose, although at lower levels compared to another bacterium from the same environment, K. rhaeticus strain AF1. PMID:26634755

  3. Identification and Characterization of an Antifungal Protein, AfAFPR9, Produced by Marine-Derived Aspergillus fumigatus R9.

    PubMed

    Rao, Qi; Guo, Wenbin; Chen, Xinhua

    2015-05-01

    A fungal strain, R9, was isolated from the South Atlantic sediment sample and identified as Aspergillus fumigatus. An antifungal protein, AfAFPR9, was purified from the culture supernatant of Aspergillus fumigatus R9. AfAFPR9 was identified to be restrictocin, which is a member of the ribosome-inactivating proteins (RIPs), by MALDI-TOF-TOF-MS. AfAFPR9 displayed antifungal activity against plant pathogenic Fusarium oxysporum, Alternaria longipes, Colletotrichum gloeosporioides, Paecilomyces variotii, and Trichoderma viride at minimum inhibitory concentrations of 0.6, 0.6, 1.2, 1.2, and 2.4 μg/disc, respectively. Moreover, AfAFPR9 exhibited a certain extent of thermostability, and metal ion and denaturant tolerance. The iodoacetamide assay showed that the disulfide bridge in AfAFPR9 was indispensable for its antifungal action. The cDNA encoding for AfAFPR9 was cloned from A. fumigatus R9 by RTPCR and heterologously expressed in E. coli. The recombinant AfAFPR9 protein exhibited obvious antifungal activity against C. gloeosporioides, T. viride, and A. longipes. These results reveal the antifungal properties of a RIP member (AfAFPR9) from marine-derived Aspergillus fumigatus and indicated its potential application in controlling plant pathogenic fungi. PMID:25394604

  4. Draft Genome Sequence of Komagataeibacter intermedius Strain AF2, a Producer of Cellulose, Isolated from Kombucha Tea

    PubMed Central

    dos Santos, Renato Augusto Corrêa; Berretta, Andresa Aparecida; Barud, Hernane da Silva; Ribeiro, Sidney José Lima; González-García, Laura Natalia; Zucchi, Tiago Domingues

    2015-01-01

    Here, we present the draft genome sequence of Komagataeibacter intermedius strain AF2, which was isolated from Kombucha tea and is capable of producing cellulose, although at lower levels compared to another bacterium from the same environment, K. rhaeticus strain AF1. PMID:26634755

  5. 40 CFR 180.1206 - Aspergillus flavus AF36; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... tolerance is established for residues of Aspergillus flavus AF36 in or on corn, field, forage; corn, field, grain; corn, field, stover; corn, field, aspirated grain fractions; corn, sweet, kernel plus cob with husk removed; corn, sweet, forage; corn, sweet, stover; corn, pop, grain; and corn, pop, stover,...

  6. 40 CFR 180.1206 - Aspergillus flavus AF36; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... tolerance is established for residues of Aspergillus flavus AF36 in or on corn, field, forage; corn, field, grain; corn, field, stover; corn, field, aspirated grain fractions; corn, sweet, kernel plus cob with husk removed; corn, sweet, forage; corn, sweet, stover; corn, pop, grain; and corn, pop, stover,...

  7. 40 CFR 180.1206 - Aspergillus flavus AF36; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... tolerance is established for residues of Aspergillus flavus AF36 in or on corn, field, forage; corn, field, grain; corn, field, stover; corn, field, aspirated grain fractions; corn, sweet, kernel plus cob with husk removed; corn, sweet, forage; corn, sweet, stover; corn, pop, grain; and corn, pop, stover,...

  8. Fracture Mechanics Testing of Titanium 6AL-4V in AF-M315E

    NASA Technical Reports Server (NTRS)

    Sampson, J. W.; Martinez, J.; McLean, C.

    2016-01-01

    The Green Propellant Infusion Mission (GPIM) will demonstrate the performance of AF-M315E monopropellant on orbit. Flight certification requires a safe-life analysis of the titanium alloy fuel tank to ensure inherent processing flaws will not cause failure during the design life of the tank. Material property inputs for this analysis require testing to determine the stress intensity factor for environment-assisted cracking (KEAC) of Ti 6Al-4V in combination with the AF-M315E monopropellant. Testing of single-edge notched, or SE(B), specimens representing the bulk tank membrane and weld material were performed in accordance with ASTM E1681. Specimens with fatigue pre-cracks were loaded into test fixtures so that the crack tips were exposed to AF-M315E at 50 C for a duration of 1,000 hours. Specimens that did not fail during exposure were opened to inspect the crack surfaces for evidence of crack growth. The threshold stress intensity value, KEAC, is the highest applied stress intensity that produced neither a failure of the specimen during the exposure nor showed evidence of crack growth. The threshold stress intensity factor for environment-assisted cracking of the Ti 6Al-4V forged tank material was found to be at least 22 ksivin and at least 31 ksivin for the weld material when exposed to AF-M315E monopropellant.

  9. K-theory of the chair tiling via AF-algebras

    NASA Astrophysics Data System (ADS)

    Julien, Antoine; Savinien, Jean

    2016-08-01

    We compute the K-theory groups of the groupoid C∗-algebra of the chair tiling, using a new method. We use exact sequences of Putnam to compute these groups from the K-theory groups of the AF-algebras of the substitution and the induced lower dimensional substitutions on edges and vertices.

  10. 28. Site Plan: AF Station P67, Fort Custer, Michigan, Plot ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    28. Site Plan: AF Station P-67, Fort Custer, Michigan, Plot Plan (to accompany FY 1956 project planning report), USACOE, 22 July 1954. - Fort Custer Military Reservation, P-67 Radar Station, .25 mile north of Dickman Road, east of Clark Road, Battle Creek, Calhoun County, MI

  11. Acutangulosides A-F, monodesmosidic saponins from the bark of Barringtonia acutangula.

    PubMed

    Mills, Clive; Carroll, Anthony R; Quinn, Ronald J

    2005-03-01

    Nine triterpene saponins, acutangulosides A-F (2-7), and acutanguloside D-F methyl esters (5a-7a) and a single triterpene aglycone (1) were isolated from a water extract of the bark of Barringtonia acutangula. Their structures were assigned on the basis of spectroscopic data. PMID:15787427

  12. Determinants and prognosis of atrial fibrillation in patients with aortic stenosis.

    PubMed

    Levy, Franck; Rusinaru, Dan; Maréchaux, Sylvestre; Charles, Vincent; Peltier, Marcel; Tribouilloy, Christophe

    2015-11-15

    Atrial fibrillation (AF) is frequently encountered in patients with aortic stenosis (AS) and its incidence also increases with age. In the general population, AF is known to increase cardiovascular risk. We sought to investigate the prognostic importance of AF associated with AS in the context of routine clinical practice. This analysis was based on 809 patients (75 ± 12 years) diagnosed with AS (aortic valve area <2 cm(2)) and normal (≥50%) ejection fraction (EF). Patients were grouped according to the presence of sinus rhythm (SR) or AF at study enrollment. The AF group comprised 141 patients (17.5%) with AF, whereas 668 patients (82.5%) were in SR at inclusion. Four-year estimates of all-cause mortality with medical and surgical management were 60 ± 5% for the AF group compared with 24 ± 2% for the SR group (p = 0.0001). On multivariate analysis, the risk of all-cause mortality was higher in the AF group than in the SR group (adjusted hazard ratio [HR] 2.47 [1.83 to 3.33], p = 0.0001). AF remained associated with excess mortality risk when the analysis was limited to asymptomatic patients (adjusted HR 2.31 [1.38 to 3.89], p = 0.002) and, respectively, patients with severe AS (adjusted HR 2.22 [1.41 to 3.49], p = 0.001). Among patients managed medically, AF was independently associated with increased risk of death in the overall study population (adjusted HR 2.52 [1.81 to 3.51], p = 0.0001), in asymptomatic AS (adjusted HR 2.12 [1.19 to 3.76], p = 0.01), and in severe AS (adjusted HR 2.23 [1.30 to 3.81], p = 0.004). In conclusion, AF is a major predictor of mortality, in both medically and surgically managed patients with AS, irrespective of the functional status and the severity. AF is, therefore, a strong marker of risk in AS and should be considered for clinical decision making. PMID:26410605

  13. POU2AF1 Functions in the Human Airway Epithelium To Regulate Expression of Host Defense Genes.

    PubMed

    Zhou, Haixia; Brekman, Angelika; Zuo, Wu-Lin; Ou, Xuemei; Shaykhiev, Renat; Agosto-Perez, Francisco J; Wang, Rui; Walters, Matthew S; Salit, Jacqueline; Strulovici-Barel, Yael; Staudt, Michelle R; Kaner, Robert J; Mezey, Jason G; Crystal, Ronald G; Wang, Guoqing

    2016-04-01

    In the process of seeking novel lung host defense regulators by analyzing genome-wide RNA sequence data from normal human airway epithelium, we detected expression of POU domain class 2-associating factor 1 (POU2AF1), a known transcription cofactor previously thought to be expressed only in lymphocytes. Lymphocyte contamination of human airway epithelial samples obtained by bronchoscopy and brushing was excluded by immunohistochemistry staining, the observation of upregulation of POU2AF1 in purified airway basal stem/progenitor cells undergoing differentiation, and analysis of differentiating single basal cell clones. Lentivirus-mediated upregulation of POU2AF1 in airway basal cells induced upregulation of host defense genes, including MX1, IFIT3, IFITM, and known POU2AF1 downstream genes HLA-DRA, ID2, ID3, IL6, and BCL6. Interestingly, expression of these genes paralleled changes of POU2AF1 expression during airway epithelium differentiation in vitro, suggesting POU2AF1 helps to maintain a host defense tone even in pathogen-free condition. Cigarette smoke, a known risk factor for airway infection, suppressed POU2AF1 expression both in vivo in humans and in vitro in human airway epithelial cultures, accompanied by deregulation of POU2AF1 downstream genes. Finally, enhancing POU2AF1 expression in human airway epithelium attenuated the suppression of host defense genes by smoking. Together, these findings suggest a novel function of POU2AF1 as a potential regulator of host defense genes in the human airway epithelium. PMID:26927796

  14. Bisphenol AF Is a Full Agonist for the Estrogen Receptor ERα but a Highly Specific Antagonist for ERβ

    PubMed Central

    Matsushima, Ayami; Liu, Xiaohui; Okada, Hiroyuki; Shimohigashi, Miki; Shimohigashi, Yasuyuki

    2010-01-01

    Background Bisphenol AF has been acknowledged to be useful for the production of CF3-containing polymers with improved chemical, thermal, and mechanical properties. Because of the lack of adequate toxicity data, bisphenol AF has been nominated for comprehensive toxicological characterization. Objectives We aimed to determine the relative preference of bisphenol AF for the human nuclear estrogenic receptors ERα and ERβ and the bisphenol A–specific estrogen-related receptor ERRγ, and to clarify structural characteristics of receptors that influence bisphenol AF binding. Methods We examined receptor-binding activities of bisphenol AF relative to [3H]17β-estradiol (for ERα and ERβ) and [3H]bisphenol A (for ERRγ). Functional luciferase reporter gene assays were performed to assess receptor activation in HeLa cells. Results We found that bisphenol AF strongly and selectively binds to ERs over ERRγ. Furthermore, bisphenol AF receptor-binding activity was three times stronger for ERβ [IC50 (median inhibitory concentration) = 18.9 nM] than for ERα. When examined using a reporter gene assay, bisphenol AF was a full agonist for ERα. In contrast, it was almost completely inactive in stimulating the basal constitutive activity of ERβ. Surprisingly, bisphenol AF acted as a distinct and strong antagonist against the activity of the endogenous ERβ agonist 17β-estradiol. Conclusion Our results suggest that bisphenol AF could function as an endocrine-disrupting chemical by acting as an agonist or antagonist to perturb physiological processes mediated through ERα and/or ERβ. PMID:20427257

  15. Predicting speech fluency and naming abilities in aphasic patients

    PubMed Central

    Wang, Jasmine; Marchina, Sarah; Norton, Andrea C.; Wan, Catherine Y.; Schlaug, Gottfried

    2013-01-01

    There is a need to identify biomarkers that predict degree of chronic speech fluency/language impairment and potential for improvement after stroke. We previously showed that the Arcuate Fasciculus lesion load (AF-LL), a combined variable of lesion site and size, predicted speech fluency in patients with chronic aphasia. In the current study, we compared lesion loads of such a structural map (i.e., AF-LL) with those of a functional map [i.e., the functional gray matter lesion load (fGM-LL)] in their ability to predict speech fluency and naming performance in a large group of patients. The fGM map was constructed from functional brain images acquired during an overt speaking task in a group of healthy elderly controls. The AF map was reconstructed from high-resolution diffusion tensor images also from a group of healthy elderly controls. In addition to these two canonical maps, a combined AF-fGM map was derived from summing fGM and AF maps. Each canonical map was overlaid with individual lesion masks of 50 chronic aphasic patients with varying degrees of impairment in speech production and fluency to calculate a functional and structural lesion load value for each patient, and to regress these values with measures of speech fluency and naming. We found that both AF-LL and fGM-LL independently predicted speech fluency and naming ability; however, AF lesion load explained most of the variance for both measures. The combined AF-fGM lesion load did not have a higher predictability than either AF-LL or fGM-LL alone. Clustering and classification methods confirmed that AF lesion load was best at stratifying patients into severe and non-severe outcome groups with 96% accuracy for speech fluency and 90% accuracy for naming. An AF-LL of greater than 4 cc was the critical threshold that determined poor fluency and naming outcomes, and constitutes the severe outcome group. Thus, surrogate markers of impairments have the potential to predict outcomes and can be used as a

  16. TYPE AF CERTIFICATE FOR TRANSPORTATION OF LOW ENRICHED URANIUM OXIDE (LEUO) FOR DISPOSAL

    SciTech Connect

    Opperman, E; Kenneth Yates, K

    2007-10-19

    Washington Savannah River Company (WSRC) operates the Savannah River Site (SRS) in Aiken, SC under contract with the U.S. Department of Energy (DOE). SRS had the need to ship 227 drums of low enriched uranium oxide (LEUO) to a disposal site. The LEUO had been packaged nearly 25 years ago in U.S. Department of Transportation (DOT) 17C 55-gallon drums and stored in a warehouse. Since the 235U enrichment was just above 1 percent by weight (wt%) the material did not qualify for the fissile material exceptions in 49 CFR 173.453, and therefore was categorized as 'fissile material' for shipping purposes. WSRC evaluated all existing Type AF packages and did not identify any feasible packaging. Applying for a new Type AF certificate of compliance was considered too costly for a one-time/one-way shipment for disposal. Down-blending the material with depleted uranium (to reduce enrichment below 1 wt% and enable shipment as low specific activity (LSA) radioactive material) was considered, but appropriate blending facilities do not exist at SRS. After reviewing all options, WSRC concluded that seeking a DOT Special Permit was the best option to enable shipment of the material for permanent disposal. WSRC submitted the Special Permit application to the DOT, and after one request-for-additional-information (RAI) the permit was considered acceptable. However, in an interesting development that resulted from the DOT Special Permit application process, it was determined that it was more appropriate for the DOE to issue a Type AF certificate [Ref. 1] for this shipping campaign. This paper will outline the DOT Special Permit application and Type AF considerations, and will discuss the issuance of the new DOE Type AF certificate of compliance.

  17. Unraveling the Activation Mechanism of Taspase1 which Controls the Oncogenic AF4-MLL Fusion Protein.

    PubMed

    Sabiani, Samaneh; Geppert, Tim; Engelbrecht, Christian; Kowarz, Eric; Schneider, Gisbert; Marschalek, Rolf

    2015-05-01

    We have recently demonstrated that Taspase1-mediated cleavage of the AF4-MLL oncoprotein results in the formation of a stable multiprotein complex which forms the key event for the onset of acute proB leukemia in mice. Therefore, Taspase1 represents a conditional oncoprotein in the context of t(4;11) leukemia. In this report, we used site-directed mutagenesis to unravel the molecular events by which Taspase1 becomes sequentially activated. Monomeric pro-enzymes form dimers which are autocatalytically processed into the enzymatically active form of Taspase1 (αββα). The active enzyme cleaves only very few target proteins, e.g., MLL, MLL4 and TFIIA at their corresponding consensus cleavage sites (CSTasp1) as well as AF4-MLL in the case of leukemogenic translocation. This knowledge was translated into the design of a dominant-negative mutant of Taspase1 (dnTASP1). As expected, simultaneous expression of the leukemogenic AF4-MLL and dnTASP1 causes the disappearance of the leukemogenic oncoprotein, because the uncleaved AF4-MLL protein (328 kDa) is subject to proteasomal degradation, while the cleaved AF4-MLL forms a stable oncogenic multi-protein complex with a very long half-life. Moreover, coexpression of dnTASP1 with a BFP-CSTasp1-GFP FRET biosensor effectively inhibits cleavage. The impact of our findings on future drug development and potential treatment options for t(4;11) leukemia will be discussed. PMID:26137584

  18. The Electrical Characteristics and Clinical Significance of the Effect of Adenosine on Dissociated Activity after Circumferential Venous Isolation in Patients with Atrial Fibrillation

    PubMed Central

    Niu, Ya-Lei; Chang, Shih-Lin; Lin, Yenn-Jiang; Lo, Li-Wei; Hu, Yu-Feng; Tuan, Ta-Chuan; Tsai, Chin-Feng; Lin, Wei-Shiang; Tsao, Hsuan-Ming; Chen, Shih-Ann

    2015-01-01

    Background Dissociated activity can occur after circumferential thoracic vein isolation for treating atrial fibrillation (AF). However, its clinical significance and response to adenosine remain unclear. Methods Fifty-three patients (10 women, 11 with non-paroxysmal AF, with mean age 54.4 ± 11.2 years) with slow dissociated activity after thoracic vein isolation for AF ablation were analyzed. Adenosine (12 mg) was injected intravenously into 30 patients, and the responses of the dissociated activities were recorded. Results The clinical characteristics and the rate of recurrence did not differ between patients with and without dissociated activity. Dissociated activity was most frequently observed at the right superior pulmonary vein (PV) (61%), left superior PV (26%), right inferior PV (5%), left inferior PV (4%), and non-PV sites (4%). The locations of dissociated activities were associated with the AF trigger sites (p = 0.004). Adenosine injection decreased the cycle length of dissociated activity in 13 patients (group 1) and increased it in 17 patients (group 2). Dissociated activity disappeared in 7 patients (41%) (group 2) after adenosine injection. During the mean 33 ± 17 months of follow-up, group 2 patients had a lower AF recurrence rate (24%) than group 1 patients (62%) (p = 0.035). Conclusions The locations of dissociated activity were closely associated with the AF trigger sites. The responses to adenosine may predict AF recurrence in patients with dissociated activity. PMID:27122888

  19. Oral anticoagulation, stroke and thromboembolism in patients with atrial fibrillation and valve bioprosthesis. The Loire Valley Atrial Fibrillation Project.

    PubMed

    Philippart, Raphael; Brunet-Bernard, Anne; Clementy, Nicolas; Bourguignon, Thierry; Mirza, Alain; Angoulvant, Denis; Babuty, Dominique; Lip, Gregory Y H; Fauchier, Laurent

    2016-05-01

    Vitamin K antagonists are currently recommended in patients with 'valvular' atrial fibrillation (AF), e. g. those having mitral stenosis or artificial heart valves. We compared thromboembolic risk in patients with 'non valvular' AF and in those with AF and biological valve replacement (valve bioprosthesis). Among 8962 AF patients seen between 2000 and 2010, a diagnosis of 'non-valvular AF' was found in 8053 (94 %). Among patients with 'valvular' AF, 549 (6 %) had a biological prosthesis. The patients with bioprosthesis were older and had a higher CHA2DS2-VASc score than those with non valvular AF. After a follow-up of 876 ± 1048 days (median 400 days, interquartile range 12-1483), the occurrence of thromboembolic events was similar in AF patients with bioprosthesis compared to those with 'non valvular' AF (hazard ratio [HR] 1.10 95 % confidence interval [CI] 0.83-1.45, p=0.52, adjusted HR 0.93, 95 %CI 0.68-1.25, p=0.61). Factors independently associated with increased risk of stroke/TE events were older age (HR 1.25, 95 %CI 1.16-1.34 per 10-year increase, p< 0.0001) and higher CHA2DS2-VASc score (HR 1.35, 95 %CI 1.24-1.46, p< 0.0001) whilst female gender (HR 0.75, 95 %CI 0.62-0.90, p=0.002), use of vitamin K antagonist (HR 0.83, 95 %CI 0.71-0.98, p=0.03) were independently associated with a lower risk of stroke/TE. Neither the presence of bioprosthesis nor the location of bioprosthesis was independent predictor for TE events. In conclusion, AF patients with bioprosthesis had a non-significantly higher risk of stroke/TE events compared to patients with non-valvular AF. Second, the CHA2DS2-VASc score was independently associated with an increased risk of TE events, and was a valuable determinant of TE risk both in AF patients with non-valvular AF as well as those with bioprosthesis, whether treated or not treated with OAC. PMID:26843425

  20. Atrial fibrillation alters the microRNA expression profiles of the left atria of patients with mitral stenosis

    PubMed Central

    2014-01-01

    Background Structural changes of the left and right atria associated with atrial fibrillation (AF) in mitral stenosis (MS) patients are well known, and alterations in microRNA (miRNA) expression profiles of the right atria have also been investigated. However, miRNA changes in the left atria still require delineation. This study evaluated alterations in miRNA expression profiles of left atrial tissues from MS patients with AF relative to those with normal sinus rhythm (NSR). Methods Sample tissues from left atrial appendages were obtained from 12 MS patients (6 with AF) during mitral valve replacement surgery. From these tissues, miRNA expression profiles were created and analyzed using a human miRNA microarray. Results were validated via reverse-transcription and quantitative PCR for 5 selected miRNAs. Potential miRNA targets were predicted and their functions and potential pathways analyzed via the miRFocus database. Results The expression levels of 22 miRNAs differed between the AF and NSR groups. Relative to NSR patients, in those with AF the expression levels of 45% (10/22) of these miRNAs were significantly higher, while those of the balance (55%, 12/22) were significantly lower. Potential miRNA targets and molecular pathways were identified. Conclusions AF alters the miRNA expression profiles of the left atria of MS patients. These findings may be useful for the biological understanding of AF in MS patients. PMID:24461008

  1. Managing atrial fibrillation in the very elderly patient: challenges and solutions

    PubMed Central

    Karamichalakis, Nikolaos; Letsas, Konstantinos P; Vlachos, Konstantinos; Georgopoulos, Stamatis; Bakalakos, Athanasios; Efremidis, Michael; Sideris, Antonios

    2015-01-01

    Atrial fibrillation (AF) is the most common arrhythmia affecting elderly patients. Management and treatment of AF in this rapidly growing population of older patients involve a comprehensive assessment that includes comorbidities, functional, and social status. The cornerstone in therapy of AF is thromboembolic protection. Anticoagulation therapy has evolved, using conventional or newer medications. Percutaneous left atrial appendage closure is a new invasive procedure evolving as an alternative to systematic anticoagulation therapy. Rate or rhythm control leads to relief in symptoms, fewer hospitalizations, and an improvement in quality of life. Invasive methods, such as catheter ablation, are the new frontier of treatment in maintaining an even sinus rhythm in this particular population. PMID:26604772

  2. Reliability of Oscillometric Blood Pressure Monitoring in Atrial Fibrillation Patients Admitted for Electric Cardioversion.

    PubMed

    Maselli, Monica; Giantin, Valter; Corrado, Domenico; Franchin, Alessandro; Attanasio, Francesca; Pengo, Valentina; Tramontano, Alessandra; De Toni, Pietro; Perissinotto, Egle; Manzato, Enzo

    2015-07-01

    The reliability of automated oscillometric blood pressure (BP) monitors in atrial fibrillation (AF) has been poorly investigated, only comparing different patients with AF and sinus rhythm (SR), and is a method influenced by individual characteristics. This study compared the reliability of the oscillometric device A&D TM-2430 (A&D Company, Tokyo, Japan) with that of a mercury sphygmomanometer in AF patients whose SR was restored after electric cardioversion (ECV). Three consecutive BP measurements were obtained on the day before and about 30 days after ECV in stable treatment conditions. Of the 100 patients studied, 63 reported an SR at follow-up, with a significant increase in systolic BP and a significant decrease in diastolic BP according to both devices. There were no significant differences between the systolic and diastolic biases before and after ECV using Bland Altman analysis (P > .05 each). The oscillometric device analyzed, using three repeated measurements, is reliable in measuring BP in AF patients. PMID:25855463

  3. Impact of allogeneic hematopoietic cell transplant in patients with myeloid neoplasms carrying spliceosomal mutations.

    PubMed

    Hamilton, Betty Ky; Visconte, Valeria; Jia, Xuefei; Tabarroki, Ali; Makishima, Hideki; Hasrouni, Edy; Abounader, Donna; Kalaycio, Matt; Sekeres, Mikkael A; Sobecks, Ronald; Duong Liu, Hien; Bolwell, Brian; Maciejewski, Jaroslaw P; Copelan, Edward; Tiu, Ramon V

    2016-06-01

    Molecular predictors of outcome are increasingly important in determining optimal therapy for myeloid neoplasms. Mutations in the spliceosomal genes (U2AF1 and SRSF2) predict for poor outcomes in myelodysplastic syndromes (MDS) and related diseases. We investigated the effect of hematopoietic cell transplant (HCT) on the negative prognostic impact of U2AF1 and SRSF2 mutations. In total, 122 patients with MDS (30%), acute myeloid leukemia (51%), myeloproliferative neoplasms (MPN) (11%), and MDS/MPN (8%) receiving a HCT from 2003 to 2012 were evaluated for mutations in U2AF1 and SRSF2 by direct sequencing. Median time of follow up was 24 months (range 0.46-110). SRSF2 mutations were detected in 11 (10%) patients and U2AF1 in 3 (3%) patients. There were no significant differences in baseline characteristics between mutated and wild-type (WT) patients. Patients carrying SRSF2 and U2AF1 mutations had similar overall survival (P = 0.84), relapse mortality (P = 0.50), and non-relapse mortality (P = 0.72) compared to WT patients. However, taking into account disease status and cytogenetics in a subset of AML patients, SRSF2 and U2AF1 mutations were associated with worse survival (HR 3.71, P = 0.035). Am. J. Hematol. 91:406-409, 2016. © 2016 Wiley Periodicals, Inc. PMID:26799334

  4. Prevalence, clinical characteristics and management of atrial fibrillation in patients with Brugada syndrome.

    PubMed

    Rodríguez-Mañero, Moisés; Namdar, Mehdi; Sarkozy, Andrea; Casado-Arroyo, Rubén; Ricciardi, Danilo; de Asmundis, Carlo; Chierchia, Gian-Battista; Wauters, Kristel; Rao, Jayakeerthi Y; Bayrak, Fatih; Van Malderen, Sophie; Brugada, Pedro

    2013-02-01

    Atrial fibrillation (AF) can be the first manifestation of latent Brugada syndrome (BS). The aim of our study was to assess the prevalence of AF as the first clinical diagnosis in patients with BS and their demographic and clinical characteristics and diagnosis management in a large cohort of patients. The patient group consisted of 611 patients with BS. The data from those with a diagnosis of AF previous to the identification of BS were analyzed (n = 35). Eleven cases were unmasked after the initiation of a class I antiarrhythmic drug and one during the establishment of general anesthesia. In the remaining population, BS was diagnosed using an ajmaline test performed mainly because of younger age in patients with lone AF (n = 13), previous syncope or sudden cardiac death (n = 3), or a clinical history of sudden cardiac death in the family (n = 5). The mean patient age was 49 ± 15 years, 21 were male patients, 14 had a family history of sudden death, 15 had had previous syncope, and 4 had survived cardiac arrest. Concomitant electrical disorder was found in 13 patients. Remarkably, 21 patients had normal findings on the baseline electrocardiogram. In conclusion, AF could be one of the first clinical manifestations of latent BS in a considerable number of patients. This identification is crucial because the treatment of these patients is subject to relevant changes. The ajmaline test plays an essential role, mainly in young patients with a family history of sudden death, despite having normal findings on a baseline electrocardiogram. PMID:23206922

  5. Prevalence of left atrial abnormalities in atrial fibrillation versus normal sinus patients

    PubMed Central

    Ketai, Loren H; Teague, Shawn D; Rissing, Stacy M

    2016-01-01

    Background Atrial fibrillation (AF) may be the cause or sequela of left atrial abnormalities and variants. Purpose To determine the prevalence of left atrial (LA) abnormalities in AF patients compared to normal sinus rhythm (NSR) patients. Material and Methods We retrospectively reviewed 281 cardiac CT examinations from 2010 to 2012, excluding patients with prior pulmonary vein ablation, known coronary artery disease, prior coronary stent placement, or coronary artery bypass grafts. The first group consisted of 159 AF patients undergoing cardiac CT prior to pulmonary vein ablation and the second group consisted of 122 NSR patients evaluated with coronary CT angiography. Demographic data were collected. LA abnormalities were analyzed. Left atrial diameter was measured on an axial view. Results A total of 281 patients were included. The male gender has significantly higher prevalence of AF than female gender, P value <0.001. Patients with AF were significantly older (mean age, 57.4 years; standard deviation [SD], 11.8 years) than NSR patients (mean age, 53.4 years; SD, 13.6 years), P value, 0.01. The left atrial diameter was greater in the AF patients (mean diameter, 4.3 cm; SD, 0.82 cm) versus the NSR patients (3.4 cm; SD, 0.58 cm), P value, <0.0001. LA diverticulum was the most prevalent variant, occurring in 28.4% of the entire patient population followed by LA pouch, occurring in 24%. There was no significant between group differences in the prevalence of these or the remainder of the LA variants. Conclusion AF patients differed significantly from NSR patients in LA size, gender, and mean age. There was no statistical significance between the two groups with regard to the LA morphologic abnormalities other than size. PMID:27358747

  6. Molecular genetic analysis of U2AF59 in Schizosaccharomyces pombe: differential sensitivity of introns to mutational inactivation.

    PubMed Central

    Romfo, C M; Lakhe-Reddy, S; Wise, J A

    1999-01-01

    The large subunit of the mammalian U2AF heterodimer (U2AF65) is essential for splicing in vitro. To expand our understanding of how this protein functions in vivo, we have created a null allele of the gene encoding the Schizosaccharomyces pombe ortholog, U2AF59, and employed it in a variety of genetic complementation assays. First, analysis of an extensive series of double amino acid substitutions indicates that this splicing factor is surprisingly refractory to mutations. Second, despite extensive structural conservation, we find that metazoan large subunit orthologs cannot substitute in vivo for fission yeast U2AF59. Third, because the activity of U2AF65 in vitro involves binding to the 3' polypyrimidine tract, we examined the splicing of introns containing or lacking this feature in a U2AF59 mutant described here as well as a previously isolated temperature-sensitive mutant (Potashkin et al., 1993, Science 262:573-575). Our data indicate that all four introns tested, including two that lack extensive runs of pyrimidines between the branchpoint and 3' splice site, show splicing defects upon shifting to the nonpermissive condition. In all cases, splicing is blocked prior to the first transesterification reaction in the mutants, consistent with the role inferred for human U2AF65 based on in vitro experiments. PMID:9917066

  7. Heart Rate at Hospital Discharge in Patients With Heart Failure Is Associated With Mortality and Rehospitalization

    PubMed Central

    Laskey, Warren K.; Alomari, Ihab; Cox, Margueritte; Schulte, Phillip J.; Zhao, Xin; Hernandez, Adrian F.; Heidenreich, Paul A.; Eapen, Zubin J.; Yancy, Clyde; Bhatt, Deepak L.; Fonarow, Gregg C.

    2015-01-01

    Background Whether heart rate upon discharge following hospitalization for heart failure is associated with long‐term adverse outcomes and whether this association differs between patients with sinus rhythm (SR) and atrial fibrillation (AF) have not been well studied. Methods and Results We conducted a retrospective cohort study from clinical registry data linked to Medicare claims for 46 217 patients participating in Get With The Guidelines®–Heart Failure. Cox proportional‐hazards models were used to estimate the association between discharge heart rate and all‐cause mortality, all‐cause readmission, and the composite outcome of mortality/readmission through 1 year. For SR and AF patients with heart rate ≥75, the association between heart rate and mortality (expressed as hazard ratio [HR] per 10 beats‐per‐minute increment) was significant at 0 to 30 days (SR: HR 1.30, 95% CI 1.22 to 1.39; AF: HR 1.23, 95% CI 1.16 to 1.29) and 31 to 365 days (SR: HR 1.15, 95% CI 1.12 to 1.20; AF: HR 1.05, 95% CI 1.01 to 1.08). Similar associations between heart rate and all‐cause readmission and the composite outcome were obtained for SR and AF patients from 0 to 30 days but only in the composite outcome for SR patients over the longer term. The HR from 0 to 30 days exceeded that from 31 to 365 days for both SR and AF patients. At heart rates <75, an association was significant for mortality only for both SR and AF patients. Conclusions Among older patients hospitalized with heart failure, higher discharge heart rate was associated with increased risks of death and rehospitalization, with higher risk in the first 30 days and for SR compared with AF. PMID:25904590

  8. Clinical Characteristics and Impact of Diabetes Mellitus on Outcomes in Patients with Nonvalvular Atrial Fibrillation

    PubMed Central

    Huang, Bi; Zhu, Jun; Liang, Yan; Zhang, Han; Tian, Li; Shao, Xinghui; Wang, Juan

    2015-01-01

    Purpose Studies have shown that diabetes mellitus (DM) is a risk factor for cardiovascular disease, including atrial fibrillation (AF); however, the clinical characteristics and prognostic impact of DM in patients with nonvalvular AF have not been well understood in China. Materials and Methods Included were 1644 consecutive patients with nonvalvular AF. Endpoints included all-cause mortality, cardiovascular mortality, stroke, major bleeding, and combined endpoint events (CEE) during a 1-year follow-up. Results The prevalence of DM was 16.8% in nonvalvular AF patients. Compared with non-diabetic AF patients, diabetic AF patients were older and tended to coexist with other cardiovascular diseases. Most patients with DM (93.5%) were eligible for anticoagulation, as determined by CHADS2 scores. However, only 11.2% of patients received anticoagulation. During a 1-year follow-up, the all-cause mortality and CEE rate in the DM group were significantly higher than those of the non-DM group, while the incidence of stroke was comparable. After multivariate adjustments, DM was still an independent risk factor for 1-year all-cause mortality [hazard ratio (HR)=1.558; 95% confidence interval (CI) 1.126-2.156; p=0.007], cardiovascular mortality (HR=1.615; 95% CI 1.052-2.479; p=0.028), and CEE (HR=1.523; 95% CI 1.098-2.112; p=0.012), yet not for stroke (HR=1.119; 95% CI 0.724-1.728; p=0.614). Conclusion DM is a common morbidity coexisting with nonvalvular AF and is associated with an increased risk of 1-year all-cause mortality, cardiovascular mortality, and CEE. However, no increased risk of stroke was found during a 1-year follow-up in patients with AF and DM. PMID:25510748

  9. Platelet Reactivity Is Independent of Left Atrial Wall Deformation in Patients with Atrial Fibrillation.

    PubMed

    Procter, Nathan; Goh, Vincent; Mahadevan, Gnanadevan; Stewart, Simon; Horowitz, John

    2016-01-01

    It has been documented recently that left atrial (LA) deformation in AF patients (while in AF) is predictive of subsequent stroke risk. Additionally, diminished LA deformation during AF correlates with the presence of LA blood stasis. Given that endothelial function is dependent on laminar blood flow, the present study sought to investigate the effect of diminished LA deformation (during AF) on platelet reactivity and inflammation in AF patients. Patients (n = 17) hospitalised with AF underwent echocardiography (while in AF) for determination of peak positive LA strain (LASp). Whole blood impedance aggregometry was used to measure extent of ADP-induced aggregation and subsequent inhibitory response to the nitric oxide (NO) donor, sodium nitroprusside. Platelet thioredoxin-interacting protein (Txnip) content was determined by immunohistochemistry. LASp tended (p = 0.078) to vary inversely with CHA2DS2VASc scores. However, mediators of inflammation (C-reactive protein, Txnip) did not correlate significantly with LASp nor did extent of ADP-induced platelet aggregation or platelet NO response. These results suggest that the thrombogenic risk associated with LA stasis is independent of secondary effects on platelet aggregability or inflammation. PMID:27069318

  10. Platelet Reactivity Is Independent of Left Atrial Wall Deformation in Patients with Atrial Fibrillation

    PubMed Central

    Procter, Nathan; Goh, Vincent; Mahadevan, Gnanadevan; Stewart, Simon; Horowitz, John

    2016-01-01

    It has been documented recently that left atrial (LA) deformation in AF patients (while in AF) is predictive of subsequent stroke risk. Additionally, diminished LA deformation during AF correlates with the presence of LA blood stasis. Given that endothelial function is dependent on laminar blood flow, the present study sought to investigate the effect of diminished LA deformation (during AF) on platelet reactivity and inflammation in AF patients. Patients (n = 17) hospitalised with AF underwent echocardiography (while in AF) for determination of peak positive LA strain (LASp). Whole blood impedance aggregometry was used to measure extent of ADP-induced aggregation and subsequent inhibitory response to the nitric oxide (NO) donor, sodium nitroprusside. Platelet thioredoxin-interacting protein (Txnip) content was determined by immunohistochemistry. LASp tended (p = 0.078) to vary inversely with CHA2DS2VASc scores. However, mediators of inflammation (C-reactive protein, Txnip) did not correlate significantly with LASp nor did extent of ADP-induced platelet aggregation or platelet NO response. These results suggest that the thrombogenic risk associated with LA stasis is independent of secondary effects on platelet aggregability or inflammation. PMID:27069318

  11. New Oral Anticoagulants May Be Particularly Useful for Asian Stroke Patients

    PubMed Central

    Bang, Oh Young; Hong, Keun-Sik; Heo, Ji Hoe; Koo, Jaseong; Kwon, Sun U.; Yu, Kyung-Ho; Bae, Hee-Joon; Lee, Byung-Chul; Yoon, Byung-Woo

    2014-01-01

    Atrial fibrillation (AF) is an emerging epidemic in both high-income and low-income countries, mainly because of global population aging. Stroke is a major complication of AF, and AF-related ischemic stroke is more disabling and more fatal than other types of ischemic stroke. However, because of concerns about bleeding complications, particularly intracranial hemorrhage, and the limitations of a narrow therapeutic window, warfarin is underused. Four large phase III randomized controlled trials in patients with non-valvular AF (RE-LY, ROCKET-AF, ARISTOTLE, and ENGAGE-AF-TIMI 48) demonstrated that new oral anticoagulants (NOACs) are superior or non-inferior to warfarin as regards their efficacy in preventing ischemic stroke and systemic embolism, and superior to warfarin in terms of intracranial hemorrhage. Among AF patients receiving warfarin, Asians compared to non-Asians are at higher risk of stroke or systemic embolism and are also more prone to develop major bleeding complications, including intracranial hemorrhage. The extra benefit offered by NOACs over warfarin appears to be greater in Asians than in non-Asians. In addition, Asians are less compliant, partly because of the frequent use of herbal remedies. Therefore, NOACs compared to warfarin may be safer and more useful in Asians than in non-Asians, especially in stroke patients. Although the use of NOACs in AF patients is rapidly increasing, guidelines for the insurance reimbursement of NOACs have not been resolved, partly because of insufficient understanding of the benefit of NOACs and partly because of cost concerns. The cost-effectiveness of NOACs has been well demonstrated in the healthcare settings of developed countries, and its magnitude would vary depending on population characteristics as well as treatment cost. Therefore, academic societies and regulatory authorities should work together to formulate a scientific healthcare policy that will effectively reduce the burden of AF-related stroke in

  12. Pathophysiologic basis of autonomic ganglionated plexus ablation in patients with atrial fibrillation.

    PubMed

    Nakagawa, Hiroshi; Scherlag, Benjamin J; Patterson, Eugene; Ikeda, Atsuhsi; Lockwood, Deborah; Jackman, Warren M

    2009-12-01

    The intrinsic cardiac autonomic nervous system (ganglionated plexuses [GP]) plays a significant role in the initiation and maintenance of atrial fibrillation (AF) in both experimental models and AF patients. Left atrial GP, located in epicardial fat pads and the ligament of Marshall, contain afferent neurons from the atrial myocardium and the central autonomic nervous system, efferent neurons (cholinergic and adrenergic neurons), and interconnecting neurons, which allow communication between GP. Stimulation of the GP produces both parasympathetic stimulation (markedly shortens action potential duration) and sympathetic stimulation (increases calcium transient) in the pulmonary vein (PV) myocardium and atrial myocardium. In a canine model, GP stimulation resulted in early afterdepolarizations, and calcium transient triggered firing in the adjacent PV and initiated AF. Fractionated atrial potentials (FAP) were consistently located in the left atrium close to the stimulated GP. Ablation of the stimulated GP eliminated the FAP surrounding the GP. In patients with paroxysmal AF, epicardial and endocardial high-frequency stimulation produced a positive vagal response (transient AV block during AF and hypotension), allowing the identification and localization of five major left atrial GP (superior left GP, inferior left GP, Marshall tract GP, anterior right GP, inferior right GP). High-density electroanatomic maps of the left atrium and PVs obtained during AF showed the FAP are located in four main left atrial areas (left atrial appendage ridge FAP area, superior-left FAP area, inferoposterior FAP area, anterior-right FAP area). All five GP are located within one of the four FAP areas. In 63 patients with paroxysmal AF, GP ablation alone (before PV antrum isolation) significantly decreased the occurrence of PV firing (47/63 patients before ablation vs 9/63 patients after ablation, P <.01). GP ablation also decreased the inducibility of sustained AF (43/63 patients vs 23

  13. Clinical trials update from the American Heart Association meeting 2010: EMPHASIS-HF, RAFT, TIM-HF, Tele-HF, ASCEND-HF, ROCKET-AF, and PROTECT.

    PubMed

    Cleland, John G F; Coletta, Alison P; Buga, Laszlo; Antony, Renjith; Pellicori, Pierpaolo; Freemantle, Nick; Clark, Andrew L

    2011-04-01

    This article provides information and a commentary on key trials relevant to the pathophysiology, prevention, and treatment of heart failure presented at the annual meeting of the American Heart Association held in Chicago in 2010. Unpublished reports should be considered as preliminary, since analyses may change in the final publication. In patients with mild heart failure (HF), EMPHASIS-HF showed that the addition of eplerenone to standard therapy was well tolerated and reduced both the risk of death and hospitalization. The addition of cardiac resynchronization therapy to implantable cardioverter defibrillator (ICD) therapy reduced the incidence of all-cause mortality and HF hospitalizations in patients with NYHA class II-III HF compared with ICD alone in RAFT. Telemonitoring failed to improve outcome compared with a high standard of conventional care in patients with chronic HF (TIM-HF study) and a telephone-based interactive voice response system failed to improve outcome in patients recently hospitalized for HF (Tele-HF study). ASCEND-HF suggested that nesiritide was ineffective but safe in patients with acute decompensated HF. ROCKET-AF suggests that the factor-Xa inhibitor rivaroxaban may be as effective as warfarin in patients with atrial fibrillation. The PROTECT study provided more data to suggest that amino-terminal B-type natriuretic peptide guided therapy may be beneficial in patients with left ventricular systolic dysfunction. PMID:21436363

  14. Oblongionosides A-F, megastigmane glycosides from the leaves of Croton oblongifolius Roxburgh.

    PubMed

    Takeshige, Yuya; Kawakami, Susumu; Matsunami, Katsuyoshi; Otsuka, Hideaki; Lhieochaiphant, Duangporn; Lhieochaiphant, Sorasak

    2012-08-01

    From the 1-BuOH-soluble fraction of a MeOH extract of the leaves of Croton oblongifolius Roxburgh, collected in Chiang Mai, Thailand, six megastigmane glycosides, named oblongionosides A-F were isolated together with eight known compounds, and their structures elucidated on the basis of spectroscopic data. Absolute structures were determined by HPLC analyses and application of the modified Mosher's method. PMID:22683317

  15. Experimental test of macroscopic models for exchange anisotropy in FM/AF bilayers

    NASA Astrophysics Data System (ADS)

    Rezende, S. M.; Azevedo, A.; de Aguiar, F. M.; Lucena, M. A.; Fermin, J. R.; Parkin, S. S. P.

    2004-05-01

    Ferromagnetic resonance measurements in two series of ferromagnetic (FM)/antiferromagnetic (AF) bilayer samples of NiFe( t)/NiO and CoFe( t)/IrMn have been used to test macroscopic models for exchange anisotropy. The domain-wall model incorporating a rotatable anisotropy field is the one that best fits the data. All fields of interfacial origin extracted from the fits show the predicted 1 t dependence with the FM layer thickness.

  16. The Splicing Factor U2AF Small Subunit Is Functionally Conserved between Fission Yeast and Humans

    PubMed Central

    Webb, Christopher J.; Wise, Jo Ann

    2004-01-01

    The small subunit of U2AF, which functions in 3′ splice site recognition, is more highly conserved than its heterodimeric partner yet is less thoroughly investigated. Remarkably, we find that the small subunit of Schizosaccharomyces pombe U2AF (U2AFSM) can be replaced in vivo by its human counterpart, demonstrating that the conservation extends to function. Precursor mRNAs accumulate in S. pombe following U2AFSM depletion in a time frame consistent with a role in splicing. A comprehensive mutational analysis reveals that all three conserved domains are required for viability. Notably, however, a tryptophan in the pseudo-RNA recognition motif implicated in a key contact with the large subunit by crystallographic data is dispensable whereas amino acids implicated in RNA recognition are critical. Mutagenesis of the two zinc-binding domains demonstrates that they are neither equivalent nor redundant. Finally, two- and three-hybrid analyses indicate that mutations with effects on large-subunit interactions are rare whereas virtually all alleles tested diminished RNA binding by the heterodimer. In addition to demonstrating extraordinary conservation of U2AF small-subunit function, these results provide new insights into the roles of individual domains and residues. PMID:15121844

  17. In vivo role of the HNF4α AF-1 activation domain revealed by exon swapping

    PubMed Central

    Briançon, Nadège; Weiss, Mary C

    2006-01-01

    The gene encoding the nuclear receptor hepatocyte nuclear factor 4α (HNF4α) generates isoforms HNF4α1 and HNF4α7 from usage of alternative promoters. In particular, HNF4α7 is expressed in the pancreas whereas HNF4α1 is found in liver, and mutations affecting HNF4α function cause impaired insulin secretion and/or hepatic defects in humans and in tissue-specific ‘knockout' mice. HNF4α1 and α7 isoforms differ exclusively by amino acids encoded by the first exon which, in HNF4α1 but not in HNF4α7, includes the activating function (AF)-1 transactivation domain. To investigate the roles of HNF4α1 and HNF4α7 in vivo, we generated mice expressing only one isoform under control of both promoters, via reciprocal swapping of the isoform-specific first exons. Unlike Hnf4α gene disruption which causes embryonic lethality, these ‘α7-only' and ‘α1-only' mice are viable, indicating functional redundancy of the isoforms. However, the former show dyslipidemia and preliminary results indicate impaired glucose tolerance for the latter, revealing functional specificities of the isoforms. These ‘knock-in' mice provide the first test in vivo of the HNF4α AF-1 function and have permitted identification of AF-1-dependent target genes. PMID:16498401

  18. Fracture Growth Testing of Titanium 6AL-4V in AF-M315E

    NASA Technical Reports Server (NTRS)

    Sampson, Jeffrey W.; Martinez, Jonathan; McLean, Christopher

    2015-01-01

    The Green Propellant Infusion Mission (GPIM) will demonstrate the performance of AF-M315E monopropellant in orbit. Flight certification requires a safe-life analysis of the titanium alloy fuel tank to ensure inherent flaws will not cause failure during the design life. Material property inputs for this analysis require testing to determine the stress intensity factor for environmentally-assisted cracking (K (sub EAC)) of Ti 6Al-4V in combination with the AF-M315E monopropellant. Testing of single-edge notched specimens SE(B) representing the bulk tank membrane and weld material were performed in accordance with ASTM E1681. Specimens with fatigue pre-cracks were loaded into test fixtures so that the crack tips were exposed to the monopropellant at 50 degrees Centigrade for a duration of 1,000 hours. Specimens that did not fail during exposure were opened to inspect the crack surfaces for evidence of crack growth. The threshold stress intensity value, KEAC, is the highest applied stress intensity that produced neither a failure of the specimen during the exposure nor showed evidence of crack growth. The threshold stress intensity factor of the Ti 6Al-4V forged tank material when exposed to AF-M315E monopropellant was found to be at least 22.0 kilopounds per square inch. The stress intensity factor of the weld material was at least 31.3 kilopounds per square inch.

  19. Loss of AF6/afadin, a marker of poor outcome in breast cancer, induces cell migration, invasiveness and tumor growth.

    PubMed

    Fournier, G; Cabaud, O; Josselin, E; Chaix, A; Adélaïde, J; Isnardon, D; Restouin, A; Castellano, R; Dubreuil, P; Chaffanet, M; Birnbaum, D; Lopez, M

    2011-09-01

    Afadin/AF6, an F-actin-binding protein, is ubiquitously expressed in epithelia and has a key role during development, through its regulatory role in cell-cell junction organization. Afadin loss of expression in 15% of breast carcinoma is associated with adverse prognosis and increased risk of metastatic relapse. To determine the role of afadin in breast cancer, we studied the functional consequences of afadin protein extinction using in vitro and in vivo models. Three different breast cancer cell lines representative of the major molecular subtypes were stably repressed for afadin expression (knockdown of afadin (afadin KD)) using RNA interference. Collective and individual migrations as well as Matrigel invasion were markedly increased in afadin KD cells. Heregulin-β1 (HRG-β1)-induced migration and invasion were increased by twofold in afadin KD cells. Conversely, ectopic expression of afadin in the afadin-negative T47D cell line inhibited spontaneous and HRG-β1-induced migrations. RAS/MAPK and SRC kinase pathways were activated in afadin KD cells. Activation levels positively correlated with migration and invasion strength. Use of MEK1/2 (U0126) and SRC kinases (SU6656) inhibitors reduced afadin-dependent migration and invasion. Afadin extinction in the SK-BR-3 cell line markedly accelerated tumor growth development in mouse mammary gland and lung metastasis formation. These results may explain why the loss of afadin expression in tumors correlates with high tumor size and poor metastasis-free survival in patients. PMID:21478912

  20. Meeting in Florida: Using Asymmetric Flow Field-Flow Fractionation (AF4) to Determine C60 Colloidal Size Distributions

    EPA Science Inventory

    The study of nanomaterials in environmental systems requires robust and specific analytical methods. Analytical methods which discriminate based on particle size and molecular composition are not widely available. Asymmetric Flow Field-Flow Fractionation (AF4) is a separation...

  1. [3H]AF-DX 116 labels subsets of muscarinic cholinergic receptors in rat brain and heart.

    PubMed

    Wang, J X; Roeske, W R; Gulya, K; Wang, W; Yamamura, H I

    1987-10-01

    The in vitro binding properties of the novel muscarinic antagonist [3H]AF-DX 116 were studied using a rapid filtration technique. Association and dissociation rates of [3H]AF-DX 116 binding were rapid at 25 degrees C (2.74 and 2.70 X 10(7) min-1 M-1 for K+1; 0.87 and 0.93 min-1 for k-1) but 20-40 times slower at 0-4 degrees C (0.13 and 0.096 X 10(7) min-1 M-1 for k+1; 0.031 and 0.022 min-1 for k-1 in cerebral cortical and cardiac membranes, respectively). Kinetic dissociation constants (Kds) were estimated to be 31.8 nM and 30.9 nM at 25 degrees C; 23.1 nM and 0-4 degrees C for the cerebral cortex and heart, respectively. In saturation studies, [3H]AF-DX 116 labeled 29 percent of the total [3H](-)QNB binding sites in the cerebral cortical membranes and 87 percent in the cardiac membranes, with Kd values of 28.9 nM and 17.9 nM, respectively. Muscarinic antagonists inhibited [3H]AF-DX 116 binding in a rank order of potency of atropine greater than dexetimide greater than AF-DX 116 greater than PZ greater than levetimide in both tissues. Except for PZ/[3H]AF-DX 116 and AF-DX 116/[3H]AF-DX 116 in the cerebral cortex, all the antagonist competition curves had Hill coefficients close to one. Carbachol and oxotremorine produced shallow inhibition curves against [3H]AF-DX 116 binding in both tissues. Regional distribution studies with [3H](-)QNB, [3H]PZ and [3H]AF-DX 116 showed that most of the muscarinic receptors in the cerebral cortex, hippocampus, nucleus accumbens and corpus striatum are of the M1 subtype while those in the brainstem, cerebellum and other lower brain regions are of the M2 subtype. These results indicate that [3H]AF-DX 116 is a useful probe for the study of heterogeneity of muscarinic cholinergic receptors. PMID:3657382

  2. Management of atrial fibrillation in patients with chronic kidney disease in Europe Results of the European Heart Rhythm Association Survey.

    PubMed

    Potpara, Tatjana S; Lenarczyk, Radoslaw; Larsen, Torben B; Deharo, Jean-Claude; Chen, Jian; Dagres, Nikolaos

    2015-12-01

    The purpose of this European Heart Rhythm (EHRA) Scientific Initiatives Committee EP Wire Survey was to assess 'real-world' practice in the management of patients with atrial fibrillation (AF) and chronic kidney disease (CKD) in the European Eelectrophysiology centres. Of 41 responding centres, 39 (95.1%) and 37 (90.2%) routinely evaluated renal function in AF patients at first presentation and during follow-up, respectively, but 13 centres (31.7%) re-assessed advanced CKD only at ≥1-year intervals. While the use of oral anticoagulants (OACs) in mild-to-moderate CKD patients was mostly guided by individual patient stroke risk, 31% of the centres used no therapy, or aspirin or the left appendage occlusion in patients with advanced CKD and HAS-BLED ≥ 3. Vitamin K antagonists (VKAs) were preferred in patients with severe CKD or under renal replacement therapy (RRT), any non-VKA in patients with mild CKD, and apixaban in patients with moderate CKD. Rhythm control was preferred in patients with mild-to-moderate CKD (48.7% of centres), and rate control in patients with severe CKD (51.2% of centres). In 20 centres (48.8%), AF ablation was not performed in advanced CKD patients. Most centres performed AF ablation on OAC, but heparin bridging was still used in >10% of centres. Our survey has shown that the importance of renal function monitoring in AF patients is well recognized in clinical practice. In patients with mild-to-moderate CKD, AF is mostly managed according to the guideline recommendations, but more data are needed to guide the management of AF in patients with severe CKD or RRT. PMID:26733617

  3. Cloning of Caenorhabditis U2AF65: an alternatively spliced RNA containing a novel exon.

    PubMed Central

    Zorio, D A; Lea, K; Blumenthal, T

    1997-01-01

    The U2 small nuclear ribonucleoprotein particle (snRNP) auxiliary factor, U2AF, is an essential splicing factor required for recognition of the polypyrimidine tract and subsequent U2 snRNP assembly at the branch point. Because Caenorhabditis elegans introns lack both polypyrimidine tract and branch point consensus sequences but have a very highly conserved UUUUCAG/R consensus at their 3' splice sites, we hypothesized that U2AF might serve to recognize this sequence and thus promote intron recognition in C. elegans. Here we report the cloning of the gene for the large subunit of U2AF, uaf-1. Three classes of cDNA were identified. In the most abundant class the open reading frame is similar to that for the U2AF65 from mammals and flies. The remaining two classes result from an alternative splicing event in which an exon containing an in-frame stop codon is inserted near the beginning of the second RNA recognition motif. However, this alternative mRNA is apparently not translated. Interestingly, the inserted exon contains 10 matches to the 3' splice site consensus. To determine whether this feature is conserved, we sequenced uaf-1 from the related nematode Caenorhabditis briggsae. It is composed of six exons, including an alternatively spliced third exon interrupting the gene at the same location as in C. elegans. uaf-1 is contained in an operon with the rab-18 gene in both species. Although the alternative exons from the two species are not highly conserved and would not encode related polypeptides, the C. briggsae alternative exon has 18 matches to the 3' splice site consensus. We hypothesize that the array of 3' splice site-like sequences in the pre-mRNA and alternatively spliced exon may have a regulatory role. The alternatively spliced RNA accumulates at high levels following starvation, suggesting that this RNA may represent an adaption for reducing U2AF65 levels when pre-mRNA levels are low. PMID:9001248

  4. Domains with transcriptional regulatory activity within the ALL1 and AF4 proteins involved in acute leukemia.

    PubMed Central

    Prasad, R; Yano, T; Sorio, C; Nakamura, T; Rallapalli, R; Gu, Y; Leshkowitz, D; Croce, C M; Canaani, E

    1995-01-01

    The ALLI gene, located at chromosome band 11q23, is involved in acute leukemia through a series of chromosome translocations and fusion to a variety of genes, most frequently to A4 and AF9. The fused genes encode chimeric proteins proteins. Because the Drosophila homologue of ALL1, trithorax, is a positive regulator of homeotic genes and acts at the level of transcription, it is conceivable that alterations in ALL1 transcriptional activity may underlie its action in malignant transformation. To begin studying this, we examined the All1, AF4, AF9, and AF17 proteins for the presence of potential transcriptional regulatory domains. This was done by fusing regions of the proteins to the yeast GAL4 DNA binding domain and assaying their effect on transcription of a reporter gene. A domain of 55 residues positioned at amino acids 2829-2883 of ALL1 was identified as a very strong activator. Further analysis of this domain by in vitro mutagenesis pointed to a core of hydrophobic and acidic residues as critical for the activity. An ALL1 domain that repressed transcription of the reporter gene coincided with the sequence homologous to a segment of DNA methyltransferase. An AF4 polypeptide containing residues 480-560 showed strong activation potential. The C-terminal segment of AF9 spanning amino acids 478-568 transactivated transcription of the reporter gene in HeLa but not in NIH 3T3 cells. These results suggest that ALL1, AF4, and probably AF9 interact with the transcriptional machinery of the cell. Images Fig. 1 Fig. 4 Fig. 5 PMID:8618864

  5. Impact of left atrial volume on outcomes of pulmonary vein isolation in patients with non-paroxysmal (persistent) and paroxysmal atrial fibrillation.

    PubMed

    Amin, Vaibhav; Finkel, Jonathan; Halpern, Ethan; Frisch, Daniel R

    2013-10-01

    Using a novel graded outcomes scale, the investigators evaluated whether left atrial (LA) volume measured by cardiac computed tomographic angiography is a predictor of pulmonary vein isolation success in patients with nonparoxysmal atrial fibrillation (AF) and paroxysmal AF (PAF). Data from 45 patients who underwent electrocardiographically gated computed tomographic angiography before pulmonary vein isolation for AF were used. LA volume was measured in the ventricular systolic and diastolic phases, defined as 40% and 75% of the interval between consecutive R waves. Outcomes were graded at 0 to 3, 3 to 6, 6 to 12, and 12 to 24 months after pulmonary vein isolation and scored on a 5-point scale: 1 = no AF recurrence off antiarrhythmic drug, 2 = no AF recurrence on antiarrhythmic drug, 3 = rare AF (<1 episode in 3 months), 4 = asymptomatic recurrent AF, and 5 = no reductions in AF frequency or severity. LA volumes were significantly larger in the nonparoxysmal AF group compared with the PAF group in systole (159.2 vs 128.2 ml, p <0.001) and diastole (137.1 vs 104.0 ml, p <0.001). In patients with PAF, larger LA volume was correlated with worse clinical outcomes in the first 12 months, but the results did not reach statistical significance (systole r = 0.25 to 0.41, diastole r = 0.20 to 0.34). In conclusion, these results show a significant difference in LA volume in patients with nonparoxysmal AF and PAF in systole and diastole. Additionally, there was a correlation between LA volume and clinical outcomes in patients with PAF, although this did not reach statistical significance. PMID:23831160

  6. Molecular characterization of a rare MLL-AF4 (MLL-AFF1) fusion rearrangement in infant leukemia.

    PubMed

    Bizarro, Susana; Cerveira, Nuno; Correia, Cecília; Lisboa, Susana; Peixoto, Ana; Norton, Lucília; Teixeira, Manuel R

    2007-10-01

    The t(4;11)(q21;q23) involving the genes MLL and AF4 (alias for AFF1) is detected in 50-70% of infant leukemia. We characterize at both the DNA and RNA level a rare MLL-AF4 fusion transcript identified in a 15-month-old girl with acute lymphoblastic leukemia. Direct sequence analysis of the reverse transcriptase-polymerase chain reaction product showed an in-frame fusion between MLL exon 9 and AF4 exon 6. We further demonstrated that the genomic breakpoints were located 1,553 bp downstream of MLL exon 9 and 1,239 bp upstream of AF4 exon 6. Four Alu repeats were detected in MLL intron 9 and two Alu repeats and one LINE1 repetitive element were identified downstream of AF4 exon 5. Finally, a 9-bp polypurine (A) tract and an 8-bp polypyrimidine (T) tract were found flanking the translocation breakpoint. In summary, we have characterized at both the RNA and the DNA level a rare MLL-AF4 fusion variant that was presumably mediated by Alu repeats or polypurine and polypyrimidine tracts located in the vicinity of genomic breakpoints. PMID:17889710

  7. Potentiation of estrogen receptor activation function 1 (AF-1) by Src/JNK through a serine 118-independent pathway.

    PubMed

    Feng, W; Webb, P; Nguyen, P; Liu, X; Li, J; Karin, M; Kushner, P J

    2001-01-01

    Estrogen receptor (ER) is activated either by ligand or by signals from tyrosine kinase-linked cell surface receptors. We investigated whether the nonreceptor Src tyrosine kinase could affect ER activity. Expression of constitutively active Src or stimulation of the endogenous Src/JNK pathway enhances transcriptional activation by the estrogen-ER complex and strongly stimulates the otherwise weak activation by the unliganded ER and the tamoxifen-ER complex. Src affects ER activation function 1 (AF-1), and not ER AF-2, and does so through its tyrosine kinase activity. This effect of Src is mediated partly through a Raf/mitogen-activated ERK kinase/extracellular signal-regulated kinase (Raf/MEK/ERK) signaling cascade and partly through a MEKK/JNKK/JNK cascade. Although, as previously shown, Src action through activated ERK stimulates AF-1 by phosphorylation at S118, Src action through activated JNK neither leads to phosphorylation of S118 nor requires S118 for its action. We therefore suggest that the Src/JNK pathway enhances AF-1 activity by modification of ER AF-1-associated proteins. Src potentiates activation functions in CREB-binding protein (CBP) and glucocorticoid receptor interacting protein 1 (GRIP1), and we discuss the possibility that the Src/JNK pathway enhances the activity of these coactivators, which are known to mediate AF-1 action. PMID:11145737

  8. AfAP2-1, An Age-Dependent Gene of Aechmea fasciata, Responds to Exogenous Ethylene Treatment

    PubMed Central

    Lei, Ming; Li, Zhi-Ying; Wang, Jia-Bin; Fu, Yun-Liu; Ao, Meng-Fei; Xu, Li

    2016-01-01

    The Bromeliaceae family is one of the most morphologically diverse families with a pantropical distribution. To schedule an appropriate flowering time for bromeliads, ethylene is commonly used to initiate flower development in adult plants. However, the mechanism by which ethylene induces flowering in adult bromeliads remains unknown. Here, we identified an APETALA2 (AP2)-like gene, AfAP2-1, in Aechmea fasciata. AfAP2-1 contains two AP2 domains and is a nuclear-localized protein. It functions as a transcriptional activator, and the activation domain is located in the C-terminal region. The expression level of AfAP2-1 is higher in juvenile plants than in adult plants, and the AfAP2-1 transcript level was rapidly and transiently reduced in plants treated with exogenous ethylene. Overexpression of AfAP2-1 in Arabidopsis thaliana results in an extremely delayed flowering phenotype. These results suggested that AfAP2-1 responds to ethylene and is a putative age-dependent flowering regulator in A. fasciata. PMID:26927090

  9. AfAP2-1, An Age-Dependent Gene of Aechmea fasciata, Responds to Exogenous Ethylene Treatment.

    PubMed

    Lei, Ming; Li, Zhi-Ying; Wang, Jia-Bin; Fu, Yun-Liu; Ao, Meng-Fei; Xu, Li

    2016-01-01

    The Bromeliaceae family is one of the most morphologically diverse families with a pantropical distribution. To schedule an appropriate flowering time for bromeliads, ethylene is commonly used to initiate flower development in adult plants. However, the mechanism by which ethylene induces flowering in adult bromeliads remains unknown. Here, we identified an APETALA2 (AP2)-like gene, AfAP2-1, in Aechmea fasciata. AfAP2-1 contains two AP2 domains and is a nuclear-localized protein. It functions as a transcriptional activator, and the activation domain is located in the C-terminal region. The expression level of AfAP2-1 is higher in juvenile plants than in adult plants, and the AfAP2-1 transcript level was rapidly and transiently reduced in plants treated with exogenous ethylene. Overexpression of AfAP2-1 in Arabidopsis thaliana results in an extremely delayed flowering phenotype. These results suggested that AfAP2-1 responds to ethylene and is a putative age-dependent flowering regulator in A. fasciata. PMID:26927090

  10. Effect of a Multidisciplinary Approach for the Management of Patients With Atrial Fibrillation in the Emergency Department on Hospital Admission Rate and Length of Stay.

    PubMed

    Ptaszek, Leon M; White, Benjamin; Lubitz, Steven A; Carnicelli, Anthony P; Heist, E Kevin; Ellinor, Patrick T; Machado, Monique; Wasfy, Jason H; Ruskin, Jeremy N; Armstrong, Katrina; Brown, David F; Biddinger, Paul D; Mansour, Moussa

    2016-07-01

    Management of atrial fibrillation (AF) in the emergency department (ED) is variable because of the absence of universally adopted treatment guidelines. To address potentially preventable hospital admissions and prolonged length of stay, an AF treatment pathway was co-developed by physicians from the cardiac electrophysiology service and the department of emergency medicine at our institution. The impact of this AF pathway on patient outcomes was evaluated with a prospective, observational study conducted in a single tertiary care center from July 1, 2013, to June 30, 2014. The primary study outcome was the rate of hospital admission. The secondary outcomes were duration of ED visit and inpatient length of stay. The 94 patients treated according to the AF pathway during the study period were less likely to be admitted than the 265 patients who received routine care (16% vs 80%, p <0.001). For admitted patients, the mean length of stay was shorter for patients treated according to the AF pathway (32 vs 85 hours, p = 0.002). The time spent in the ED was longer for patients in the AF pathway (16 vs 85 hours, p <0.001). Utilization of a multidisciplinary pathway for management of AF in the ED led to a significant reduction in the rate of hospital admission. Patients who were admitted after receiving care according to the AF pathway had a shorter length of stay. In conclusion, utilization of a multidisciplinary AF pathway resulted in a 5-fold reduction in admission rate and >2-fold reduction length of stay for admitted patients. PMID:27206910

  11. Using new non-invasive quick method to detect Borrelia Burgdorferi (B.B.) infection from specific parts of the heart in "seemingly normal" ECGs, and from the ECGs of Atrial Fibrillation (AF), a majority of AF ECGs are found to have: 1) Significant B.B. infection, 2) Markedly increased ANP, 3) Increased Cardiac Troponin I & 4) Markedly reduced Taurine. These 4 factors were mainly localized at infected areas of the SA node area, R-&L-Atria & pulmonary veins at the L-atrium.

    PubMed

    Omura, Yoshiaki; Lu, Dominic; Jones, Marilyn K; Nihrane, Abdallah; Duvvi, Harsha; Yapor, Dario; Shimotsuura, Yasuhiro; Ohki, Motomu

    2015-01-01

    Lyme disease is found in a majority of people we tested. Once Borrelia Burgdorferi (B.B.) spirochete enters human body, it not only causes pain by infecting joints, but it also often enters the brain and the heart. Infection of brain can be quickly detected from the pupil and infection of the heart by ECGs non-invasively. By evaluating recorded ECGs of atrial fibrillation (AF), using U.S. patented non-invasive highly sensitive electromagnetic field (EMF) resonance phenomenon between 2 identical molecules or between a molecule and its antibody, we examined 25 different AF patients' ECGs and found the majority of them suffer from various degrees of B.B. spirochete infection in SA node areas, also in the right & left atria, and pulmonary vein near and around its junction at left atrium & lesser degrees of infection at the AV node & His Bundle. When B.B. infection reaches over 224-600ng or higher at these areas, AF often appears in the majority of all AF analyzed. In order to develop AF, the 4 abnormal factors must be present simultaneously: 1) B.B. infection must be increased to 224-600ng or higher, 2) Atrial Natriuretic Peptide (ANP) must be markedly reduced from normal value of less than 4ng to over 100-400ng, 3) A significant increase of Cardiac Troponin I from normal value of less than 3ng to over 12ng and 4) Taurine must also be markedly reduced from normal value of 4-6ng to 0.25ng. These 4 changes were mainly found only at infected sites of the SA node area, both atria and between the end of the T wave & the beginning of the SA node area, which corresponds to U waves at recorded ECG. Origin of the U wave is mainly due to abnormal electrical potential of pulmonary vein at L-atrium. If all 4 factors do not occur at the infection site, no AF will develop. In seemingly normal ECGs, if using this method, one can detect invisible B.B. infection in early stages. Long before AF appears, AF can be prevented by improved treatment with Amoxicillin 500ng 3 times

  12. Meta-Analysis of Anticoagulation Use, Stroke, Thromboembolism, Bleeding, and Mortality in Patients With Atrial Fibrillation on Dialysis.

    PubMed

    Wong, Christopher X; Odutayo, Ayodele; Emdin, Connor A; Kinnear, Ned J; Sun, Michelle T

    2016-06-15

    Atrial fibrillation (AF) is common in patients on dialysis. Although randomized trials of anticoagulation for AF have demonstrated striking reductions in stroke, these trials did not recruit patients on dialysis. We thus undertook this systematic review and meta-analysis of observational studies including patients with AF on dialysis that reported associations of anticoagulation use. Twenty studies involving 529,741 subjects and 31,321 patients with AF on dialysis were identified. Anticoagulation was associated with a 45% (95% CI 13% to 88%) increased risk of any stroke, reflecting a nonsignificant 13% (95% CI -4% to 34%) increased ischemic stroke risk and 38% (95% CI 3% to 85%) increased hemorrhagic stroke risk. There was also a 44% (95% CI 38% to 56%) lower risk of any thromboembolism, and a 31% (95% CI 12% to 53%) increased risk of any bleeding but no clear association with cardiovascular death (relative risk 0.99, 95% CI 0.86 to 1.15) or all-cause mortality (relative risk 0.97, 95% CI 0.90 to 1.04). Incident event rates were similar or worse in patients on anticoagulation. In conclusion, these observational analyses provide little supporting evidence of benefit, and instead suggest harm, from anticoagulation in patients on dialysis with AF. These results raise the possibility that the effects of anticoagulation in patients with AF on dialysis may not be similar to the clear benefit of anticoagulation seen in patients with AF without end-stage renal disease. Randomized trials are required to definitively evaluate the safety and efficacy of anticoagulation for AF in the dialysis setting. PMID:27237624

  13. Revisiting the biology of infant t(4;11)/MLL-AF4+ B-cell acute lymphoblastic leukemia.

    PubMed

    Sanjuan-Pla, Alejandra; Bueno, Clara; Prieto, Cristina; Acha, Pamela; Stam, Ronald W; Marschalek, Rolf; Menéndez, Pablo

    2015-12-17

    Infant B-cell acute lymphoblastic leukemia (B-ALL) accounts for 10% of childhood ALL. The genetic hallmark of most infant B-ALL is chromosomal rearrangements of the mixed-lineage leukemia (MLL) gene. Despite improvement in the clinical management and survival (∼85-90%) of childhood B-ALL, the outcome of infants with MLL-rearranged (MLL-r) B-ALL remains dismal, with overall survival <35%. Among MLL-r infant B-ALL, t(4;11)+ patients harboring the fusion MLL-AF4 (MA4) display a particularly poor prognosis and a pro-B/mixed phenotype. Studies in monozygotic twins and archived blood spots have provided compelling evidence of a single cell of prenatal origin as the target for MA4 fusion, explaining the brief leukemia latency. Despite its aggressiveness and short latency, current progress on its etiology, pathogenesis, and cellular origin is limited as evidenced by the lack of mouse/human models recapitulating the disease phenotype/latency. We propose this is because infant cancer is from an etiologic and pathogenesis standpoint distinct from adult cancer and should be seen as a developmental disease. This is supported by whole-genome sequencing studies suggesting that opposite to the view of cancer as a "multiple-and-sequential-hit" model, t(4;11) alone might be sufficient to spawn leukemia. The stable genome of these patients suggests that, in infant developmental cancer, one "big-hit" might be sufficient for overt disease and supports a key contribution of epigenetics and a prenatal cell of origin during a critical developmental window of stem cell vulnerability in the leukemia pathogenesis. Here, we revisit the biology of t(4;11)+ infant B-ALL with an emphasis on its origin, genetics, and disease models. PMID:26463423

  14. Revisiting the biology of infant t(4;11)/MLL-AF4+ B-cell acute lymphoblastic leukemia

    PubMed Central

    Bueno, Clara; Prieto, Cristina; Acha, Pamela; Stam, Ronald W.; Marschalek, Rolf; Menéndez, Pablo

    2015-01-01

    Infant B-cell acute lymphoblastic leukemia (B-ALL) accounts for 10% of childhood ALL. The genetic hallmark of most infant B-ALL is chromosomal rearrangements of the mixed-lineage leukemia (MLL) gene. Despite improvement in the clinical management and survival (∼85-90%) of childhood B-ALL, the outcome of infants with MLL-rearranged (MLL-r) B-ALL remains dismal, with overall survival <35%. Among MLL-r infant B-ALL, t(4;11)+ patients harboring the fusion MLL-AF4 (MA4) display a particularly poor prognosis and a pro-B/mixed phenotype. Studies in monozygotic twins and archived blood spots have provided compelling evidence of a single cell of prenatal origin as the target for MA4 fusion, explaining the brief leukemia latency. Despite its aggressiveness and short latency, current progress on its etiology, pathogenesis, and cellular origin is limited as evidenced by the lack of mouse/human models recapitulating the disease phenotype/latency. We propose this is because infant cancer is from an etiologic and pathogenesis standpoint distinct from adult cancer and should be seen as a developmental disease. This is supported by whole-genome sequencing studies suggesting that opposite to the view of cancer as a “multiple-and-sequential-hit” model, t(4;11) alone might be sufficient to spawn leukemia. The stable genome of these patients suggests that, in infant developmental cancer, one “big-hit” might be sufficient for overt disease and supports a key contribution of epigenetics and a prenatal cell of origin during a critical developmental window of stem cell vulnerability in the leukemia pathogenesis. Here, we revisit the biology of t(4;11)+ infant B-ALL with an emphasis on its origin, genetics, and disease models. PMID:26463423

  15. The t(10;11)(p13;q14) in the U937 cell line results in the fusion of the AF10 gene and CALM, encoding a new member of the AP-3 clathrin assembly protein family.

    PubMed Central

    Dreyling, M H; Martinez-Climent, J A; Zheng, M; Mao, J; Rowley, J D; Bohlander, S K

    1996-01-01

    The translocation t(10;11)(p13;q14) is a recurring chromosomal abnormality that has been observed in patients with acute lymphoblastic leukemia as well as acute myeloid leukemia. We have recently reported that the monocytic cell line U937 has a t(10;11)(p13;q14) translocation. Using a combination of positional cloning and candidate gene approach, we cloned the breakpoint and were able to show that AF10 is fused to a novel gene that we named CALM (Clathrin Assembly Lymphoid Myeloid leukemia gene) located at 11q14. AF10, a putative transcription factor, had recently been cloned as one of the fusion partners of MLL. CALM has a very high homology in its N-terminal third to the murine ap-3 gene which is one of the clathrin assembly proteins. The N-terminal region of ap-3 has been shown to bind to clathrin and to have a high-affinity binding site for phosphoinositols. The identification of the CALM/AF10 fusion gene in the widely used U937 cell line will contribute to our understanding of the malignant phenotype of this line. Images Fig. 1 Fig. 3 PMID:8643484

  16. Adjuvant Chinese Herbal Products for Preventing Ischemic Stroke in Patients with Atrial Fibrillation

    PubMed Central

    Muo, Chih-Hsin; Chiu, Hsienhsueh Elley; Liu, Chun-Ting

    2016-01-01

    Objective Chinese herbal products (CHPs) are widely used for atrial fibrillation (AF) in Taiwan. We investigated the effect of adjuvant CHPs in preventing ischemic stroke in patients with AF. Methods Taiwanese patients in the Health Insurance Database newly diagnosed with AF during 2000–2011 were enrolled. Medication treatment with/without CHPs was administered within 7 days after the AF diagnosis. The clinical endpoint was an ischemic stroke. The Chi-square test, Fisher’s exact test, and Student t test were used to examine differences between the traditional Chinese medicine (TCM) and non-TCM cohorts. Cox proportional hazard regression was used to assess the risk for ischemic stroke between two cohorts. Results Three hundred and eleven patients underwent TCM treatment and 1715 patients did not. Compared to non-TCM users, TCM users had a lower incidence of stroke (12.59% vs. 1.93%, respectively) and lower risk of stroke [CHA2DS2-VASc score = 0–2 (hazard ratio = 0.20; 95% confidence interval = 0.06–0.65)]. Compared to non-TCM users, the stroke risk was significantly lower in TCM users with AF who were female or younger than 65 years, but not in males, people more than 65 years old, or people with comorbidities. Compared to TCM users, non-TCM users who received conventional treatment had a higher ischemic stroke risk. The risk for AF-related hospitalization was significantly lower in TCM users (0.64%) than in non-TCM users (38.1%). Conclusions Users of TCM with AF have a lower risk of new-onset ischemic stroke. Therefore, adjuvant CHP therapy may have a protective effect and may be used in AF patients to prevent ischemic stroke. PMID:27428543

  17. Antithrombotic treatment in elderly patients with atrial fibrillation.

    PubMed

    Suárez Fernández, C; Camafort, M; Cepeda Rodrigo, J M; Díez-Manglano, J; Formiga, F; Pose Reino, A; Tiberio, G; Mostaza, J M

    2015-04-01

    Atrial fibrillation (AF) in the elderly is a complex condition due to the high number of frequently associated comorbidities, such as cardiovascular and kidney disease, cognitive disorders, falls and polypharmacy. Except when contraindicated, anticoagulation is necessary for preventing thromboembolic events in this population. Both vitamin K antagonists and direct oral anticoagulants (dabigatran, rivaroxaban and apixaban) are indicated in this context. Renal function should be closely monitored for this age group when these drugs are used. In recent years, various clinical practice guidelines have been published on patients with AF. The majority of these guidelines make specific recommendations on the clinical characteristics and treatment of elderly patients. In this update, we review the specific comments on the recommendations concerning antithrombotic treatment in elderly patients with nonvalvular AF. PMID:25618495

  18. Individual and Combined Risk Factors for Incident Atrial Fibrillation and Incident Stroke: An Analysis of 3 Million At-Risk US Patients

    PubMed Central

    Chyou, Janice Y; Hunter, Tina D; Mollenkopf, Sarah A; Turakhia, Mintu P; Reynolds, Matthew R

    2015-01-01

    Background The incremental effects of risk factor combinations for atrial fibrillation (AF) and stroke are incompletely understood. We sought to quantify the risks of incident AF and stroke for combinations of established risk factors in a large US sample. Methods and Results Patients with no evidence of AF or stroke in 2007 were stratified by combinations of the following risk factors: heart failure, hypertension, diabetes, age 65 to 74, age ≥75, coronary artery disease, and chronic kidney disease. Patients with ≥2 of the first 5 or ≥3 of the first 7, classified as “high-risk,” and an age-matched sample of patients with fewer risk factors, classified as “low-risk,” were followed over 2008–2010 for incident AF and stroke. Annualized incidence rates and risks were quantified for each combination of factors by using Cox regression. Annualized incidence rates for AF, stroke, and both were 3.59%, 3.27%, and 0.62% in 1 851 653 high-risk patients and 1.32%, 1.48%, and 0.18% in 1 156 221 low-risk patients, respectively. Among patients with 1 risk factor, those with age ≥75 had the highest hazards of incident AF and stroke (HR 9.2, 6.9). Among patients with 2 risk factors, those with age ≥75 and heart failure had the highest annualized incidence rates of AF and stroke (10.2%, 5.9%). The combination of age ≥75 and hypertension was prevalent and had the highest incidences of AF and stroke. Conclusions Adults with combinations of known risk factors are at increased risk of incident AF and stroke, but combinations of risk factors are not always additive. PMID:26206736

  19. AF710B, a Novel M1/σ1 Agonist with Therapeutic Efficacy in Animal Models of Alzheimer’s Disease.

    PubMed

    Fisher, Abraham; Bezprozvanny, Ilya; Wu, Lili; Ryskamp, Daniel A; Bar-Ner, Nira; Natan, Niva; Brandeis, Rachel; Elkon, Hanoch; Nahum, Victoria; Gershonov, Eitan; LaFerla, Frank M; Medeiros, Rodrigo

    2016-01-01

    We previously developed orthosteric M1 muscarinic agonists (e.g. AF102B, AF267B and AF292), which act as cognitive enhancers and potential disease modifiers. We now report on a novel compound, AF710B, a highly potent and selective allosteric M1 muscarinic and σ1 receptor agonist. AF710B exhibits an allosteric agonistic profile on the M1 muscarinic receptor; very low concentrations of AF710B significantly potentiated the binding and efficacy of carbachol on M1 receptors and their downstream effects (p-ERK1/2, p-CREB). AF710B (1-30 µg/kg, p.o.) was a potent and safe cognitive enhancer in rats treated with the M1 antagonist trihexyphenidyl (passive avoidance impairment). These effects of AF710B involve σ1 receptor activation. In agreement with its antiamnesic properties, AF710B (at 30 nM), via activation of M1 and a possible involvement of σ1 receptors, rescued mushroom synapse loss in PS1-KI and APP-KI neuronal cultures, while AF267B (1 µM) was less potent in PS1-KI and ineffective in APP-KI models, respectively. In female 3xTg-AD mice, AF710B (10 µg/kg, i.p./daily/2 months) (i) mitigated cognitive impairments in the Morris water maze; (ii) decreased BACE1, GSK3β activity, p25/CDK5, neuroinflammation, soluble and insoluble Aβ40, Aβ42, plaques and tau pathologies. AF710B differs from conventional σ1 and M1 muscarinic (orthosteric, allosteric or bitopic) agonists. These results highlight AF710B as a potential treatment for Alzheimer's disease (e.g. improving cognitive deficits, synaptic loss, amyloid and tau pathologies, and neuroinflammation) with a superior profile over a plethora of other therapeutic strategies. PMID:26606130

  20. Biofilm Filtrates of Pseudomonas aeruginosa Strains Isolated from Cystic Fibrosis Patients Inhibit Preformed Aspergillus fumigatus Biofilms via Apoptosis

    PubMed Central

    Shirazi, Fazal; Ferreira, Jose A. G.; Stevens, David A.; Clemons, Karl V.; Kontoyiannis, Dimitrios P.

    2016-01-01

    Pseudomonas aeruginosa (Pa) and Aspergillus fumigatus (Af) colonize cystic fibrosis (CF) patient airways. Pa culture filtrates inhibit Af biofilms, and Pa non-CF, mucoid (Muc-CF) and nonmucoid CF (NMuc-CF) isolates form an ascending inhibitory hierarchy. We hypothesized this activity is mediated through apoptosis induction. One Af and three Pa (non-CF, Muc-CF, NMuc-CF) reference isolates were studied. Af biofilm was formed in 96 well plates for 16 h ± Pa biofilm filtrates. After 24 h, apoptosis was characterized by viability dye DiBAc, reactive oxygen species (ROS) generation, mitochondrial membrane depolarization, DNA fragmentation and metacaspase activity. Muc-CF and NMuc-CF filtrates inhibited and damaged Af biofilm (p<0.0001). Intracellular ROS levels were elevated (p<0.001) in NMuc-CF-treated Af biofilms (3.7- fold) compared to treatment with filtrates from Muc-CF- (2.5- fold) or non-CF Pa (1.7- fold). Depolarization of mitochondrial potential was greater upon exposure to NMuc-CF (2.4-fold) compared to Muc-CF (1.8-fold) or non-CF (1.25-fold) (p<0.0001) filtrates. Exposure to filtrates resulted in more DNA fragmentation in Af biofilm, compared to control, mediated by metacaspase activation. In conclusion, filtrates from CF-Pa isolates were more inhibitory against Af biofilms than from non-CF. The apoptotic effect involves mitochondrial membrane damage associated with metacaspase activation. PMID:26930399

  1. The target cell of transformation is distinct from the leukemia stem cell in murine CALM/AF10 leukemia models.

    PubMed

    Dutta, S; Krause, A; Vosberg, S; Herold, T; Ksienzyk, B; Quintanilla-Martinez, L; Tizazu, B; Chopra, M; Graf, A; Krebs, S; Blum, H; Greif, P A; Vetter, A; Metzeler, K; Rothenberg-Thurley, M; Schneider, M R; Dahlhoff, M; Spiekermann, K; Zimber-Strobl, U; Wolf, E; Bohlander, S K

    2016-05-01

    The CALM/AF10 fusion gene is found in various hematological malignancies including acute myeloid leukemia (AML), T-cell acute lymphoblastic leukemia and malignant lymphoma. We have previously identified the leukemia stem cell (LSC) in a CALM/AF10-driven murine bone marrow transplant AML model as B220+ lymphoid cells with B-cell characteristics. To identify the target cell for leukemic transformation or 'cell of origin of leukemia' (COL) in non-disturbed steady-state hematopoiesis, we inserted the CALM/AF10 fusion gene preceded by a loxP-flanked transcriptional stop cassette into the Rosa26 locus. Vav-Cre-induced panhematopoietic expression of the CALM/AF10 fusion gene led to acute leukemia with a median latency of 12 months. Mice expressing CALM/AF10 in the B-lymphoid compartment using Mb1-Cre or CD19-Cre inducer lines did not develop leukemia. Leukemias had a predominantly myeloid phenotype but showed coexpression of the B-cell marker B220, and had clonal B-cell receptor rearrangements. Using whole-exome sequencing, we identified an average of two to three additional mutations per leukemia, including activating mutations in known oncogenes such as FLT3 and PTPN11. Our results show that the COL for CALM/AF10 leukemia is a stem or early progenitor cell and not a cell of B-cell lineage with a phenotype similar to that of the LSC in CALM/AF10+ leukemia. PMID:26686248

  2. Quality control in boar semen production by use of the FACSCount AF system.

    PubMed

    Christensen, Preben; Knudsen, Dorte B; Wachmann, Henrik; Madsen, Mads T

    2004-10-01

    A simple and rapid flow cytometric method has recently been developed for simultaneous determination of sperm concentration and viability in semen from domestic animals. Use of SYBR-14 trade mark in combination with propidium iodide (PI) allows estimation of the proportion of live sperm (viability). An internal standard of fluorescent microspheres (beads) makes it possible to determine the sperm concentration during the same analysis. In the first experiment, the relationship between sperm viability and litter size was investigated. The second experiment explored whether a smaller variation in the number of motile sperm per insemination dose could be obtained using the FACSCount AF flow cytometer than using a spectrophotometer. Results in the first experiment show that sperm viability is closer related to litter size than is the traditionally used motility parameter. Although the flow cytometer is precise and objective, a limited effect on litter size should be anticipated if ejaculates are selected for insemination according to the percentage of viable sperm. However, the present trial used large insemination doses (2.3 x 10(9) motile sperm/dose) which partially compensate for the differences in motility and viability between boars and ejaculates. In the second experiment it was found that variation in the number of motile sperm per insemination dose could be reduced significantly if the FACSCount AF flow cytometer rather than the Corning 254 spectrophotometer was used for determination of sperm concentration in the raw semen. It is concluded that the FACSCount AF flow cytometer is a strong tool for improvement of the quality control in artificial insemination (AI) centres. PMID:15325548

  3. Prospective and clinical validation of ALK immunohistochemistry: results from the phase I/II study of alectinib for ALK-positive lung cancer (AF-001JP study)

    PubMed Central

    Takeuchi, K.; Togashi, Y.; Kamihara, Y.; Fukuyama, T.; Yoshioka, H.; Inoue, A.; Katsuki, H.; Kiura, K.; Nakagawa, K.; Seto, T.; Maemondo, M.; Hida, T.; Harada, M.; Ohe, Y.; Nogami, N.; Yamamoto, N.; Nishio, M.; Tamura, T.

    2016-01-01

    Background Anaplastic lymphoma kinase (ALK) fusions need to be accurately and efficiently detected for ALK inhibitor therapy. Fluorescence in situ hybridization (FISH) remains the reference test. Although increasing data are supporting that ALK immunohistochemistry (IHC) is highly concordant with FISH, IHC screening needed to be clinically and prospectively validated. Patients and methods In the AF-001JP trial for alectinib, 436 patients were screened for ALK fusions through IHC (n = 384) confirmed with FISH (n = 181), multiplex RT-PCR (n = 68), or both (n = 16). IHC results were scored with iScore. Result ALK fusion was positive in 137 patients and negative in 250 patients. Since the presence of cancer cells in the samples for RT-PCR was not confirmed, ALK fusion negativity could not be ascertained in 49 patients. IHC interpreted with iScore showed a 99.4% (173/174) concordance with FISH. All 41 patients who had iScore 3 and were enrolled in phase II showed at least 30% tumor reduction with 92.7% overall response rate. Two IHC-positive patients with an atypical FISH pattern responded to ALK inhibitor therapy. The reduction rate was not correlated with IHC staining intensity. Conclusions Our study showed (i) that when sufficiently sensitive and appropriately interpreted, IHC can be a stand-alone diagnostic for ALK inhibitor therapies; (ii) that when atypical FISH patterns are accompanied by IHC positivity, the patients should be considered as candidates for ALK inhibitor therapies, and (iii) that the expression level of ALK fusion is not related to the level of response to ALK inhibitors and is thus not required for patient selection. Registration number JapicCTI-101264 (This study is registered with the Japan Pharmaceutical Information Center). PMID:26487585

  4. The strainrange partitioning behavior of an advanced gas turbine disk alloy, AF2-1DA

    NASA Technical Reports Server (NTRS)

    Halford, G. R.; Nachtigall, A. J.

    1979-01-01

    The low-cycle, creep-fatigue characteristics of the advanced gas turbine disk alloy, AF2-1DA have been determined at 1400 F and are presented in terms of the method of strainrange partitioning (SRP). The mean stresses which develop in the PC and CP type SRP cycles at the lowest inelastic strainrange were observed to influence the cyclic lives to a greater extent than the creep effects and hence interfered with a conventional interpretation of the results by SRP. A procedure is proposed for dealing with the mean stress effects on life which is compatible with SRP.

  5. Direct interactions in the recognition between the environmental estrogen bisphenol AF and human serum albumin.

    PubMed

    Yang, Lijun; Lv, Junna; Wang, Xin; Zhang, Jing; Li, Qi; Zhang, Tingting; Zhang, Zhenzhen; Zhang, Lei

    2015-08-01

    Bisphenol AF (BPAF) was used as a model compound to investigate the binding mechanism between the endocrine disrupting compound and human serum albumin (HSA) using multispectroscopic techniques and molecular modeling method at the protein level. The results indicated that BPAF was indeed bound to HSA and located in the hydrophobic pocket of HSA on subdomain IIA through hydrogen bond and van der Waals interactions. The fluorescence quenching data showed that the binding of BPAF and HSA quenched the intrinsic fluorescence of HSA, and the static quenching constants were acquired. PMID:25694370

  6. Spectral analysis of LBV stars in M31: AF And and Var 15

    NASA Astrophysics Data System (ADS)

    Valeev, A. F.; Sholukhova, O.; Fabrika, S.

    2015-01-01

    We study spectra of two bona fide LBV stars in M31: AF And and Var 15. The spectra were obtained with the 6-m telescope (Russia) from 2005 to 2012. The model spectra were calculated with the CMFGEN code. We have not found strong changes in the spectra of the LBV stars in that time interval, however a certain variability has been detected. We estimate the star and wind parameters, such as luminosity, temperature, raduis, mass loss rate, escape velocity, hydrogen content, and reddening. We study the stars on the Hertzsprung-Russell diagram and find their initial masses using evolutionary tracks by Meynet et al. (1994).

  7. Vobatensines A-F, Cytotoxic Iboga-Vobasine Bisindoles from Tabernaemontana corymbosa.

    PubMed

    Sim, Dawn Su-Yin; Teoh, Wuen-Yew; Sim, Kae-Shin; Lim, Siew-Huah; Thomas, Noel F; Low, Yun-Yee; Kam, Toh-Seok

    2016-04-22

    Six new bisindole alkaloids of the iboga-vobasine type, vobatensines A-F (1-6), in addition to four known bisindoles (8-11), were isolated from a stem bark extract of a Malayan Tabernaemontana corymbosa. The structures of these alkaloids were determined based on analysis of the spectroscopic data and in the case of vobatensines A (1), B (2), and 16'-decarbomethoxyvoacamine (8) also confirmed by partial syntheses. Nine of these alkaloids (1-5, 8-11) showed pronounced in vitro growth inhibitory activity against human KB, PC-3, LNCaP, HCT 116, HT-29, MCF7, MDA-MB-231, and A549 cancer cells. PMID:26918761

  8. Factors related to sinus rhythm at discharge after radiofrequency ablation of permanent atrial fibrillation in patients undergoing mitral valve surgery.

    PubMed

    Rostagno, Carlo; Gelsomino, Sandro; Capecchi, Irene; Rossi, Alessandra; Montesi, Gian Franco; Stefàno, Pier Luigi

    2016-04-01

    Late recovery of sinus rhythm is unusual in patients with permanent AF treated by (radiofrequency) RF maze procedure during mitral valve surgery. Identification of clinical and instrumental preoperative factors predictive of early success of RF ablation in patients with permanent AF undergoing mitral valve surgery may improve selection of subjects to obtain long-term results. Hundred and thirty consecutive patients with permanent AF and mitral valve disease underwent modified RF maze procedure during concomitant mitral valve surgery. Rheumatic valve disease (61 pts) and mitral valve prolapse (41 pts) were the more common aetiology of valve abnormalities. Mitral valve replacement was performed in 54 % of patients and mitral valve repair in the remaining 46 %. Four patients died after surgery. At discharge, 87 patients (69 %) were in sinus rhythm (group 1) and 43 patients in AF persisted (group 2). At an average 24-month follow-up, sinus rhythm was present in 67 % of patients, and 33 % were in atrial fibrillation. In this period, late recovery of sinus rhythm was observed only in five patients, while eight discharged in sinus rhythm developed again atrial fibrillation. Among preoperative parameters at univariate analysis female sex, atrial fibrillation >24 months, left atrial diameter >54 mm, left atrial area >24 cm(2), rheumatic valve disease and NYHA class were associated with persistence of AF. At Cox regression multivariate analysis, increased left atrial area (OR 1.07 per unit increase-95 % CI 1.01-1.131) and rheumatic aetiology of valve disease (OR 4.52, 95 % CI 1.65-12.4) were associated with persistence of AF at hospital discharge. Persistence of AF after RF ablation in patients undergoing mitral valve surgery is related to aetiology, e.g. rheumatic valve disease, and to increasing left atrial diameter. Due to low rate of late recovery of sinus rhythm, indication to RF ablation associated with MV surgery should be carefully considered in patients with large

  9. Asian Patients with Stroke plus Atrial Fibrillation and the Dose of Non-Vitamin K Oral Anticoagulants

    PubMed Central

    Bang, Oh Young; Hong, Keun-Sik; Heo, Ji Hoe

    2016-01-01

    After recent randomized control trials (RCTs), non-vitamin K oral anticoagulants (NAOAs) are now widely being used in patients with atrial fibrillation (AF) worldwide. However, current guidelines for the use of NOACs in patients with AF are derived mostly using a Caucasian population and non-stroke patients. Relatively few Asian patients with AF and stroke are included in the recent RCTs. As a result, the optimal use of NOACs in this particular group of patients is remains to be settled. The optimal dose of NOACs and response to current dose of NOACs of Asian patients with AF and stroke may differ from those of westerners and patients without stroke. We reviewed available research on NOACs by searching PubMed and ClinicalTrials.gov published in English up to December 2015. In this review, the characteristics of Asian AF patients with prior stroke/transient ischemic attack, which might influence the efficacy and safety profiles of NOACs, are discussed. In addition, we summarize the risk factors for bleeding complications on NOACs, which are related or unrelated with the blood level of NOACs. Lastly, we provide recent data of reduced dose of NOACs from RCTs or large cohorts. The results reviewed herein call for clinical trials to test whether a reduced dose of NOACs is beneficial in Asian patients with AF and stroke. In the meantime, further researches are needed to establish the safety and efficacy of dose-adjusted NOACs considering both blood levels of NOACs and fragility of patients in Asian patients with AF and stroke. PMID:27170995

  10. Usefulness of severe cardiac sympathetic dysfunction to predict the occurrence of rapid atrial fibrillation in patients with Wolff-Parkinson-White syndrome.

    PubMed

    Akutsu, Yasushi; Kaneko, Kyouichi; Kodama, Yusuke; Li, Hui-Ling; Asano, Taku; Suyama, Jumpei; Tanno, Kaoru; Namiki, Atsuo; Shinozuka, Akira; Gokan, Takehiko; Kobayashi, Youichi

    2013-09-01

    Atrial fibrillation (AF) can be a potentially life-threatening arrhythmia when it conducts rapidly through the accessory pathway, which was not predicted by the noninvasive method. We evaluated the cardiac sympathetic activity for predicting the occurrence of AF in patients with Wolff-Parkinson-White (WPW) syndrome. Iodine-123 metaiodobenzylguanidine scintigraphy was performed under stable sinus rhythm conditions at rest <1 week before an electrophysiologic study (EPS) to assess the sympathetic activity using the heart/mediastinum (H/M) ratio in 45 consecutive patients with WPW who had a history of supraventricular tachycardia (mean ± SD, age: 47 ± 17 years, 42.2% women). The study also included 15 normal healthy volunteers (56 ± 17 years, 40% women). The H/M ratio was lower in patients with WPW syndrome than in the normal control group, and in the 15 patients with AF induced during EPS than in the 30 patients without AF (p <0.0001). The sensitivity of H/M ratio ≤2.8 for predicting the AF induced during EPS was 75% in 12 of 16 patients, and the specificity was 89.7% in 26 of 29 patients. The H/M ratio was positively correlated with anterograde effective refractory period (r = 0.514, p <0.0001). The sensitivity of H/M ratio ≤2.75 for predicting the AF with a short anterograde effective refractory period (≤250 ms) was 91.7% in 11 of 12 patients, and the specificity was 90.9% in 30 of 33 patients. In conclusion, the severe cardiac sympathetic dysfunction was associated with the occurrence of AF, particularly in those with rapid AF and in patients with WPW syndrome. PMID:23711805

  11. [GISE/AIAC position paper on percutaneous left atrial appendage occlusion in patients with nonvalvular atrial fibrillation: recommendations for patient selection, facilities, competences, organizing and training requirements].

    PubMed

    Berti, Sergio; Themistoclakis, Sakis; Santoro, Gennaro; De Ponti, Roberto; Danna, Paolo; Zecchin, Massimo; Bedogni, Francesco; Padeletti, Luigi

    2014-09-01

    Thromboembolism from the left atrial appendage is the most feared complication in patients with atrial fibrillation (AF). The cornerstone for the management of chronic nonvalvular AF is stroke reduction with oral anticoagulation (OAC). However, poor compliance, maintaining a narrow therapeutic window, and major side effects such as bleeding have severely limited its use, creating a therapeutic dilemma. About 20% of AF patients do not receive OAC due to contraindications and less than half of AF patients are not on OAC due to reluctance of the prescribing physician and/or patient non-compliance. Fortunately, over the past decade, the introduction of percutaneous approaches for left atrial appendage occlusion has offered a viable alternative to the management of nonvalvular AF in patients with OAC contraindication. Occlusion devices such as the Amplatzer Cardiac Plug and Watch man device have shown their noninferiority to OAC for stroke prophylaxis with less bleeding complications, while more recently some new devices have been introduced. The aim of this position paper is to review the most relevant clinical aspects of left atrial appendage occlusion from patient selection to periprocedural and follow-up management. In addition, the importance of a medical team and an organizational environment adequate to optimize all the steps of this procedure is discussed. PMID:25298359

  12. Pharmacotherapy for atrial fibrillation in elderly hospitalized patients with comorbid congestive heart failure in australia: A retrospective study

    PubMed Central

    Wang, Lexin; Curran, Shane; Ball, Patrick; White, Fiona

    2008-01-01

    Background: Despite the proven effectiveness of antiplatelet and anticoagulation treatment for atrial fibrillation (AF), their use has been suboptimal in practice, particularly in rural areas of Australia. Objective: The aim of this study was to describe medication use in the management of AF in elderly hospitalized patients with comorbid congestive heart failure (CHF). Methods: The hospital records of patients with a diagnosis of AF and CHF were reviewed in a rural Australian medical center. All the patients were hospitalized because of significant systolic ventricular dysfunction. The collected data included age, sex, weight, presenting symptoms of AF, and principle diagnosis on admission; medical history; and history of smoking and alcohol consumption. Electrocardiogram before hospital discharge was also retrieved from patient's medical records and was analyzed by the investigators. Cardiovascular and noncardiovascular drugs administered during the hospital stay and at discharge were also documented. Comparison of antiarrhythmic and anticoagulant drugs was made between patients who had AF while hospitalized and those who had a history of AF but were in sinus rhythm while hospitalized. When patients had ≥2 moderate risk factors (eg, age ≥75 years, hypertension, CHF, left ventricular ejection fraction ≤35%, diabetes mellitus) or ≥1 high risk factor (eg, previous stroke, transient ischemic attack or embolism, mitral valve stenosis, or prosthetic heart valve), they were defined as being eligible for anticoagulation treatment. Results: One hundred forty patients (74 men, 66 women; mean [SD] age, 77.1 [6.9] years; all were white) had a diagnosis of AF and were selected for the study. Of these, 92 patients (65.7%) (47 women, 45 men; mean [SD] age, 77.4 [9–2] years) had continuous AF and 48 patients (34.3%) (29 men, 19 women; mean [SD] age, 76.3 [12.4] years) had a history of AF but were in sinus rhythm at admission and discharge. The most commonly used

  13. Cost analysis of periprocedural imaging in patients undergoing catheter ablation for atrial fibrillation.

    PubMed

    Pokorney, Sean D; Hammill, Bradley G; Qualls, Laura G; Steinberg, Benjamin A; Curtis, Lesley H; Piccini, Jonathan P

    2014-07-15

    Cardiovascular imaging is an important part of procedural planning and safety for catheter ablation of atrial fibrillation (AF). However, the costs of imaging surrounding catheter ablation of AF have not been described. Medicare fee-for-service data were used to evaluate Medicare expenditures before, during, and after catheter ablation for AF from July 2007 to December 2009. Among 11,525 patients who underwent catheter ablation for AF, the mean overall expenditure on the day of the procedure was $14,455 (SD $7,441). The mean imaging expenditure in the periprocedural period, which included the 30 days before the catheter ablation and the day of the ablation itself, was $884 (SD $455). Periprocedural imaging expenditures varied by the imaging strategy used, ranging from a mean of $557 (SD $269) for patients with electroanatomic mapping only to $1,234 (SD $461) for patients with electroanatomic mapping, transesophageal echocardiogram, and computed tomography or magnetic resonance imaging. Mean patient-level imaging expenditures varied by provider (mean $872, SD $249). Periprocedural imaging expenditures also varied by patient risk, with mean expenditures of $862 (SD $444) for patients with a CHADS2 score of ≥2 compared with $907 (SD $466) for CHADS2 score<2 (p<0.001). In conclusion, periprocedural imaging accounts for approximately 6% of mean Medicare expenditures for catheter ablation of AF. The expenditures for periprocedural imaging vary both at the patient and at the provider level and they are inversely related to stroke risk by CHADS2 score. PMID:24952929

  14. Identification of patients with atrial fibrillation in UK community pharmacy: an evaluation of a new service.

    PubMed

    Twigg, M J; Thornley, T; Scobie, N

    2016-08-01

    Background Many patients with atrial fibrillation (AF) are asymptomatic and diagnosed via opportunistic screening. Community pharmacy has been advocated as a potential resource for opportunistic screening and lifestyle interventions. Objective The objective of this evaluation is to describe the outcomes from an AF service, in terms of referrals and interventions provided to patients identified as not at risk. Methods Eligibility was assessed from pharmacy records and the completion of a short questionnaire. Once consented, patients were screened for AF and their blood pressure was measured. Results Of 594 patients screened, nine were identified as at risk of having AF and were referred to their GP. The service also identified 109 patients with undiagnosed hypertension, 176 patients with a Body Mass Index >30, 131 with an Audit-C score >5 and 59 smokers. Pharmacists provided 413 interventions in 326 patients aimed at weight reduction (239), alcohol consumption (123) and smoking cessation (51). Conclusion This evaluation characterises the interventions provided to, not only those identified with the target condition-in this case AF-but also those without it. The true outcome of these additional interventions, along with appropriate follow-up, should be the focus of future studies. PMID:27107584

  15. Injury of the Arcuate Fasciculus in the Nondominant Hemisphere by Subfalcine Herniation in Patients with Intracerebral Hemorrhage : Two Case Reports and Literature Review

    PubMed Central

    Jang, Sung Ho; Kim, Seong Ho

    2016-01-01

    Using diffusion tensor tractography (DTT), we demonstrated injury of the arcuate fasciculus (AF) in the nondominant hemisphere in two patients who showed subfalcine herniation after intracerebral hemorrhage (ICH) in the dominant hemisphere. Two patients (patient 1 and patient 2) with ICH and six age-matched control patients who have ICH on the left corona radiata and basal ganglia without subfalcine herniation were recruited for this study. DTT was performed at one month after onset in patient 1 and patient 2. AFs of both hemispheres in both patients were disrupted between Wernicke's and Broca's areas. The fractional anisotropy value and tract numbers of the right AFs in both patients were found to be more than two standard deviations lower than those of control patients. In contrast, the apparent diffusion coefficient value was more than two standard deviations higher than those of control patients. Using the configuration and parameters of DTT, we confirmed injury of the AF in the nondominant hemisphere in two patients with subfalcine herniation following ICH in the dominant hemisphere. Therefore, DTT would be a useful tool for detection of underlying injury of the AF in the nondominant hemisphere in patients with subfalcine herniation. PMID:27226866

  16. An extended U2AF65–RNA-binding domain recognizes the 3′ splice site signal

    PubMed Central

    Agrawal, Anant A.; Salsi, Enea; Chatrikhi, Rakesh; Henderson, Steven; Jenkins, Jermaine L.; Green, Michael R.; Ermolenko, Dmitri N.; Kielkopf, Clara L.

    2016-01-01

    How the essential pre-mRNA splicing factor U2AF65 recognizes the polypyrimidine (Py) signals of the major class of 3′ splice sites in human gene transcripts remains incompletely understood. We determined four structures of an extended U2AF65–RNA-binding domain bound to Py-tract oligonucleotides at resolutions between 2.0 and 1.5 Å. These structures together with RNA binding and splicing assays reveal unforeseen roles for U2AF65 inter-domain residues in recognizing a contiguous, nine-nucleotide Py tract. The U2AF65 linker residues between the dual RNA recognition motifs (RRMs) recognize the central nucleotide, whereas the N- and C-terminal RRM extensions recognize the 3′ terminus and third nucleotide. Single-molecule FRET experiments suggest that conformational selection and induced fit of the U2AF65 RRMs are complementary mechanisms for Py-tract association. Altogether, these results advance the mechanistic understanding of molecular recognition for a major class of splice site signals. PMID:26952537

  17. A novel 3′ splice site recognition by the two zinc fingers in the U2AF small subunit

    PubMed Central

    Yoshida, Hisashi; Park, Sam-Yong; Oda, Takashi; Akiyoshi, Taeko; Sato, Mamoru; Shirouzu, Mikako; Tsuda, Kengo; Kuwasako, Kanako; Unzai, Satoru; Muto, Yutaka; Urano, Takeshi; Obayashi, Eiji

    2015-01-01

    The pre-mRNA splicing reaction of eukaryotic cells has to be carried out extremely accurately, as failure to recognize the splice sites correctly causes serious disease. The small subunit of the U2AF heterodimer is essential for the determination of 3′ splice sites in pre-mRNA splicing, and several single-residue mutations of the U2AF small subunit cause severe disorders such as myelodysplastic syndromes. However, the mechanism of RNA recognition is poorly understood. Here we solved the crystal structure of the U2AF small subunit (U2AF23) from fission yeast, consisting of an RNA recognition motif (RRM) domain flanked by two conserved CCCH-type zinc fingers (ZFs). The two ZFs are positioned side by side on the β sheet of the RRM domain. Further mutational analysis revealed that the ZFs bind cooperatively to the target RNA sequence, but the RRM domain acts simply as a scaffold to organize the ZFs and does not itself contact the RNA directly. This completely novel and unexpected mode of RNA-binding mechanism by the U2AF small subunit sheds light on splicing errors caused by mutations of this highly conserved protein. PMID:26215567

  18. Impact of Intensive Glycemic Control on the Incidence of Atrial Fibrillation and Associated Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus (from the ACCORD Study)

    PubMed Central

    Fatemi, Omid; Yuriditsky, Eugene; Tsioufis, Costas; Tsachris, Demetrios; Morgan, Timothy; Basile, Jan; Bigger, Thomas; Cushman, William; Goff, David; Soliman, Elsayed Z.; Thomas, Abraham; Papademetriou, Vasilios

    2014-01-01

    Atrial fibrillation (AF) is prevalent among individuals with type 2 diabetes mellitus (DM), and is associated with markers of poor glycemic control; however the impact of glycemic control on incident AF and outcomes is unknown. We sought to prospectively evaluate if intensive glycemic control in individuals with DM impacts incident AF, and to evaluate morbidity and mortality among individuals with DM and incident AF. We studied 10,082 individuals with DM from the ACCORD cohort in a randomized, double-blind fashion. Participants were randomized to an intensive therapeutic strategy targeting a glycated hemoglobin level of <6.0%, or a standard strategy targeting a glycated hemoglobin of 7.0-7.9%. Incident AF occurred in 159 patients (1.58%) over the follow-up period at a rate of 5.9/1,000 person-years in the intensive-therapy group, and a rate of 6.37/1,000 person-years in the standard-therapy group (p=0.52). In a multivariate model, predictors of incident AF were age, weight, diastolic blood pressure, heart rate, and heart failure history. Patients with DM and new-onset AF had a HR of 2.65 for all-cause mortality (95% CI 1.8-3.86, p<0.0001), HR of 2.1 for myocardial infarction (95% CI 1.33-3.31, p=0.0015), and HR of 3.80 for development of heart failure (95% CI 2.48-5.84, p<0.0001). In conclusion, intensive glycemic control did not impact rate of new-onset AF. Patients with DM and incident AF had an increased risk for morbidity and mortality as compared to those without AF. PMID:25159234

  19. Predictors and long-term clinical outcomes of newly developed atrial fibrillation in patients with cardiac implantable electronic devices

    PubMed Central

    Kim, Bum Sung; Chun, Kwang Jin; Hwang, Jin kyung; Park, Seung-Jung; Park, Kyoung-Min; Kim, June Soo; On, Young Keun

    2016-01-01

    Abstract Objective: To evaluate predictors and long-term prognosis of atrial fibrillation (AF) following cardiac implantable electronic device (CIED) implantation in patients without history of AF. Methods: From May 1994 to April 2014, 1825 patients with CIED were enrolled in a retrospective, single-center registry. A total of 880 patients from the registry without prior documented AF history were included in the final analysis and were placed into either non-detected AF (NDAF) group or CIED-detected AF group according to development of AF over a follow-up period of 7 years. AF development was defined as any paroxysmal atrial tachyarrhythmia (atrial rate ≥ 180 beats/min) lasting at least 5 minutes according to CIED records. Results: Overall, 122 (13.8%) of the 880 patients experienced new development of AF during follow-up period. According to multivariate analysis, the independent predictors for development of AF were prior heart failure (hazard ratio [HR], 2.40; 95% confidence interval [CI], 1.50–3.85; P < 0.001), prior sinus node dysfunction (HR, 2.33; 95% CI, 1.62–3.55; P < 0.001), and left atrium volume index of 38.5 mL/m2 or more (HR, 2.01; 95% CI, 1.23–3.30; P = 0.005). In CDAF group, the risk of heart failure readmission (adjusted HR, 3.79; 95% CI, 1.99–7.22; P < 0.001) and stroke readmission (adjusted HR, 5.33; 95% CI, 1.58–17.97; P = 0.007) was higher than in nondetected AF group. Conclusion: In patients with CIED, prior history of heart failure, sinus node dysfunction, and LA volume index ≥38.5 mL/m2 were independent predictors of new AF cases. Newly developed AF was significantly associated with increased risk of HF and stroke readmission, according to long-term follow up. PMID:27428213

  20. XANTUS: rationale and design of a noninterventional study of rivaroxaban for the prevention of stroke in patients with atrial fibrillation

    PubMed Central

    Camm, A John; Amarenco, Pierre; Haas, Sylvia; Hess, Susanne; Kirchhof, Paulus; van Eickels, Martin; Turpie, Alexander GG

    2014-01-01

    Atrial fibrillation (AF) is associated with a fivefold increase in the risk of stroke. The Phase III ROCKET AF (Rivaroxaban Once-Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) trial showed that rivaroxaban, an oral, direct Factor Xa inhibitor, was noninferior to warfarin for the reduction of stroke or systemic embolism in patients with AF. Compared with warfarin, rivaroxaban significantly reduced rates of intracranial and fatal hemorrhages, although not rates of bleeding overall. XANTUS (Xarelto® for Prevention of Stroke in Patients with Atrial Fibrillation) is a prospective, international, observational, postauthorization, noninterventional study designed to collect safety and efficacy data on the use of rivaroxaban for stroke prevention in AF in routine clinical practice. The key goal is to determine whether the safety profile of rivaroxaban established in ROCKET AF is also observed in routine clinical practice. XANTUS is designed as a single-arm cohort study to minimize selection bias, and will enroll approximately 6,000 patients (mostly from Europe) with nonvalvular AF prescribed rivaroxaban, irrespective of their level of stroke risk. Overall duration of follow-up will be 1 year; the first patient was enrolled in June 2012. Similar studies (XANTUS-EL [Xarelto® for Prevention of Stroke in Patients with Nonvalvular Atrial Fibrillation, Eastern Europe, Middle East, Africa and Latin America] and XANAP [Xarelto® for Prevention of Stroke in Patients with Atrial Fibrillation in Asia-Pacific]) are ongoing in Latin America and Asia-Pacific. Data from these studies will supplement those from ROCKET AF and provide practical information concerning the use of rivaroxaban for stroke prevention in AF. PMID:25083135

  1. AF-DHNN: Fuzzy Clustering and Inference-Based Node Fault Diagnosis Method for Fire Detection.

    PubMed

    Jin, Shan; Cui, Wen; Jin, Zhigang; Wang, Ying

    2015-01-01

    Wireless Sensor Networks (WSNs) have been utilized for node fault diagnosis in the fire detection field since the 1990s. However, the traditional methods have some problems, including complicated system structures, intensive computation needs, unsteady data detection and local minimum values. In this paper, a new diagnosis mechanism for WSN nodes is proposed, which is based on fuzzy theory and an Adaptive Fuzzy Discrete Hopfield Neural Network (AF-DHNN). First, the original status of each sensor over time is obtained with two features. One is the root mean square of the filtered signal (FRMS), the other is the normalized summation of the positive amplitudes of the difference spectrum between the measured signal and the healthy one (NSDS). Secondly, distributed fuzzy inference is introduced. The evident abnormal nodes' status is pre-alarmed to save time. Thirdly, according to the dimensions of the diagnostic data, an adaptive diagnostic status system is established with a Fuzzy C-Means Algorithm (FCMA) and Sorting and Classification Algorithm to reducing the complexity of the fault determination. Fourthly, a Discrete Hopfield Neural Network (DHNN) with iterations is improved with the optimization of the sensors' detected status information and standard diagnostic levels, with which the associative memory is achieved, and the search efficiency is improved. The experimental results show that the AF-DHNN method can diagnose abnormal WSN node faults promptly and effectively, which improves the WSN reliability. PMID:26193280

  2. AF-DHNN: Fuzzy Clustering and Inference-Based Node Fault Diagnosis Method for Fire Detection

    PubMed Central

    Jin, Shan; Cui, Wen; Jin, Zhigang; Wang, Ying

    2015-01-01

    Wireless Sensor Networks (WSNs) have been utilized for node fault diagnosis in the fire detection field since the 1990s. However, the traditional methods have some problems, including complicated system structures, intensive computation needs, unsteady data detection and local minimum values. In this paper, a new diagnosis mechanism for WSN nodes is proposed, which is based on fuzzy theory and an Adaptive Fuzzy Discrete Hopfield Neural Network (AF-DHNN). First, the original status of each sensor over time is obtained with two features. One is the root mean square of the filtered signal (FRMS), the other is the normalized summation of the positive amplitudes of the difference spectrum between the measured signal and the healthy one (NSDS). Secondly, distributed fuzzy inference is introduced. The evident abnormal nodes’ status is pre-alarmed to save time. Thirdly, according to the dimensions of the diagnostic data, an adaptive diagnostic status system is established with a Fuzzy C-Means Algorithm (FCMA) and Sorting and Classification Algorithm to reducing the complexity of the fault determination. Fourthly, a Discrete Hopfield Neural Network (DHNN) with iterations is improved with the optimization of the sensors’ detected status information and standard diagnostic levels, with which the associative memory is achieved, and the search efficiency is improved. The experimental results show that the AF-DHNN method can diagnose abnormal WSN node faults promptly and effectively, which improves the WSN reliability. PMID:26193280

  3. [Refractory primary myeloid sarcoma of the breast with MLL-AF9 rearrangement].

    PubMed

    Uchida, Emi; Watanabe, Ken; Oshikawa, Gaku; Sakashita, Chizuko; Kurosu, Tetsuya; Fukuda, Tetsuya; Arai, Ayako; Murakami, Naomi; Miura, Osamu; Yamamoto, Masahide

    2016-01-01

    A 28-year-old woman presented with a right breast mass and axillary lymphadenopathy. Biopsy of the breast mass revealed myeloid sarcoma (MS) staining positive for CD4, CD13, CD33, and CD68/KP-1. Bone marrow aspiration revealed leukemic cell infiltration (9%). Leukemic cells possessed cytogenetic abnormalities of +8 and t(9;11)(p22;q23) with +22 (lymph node only), and molecular analyses confirmed the MLL-AF9 fusion gene. After induction chemotherapy and 2(nd) consolidation therapy, complete remission was maintained. However, during consolidation radiotherapy for the breast mass, the disease progressed in both the breast and bone marrow. She received re-induction therapy and proceeded to allogeneic stem cell transplantation. However, the disease relapsed in the breast soon after transplantation, and she died from disease progression. Trisomy 8 and the MLL-AF9 fusion gene have been reported in cases with MS in the breast. Trisomy 22 found additionally and exclusively in the extramedullary lesion implies extramedullary progression of MS from the medullary site of origin and may have been associated with the distinctive therapy resistance of these lesions in our case. PMID:26861104

  4. Intracardiac impedance response during acute AF internal cardioversion using novel rectilinear and capacitor-discharge waveforms.

    PubMed

    Rababah, A S; Walsh, S J; Manoharan, G; Walsh, P R; Escalona, O J

    2016-07-01

    Intracardiac impedance (ICI) is a major determinant of success during internal cardioversion of atrial fibrillation (AF). However, there have been few studies that have examined the dynamic behaviour of atrial impedance during internal cardioversion in relation to clinical outcome. In this study, voltage and current waveforms captured during internal cardioversion of acute AF in ovine models using novel radiofrequency (RF) generated low-tilt rectilinear and conventional capacitor-discharge based shock waveforms were retrospectively analysed using a digital signal processing algorithm to investigate the dynamic behaviour of atrial impedance during cardioversion. The algorithm was specifically designed to facilitate the simultaneous analysis of multiple impedance parameters, including: mean intracardiac impedance (Z M), intracardiac impedance variance (ICIV) and impedance amplitude spectrum area (IAMSA) for each cardioversion event. A significant reduction in ICI was observed when comparing two successive shocks of increasing energy where cardioversion outcome was successful. In addition, ICIV and IAMSA variables were found to inversely correlate to the magnitude of energy delivered; with a stronger correlation found to the former parameter. In conclusion, ICIV and IAMSA have been evidenced as two key dynamic intracardiac impedance variables that may prove useful in better understanding of the cardioversion process and that could potentially act as prognostic markers with respect to clinical outcome. PMID:27328164

  5. Advanced Compatibility Characterization Of AF-M315E With Spacecraft Propulsion System Materials Project

    NASA Technical Reports Server (NTRS)

    McClure, Mark B.; Greene, Benjamin

    2014-01-01

    All spacecraft require propulsion systems for thrust and maneuvering. Propulsion systems can be chemical, nuclear, electrical, cold gas or combinations thereof. Chemical propulsion has proven to be the most reliable technology since the deployment of launch vehicles. Performance, storability, and handling are three important aspects of liquid chemical propulsion. Bipropellant systems require a fuel and an oxidizer for propulsion, but monopropellants only require a fuel and a catalyst for propulsion and are therefore simpler and lighter. Hydrazine is the state of the art propellant for monopropellant systems, but has drawbacks because it is highly hazardous to human health, which requires extensive care in handling, complex ground ops due to safety and environmental considerations, and lengthy turnaround times for reusable spacecraft. All users of hydrazine monopropellant must contend with these issues and their associated costs. The development of a new monopropellant, intended to replace hydrazine, has been in progress for years. This project will apply advanced techniques to characterize the engineering properties of materials used in AF-M315E propulsion systems after propellant exposure. AF-M315E monopropellant has been selected HQ's Green Propellant Infusion Mission (GPIM) to replace toxic hydrazine for improved performance and reduce safety and health issues that will shorten reusable spacecraft turn-around time. In addition, this project will fundamentally strengthen JSC's core competency to evaluate, use and infuse liquid propellant systems.

  6. Development of FDR-AF (Frictional Drag Reduction Anti-Fouling) Marine Coating

    NASA Astrophysics Data System (ADS)

    Lee, Inwon; Park, Hyun; Chun, Ho Hwan; GCRC-SOP Team

    2013-11-01

    In this study, a novel skin-friction reducing marine paint has been developed by mixing fine powder of PEO(PolyEthyleneOxide) with SPC (Self-Polishing Copolymer) AF (Anti-Fouling) paint. The PEO is well known as one of drag reducing agent to exhibit Toms effect, the attenuation of turbulent flows by long chain polymer molecules in the near wall region. The frictional drag reduction has been implemented by injecting such polymer solutions to liquid flows. However, the injection holes have been a significant obstacle to marine application. The present PEO-containing marine paint is proposed as an alternative to realize Toms effect without any hole on the ship surface. The erosion mechanism of SPC paint resin and the subsequent dissolution of PEO enable the controlled release of PEO solution from the coating. Various tests such as towing tank drag measurement of flat plate and turbulence measurement in circulating water tunnel demonstrated over 10% frictional drag reduction compared with conventional AF paint. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) through GCRC-SOP(No. 2011-0030013).

  7. Relation of vitamin D deficiency and new-onset atrial fibrillation among hypertensive patients.

    PubMed

    Ozcan, Ozgur Ulas; Gurlek, Adalet; Gursoy, Eren; Gerede, Demet Menekse; Erol, Cetin

    2015-04-01

    Vitamin D deficiency is associated with various cardiovascular disorders including hypertension, coronary artery disease, and heart failure. The renin-angiotensin-aldosterone system (RAS) axis is activated in vitamin D deficiency. The RAS axis also plays a role in the pathophysiology of atrial fibrillation (AF). We aimed to investigate whether vitamin D deficiency is a risk factor for the development of new-onset AF in hypertension. A total of 227 hypertensive patients were enrolled, of whom 137 had new-onset AF; 90 patients without AF were included in the control group. The age of the patient, left atrial diameter, and vitamin D deficiency increased the probability of new-onset AF independent from confounding factors (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.01-1.08; P = .03 for age; OR, 1.88; 95% CI, 1.15-3.45; P = .03 for left atrial diameter; OR, 1.68; 95% CI, 1.18-2.64; P = .03 for vitamin D deficiency). Vitamin D deficiency is associated with new-onset AF in hypertension. PMID:25753298

  8. Comprehensive mutation scanning of KCNQ1 in 111 Han Chinese patients with lone atrial fibrillation

    PubMed Central

    Chen, Lin Y; Goh, June M; Wong, Raymond C; Hsu, Li-Fern; Foo, David; Benditt, David G; Ling, Lieng H; Heng, Chew K

    2010-01-01

    Objective To determine the extent to which genetic variation in the potassium channel gene KCNQ1 causes atrial fibrillation (AF). Design Case–control study. Setting National University Hospital, Singapore. Patients Han Chinese patients (n=111) with lone AF (onset <60 years and lacking risk factors) and 265 Han Chinese controls. Interventions Blood draw, 12-lead electrocardiogram and transthoracic echocardiogram were performed on patients with AF at enrolment. Main outcome measures DNA sequence variants in the coding region and exon–intron boundaries of KCNQ1 as detected by direct sequencing. Results Four previously reported coding variants were identified: I145I, S546S, P448R and G643S. An additional 19 non-coding variants were identified, nine of which are newly reported. None were predicted to create a cryptic splicing site. The allele frequencies of the two non-synonymous variants did not differ significantly in the AF cases compared with 265 Han Chinese controls (P448R: 10.8% in cases vs 8.6% in controls, p=0.41; G643S: 1.4% in cases vs 0.8% in controls, p=0.43). Conclusions Comprehensive mutation scanning of KCNQ1 did not identify novel pathogenic mutations or risk-conferring polymorphisms. As in Caucasians, genetic variation in KCNQ1 is not a common cause of AF in Han Chinese. Routine genetic testing of KCNQ1 for AF is, therefore, not warranted. PMID:27325960

  9. Practical management of patients on apixaban: a consensus guide

    PubMed Central

    2013-01-01

    Background Atrial fibrillation (AF) is a common tachyarrhythmia in Australia, with a prevalence over 10% in older patients. AF is the leading preventable cause of ischaemic stroke, and strokes due to AF have a higher mortality and morbidity. Stroke prevention is therefore a key management strategy for AF patients, in addition to rate and rhythm control. Anticoagulation with warfarin has been an enduring gold standard for stroke prevention in NVAF patients. In Australia, three novel oral anticoagulants (NOACs), apixaban, dabigatran and rivaroxaban are now approved and reimbursed for stroke prevention in patients with non-valvular AF (NVAF). International European Cardiology guidelines now recommend either a NOAC or warfarin for NVAF patients with a CHA2DS2-VASc score ≥2, unless contraindicated. Apixaban is a direct factor Xa inhibitor with a 12-hour half-life and 25% renal excretion that was found in a large trial of NVAF patients to be superior to warfarin in preventing stroke or systemic embolism. In this trial population, apixaban also resulted in less bleeding and a lower mortality rate than warfarin. Methods Clinical experience with apixaban outside of clinical trials has been limited, and there is currently little evidence to guide the management of bleeding or invasive procedures in patients taking apixaban. The relevant currently available animal and ex vivo human data were collected, analyzed and summarized. Results This multi-disciplinary consensus statement has been written to serve as a guide for healthcare practitioners prescribing apixaban in Australia, with a focus on acute and emergency management. Conclusions The predictable pharmacokinetics and minimal drug interactions of apixaban should allow for safe anticoagulation in the majority of patients, including temporary interruption for elective procedures. In the absence of published data, patients actively bleeding on apixaban should receive standard supportive treatment. Quantitative assays of

  10. The Abundance of Epicardial Adipose Tissue Surrounding Left Atrium Is Associated With the Occurrence of Stroke in Patients With Atrial Fibrillation.

    PubMed

    Tsao, Hsuan-Ming; Hu, Wei-Chih; Tsai, Ping-Huang; Lee, Chao-Lin; Liu, Fang-Chun; Wang, Hsueh-Han; Lo, Li-Wei; Chang, Shih-Lin; Chao, Tze-Fan; Chen, Shih-Ann

    2016-04-01

    Epicardial adipose tissue (EAT) is positively associated with risk factors for cardiovascular disease, but the role of EAT in the development of atrial fibrillation (AF)-related stroke and its association with the anatomical and functional remodeling of the left atrium (LA) have not been elucidated.This was a comparative cross-sectional study. Twenty-seven patients with paroxysmal or persistent AF and cardioembolic stroke were selected and compared with 68 age- and sex-matched AF patients without stroke. In addition, 20 controls without a history of AF or stroke were included. The periatrial EAT and the structural and functional properties of the LA and left ventricle were evaluated using contrast-enhanced 64-slice multidetector computed tomography during sinus rhythm. Total EAT around the LA was significantly increased across the groups (control vs AF vs AF-related stroke, P < 0.001). The volumes of the LA and the LA appendage (LAA) were also significantly increased across the 3 groups (P < 0.001 for each). The emptying fraction of the LA and LAA and the booster-pump function of the LA and LAA were all reduced across the 3 groups (P < 0.001 for all). In addition, the Hounsfield unit (HU) ratio of the LAA to the ascending aorta (LAA/AA) was also decreased in patients with stroke (P < 0.001). Furthermore, EAT had a negative correlation with the dynamic function of the LA, LAA, and the HU ratio. After a multivariate analysis, increased EAT (P < 0.001) was shown to be independently associated with the occurrence of AF-related stroke.Periatrial EAT was increased and was correlated with atrial dysfunction in patients with AF-related stroke. Hence, EAT assessment may potentially offer an incremental value for grading the risk of cardioembolic stroke in patients with AF. PMID:27057876

  11. The planar cell polarity (PCP) protein Diversin translocates to the nucleus to interact with the transcription factor AF9

    SciTech Connect

    Haribaskar, Ramachandran; Puetz, Michael; Schupp, Birte; Skouloudaki, Kassiani; Bietenbeck, Andreas; Walz, Gerd; Schaefer, Tobias

    2009-09-11

    The planar cell polarity (PCP) pathway, a {beta}-catenin-independent branch of the Wnt signaling pathway, orients cells and their appendages with respect to the body axes. Diversin, the mammalian homolog of the Drosophila PCP protein Diego, acts as a molecular switch that blocks {beta}-catenin-dependent and promotes {beta}-catenin-independent Wnt signaling. We report now that Diversin, containing several nuclear localization signals, translocates to the nucleus, where it interacts with the transcription factor AF9. Both Diversin and AF9 block canonical Wnt signaling; however, this occurs independently of each other, and does not require nuclear Diversin. In contrast, AF9 strongly augments the Diversin-driven activation of c-Jun N-terminal kinase (JNK)-dependent gene expression in the nucleus, and this augmentation largely depends on the presence of nuclear Diversin. Thus, our findings reveal that components of the PCP cascade translocate to the nucleus to participate in transcriptional regulation and PCP signaling.

  12. Race- and sex-related differences in care for patients newly diagnosed with atrial fibrillation

    PubMed Central

    Bhave, Prashant D.; Lu, Xin; Girotra, Saket; Kamel, Hooman; Sarrazin, Mary S. Vaughan

    2016-01-01

    BACKGROUND Atrial fibrillation (AF) is associated with an increased risk of stroke and death. Uniform utilization of appropriate therapies for AF may help reduce those risks. OBJECTIVE We sought to determine whether significant race and sex differences exist in the treatment of newly diagnosed AF in Medicare beneficiaries. METHODS We used administrative encounter data for Medicare beneficiaries to identify patients with newly diagnosed AF during 2010–2011. Services received after initial AF diagnosis were cataloged, including visits with a cardiologist or electrophysiolo-gist, catheter ablation procedures, and use of oral anticoagulants, rate control agents, and antiarrhythmic drugs. RESULTS Overall, 517,941 patients met study criteria, of whom 452,986 (87%) were white, 36,425 (7%) black, and 28,530 (6%) Hispanic. Male patients comprised 209,788 (41%) of the cohort. In multivariate analysis, there were statistically significant differences in the use of AF-related services by both race and sex, with white patients and male patients receiving the most care. The most notable disparities were for catheter ablation (Hispanic vs white: adjusted hazard ratio [AHR] 0.70; 95% confidence interval [CI] 0.63–0.79; P < .001; female vs male: AHR 0.65; 95% CI 0.63–0.68; P < .001) and receipt of oral anticoagulation (black vs white: AHR 0.94; 95% CI 0.92–0.95; P < .001; Hispanic vs white: AHR 0.94; 95% CI 0.93–0.97; P < .001; female vs male: AHR 0.93; 95% CI 0.93–0.94; P < .001). CONCLUSION Race and sex appear to have a significant effect on the health care provided to this cohort of Medicare beneficiaries diagnosed with AF. Possible explanations include racial differences in access, patient preferences, treatment bias, and unmeasured clinical characteristics. PMID:25814418

  13. Linear Ablation Following Pulmonary Vein Isolation in Patients with Atrial Fibrillation: A Meta-Analysis.

    PubMed

    Zhang, Zhiwei; Letsas, Konstantinos P; Zhang, Nixiao; Efremidis, Michael; Xu, Gang; Li, Guangping; Liu, Tong

    2016-06-01

    Previous studies have given conflicting data regarding the long-term adjunctive efficacy of linear lesions (LLs) on top of pulmonary vein isolation (PVI) as an ablation strategy in patients with atrial fibrillation (AF). The aim of this meta-analysis was to provide a detailed analysis of the available randomized controlled trials (RCTs) regarding the efficacy of LL following PVI in AF patients. Current databases were searched until October 2015. The primary outcome end point of the meta-analysis was recurrence of any symptomatic or documented episode of AF or atrial tachycardia after a single ablation procedure with or without the use of antiarrhythmic drugs. Ten RCTs with a total of 1,446 patients were included in the meta-analysis. The pooled analysis of five trials concerning persistent AF (PeAF) patients (400 in PVI plus LL group and 182 in PVI alone group) suggested that the addition of LL following PVI does not lead to a significant reduction in recurrent atrial tachyarrhythmias compared with PVI alone (relative ratio [RR] = 0.73, 95% confidence interval [CI]: 0.44-1.21, P = 0.22). Similarly, there was no incremental benefit of additional LL in long-term outcomes in paroxysmal AF (PAF) patients (RR = 0.85, 95% CI: 0.68-1.05, P = 0.13). Pooling the results of all eligible trials suggested that PVI plus LL compared with PVI alone significantly increased radiofrequency time (P = 0.0002), fluoroscopy time (P < 0.00001), and procedure time (P < 0.0001). This meta-analysis suggests that LL following PVI does not provide additional benefit to sinus rhythm maintenance in patients with PeAF and PAF. PMID:26970360

  14. High morbidity in myocardial infarction and heart failure patients after gastric cancer surgery

    PubMed Central

    Jeong, Sang-Ho; Kim, Young-Woo; Yu, Wansik; Lee, Sang Ho; Park, Young Kyu; Park, Seong-Heum; Jeong, In Ho; Lee, Sang Eok; Park, Yongwhi; Lee, Young-Joon

    2015-01-01

    AIM: To evaluate to morbidity and mortality differences between 4 underlying heart diseases, myocardial infarction (MI), angina pectoris (Angina), heart failure (HF), and atrial fibrillation (AF), after radical surgery for gastric cancer. METHODS: We retrospectively collected data from 221 patients of a total of 15167 patients who underwent radical gastrectomy and were preoperatively diagnosed with a history of Angina, MI, HF, or AF in 8 hospitals. RESULTS: We find that the total morbidity rate is significantly higher in the MI group (44%) than the Angina (15.7%), AF (18.8%), and HF (23.1%) groups (P < 0.01). Moreover, we note that the risk for postoperative cardiac problems is higher in patients with a history of HF (23.1%) than patients with a history of Angina (2.2%), AF (4.3%), or MI (6%; P = 0.01). The HF and MI groups each have 1 case of cardiogenic mortality. CONCLUSION: We conclude that MI patients have a higher risk of morbidity, and HF patients have a higher risk of postoperative cardiac problems than Angina or AF. PMID:26074701

  15. Impact of Global Geographic Region on Time in Therapeutic Range on Warfarin Anticoagulant Therapy: Data From the ROCKET AF Clinical Trial

    PubMed Central

    Singer, Daniel E.; Hellkamp, Anne S.; Piccini, Jonathan P.; Mahaffey, Kenneth W.; Lokhnygina, Yuliya; Pan, Guohua; Halperin, Jonathan L.; Becker, Richard C.; Breithardt, Günter; Hankey, Graeme J.; Hacke, Werner; Nessel, Christopher C.; Patel, Manesh R.; Califf, Robert M.; Fox, Keith A. A.

    2013-01-01

    Background Vitamin K antagonist (VKA) therapy remains the most common method of stroke prevention in patients with atrial fibrillation. Time in therapeutic range (TTR) is a widely cited measure of the quality of VKA therapy. We sought to identify factors associated with TTR in a large, international clinical trial. Methods and Results TTR (international normalized ratio [INR] 2.0 to 3.0) was determined using standard linear interpolation in patients randomized to warfarin in the ROCKET AF trial. Factors associated with TTR at the individual patient level (i‐TTR) were determined via multivariable linear regression. Among 6983 patients taking warfarin, recruited from 45 countries grouped into 7 regions, the mean i‐TTR was 55.2% (SD 21.3%) and the median i‐TTR was 57.9% (interquartile range 43.0% to 70.6%). The mean time with INR <2 was 29.1% and the mean time with an INR >3 was 15.7%. While multiple clinical features were associated with i‐TTR, dominant determinants were previous warfarin use (mean i‐TTR of 61.1% for warfarin‐experienced versus 47.4% in VKA‐naïve patients) and geographic region where patients were managed (mean i‐TTR varied from 64.1% to 35.9%). These effects persisted in multivariable analysis. Regions with the lowest i‐TTRs had INR distributions shifted toward lower INR values and had longer inter‐INR test intervals. Conclusions Independent of patient clinical features, the regional location of medical care is a dominant determinant of variation in i‐TTR in global studies of warfarin. Regional differences in mean i‐TTR are heavily influenced by subtherapeutic INR values and are associated with reduced frequency of INR testing. Clinical Trial Registration URL: ClinicalTrials.gov. Unique identifier: NCT00403767. PMID:23525418

  16. Anticoagulation in patients with atrial fibrillation undergoing coronary stent implantation.

    PubMed

    Bernard, A; Fauchier, L; Pellegrin, C; Clementy, N; Saint Etienne, C; Banerjee, A; Naudin, D; Angoulvant, D

    2013-09-01

    In patients with atrial fibrillation (AF) undergoing coronary stent implantation, the optimal antithrombotic strategy is unclear. We evaluated whether use of oral anticoagulation (OAC) was associated with any benefit in morbidity or mortality in patients with AF, high risk of thromboembolism (TE) (CHA2DS2-VASC score ≥ 2) and coronary stent implantation. Among 8,962 unselected patients with AF seen between 2000 and 2010, a total of 2,709 (30%) had coronary artery disease and 417/2,709 (15%) underwent stent implantation while having CHA2DS2-VASC score ≥ 2. During follow-up (median=650 days), all TE, bleeding episodes, and major adverse cardiac events (i.e. death, acute myocardial infarction, target lesion revascularisation) were recorded. At discharge, 97/417 patients (23%) received OAC, which was more likely to be prescribed in patients with permanent AF and in those treated for elective stent implantation. The incidence of outcome event rates was not significantly different in patients treated and those not treated with OAC. However, in multivariate analysis, the lack of OAC at discharge was independently associated with increased risk of death/stroke/systemic TE (relative risk [RR] =2.18, 95% confidence interval [CI] 1.02-4.67, p=0.04), with older age (RR =1.12, 1.04-1.20, p=0.003), heart failure (RR =3.26, 1.18-9.01, p=0.02), and history of stroke (RR =18.87, 3.11-111.11, p=0.001). In conclusion, in patients with AF and high thromboembolic risk after stent implantation, use of OAC was independently associated with decreased risk of subsequent death/stroke/systemic TE, suggesting that OAC should be systematically used in this patient population. PMID:23846210

  17. The MLL fusion gene, MLL-AF4, regulates cyclin-dependent kinase inhibitor CDKN1B (p27kip1) expression

    PubMed Central

    Xia, Zhen-Biao; Popovic, Relja; Chen, Jing; Theisler, Catherine; Stuart, Tara; Santillan, Donna A.; Erfurth, Frank; Diaz, Manuel O.; Zeleznik-Le, Nancy J.

    2005-01-01

    MLL, involved in many chromosomal translocations associated with acute myeloid and lymphoid leukemia, has >50 known partner genes with which it is able to form in-frame fusions. Characterizing important downstream target genes of MLL and of MLL fusion proteins may provide rational therapeutic strategies for the treatment of MLL-associated leukemia. We explored downstream target genes of the most prevalent MLL fusion protein, MLL-AF4. To this end, we developed inducible MLL-AF4 fusion cell lines in different backgrounds. Overexpression of MLL-AF4 does not lead to increased proliferation in either cell line, but rather, cell growth was slowed compared with similar cell lines inducibly expressing truncated MLL. We found that in the MLL-AF4-induced cell lines, the expression of the cyclin-dependent kinase inhibitor gene CDKN1B was dramatically changed at both the RNA and protein (p27kip1) levels. In contrast, the expression levels of CDKN1A (p21) and CDKN2A (p16) were unchanged. To explore whether CDKN1B might be a direct target of MLL and of MLL-AF4, we used chromatin immunoprecipitation (ChIP) assays and luciferase reporter gene assays. MLL-AF4 binds to the CDKN1B promoter in vivo and regulates CDKN1B promoter activity. Further, we confirmed CDKN1B promoter binding by ChIP in MLL-AF4 as well as in MLL-AF9 leukemia cell lines. Our results suggest that CDKN1B is a downstream target of MLL and of MLL-AF4, and that, depending on the background cell type, MLL-AF4 inhibits or activates CDKN1B expression. This finding may have implications in terms of leukemia stem cell resistance to chemotherapy in MLL-AF4 leukemias. PMID:16169901

  18. Fluorous Polymeric Membranes for Ionophore-Based Ion-Selective Potentiometry: How Inert is Teflon AF?

    PubMed Central

    Lai, Chun-Ze; Koseoglu, Secil S.; Lugert, Elizabeth C.; Boswell, Paul G.; Rábai, József; Lodge, Timothy P.; Bühlmann, Philippe

    2011-01-01

    Fluorous media are the least polar and polarizable condensed phases known. Their use as membrane materials considerably increases the selectivity and robustness of ion-selective electrodes (ISEs). In this research, a fluorous amorphous perfluoropolymer was used for the first time as a matrix for an ISE membrane. Electrodes for pH measurements with membranes composed of poly[4,5-difluoro-2,2-bis(trifluoromethyl)-1,3-dioxole]-co-poly(tetrafluoroethylene) (87% dioxole monomer content; known as Teflon AF2400) as polymer matrix, a linear perfluorooligoether as plasticizer, sodium tetrakis[3,5-bis(perfluorohexyl)phenyl]borate providing for ionic sites, and bis[(perfluorooctyl)propyl]-2,2,2-trifluoroethylamine as H+-ionophore were investigated. All electrodes had excellent potentiometric selectivities, showed Nernstian responses to H+ over a wide pH range, exhibited enhanced mechanical stability and maintained their selectivity over at least four weeks. For membranes of low ionophore concentration, the polymer affected the sensor selectivity noticeably at polymer concentrations exceeding 15%. Also, the membrane resistance increased quite strongly at high polymer concentrations, which cannot be explained by the Mackie–Meares obstruction model. The selectivities and resistances depend on the polymer concentration because of a functional group associated with Teflon AF2400, with a concentration of one functional group per 854 monomer units of the polymer. In the fluorous environment of these membranes, this functional group binds to Na+, K+, Ca2+, and the unprotonated ionophore with binding constants of 103.5, 101.8, 106.8 and 104.4 M−1, respectively. Potentiometric and spectroscopic evidence indicates that these functional groups are COOH groups formed by the hydrolysis of carboxylic acid fluoride (COF) groups originally present in Teflon AF2400. The use of higher ionophore concentrations removes the undesirable effect of these COOH groups almost completely

  19. Electrical PR Interval Variation Predicts New Occurrence of Atrial Fibrillation in Patients With Frequent Premature Atrial Contractions

    PubMed Central

    Chun, Kwang Jin; Hwang, Jin Kyung; Park, Seung-Jung; On, Young Keun; Kim, June Soo; Park, Kyoung-Min

    2016-01-01

    Abstract Atrial fibrillation (AF) is associated with the autonomic nervous system (ANS), and fluctuation of autonomic tone is more prominent in patients with AF. As autonomic tone affects the heart rate (HR), and there is an inverse relationship between HR and PR interval, PR interval variation could be greater in patients with AF than in those without AF. The purpose of this study was to investigate the correlation between PR interval variation and new-onset AF in patients with frequent PACs. We retrospectively enrolled 207 patients with frequent PACs who underwent electrocardiographs at least 4 times during the follow-up period. The PR variation was calculated by subtracting the minimum PR interval from the maximum PR interval. The outcomes were new occurrence of AF and all-cause mortality during the follow-up period. During a median follow-up of 8.3 years, 24 patients (11.6%) developed new-onset AF. Univariate analysis showed that prolonged PR interval (PR interval > 200 ms, P = 0.021), long PR variation (PR variation > 36.5 ms, P = 0.018), and PR variation (P = 0.004) as a continuous variable were associated with an increased risk of AF. Cox regression analysis showed that prolonged PR interval (hazard ratio = 3.321, 95% CI 1.064–10.362, P = 0.039) and PR variation (hazard ratio = 1.013, 95% CI 1.002–1.024, P = 0.022) were independent predictors for new-onset AF. However, PR variation and prolonged PR interval were not associated with all-cause mortality (P = 0.465 and 0.774, respectively). PR interval variation and prolonged PR interval are independent risk factors for new-onset AF in patients with frequent PACs. However we were unable to determine a cut-off value of PR interval variation for new-onset AF. PMID:27057868

  20. Electrical PR Interval Variation Predicts New Occurrence of Atrial Fibrillation in Patients With Frequent Premature Atrial Contractions.

    PubMed

    Chun, Kwang Jin; Hwang, Jin Kyung; Park, Seung-Jung; On, Young Keun; Kim, June Soo; Park, Kyoung-Min

    2016-04-01

    Atrial fibrillation (AF) is associated with the autonomic nervous system (ANS), and fluctuation of autonomic tone is more prominent in patients with AF. As autonomic tone affects the heart rate (HR), and there is an inverse relationship between HR and PR interval, PR interval variation could be greater in patients with AF than in those without AF. The purpose of this study was to investigate the correlation between PR interval variation and new-onset AF in patients with frequent PACs.We retrospectively enrolled 207 patients with frequent PACs who underwent electrocardiographs at least 4 times during the follow-up period. The PR variation was calculated by subtracting the minimum PR interval from the maximum PR interval. The outcomes were new occurrence of AF and all-cause mortality during the follow-up period.During a median follow-up of 8.3 years, 24 patients (11.6%) developed new-onset AF. Univariate analysis showed that prolonged PR interval (PR interval > 200 ms, P = 0.021), long PR variation (PR variation > 36.5 ms, P = 0.018), and PR variation (P = 0.004) as a continuous variable were associated with an increased risk of AF. Cox regression analysis showed that prolonged PR interval (hazard ratio = 3.321, 95% CI 1.064-10.362, P = 0.039) and PR variation (hazard ratio = 1.013, 95% CI 1.002-1.024, P = 0.022) were independent predictors for new-onset AF. However, PR variation and prolonged PR interval were not associated with all-cause mortality (P = 0.465 and 0.774, respectively).PR interval variation and prolonged PR interval are independent risk factors for new-onset AF in patients with frequent PACs. However we were unable to determine a cut-off value of PR interval variation for new-onset AF. PMID:27057868

  1. A case-based approach to implementing guidelines for stroke prevention in patients with atrial fibrillation: balancing the risks and benefits.

    PubMed

    Amin, Alpesh; Deitelzweig, Steven

    2015-01-01

    Atrial fibrillation (AF) puts patients at risk of complications, including stroke. Warfarin therapy has been the mainstay of antithrombotic treatment for reducing the risk of stroke in AF. However, warfarin has limitations that have motivated development of several novel oral anticoagulants (NOACs), including dabigatran, rivaroxaban, apixaban, and edoxaban. Clinical trials demonstrate that the NOACs offer efficacy and safety that are equivalent to, or better than, those of warfarin for reducing the risk of stroke in patients with nonvalvular AF. This review examines stroke risk reduction in patients with AF from the perspective of the clinician balancing the risks and benefits of treatment options, evaluates the most recent guidelines, and discusses 2 hypothetical patient cases to better illustrate how clinicians may apply available data in the clinical setting. We reviewed guidelines for the reduction of stroke risk in AF and data from clinical trials on the NOACs. Choosing antithrombotic treatment involves assessing the benefits of therapy versus its risks. Risk indexes, including CHADS2, CHA2DS2-VASc, and HAS-BLED can help determine how to treat patients with AF. Current guidelines suggest using these risk indexes to customize treatment to individual patients. Many current treatment guidelines also incorporate recommendations for the use of NOACs as an alternative to warfarin. As additional data emerge and guidelines are updated, these recommendations will likely evolve. In the interim, clinicians may consider published guidelines and clinical trial results on NOACs. Real-world experience will provide clinicians with additional insight into their treatment decisions. PMID:26300695

  2. Magnesium deficiency may be an important determinant of ventricular ectopy in digitalised patients with chronic atrial fibrillation.

    PubMed Central

    Lewis, R; Durnin, C; McLay, J; McEwen, J; McDevitt, D G

    1991-01-01

    Digitalised patients with chronic atrial fibrillation (AF) have a high prevalence of ventricular premature beats (VPB); magnesium deficiency may be a contributory factor. We have used a magnesium loading-test to examine the relationship between ventricular ectopy and magnesium status in 14 digitalised patients with chronic AF. Among seven patients with infrequent VPB (less than 250 24 h-1; mean 107 24 h-1) mean magnesium retention was 10.1% and four subjects retained no significant quantities of magnesium, indicating magnesium repletion. Among the remaining seven patients, mean magnesium retention was significantly higher (33.1%, P less than 0.02) and all patients retained 20% or more of the load given. There was an overall relationship between Mg retention and numbers of VPB (rs = 0.54; P less than 0.05). Magnesium deficiency may be determinant of ventricular ectopy in digitalised patients with chronic AF. PMID:1710915

  3. An international longitudinal registry of patients with atrial fibrillation at risk of stroke (GARFIELD): the UK protocol

    PubMed Central

    2013-01-01

    Background Atrial fibrillation (AF) is an independent risk factor for stroke and a significant predictor of mortality. Evidence-based guidelines for stroke prevention in AF recommend antithrombotic therapy corresponding to the risk of stroke. In practice, many patients with AF do not receive the appropriate antithrombotic therapy and are left either unprotected or inadequately protected against stroke. The purpose of the Global Anticoagulant Registry in the FIELD (GARFIELD) is to determine the real-life management and outcomes of patients newly diagnosed with non-valvular AF. Methods/design GARFIELD is an observational, international registry of newly diagnosed AF patients with at least one additional investigator-defined risk factor for stroke. The aim is to enrol 55,000 patients at more than 1000 centres in 50 countries worldwide. Enrolment will take place in five independent, sequential, prospective cohorts; the first cohort includes a retrospective validation cohort. Each cohort will be followed up for 2 years. The UK stands to be a significant contributor to GARFIELD, aiming to enrol 4,582 patients, and reflecting the care environment in which patients with AF are managed. The UK protocol will also focus on better understanding the validity of the two main stroke risk scores (CHADS2 and CHA2DS2VASC) and the HAS-BLED bleeding risk score, in the context of a diverse patient population. Discussion The GARFIELD registry will describe how therapeutic strategies, patient care, and clinical outcomes evolve over time. This study will provide UK-specific comprehensive data that will allow a range of evaluations both at a national level and in relation to global data and contribute to a better understanding of AF management in the UK. Trial registration ClinicalTrial.gov: NCT01090362 PMID:23617744

  4. Atrial structural remodeling in patients with atrial chronic fibrillations and in animal models.

    PubMed

    Laky, D; Parascan, Liliana; Cândea, V

    2011-01-01

    Arrhythmia's atrium fibrillation (AF) is the most often met in clinical setting and it is associated with an increased in mortality risk. For profound the structural changes in chronic AF, we are studied the morphological changes of atrium biopsies to be effected at 175 patients. With sustained AF malformative and valvular acquired cardiac diseases operated under extracorporeal circulation. Similar studies we are effected to 11 dogs with partial coronary obstructions to a made periodical EKG investigations. The morphological changes mainly concern accommodation (dedifferentiation) of cardiomyocytes (particularly at experimental model) and mal-accommodation (degeneration of cells with fibrosis replacement features) particularly in acquired valvular diseases. These changes were often interfered. Over study, maintain the hypothesis that the structural changes to be an accommodation more than degenerative response to AF. PMID:21424038

  5. [Catheter ablation in patients with atrial fibrillation: what will change in daily practice?].

    PubMed

    van der Voort, Pepijn H

    2013-01-01

    A recent publication compared catheter ablation and antiarrhythmic drugs as initial therapy for paroxysmal atrial fibrillation. No difference was seen in the primary endpoint of the cumulative AF burden over two years. The burden of AF was documented objectively by a series of 7-day continuous ECG recordings; a method that will evolve as a gold standard for measuring the AF burden. The major shortcoming of the study was an obsolete ablation endpoint, lacking verification of pulmonary vein isolation. Other drawbacks were the fact that ablations were not exclusively carried out in high-volume centres and a high cross-over rate in the drug group. Also, although the primary endpoint was not significantly different, several secondary outcomes obviously favoured ablation. Outcomes in both the ablation and drug groups were relatively good, and this study will not change the current practice for the majority of paroxysmal AF patients, although catheter ablation could be performed as the initial therapy. PMID:23548191

  6. Comparison of effectiveness of carvedilol versus bisoprolol for prevention of postdischarge atrial fibrillation after coronary artery bypass grafting in patients with heart failure.

    PubMed

    Marazzi, Giuseppe; Iellamo, Ferdinando; Volterrani, Maurizio; Caminiti, Giuseppe; Madonna, Mariapina; Arisi, Giovanna; Massaro, Rosalba; Righi, Daniela; Rosano, Giuseppe M C

    2011-01-15

    Atrial fibrillation (AF) occurs frequently soon after coronary artery bypass grafting (CABG) and often results in increased mortality and morbidity, particularly in patients with heart failure. New-onset AF is also a common event in the early period after discharge from a cardiac surgery clinic. Current guidelines recommend β blockers as first-line medication for the prevention of AF after CABG. In this prospective study, we investigated the effectiveness of the highly selective β1 receptor antagonist bisoprolol compared to the less selective β blocker carvedilol in preventing postdischarge AF after CABG in patients with decreased left ventricular function. Three hundred twenty patients (231 men, 89 women, mean age 66 ± 10 years) with ejection fraction <40% who underwent CABG and were then referred to an in-hospital cardiac rehabilitation program were randomized to receive bisoprolol (n = 160) or carvedilol (n = 160) starting 4 to 5 days after surgery. Bisoprolol was started at 1.25 mg 1 time/day and carvedilol was started 3.125 mg 2 times/day. All patients underwent continuous telemetric electrocardiographic monitoring for 5 days after entry in the study and thereafter 2 times/day routinely up to hospital discharge. During follow-up, 23 patients (14.6%) in the bisoprolol group and 37 patients (23%) in the carvedilol group developed AF (relative risk 0.6, confidence interval 0.4 to 0.9, p = 0.032). Twenty-six percent of all AF episodes were asymptomatic. At the 4-week outpatient visit, those in the bisoprolol group showed a significantly greater decrease in heart rate, being in sinus rhythm or AF (-15.6 ± 3 vs -9.4 ± 3 beats/min, p = 0.021), whereas changes in systolic and diastolic blood pressures did not differ significantly. In conclusion, bisoprolol is more effective than carvedilol in decreasing the incidence of postdischarge AF after CABG in patients with decreased left ventricular function. PMID:21129714

  7. Gender, Race, and Health Insurance Status in Patients Undergoing Catheter Ablation for Atrial Fibrillation.

    PubMed

    Patel, Nileshkumar; Deshmukh, Abhishek; Thakkar, Badal; Coffey, James O; Agnihotri, Kanishk; Patel, Achint; Ainani, Nitesh; Nalluri, Nikhil; Patel, Nilay; Patel, Nish; Patel, Neil; Badheka, Apurva O; Kowalski, Marcin; Hendel, Robert; Viles-Gonzalez, Juan; Noseworthy, Peter A; Asirvatham, Samuel; Lo, Kaming; Myerburg, Robert J; Mitrani, Raul D

    2016-04-01

    Catheter ablation for atrial fibrillation (AF) has emerged as a popular procedure. The purpose of this study was to examine whether there exist differences or disparities in ablation utilization across gender, socioeconomic class, insurance, or race. Using the Nationwide Inpatient Sample (2000 to 2012), we identified adults hospitalized with a principal diagnosis of AF by ICD 9 code 427.31 who had catheter ablation (ICD 9 code-37.34). We stratified patients by race, insurance status, age, gender, and hospital characteristics. A hierarchical multivariate mixed-effect model was created to identify the independent predictors of AF ablation. Among an estimated total of 3,508,122 patients (extrapolated from 20% Nationwide Inpatient Sample) hospitalized with a diagnosis of AF in the United States from the year 2000 to 2012, 102,469 patients (2.9%) underwent catheter ablations. The number of ablations was increased by 940%, from 1,439 in 2000 to 15,090 in 2012. There were significant differences according to gender, race, and health insurance status, which persisted even after adjustment for other risk factors. Female gender (0.83 [95% CI 0.79 to 0.87; p <0.001]), black (0.49 [95% CI 0.44 to 0.55; p <0.001]), and Hispanic race (0.64 [95% CI 0.56 to 0.72; p <0.001]) were associated with lower likelihoods of undergoing an AF ablation. Medicare (0.93, 0.88 to 0.98, <0.001) or Medicaid (0.67, 0.59 to 0.76, <0.001) coverage and uninsured patients (0.55, 0.49 to 0.62, <0.001) also had lower rates of AF ablation compared to patients with private insurance. In conclusion we found differences in utilization of catheter ablation for AF based on gender, race, and insurance status that persisted over time. PMID:26899494

  8. Cognitive function and adherence to anticoagulation treatment in patients with atrial fibrillation

    PubMed Central

    Jankowska-Polańska, Beata; Katarzyna, Lomper; Lidia, Alberska; Joanna, Jaroch; Dudek, Krzysztof; Izabella, Uchmanowicz

    2016-01-01

    Background Medication adherence is an integral part of the comprehensive care of patients with atrial fibrillation (AF) receiving oral anticoagulations (OACs) therapy. Many patients with AF are elderly and may suffer from some form of cognitive impairment. This study was conducted to investigate whether cognitive impairment affects the level of adherence to anticoagulation treatment in AF patients. Methods The study involved 111 AF patients (mean age, 73.5 ± 8.3 years) treated with OACs. Cognitive function was assessed using the Mini Mental State Examination (MMSE). The level of adherence was assessed by the 8-item Morisky Medication Adherence Scale (MMAS-8). Scores on the MMAS-8 range from 0 to 8, with scores < 6 reflecting low adherence, 6 to < 8 medium adherence, and 8 high adherence. Results 46.9% of AF patients had low adherence, 18.8% had moderate adherence, and 33.3% had high adherence to OACs. Patients with lower adherence were older than those with moderate or high adherence (76.6 ± 8.7 vs. 71.3 ± 6.4 vs. 71.1 ± 6.7 years) and obtained low MMSE scores, indicating cognitive disorders or dementia (MMSE = 22.3 ± 4.2). Patients with moderate or high adherence obtained high MMSE test results (27.5 ± 1.7 and 27.5 ± 3.6). According to Spearman's rank correlation, worse adherence to treatment with OACs was determined by older age (rS = −0.372) and lower MMSE scores (rS = 0.717). According to multivariate regression analysis, the level of cognitive function was a significant independent predictor of adherence (b = 1.139). Conclusions Cognitive impairment is an independent determinant of compliance with pharmacological therapy in elderly patients with AF. Lower adherence, beyond the assessment of cognitive function, is related to the age of patients. PMID:27605935

  9. Atrial Fibrillation on Intensive Care Unit Admission Independently Increases the Risk of Weaning Failure in Nonheart Failure Mechanically Ventilated Patients in a Medical Intensive Care Unit

    PubMed Central

    Tseng, Yen-Han; Ko, Hsin-Kuo; Tseng, Yen-Chiang; Lin, Yi-Hsuan; Kou, Yu Ru

    2016-01-01

    Abstract Atrial fibrillation (AF) is one of the most frequent arrhythmias in clinical practice. Previous studies have reported the influence of AF on patients with heart failure (HF). The effect of AF on the non-HF critically ill patients in a medical intensive care unit (ICU) remains largely unclear. The study aimed to investigate the impact of AF presenting on ICU admission on the weaning outcome of non-HF mechanically ventilated patients in a medical ICU. A retrospective observational case–control study was conducted over a 1-year period in a medical ICU at Taipei Veterans General Hospital, a tertiary medical center in north Taiwan. Non-HF mechanically ventilated patients who were successful in their spontaneous breathing trial and underwent ventilator discontinuation were enrolled. The primary outcome measure was the ventilator status after the first episode of ventilator discontinuation. A total of 285 non-HF patients enrolled were divided into AF (n = 62) and non-AF (n = 223) groups. Compared with the non-AF patients, the AF patients were significantly associated with old age (P = 0.002), a higher rate of acute respiratory distress syndrome causing respiratory failure (P = 0.015), a higher percentage of sepsis before liberation from mechanical ventilation (MV) (P = 0.004), and a higher serum level of blood urea nitrogen on the day of liberation from MV (P = 0.003). Multivariate logistic regression analysis demonstrated that AF independently increased the risk of weaning failure [adjusted odds ratio (AOR), 3.268; 95% confidence interval (CI), 1.254–8.517; P = 0.015]. Furthermore, the AF patients were found to be independently associated with a high rate of ventilator dependence (log rank test, P = 0.026), prolonged total ventilator use (AOR, 1.979; 95% CI, 1.032–3.794; P = 0.040), increased length of ICU stay (AOR, 2.256; 95% CI, 1.049–4.849; P = 0.037), increased length of hospital stay (AOR, 2.921; 95% CI, 1

  10. Fusagerins A-F, New Alkaloids from the Fungus Fusarium sp.

    PubMed

    Wen, Hao; Li, Yan; Liu, Xingzhong; Ye, Wencai; Yao, Xinsheng; Che, Yongsheng

    2015-08-01

    Fusagerins A-F (1-6), six new alkaloids including a unique one with the rare a-(N-formyl)carboxamide moiety (1), a hydantoin (imidazolidin-2,4-dione) derivative (2), and four fungerin analogues (3-6), were isolated from the crude extract of the fungus Fusarium sp., together with the known compound fungerin (7). Compound 2 was isolated as a racemate and further separated into two enantiomers on a chiral HPLC column. The structures of 1-6 were determined mainly by NMR experiments, and the absolute configuration of 1 and 2 was assigned by electronic circular dichroism (ECD) calculations. Compound 7 showed antibacterial activity against Staphylococcus aureus and Streptococcus pneumoniae, and weak cytotoxicity against the T24 cells. PMID:26329590

  11. RNA structure replaces the need for U2AF2 in splicing

    PubMed Central

    Lin, Chien-Ling; Taggart, Allison J.; Lim, Kian Huat; Cygan, Kamil J.; Ferraris, Luciana; Creton, Robbert; Huang, Yen-Tsung; Fairbrother, William G.

    2016-01-01

    RNA secondary structure plays an integral role in catalytic, ribosomal, small nuclear, micro, and transfer RNAs. Discovering a prevalent role for secondary structure in pre-mRNAs has proven more elusive. By utilizing a variety of computational and biochemical approaches, we present evidence for a class of nuclear introns that relies upon secondary structure for correct splicing. These introns are defined by simple repeat expansions of complementary AC and GT dimers that co-occur at opposite boundaries of an intron to form a bridging structure that enforces correct splice site pairing. Remarkably, this class of introns does not require U2AF2, a core component of the spliceosome, for its processing. Phylogenetic analysis suggests that this mechanism was present in the ancestral vertebrate lineage prior to the divergence of tetrapods from teleosts. While largely lost from land dwelling vertebrates, this class of introns is found in 10% of all zebrafish genes. PMID:26566657

  12. AF-GEOSpace Version 2.0: Space Environment Software Products for 2002

    NASA Astrophysics Data System (ADS)

    Hilmer, R. V.; Ginet, G. P.; Hall, T.; Holeman, E.; Tautz, M.

    2002-05-01

    AF-GEOSpace Version 2.0 (release 2002 on WindowsNT/2000/XP) is a graphics-intensive software program developed by AFRL with space environment models and applications. It has grown steadily to become a development tool for automated space weather visualization products and helps with a variety of tasks: orbit specification for radiation hazard avoidance; satellite design assessment and post-event analysis; solar disturbance effects forecasting; frequency and antenna management for radar and HF communications; determination of link outage regions for active ionospheric conditions; and physics research and education. The object-oriented C++ code is divided into five module classes. Science Modules control science models to give output data on user-specified grids. Application Modules manipulate these data and provide orbit generation and magnetic field line tracing capabilities. Data Modules read and assist with the analysis of user-generated data sets. Graphics Modules enable the display of features such as plane slices, magnetic field lines, line plots, axes, the Earth, stars, and satellites. Worksheet Modules provide commonly requested coordinate transformations and calendar conversion tools. Common input data archive sets, application modules, and 1-, 2-, and 3-D visualization tools are provided to all models. The code documentation includes detailed examples with click-by-click instructions for investigating phenomena that have well known effects on communications and spacecraft systems. AF-GEOSpace Version 2.0 builds on the success of its predecessors. The first release (Version 1.21, 1996/IRIX on SGI) contained radiation belt particle flux and dose models derived from CRRES satellite data, an aurora model, an ionosphere model, and ionospheric HF ray tracing capabilities. Next (Version 1.4, 1999/IRIX on SGI) science modules were added related to cosmic rays and solar protons, low-Earth orbit radiation dosages, single event effects probability maps, ionospheric

  13. Fatigue life estimation program for Part 23 airplanes, `AFS.FOR`

    SciTech Connect

    Kaul, S.K.

    1993-12-31

    The purpose of this paper is to introduce to the general aviation industry a computer program which estimates the safe fatigue life of any Federal Aviation Regulation (FAR) Part 23 airplane. The algorithm uses the methodology (Miner`s Linear Cumulative Damage Theory) and the various data presented in the Federal Aviation Administration (FAA) Report No. AFS-120-73-2, dated May 1973. The program is written in FORTRAN 77 language and is executable on a desk top personal computer. The program prompts the user for the input data needed and provides a variety of options for its intended use. The program is envisaged to be released through issuance of a FAA report, which will contain the appropriate comments, instructions, warnings and limitations.

  14. Hypocriols A-F, Heterodimeric Botryane Ethers from Hypocrea sp., an Insect-Associated Fungus.

    PubMed

    Ren, Fengxia; Zhu, Shuaiming; Wang, Bo; Li, Li; Liu, Xingzhong; Su, Ruibin; Che, Yongsheng

    2016-07-22

    The new heterodimeric botryane ethers hypocriols A-F (1-6) and the known compounds 4β-acetoxy-9β,10β,15α-trihydroxyprobotrydial (7), dihydrobotrydial (8), 10-oxodehydrodihydrobotrydial (9), and dehydrobotrydienol (10) were isolated from the solid cultures of an insect-associated fungus Hypocrea sp. The structures of 1-6 were elucidated primarily by NMR experiments. The absolute configuration of 1 was assigned using the modified Mosher method and electronic circular dichroism (ECD) calculations, whereas those for 3-5, and 2 and 6 were deduced via ECD calculations and circular dichroism data, respectively. Compounds 1-6 appear to be the first heterodimeric botryane ethers and showed antiproliferative effects against a small panel of four human tumor cell lines. PMID:27328173

  15. Astershionones A-F, six new anti-HBV shionane-type triterpenes from Aster tataricus.

    PubMed

    Zhou, Wen-Bing; Zeng, Guang-Zhi; Xu, Hui-Min; He, Wen-Jun; Zhang, Yu-Mei; Tan, Ning-Hua

    2014-03-01

    Six new shionane-type triterpenes, astershionones A-F (1-6), were obtained from the roots and rhizomes of Aster tataricus. Their structures were elucidated on the basis of spectroscopic data, mainly NMR and MS data. The absolute configuration of 1 was determined by single crystal X-ray diffraction analysis and CD analysis. 3 showed inhibitory activity against HBsAg and HBeAg secretion with IC50 values of 23.0 and 23.1 μM, and cytotoxicity against HepG 2.2.15 cells with a CC50 value of 170.5 μM. 3 also exhibited inhibitory activity against HBV DNA replication with an IC50 value of 22.4 μM. PMID:24393620

  16. Hot-Fire Testing of a 1N AF-M315E Thruster

    NASA Technical Reports Server (NTRS)

    Burnside, Christopher G.; Pedersen, Kevin; Pierce, Charles W.

    2015-01-01

    This hot-fire test continues NASA investigation of green propellant technologies for future missions. To show the potential for green propellants to replace some hydrazine systems in future spacecraft, NASA Marshall Space Flight Center (MSFC) is continuing to embark on hot-fire test campaigns with various green propellant blends. NASA completed a hot-fire test of a 1N AF-M315E monopropellant thruster at the Marshall Space Flight Center in the small altitude test stand located in building 4205. The thruster is a ground test article used for basic performance determination and catalyst studies. The purpose of the hot-fire testing was for performance determination of a 1N size thruster and form a baseline from which to study catalyst performance and life with follow-on testing to be conducted at a later date. The thruster performed as expected. The result of the hot-fire testing are presented in this paper and presentation.

  17. [ANMCO/AIAC/SICI-GISE/SIC/SICCH Consensus document: Percutaneous left atrial appendage occlusion in patients with nonvalvular atrial fibrillation: indications, patient selection, competences, organization, and operator training].

    PubMed

    Casu, Gavino; Gulizia, Michele Massimo; Molon, Giulio; Mazzone, Patrizio; Audo, Andrea; Casolo, Giancarlo; Di Lorenzo, Emilio; Portoghese, Michele; Pristipino, Christian; Ricci, Renato Pietro; Themistoclakis, Sakis; Padeletti, Luigi; Tondo, Claudio; Berti, Sergio; Oreglia, Jacopo Andrea; Gerosa, Gino; Zanobini, Marco; Ussia, Gian Paolo; Musumeci, Giuseppe; Romeo, Francesco; Di Bartolomeo, Roberto

    2016-01-01

    Atrial fibrillation (AF) is the most common arrhythmia and its prevalence is increasing due to the progressive aging of the population. About 20% of strokes are attributable to AF and AF patients are at 5-fold increased risk of stroke. The mainstay of treatment of AF is the prevention of thromboembolic complications with oral anticoagulation therapy. Drug treatment for many years has been based on the use of vitamin K antagonists, but recently newer and safer molecules have been introduced (dabigatran etexilate, rivaroxaban, apixaban and edoxaban). Despite these advances, many patients still do not receive adequate anticoagulation therapy because of contraindications (relative and absolute) to this treatment. Over the last decade, percutaneous closure of left atrial appendage, main site of thrombus formation during AF, proved effective in reducing thromboembolic complications, thus offering a valid medical treatment especially in patients at increased bleeding risk. The aim of this consensus document is to review the main aspects of left atrial appendage occlusion (selection and multidisciplinary assessment of patients, currently available methods and devices, requirements for centers and operators, associated therapies and follow-up modalities) having as a ground the significant evolution of techniques and the available relevant clinical data. PMID:27571335

  18. AF printability check with a full-chip 3D resist profile model

    NASA Astrophysics Data System (ADS)

    Wu, Cheng-En R.; Chang, Jason; Song, Hua; Shiely, James

    2013-09-01

    A single compact resist model capable of predicting 3D resist profile is strongly demanded for the advanced technology nodes to avoid the potential hotspots due to imperfect resist pattern shape and its lack of resistance in the subsequent etch process. In this work, we propose a resist 3D (R3D) compact model that takes acidz-diffusion effect into account. The chemical reaction between acid and base along z-direction is treated as second order effect that is absorbed into the anisotropic diffusion length as a fitting parameter. Meanwhile, the resist model in the x-y wafer plane is still kept in general by applying the compact solution of 2D reaction-diffusion equation. In order to have the 2D contour predictability at arbitrary resist height, calibration from entire 3D data (CDs at several heights) areconducted simultaneously witha single cost function so that the R3D compact model is described by a common set of resist free parameters and threshold for all resist heights. With the low energy approximation, the acid z-diffusion effect is equivalent to a z-diffused TCC that takes the form of linear combination of pure optical TCCs sampled at discrete image-depth which can be pre-calculated. With this benefit, the R3D compact model offers a more physical approach but adds no runtime concern on the OPC and verification applications. The predicted resist cross-section profiles from our test patterns are compared those computed with rigorous lithography simulator SLITHO and show very good matching results between them. The demonstration of the AF printability check from the predicted cross-section profile at AF indicates the success of our R3D compact model.

  19. EACVI/EHRA Expert Consensus Document on the role of multi-modality imaging for the evaluation of patients with atrial fibrillation.

    PubMed

    Donal, Erwan; Lip, Gregory Y H; Galderisi, Maurizio; Goette, Andreas; Shah, Dipen; Marwan, Mohamed; Lederlin, Mathieu; Mondillo, Sergio; Edvardsen, Thor; Sitges, Marta; Grapsa, Julia; Garbi, Madalina; Senior, Roxy; Gimelli, Alessia; Potpara, Tatjana S; Van Gelder, Isabelle C; Gorenek, Bulent; Mabo, Philippe; Lancellotti, Patrizio; Kuck, Karl-Heinz; Popescu, Bogdan A; Hindricks, Gerhard; Habib, Gilbert; Cardim, Nuno M; Cosyns, Bernard; Delgado, Victoria; Haugaa, Kristina H; Muraru, Denisa; Nieman, Koen; Boriani, Giuseppe; Cohen, Ariel

    2016-04-01

    Atrial fibrillation (AF) is the commonest cardiac rhythm disorder. Evaluation of patients with AF requires an electrocardiogram, but imaging techniques should be considered for defining management and driving treatment. The present document is an expert consensus from the European Association of Cardiovascular Imaging (EACVI) and the European Heart Rhythm Association. The clinical value of echocardiography, cardiac magnetic resonance (CMR), computed tomography (CT), and nuclear imaging in AF patients are challenged. Left atrial (LA) volume and strain in echocardiography as well as assessment of LA fibrosis in CMR are discussed. The value of CT, especially in planning interventions, is highlighted. Fourteen consensus statements have been reached. These may serve as a guide for both imagers and electrophysiologists for best selecting the imaging technique and for best interpreting its results in AF patients. PMID:26864186

  20. Roles of two-component system AfsQ1/Q2 in regulating biosynthesis of the yellow-pigmented coelimycin P2 in Streptomyces coelicolor.

    PubMed

    Chen, Shuangshuang; Zheng, Guosong; Zhu, Hong; He, Huiqi; Chen, Lei; Zhang, Weiwen; Jiang, Weihong; Lu, Yinhua

    2016-08-01

    We previously demonstrated that in Streptomyces coelicolor two-component system AfsQ1/Q2 activates the production of the yellow-colored coelimycin P2 (also named as yCPK) on glutamate-supplemented minimal medium, and the response regulator AfsQ1 could specifically bind to the intergenic region between two structural genes, cpkA and cpkD Here, a more in-depth investigation was performed to elucidate the mechanism underlying the role of AfsQ1/Q2 in regulating coelimycin P2 biosynthesis. Deletion of afsQ1/Q2 resulted in markedly decreased expression of the whole coelimycin P2 biosynthetic gene cluster. Electrophoretic mobility shift assays revealed that AfsQ1 bound only to the target site identified previously, but not to any other promoters in the gene cluster. Mutations of AfsQ1-binding motif only resulted in drastically reduced transcription of the cpkA/B/C operon (encoding three type I polyketide synthases) and intriguingly, led to enhanced expression of some coelimcyin P2 genes, particularly accA1 and scF These results suggested the direct role of AfsQ1/Q2 in regulating coelimycin production, which is directly mediated by the structural genes, but not the cluster-situated regulatory genes, and also implied that other unknown mechanisms may be involved in AfsQ1/Q2-mediated regulation of coelimycin P2 biosynthesis. PMID:27313101

  1. 75 FR 9596 - Notice of Filing of a Pesticide Petition for Residues of a Aspergillus flavus AF36 on Corn Food...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-03

    ... From the Federal Register Online via the Government Publishing Office ENVIRONMENTAL PROTECTION AGENCY Notice of Filing of a Pesticide Petition for Residues of a Aspergillus flavus AF36 on Corn Food... residues of the antifungal ] agent, Aspergillus flavus AF36, in or on corn food and feed commodities....

  2. Clone-derived human AF-amniotic fluid stem cells are capable of skeletal myogenic differentiation in vitro and in vivo.

    PubMed

    Ma, Xiaorong; Zhang, Shengli; Zhou, Junmei; Chen, Baisong; Shang, Yafeng; Gao, Tongbing; Wang, Xue; Xie, Hua; Chen, Fang

    2012-08-01

    Stem cell-based therapy may be the most promising method to cure skeletal muscle degenerative diseases such as Duchenne muscular dystrophy (DMD) and trauma in the future. Human amniotic fluid is enriched with early-stage stem cells from developing fetuses and these cells have cardiomyogenic potential both in vitro and in vivo. In the present study, we investigated the characteristics of human amniotic fluid-derived AF-type stem (HAF-AFS) cells by flow cytometry, immunofluorescence staining, reverse-transcription polymerase chain reaction, and osteogenic and adipogenic differentiation analysis. After confirming the stemness of HAF-AFS cells, we tested whether HAF-AFS cells could differentiate into skeletal myogenic cells in vitro and incorporate into regenerating skeletal muscle in vivo. By temporary exposure to the DNA demethylation agent 5-aza-2'-deoxycytidine (5-Aza dC) or co-cultured with C2C12 myoblasts, HAF-AFS cells differentiated into skeletal myogenic cells, expressing skeletal myogenic cell-specific markers such as Desmin, Troponin I (Tn I) and α-Actinin. Four weeks after transplantation into cardiotoxin-injured and X-ray-irradiated tibialis anterior (TA) muscles of NOD/SCID mice, HAF-AFS cells survived, differentiated into myogenic precursor cells and fused with host myofibres. The findings that HAF-AFS cells differentiate into myogenic cells in vitro and incorporate in skeletal muscle regeneration in vivo hold the promise of HAF-AFS cell-based therapy for skeletal muscle degenerative diseases. PMID:22396316

  3. Evaluation of the Sustainability and Clinical Outcome of Alternatives for Families: A Cognitive-Behavioral Therapy (AF-CBT) in a Child Protection Center

    ERIC Educational Resources Information Center

    Kolko, David J.; Iselin, Anne-Marie R.; Gully, Kevin J.

    2011-01-01

    This paper examines the sustainability and outcome of Alternatives for Families: A Cognitive-Behavioral Therapy (AF-CBT) as delivered by practitioners in a community-based child protection program who had received training in the model several years earlier. Formerly described as Abuse-Focused CBT, AF-CBT is an evidence-based treatment (EBT) for…

  4. E1AF/PEA3 activates the Rho/Rho-associated kinase pathway to increase the malignancy potential of non-small-cell lung cancer cells.

    PubMed

    Hakuma, Nobuyuki; Kinoshita, Ichiro; Shimizu, Yasushi; Yamazaki, Koichi; Yoshida, Koichi; Nishimura, Masaharu; Dosaka-Akita, Hirotoshi

    2005-12-01

    E1AF/PEA3, an Ets family transcription factor, is frequently overexpressed in non-small-cell lung cancers (NSCLCs). Overexpression of E1AF increases motility and invasion of VMRC-LCD and NCI-H226 NSCLC cells, which lack endogenous E1AF expression, and the effect is synergistically increased by hepatocyte growth factor (HGF). The small GTPase Rho/Rho-associated kinase (ROCK) pathway is also involved in motility and invasion. To determine the role of the Rho/ROCK pathway in malignant phenotypes induced by E1AF, we analyzed VMRC-LCD cells transfected with an E1AF expression vector (LCD-E1AF cells) or with empty vector (LCD-vector cells). LCD-E1AF cells had more GTP-bound (active) Rho than LCD-vector cells and Rho activation was synergistically increased by HGF. The Rho activation by E1AF and HGF was also shown in NCI-H226 cells. Phosphorylation of myosin light chain (MLC), a downstream effector of ROCK signaling, was higher in LCD-E1AF cells than in LCD-vector cells, especially under HGF treatment. A specific ROCK inhibitor, Y27632, strongly suppressed MLC phosphorylation, cell motility, and invasion. In nude mice implanted s.c. and intrapulmonarily, LCD-E1AF cells made more local tumors than LCD-vector cells (six of six versus one of seven mice and four of seven versus one of seven mice, respectively). Three of the four mice with lung tumors from LCD-E1AF cells had lymph node metastases whereas the mouse with LCD-vector tumors did not. LCD-E1AF tumors showed higher MLC phosphorylation than LCD-vector tumors. These results suggest that E1AF activates the Rho/ROCK pathway in an HGF-enhanced manner and its activation is important in E1AF-induced motility and invasion as well as tumorigenesis and metastasis in NSCLC cells. PMID:16322223

  5. Characterization of extractable soil organic matter pools from African Dark Earths (AfDE): A case study in historical biochar and organic waste amendments

    NASA Astrophysics Data System (ADS)

    Fujiu, Manna; Plante, Alain; Ohno, Tsutomu; Solomon, Dawit; Lehmann, Johannes; Fraser, James; Leach, Melissa; Fairhead, James

    2014-05-01

    Anthropogenic Dark Earths are soils generated through long-term human inputs of organic and pyrogenic materials. These soils were originally discovered in the Amazon, and have since been found in Australia and in this case in Africa. African Dark Earths (AfDE) are black, highly fertile and carbon-rich soils that were formed from the original highly-weathered infertile yellowish to red Oxisols and Ultisols through an extant but hitherto overlooked climate-smart sustainable soil management system that has long been an important feature of the indigenous West African agricultural repertoire. Studies have demonstrated that ADE soils in general have significantly different organic matter properties compared to adjacent non-DE soils, largely attributable to the presence of high concentrations of ash-derived carbon. Quantification and characterization of bulk soil organic matter of several (n=11) AfDE and non-AfDE pairs of surface (0-15 cm) soils using thermal analysis techniques (TG-DSC-EGA) confirmed substantial differences in SOM composition and the presence of pyrogenic C. Such pyrogenic organic matter is generally considered recalcitrant or relatively stable, but the goal of the current study was to characterize the presumably labile, more rapidly cycling, pools of C in AfDEs through the characterization of hot water- and pyrophosphate-extractable fractions, referred to as HWEOC and PyroC respectively. Extracts were analyzed for carbon content, as well as composition using fluorescence (EEM/PARAFAC) and high resolution mass spectrometry (FTICR-MS). The amount of extractable C as a proportion of total soil C was relatively low: less than ~0.8% for HWEOC and 2.8% for PyroC. The proportion of HWEOC did not differ (P = 0.18, paired t-test) between the AfDE and the non-AfDE soils, while the proportions of PyroC were significantly larger (P = 0.001) in the AfDE soils compared to the non-AfDE soils. Preliminary analysis of the EEM/PARAFAC data suggests that AfDE samples had

  6. Old age, high risk medication, polypharmacy: a ‘trilogy’ of risks in older patients with atrial fibrillation

    PubMed Central

    2015-01-01

    Background: The safety of pharmacotherapy in atrial fibrillation (AF) is compounded by a trilogy of risks old age, high-risk medications (e.g., antithrombotics, antiarrhythmics), polypharmacy due to multiple patient comorbidities. However, to date, scarce study has investigated the use of polypharmacy (including potentially inappropriate medication (PIM)) in AF patients, and how this may contribute to their overall risk of medication misadventure. Objectives: To review the extent of polypharmacy and PIM use in older patients (65 years or older) with AF. Methods: Information was extracted from a database characterising a cohort of older AF patients treated in general practice in New South Wales, Australia. Patient characteristics, number and types of drugs, the degree of PIM use were recorded. The predictors for the use of polypharmacy in older AF patients were identified. Results: Overall, 367 patients (mean age 77.8 years) were reviewed, among which 94.8% used 5 medications or more and over half used 10 medications or more. Cardiovascular agents were most commonly used (98.9%), followed by antithrombotics (90.7%). Among agents deemed PIMs, digoxin (30.2%) was the most frequently used, followed by benzodiazepines (19.6%), and sotalol (9.8%). AF patients using polypharmacy were more likely to have low bleeding risk (OR=10.97), representing those patients in whom high-risk antithrombotics are mostly indicated. Patients with major-polypharmacy (5-9 medications) are more likely to have obstructive pulmonary diseases (OR=2.32), upper gastrointestinal diseases (OR=2.02) and poor physical function (OR=1.04), but less likely to have cognitive impairment (OR=0.27). Conclusion: Polypharmacy affects oldest AF patients, comprising medications that are indicated for AF, yet regarded as PIMs. Patients with lower risk of bleeding, obstructive pulmonary diseases, upper gastrointestinal diseases and poor physical function are also at higher risk of using higher number of

  7. European Society of Cardiology Guideline-Adherent Antithrombotic Treatment and Risk of Mortality in Asian Patients with Atrial Fibrillation.

    PubMed

    Li, Cheng-Hung; Liu, Chia-Jen; Chou, Annie Y; Chao, Tze-Fan; Tuan, Ta-Chuan; Chen, Su-Jung; Wang, Kang-Ling; Lin, Yenn-Jiang; Chang, Shih-Lin; Lo, Li-Wei; Hu, Yu-Feng; Chung, Fa-Po; Liao, Jo-Nan; Chen, Tzeng-Ji; Wu, Tsu-Juey; Chen, Shih-Ann

    2016-01-01

    This study compared the risk of mortality in atrial fibrillation (AF) patients treated adherent to the 2012 European Society of Cardiology (ESC) guidelines for stroke prevention and those who were not treated according to guideline recommendations. This study used the Taiwan National Health Insurance Research Database. From 1996 to 2011, 354,649 newly diagnosed AF patients were identified as the study population. Among the study cohort, 45,595 and 309,054 patients were defined as Guideline-Adherent and Non-Adherent groups, respectively. During the follow up of 1,480,280 person-years, 133,552 (37.7%) patients experienced mortality. The risk of mortality was lower among AF patients whose treatment was adherent to the guideline recommendation for stroke prevention than those whose treatment was not (annual risk of mortality = 4.3% versus 10.0%) with an adjusted hazard ratio of 0.62 (95% confidence interval = 0.61-0.64, p value < 0.001) after adjusting for age, gender, CHA2DS2-VASc score and antiplatelet therapy. The findings were consistently observed after propensity matching analysis. In conclusion, the risk of mortality was lower for AF patients who were treated according to the antithrombotic recommendations of the 2012 ESC guidelines, guided by the CHA2DS2-VASc score. Better efforts to implement guidelines would lead to improved outcomes for patients with AF. PMID:27498702

  8. European Society of Cardiology Guideline-Adherent Antithrombotic Treatment and Risk of Mortality in Asian Patients with Atrial Fibrillation

    PubMed Central

    Li, Cheng-Hung; Liu, Chia-Jen; Chou, Annie Y.; Chao, Tze-Fan; Tuan, Ta-Chuan; Chen, Su-Jung; Wang, Kang-Ling; Lin, Yenn-Jiang; Chang, Shih-Lin; Lo, Li-Wei; Hu, Yu-Feng; Chung, Fa-Po; Liao, Jo-Nan; Chen, Tzeng-Ji; Wu, Tsu-Juey; Chen, Shih-Ann

    2016-01-01

    This study compared the risk of mortality in atrial fibrillation (AF) patients treated adherent to the 2012 European Society of Cardiology (ESC) guidelines for stroke prevention and those who were not treated according to guideline recommendations. This study used the Taiwan National Health Insurance Research Database. From 1996 to 2011, 354,649 newly diagnosed AF patients were identified as the study population. Among the study cohort, 45,595 and 309,054 patients were defined as Guideline-Adherent and Non-Adherent groups, respectively. During the follow up of 1,480,280 person-years, 133,552 (37.7%) patients experienced mortality. The risk of mortality was lower among AF patients whose treatment was adherent to the guideline recommendation for stroke prevention than those whose treatment was not (annual risk of mortality = 4.3% versus 10.0%) with an adjusted hazard ratio of 0.62 (95% confidence interval = 0.61–0.64, p value < 0.001) after adjusting for age, gender, CHA2DS2-VASc score and antiplatelet therapy. The findings were consistently observed after propensity matching analysis. In conclusion, the risk of mortality was lower for AF patients who were treated according to the antithrombotic recommendations of the 2012 ESC guidelines, guided by the CHA2DS2-VASc score. Better efforts to implement guidelines would lead to improved outcomes for patients with AF. PMID:27498702

  9. Verbesinosides A-F, Novel 15,27-Cyclooleanane Saponins from the American Native Plant Verbesina virginica

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Verbesinosides A-F (1-6), six novel 15,27-cyclooleanane-type triterpenoid saponins carrying different aromatic acyl moieties on the aglycone, were isolated from the leaf and flower of Verbesina virginica. Their structures were established by interpretation of spectroscopic data and chemical methods....

  10. The Implementation of Collaborative Learning Using AfL through Giving Feedback Strategy for Improving Students’ Attention to Mathematics Lesson

    NASA Astrophysics Data System (ADS)

    Kurniasih, R.; Sujadi, I.; Pramesti, G.

    2016-02-01

    This research aims to describe the process of implementation collaborative learning with AfL through giving feedback strategy for improving students’ attention to mathematics lesson. Data which is collected in this research are students’ attention towards learning and students’ achievement. The result of this research showed that the learning steps by using collaborative learning with AfL through giving feedback strategy which can improve students’ attention are: 1) pre activity: the teacher delivers the purpose of the learning, successful criteria, apperception, and motivation. 2) main activity: the teacher gives the background of learning activity, explains learning materials at a glance, divides students discuss, the teacher observes and guides students to the problem solving, present their discussion result, gives feedback, the students do AfL problem and the answer is collected and result will be given before next meeting. 3) post activity: the teacher with students concludes the material. Test result, the percentage of students who complete the examination in the second cycle is 77.27%. Based on those results can be concluded that the implementation of collaborative learning using AfL through giving feedback can improve students’ attention towards learning and students’ achievement of XI IPA Students MA Al-Islam Jamsaren Surakarta academic year 2013/2014.

  11. Determining Aqueous Fullerene Particle Size Distributions by Asymmetric Flow Field-Flow Fractionation (AF4) without Surfactants

    EPA Science Inventory

    To determine the behavior of nanoparticles in environmental systems, methods must be developed to measure nanoparticle size. Asymmetric Flow Field Flow Fractionation (AF4) is an aqueous compatible size separation technique which is able to separate particles from 1 nm to 10 µm in...

  12. Ultrasound body composition traits response to an endotoxin challenge in Brahman heifers supplemented with Omnigen-AF

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study examined the effect of feeding OmniGen-AF (OG; Prince Agri Products) on the body composition traits response of newly-weaned heifers to an endotoxin (lipopolysaccharide; LPS) challenge. Brahman heifers (n=24; 183 ± 5 kg) from the Texas AgriLife Research Center in Overton, TX, were separat...

  13. Reworking Practice through an AfL Project: An Analysis of Teachers' Collaborative Engagement with New Assessment Guidelines

    ERIC Educational Resources Information Center

    Hermansen, Hege; Nerland, Monika

    2014-01-01

    In recent years, the concept of Assessment for Learning (AfL) has travelled across countries, giving rise to a range of educational policy initiatives and school development projects. While researchers have focused on issues such as how formative assessment can support student learning and lead to more efficient classroom practices, less attention…

  14. Context, Context, Context: New Gene Programs Linked to Bad Behavior in MLL-AF9-Initiated Leukemia.

    PubMed

    Watanabe, Tatsuro; Ernst, Patricia

    2016-07-11

    In this issue of Cancer Cell, Stavropoulou et al. report that expression of the MLL-AF9 fusion results in acute myelogenous leukemia (AML) with different behaviors depending on cell context, which leads them to identify a transcriptional signature surprisingly resembling that of the epithelial-to-mesenchymal (EMT) transition, correlating with aggressiveness of disease. PMID:27411579

  15. Effect of Carvedilol on Reduction in Heart Rate in Patients With Chronic Atrial Fibrillation

    PubMed Central

    Kodani, Eitaro; Matsumoto, Shin; Igawa, Osamu; Kusama, Yoshiki; Atarashi, Hirotsugu

    2013-01-01

    Background Currently, β-blockers are used most frequently for the purpose of heart rate (HR) control in patients with atrial fibrillation (AF) in worldwide. Carvedilol is one of common β-blockers and known to be effective for hypertension and heart failure. However, little can be found the information about the HR-lowering effect of carvedilol in patients with AF without heart failure. Therefore, we conducted this study to investigate the effect of carvedilol on HR in 3-minute electrocardiogram (ECG) and total heart beats (THBs) in 24-hour Holter ECG monitoring in patients with persistent or permanent AF. Methods A total of 13 hypertensive patients (73 ± 12 years, 7 males) with AF and HR 90 bpm or more were enrolled. All patients received carvedilol from 5 mg/day. The dose of drug was titrated every 4 weeks and raised to 10 or 20 mg/day if HR was 80 bpm or more. Results Mean HR was decreased from 101.9 ± 13.9 to 85.2 ± 15.2 bpm (P < 0.05) after treatment with carvedilol. THBs were also significantly decreased from 128 to 115 × 1,000/day (P < 0.001). Percent reduction in HR and THBs were 13.9% and 10.7%, respectively. The scores of Atrial Fibrillation Quality of Life Questionnaire (AFQLQ) did not change. Only one patient was required to discontinue carvedilol due to congestive heart failure. Conclusions We observed that carvedilol certainly reduced HR in patients with chronic AF. We believe that the effect of carvedilol on the reduction in HR can contribute to the management of AF patients treated with rate-control strategy. PMID:24171057

  16. QUest for the Arrhythmogenic Substrate of Atrial fibRillation in Patients Undergoing Cardiac Surgery (QUASAR Study): Rationale and Design.

    PubMed

    van der Does, Lisette J M E; Yaksh, Ameeta; Kik, Charles; Knops, Paul; Lanters, Eva A H; Teuwen, Christophe P; Oei, Frans B S; van de Woestijne, Pieter C; Bekkers, Jos A; Bogers, Ad J J C; Allessie, Maurits A; de Groot, Natasja M S

    2016-06-01

    The heterogeneous presentation and progression of atrial fibrillation (AF) implicate the existence of different pathophysiological processes. Individualized diagnosis and therapy of the arrhythmogenic substrate underlying AF may be required to improve treatment outcomes. Therefore, this single-center study aims to identify the arrhythmogenic areas underlying AF by intra-operative, high-resolution, multi-site epicardial mapping in 600 patients with different heart diseases. Participants are divided into 12 groups according to the underlying heart diseases and presence of prior AF episodes. Mapping is performed with a 192-electrode array for 5-10 s during sinus rhythm and (induced) AF of the entire atrial surface. Local activation times are converted into activation and wave maps from which various electrophysiological parameters are derived. Postoperative cardiac rhythm registrations and a 5-year follow-up will show the incidence of postoperative and persistent AF. This project provides the first step in the development of a tool for individual AF diagnosis and treatment. PMID:26935733

  17. Effect of bucindolol on heart failure outcomes and heart rate response in patients with reduced ejection fraction heart failure and atrial fibrillation

    PubMed Central

    Kao, David P.; Davis, Gordon; Aleong, Ryan; O'Connor, Christopher M.; Fiuzat, Mona; Carson, Peter E.; Anand, Inder S.; Plehn, Jonathan F.; Gottlieb, Stephen S.; Silver, Marc A.; Lindenfeld, JoAnn; Miller, Alan B.; White, Michel; Murphy, Guinevere A.; Sauer, Will; Bristow, Michael R.

    2013-01-01

    Aims There is little evidence of beta-blocker treatment benefit in patients with heart failure and reduced left ventricular ejection fraction (HFREF) and atrial fibrillation (AF). We investigated the effects of bucindolol in HFREF patients with AF enrolled in the Beta-blocker Evaluation of Survival Trial (BEST). Methods and results A post-hoc analysis of patients in BEST with and without AF was performed to estimate the effect of bucindolol on mortality and hospitalization. Patients were also evaluated for treatment effects on heart rate and the influence of beta1-adrenergic receptor position 389 (β1389) arginine (Arg) vs. glycine (Gly) genotypes. In the 303/2708 patients in AF, patients receiving bucindolol were more likely to achieve a resting heart rate ≤80 b.p.m. at 3 months (P < 0.005) in the absence of treatment-limiting bradycardia. In AF patients and sinus rhythm (SR) patients who achieved a resting heart rate ≤80 b.p.m., there were beneficial treatment effects on cardiovascular mortality/cardiovascular hospitalization [hazard ratio (HR) 0.61, P = 0.025, and 0.79, P = 0.002]. Without achieving a resting heart rate ≤80 b.p.m., there were no treatment effects on events in either group. β1389-Arg/Arg AF patients had nominally significant reductions in all-cause mortality/HF hospitalization and cardiovascular mortality/hospitalization with bucindolol (HR 0.23, P = 0.037 and 0.28, P = 0.039), whereas Gly carriers did not. There was no evidence of diminished heart rate response in β1389-Arg homozygotes. Conclusion In HFREF patients with AF, bucindolol was associated with reductions in composite HF endpoints in those who achieved a resting heart rate ≤80 b.p.m. and nominally in those with the β1389-Arg homozygous genotype. PMID:23223178

  18. Phosphorylation of the AfsR product, a global regulatory protein for secondary-metabolite formation in Streptomyces coelicolor A3(2).

    PubMed Central

    Hong, S K; Kito, M; Beppu, T; Horinouchi, S

    1991-01-01

    The AfsR protein is essential for the biosynthesis at the wild-type level of A-factor, actinorhodin, and undecylprodigiosin in Streptomyces coelicolor A3(2) and Streptomyces lividans. Because overexpression of the afsR gene caused some deleterious effect on these strains, a multicopy plasmid carrying the whole afsR gene was introduced into Streptomyces griseus, from which a crude cell lysate was prepared as a protein source. The AfsR protein was purified to homogeneity from the cytoplasmic fraction through several steps of chromatography, including affinity column chromatography with ATP-agarose and use of anti-AfsR antibody for its detection. The molecular weight of AfsR was estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by gel filtration to be 105,300, which is in good agreement with that deduced from the nucleotide sequence of afsR. The purified AfsR protein was found to be phosphorylated through the transfer of the gamma-phosphate group of ATP in the presence of the cell extracts of S. coelicolor A3(2) and S. lividans. This phosphorylation proceeded very rapidly, and no competition was observed with CTP, GTP, UTP, or cyclic AMP. In the cell extract of S. griseus, no activity phosphorylating the AfsR protein was detected, suggesting that this activity is not generally present in Streptomyces spp. but is specific to certain species. It is conceivable that the extent of phosphorylation of the AfsR protein modulates its regulatory activity which, in turn, regulates expression of some target gene(s) involved in the secondary-metabolite formation in S. coelicolor A3(2). Images PMID:2007554

  19. Impact of Additional Transthoracic Electrical Cardioversion on Cardiac Function and Atrial Fibrillation Recurrence in Patients with Persistent Atrial Fibrillation Who Underwent Radiofrequency Catheter Ablation

    PubMed Central

    Wang, Deguo; Zhang, Fengxiang; Wang, Ancai

    2016-01-01

    Backgrounds and Objective. During the procession of radiofrequency catheter ablation (RFCA) in persistent atrial fibrillation (AF), transthoracic electrical cardioversion (ECV) is required to terminate AF. The purpose of this study was to determine the impact of additional ECV on cardiac function and recurrence of AF. Methods and Results. Persistent AF patients received extensive encircling pulmonary vein isolation (PVI) and additional line ablation. Patients were divided into two groups based on whether they need transthoracic electrical cardioversion to terminate AF: electrical cardioversion (ECV group) and nonelectrical cardioversion (NECV group). Among 111 subjects, 35 patients were returned to sinus rhythm after ablation by ECV (ECV group) and 76 patients had AF termination after the ablation processions (NECV group). During the 12-month follow-ups, the recurrence ratio of patients was comparable in ECV group (15/35) and NECV group (34/76) (44.14% versus 44.74%, P = 0.853). Although left atrial diameters (LAD) decreased significantly in both groups, there were no significant differences in LAD and left ventricular cardiac function between ECV group and NECV group. Conclusions. This study revealed that ECV has no significant impact on the maintenance of SR and the recovery of cardiac function. Therefore, ECV could be applied safely to recover SR during the procedure of catheter ablation of persistent atrial fibrillation. PMID:27022500

  20. Common data model for natural language processing based on two existing standard information models: CDA+GrAF.

    PubMed

    Meystre, Stéphane M; Lee, Sanghoon; Jung, Chai Young; Chevrier, Raphaël D

    2012-08-01

    An increasing need for collaboration and resources sharing in the Natural Language Processing (NLP) research and development community motivates efforts to create and share a common data model and a common terminology for all information annotated and extracted from clinical text. We have combined two existing standards: the HL7 Clinical Document Architecture (CDA), and the ISO Graph Annotation Format (GrAF; in development), to develop such a data model entitled "CDA+GrAF". We experimented with several methods to combine these existing standards, and eventually selected a method wrapping separate CDA and GrAF parts in a common standoff annotation (i.e., separate from the annotated text) XML document. Two use cases, clinical document sections, and the 2010 i2b2/VA NLP Challenge (i.e., problems, tests, and treatments, with their assertions and relations), were used to create examples of such standoff annotation documents, and were successfully validated with the XML schemata provided with both standards. We developed a tool to automatically translate annotation documents from the 2010 i2b2/VA NLP Challenge format to GrAF, and automatically generated 50 annotation documents using this tool, all successfully validated. Finally, we adapted the XSL stylesheet provided with HL7 CDA to allow viewing annotation XML documents in a web browser, and plan to adapt existing tools for translating annotation documents between CDA+GrAF and the UIMA and GATE frameworks. This common data model may ease directly comparing NLP tools and applications, combining their output, transforming and "translating" annotations between different NLP applications, and eventually "plug-and-play" of different modules in NLP applications. PMID:22197801

  1. Unraveling the Activation Mechanism of Taspase1 which Controls the Oncogenic AF4–MLL Fusion Protein

    PubMed Central

    Sabiani, Samaneh; Geppert, Tim; Engelbrecht, Christian; Kowarz, Eric; Schneider, Gisbert; Marschalek, Rolf

    2015-01-01

    We have recently demonstrated that Taspase1-mediated cleavage of the AF4–MLL oncoprotein results in the formation of a stable multiprotein complex which forms the key event for the onset of acute proB leukemia in mice. Therefore, Taspase1 represents a conditional oncoprotein in the context of t(4;11) leukemia. In this report, we used site-directed mutagenesis to unravel the molecular events by which Taspase1 becomes sequentially activated. Monomeric pro-enzymes form dimers which are autocatalytically processed into the enzymatically active form of Taspase1 (αββα). The active enzyme cleaves only very few target proteins, e.g., MLL, MLL4 and TFIIA at their corresponding consensus cleavage sites (CSTasp1) as well as AF4–MLL in the case of leukemogenic translocation. This knowledge was translated into the design of a dominant-negative mutant of Taspase1 (dnTASP1). As expected, simultaneous expression of the leukemogenic AF4–MLL and dnTASP1 causes the disappearance of the leukemogenic oncoprotein, because the uncleaved AF4–MLL protein (328 kDa) is subject to proteasomal degradation, while the cleaved AF4–MLL forms a stable oncogenic multi-protein complex with a very long half-life. Moreover, coexpression of dnTASP1 with a BFP-CSTasp1-GFP FRET biosensor effectively inhibits cleavage. The impact of our findings on future drug development and potential treatment options for t(4;11) leukemia will be discussed. PMID:26137584

  2. Proarrhythmic and Torsadogenic Effects of Potassium Channel Blockers in Patients.

    PubMed

    McCauley, Mark; Vallabhajosyula, Sharath; Darbar, Dawood

    2016-06-01

    The most common arrhythmia requiring drug treatment is atrial fibrillation (AF), which affects 2 to 5 million Americans and continues to be a major cause of morbidity and increased mortality. Despite recent advances in catheter-based and surgical therapies, antiarrhythmic drugs continue to be the mainstay of therapy for most patients with symptomatic AF. However, many antiarrhythmics block the rapid component of the cardiac delayed rectifier potassium current (IKr) as a major mechanism of action, and marked QT prolongation and pause-dependent polymorphic ventricular tachycardia (torsades de pointes) are major class toxicities. PMID:27261836

  3. Use of Anticoagulant Warfarin in Patients Presenting With Atrial Fibrillation in a Tertiary Level Hospital.

    PubMed

    Islam, M S; Islam, M A; Azad, A K; Banerjee, S K; Ahmed, C M; Haque, H; Ahmed, M K; Rumki, R S; Mahmood, M; Rashid, F B

    2016-07-01

    Atrial fibrillation (AF) is the most common sustained arrhythmia in the World, occurring in approximately 0.4% of the general population. The purpose of the present study was to see the trend of use of warfarin in hospital admitted patients with atrial fibrillation. It was conducted in the department of cardiology, University Cardiac Centre, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh from January 2008 to January 2009. A total of 150 patients with atrial fibrillation were enrolled in this study. Out of them, male were 60(40%) and female 90(60%); age range 22-79 years. Most common presenting symptoms were palpitation (80%) & dyspnoea (70%). Chronic rheumatic heart disease (Mitral stenosis) (33%) was found in most cases followed by IHD (22%), hypertension (21%). According to CHADS₂ score, most of the patients belonged to moderate risk group (47%) and 32% in low risk group. Anticoagulation with warfarin was used in 40% cases of valvular AF & 25% patients with non valvular AF. Among non valvular AF, it was prescribed for 38% in high risk group, 34% in moderate risk & 3% in low risk group. The study states that warfarin is underused in both valvular & non valvular AF. PMID:27612901

  4. Real-world characteristics of hospitalized frail elderly patients with atrial fibrillation: can we improve the current prescription of anticoagulants?

    PubMed Central

    Annoni, Giorgio; Mazzola, Paolo

    2016-01-01

    Background In elderly patients, especially those older than 80 years, atrial fibrillation (AF) is associated with an almost 25% increased risk of stroke. Stroke prophylaxis with anticoagulants is therefore highly recommended. The prevalence of factors that have been associated with a lower rate of prescription and adherence to anticoagulant therapy in these patients is little known. The objective of this study was to explore the clinical characteristics of elderly subjects, with and without AF, consecutively admitted to an acute geriatric unit, discussing factors that may decrease the persistence on stroke prophylaxis therapy. We also highlight possible strategies to overcome the barriers conditioning the current underuse of oral anticoagulants in this segment of the population. Methods A retrospective observational study was performed on a cohort of elderly patients with and without AF admitted to the Acute Geriatric Unit of San Gerardo Hospital (Monza, Italy). Results Compared to patients without AF (n = 1216), those with AF (n = 403) had a higher Charlson Comorbidity Index (3 vs. 2, P < 0.001), number of administered drugs (4 vs. 3, P < 0.001), rate of heart failure (36.5% vs. 12%, P < 0.001) and chronic kidney disease (20.6 vs. 13.2, P < 0.001). Many patients with AF were frail (54%) or pre-frail (29%). Conclusions Elderly patients with AF have higher rates of conditions that affect adherence to traditional anticoagulant therapy (vitamin K antagonists, VKA). New direct oral anticoagulants (DOAs) can help overcome this problem. In order to prescribe the most appropriate VKA or DOAs, with the best efficacy/safety profile and the highest compliance, a comprehensive geriatric assessment should always accompany the scores for thrombotic and hemorrhagic risk stratification. PMID:27103917

  5. Calpain-Calcineurin-Nuclear Factor Signaling and the Development of Atrial Fibrillation in Patients with Valvular Heart Disease and Diabetes

    PubMed Central

    Zhao, Yong; Cui, Guo-ming; Zhou, Nan-nan; Li, Cong; Zhang, Qing; Sun, Hui; Han, Bo; Zou, Cheng-wei; Wang, Li-juan; Li, Xiao-dong; Wang, Jian-chun

    2016-01-01

    Calpain, calcineurin (CaN), and nuclear factor of activated T cell (NFAT) play a key role in the development of atrial fibrillation. Patients with valvular heart disease (VHD) are prone to develop atrial fibrillation (AF). Thus, our current study was aimed at investigating whether activation of calpain-CaN-NFAT pathway is associated with the incidence of AF in the patients with VHD and diabetes. The expressions of calpain 2 and alpha- and beta-isoforms of CaN catalytic subunit (CnA) as well as NFAT-c3 and NFAT-c4 were quantified by quantitative reverse transcription-polymerase chain reaction in atrial tissues from 77 hospitalized patients with VHD and diabetes. The relevant protein content was measured by Western blot and calpain 2 in human atrium was localized by immunohistochemistry. We found that the expressions of calpain 2, CnA alpha and CnA beta, and NFAT-c3 but not NFAT-c4 were significantly elevated in the samples from patients with AF compared to those with sinus rhythm (SR). Elevated protein levels of calpain 2 and CnA were observed in patients with AF, and so was the enhanced localization of calpain 2. We thereby concluded that CaN together with its upstream molecule, calpain 2, and its downstream effector, NFAT-c3, might contribute to the development of AF in patients with VHD and diabetes. PMID:27123462

  6. Usefulness of New-Onset Atrial Fibrillation, as a Strong Predictor of Heart Failure and Death in Patients With Native Left-Sided Infective Endocarditis.

    PubMed

    Ferrera, Carlos; Vilacosta, Isidre; Fernández, Cristina; López, Javier; Sarriá, Cristina; Olmos, Carmen; Vivas, David; Sáez, Carmen; Sánchez-Enrique, Cristina; Ortiz-Bautista, Carlos; San Román, José Alberto

    2016-02-01

    Atrial fibrillation (AF) is the most common cardiac arrhythmia in adults and has been independently related to increased morbidity and mortality. AF is a frequent arrhythmia in infective endocarditis (IE). Nevertheless, there are no data on how AF affects the clinical outcome of patients with endocarditis. Our purpose was to investigate patient characteristics, microbiology, echocardiographic findings, in-hospital course, and prognosis of patients with IE who develop new-onset AF (NAF) and compare them with those who remained in sinus rhythm (SR) or had previous AF (PAF). From 1997 to 2014, 507 consecutive patients with native left-sided IE were prospectively recruited at 3 tertiary care centers. We distinguished 3 groups according to the type of baseline heart rhythm during hospitalization and previous history of AF: NAF group (n = 52), patients with no previous history of AF and who were diagnosed as having NAF during hospitalization; SR group (n = 380), patients who remained in SR; and PAF group (n = 75), patients with PAF. Patients with NAF were older than those who remained in SR (68.3 vs 59.6 years, p <0.001). At admission, heart failure was more common in NAF group (53% vs 34.3%, p <0.001), whereas stroke (p = 0.427) was equally frequent in all groups. During hospitalization, embolic events occurred similarly (p = 0.411). In the multivariate analysis, NAF was independently associated with heart failure (odds ratio 3.56, p <0.01) and mortality (odds ratio 1.91, p = 0.04). In conclusion, the occurrence of NAF in patients with IE was strongly associated with heart failure and higher in-hospital mortality independently from other relevant clinical variables. PMID:26762724

  7. The Problem of Atrial Fibrillation in Patients with Chronic Kidney Disease.

    PubMed

    Franczyk, Beata; Gluba-Brzózka, Anna; Ciałkowska-Rysz, Aleksandra; Banach, Maciej; Rysz, Jacek

    2016-01-01

    Chronic kidney disease (CKD) is associated with the risk of multiple life-threatening complications such as: progression to chronic renal failure and cardiovascular disease including coronary heart disease, heart failure and peripheral arterial disease. Also, atrial fibrillation (AF) is common in this group of patients. Factors contributing to the occurrence of AF in patients undergoing dialysis include: age, presence of coronary heart disease, echocardiographic abnormalities (low ejection fraction, atrial enlargement, valvular calcification, left ventricular hypertrophy), heart failure, chronic obstructive pulmonary disease, hypertension, stroke, malnutrition (low levels of albumin, total cholesterol and high-density lipoprotein (HDL), secondary hyperparathyroidism, low predialysis systolic blood pressure, duration of renal replacement therapy as well as the method of renal replacement therapy (more frequent in haemodialysis patients). The optimal management of thromboprophylaxis in patients with CKD and AF is complex due to the fact that in patients with CKD many physiologic mechanisms are altered which lead to substantial changes in haemostasis and thus this group of patients is characterized by an increased risk of thrombotic and haemorrhagic complications. Recommendations concerning the treatment of patients with AF do not include guidelines on how to manage patients with advanced CKD, due to the lack of large randomized trials assessing the efficacy and benefits of drugs in these patients. Patients with CKD and permanent, persistent, and paroxysmal AF ought to be treated as a group with high risk of bleeding and ischaemic stroke. In case of patients with no or only one moderate risk factors, it seems that anticoagulation with antiplatelet drugs can be considered as efficient therapy, while in patients with ≥2 risk factors an oral anticoagulation therapy may be used. During long-term treatment, the international normalized ratio (INR) must be controlled at

  8. Doppler images and the underlying dynamo. The case of AF Leporis

    NASA Astrophysics Data System (ADS)

    Järvinen, S. P.; Arlt, R.; Hackman, T.; Marsden, S. C.; Küker, M.; Ilyin, I. V.; Berdyugina, S. V.; Strassmeier, K. G.; Waite, I. A.

    2015-02-01

    Context. The (Zeeman-)Doppler imaging studies of solar-type stars very often reveal large high-latitude spots. This also includes F stars that possess relatively shallow convection zones, indicating that the dynamo operating in these stars differs from the solar dynamo. Aims: We aim to determine whether mean-field dynamo models of late-F type dwarf stars can reproduce the surface features recovered in Doppler maps. In particular, we wish to test whether the models can reproduce the high-latitude spots observed on some F dwarfs. Methods: The photometric inversions and the surface temperature maps of AF Lep were obtained using the Occamian-approach inversion technique. Low signal-to-noise spectroscopic data were improved by applying the least-squares deconvolution method. The locations of strong magnetic flux in the stellar tachocline as well as the surface fields obtained from mean-field dynamo solutions were compared with the observed surface temperature maps. Results: The photometric record of AF Lep reveals both long- and short-term variability. However, the current data set is too short for cycle-length estimates. From the photometry, we have determined the rotation period of the star to be 0.9660 ± 0.0023 days. The surface temperature maps show a dominant, but evolving, high-latitude (around +65°) spot. Detailed study of the photometry reveals that sometimes the spot coverage varies only marginally over a long time, and at other times it varies rapidly. Of a suite of dynamo models, the model with a radiative interior rotating as fast as the convection zone at the equator delivered the highest compatibility with the obtained Doppler images. Partially based on observations made with the Nordic Optical Telescope, operated by the Nordic Optical Telescope Scientific Association at the Observatorio del Roque de los Muchachos, La Palma, Spain, of the Instituto de Astrofísica de Canarias.Based partly on STELLA SES data.Tables 1-3 and Figs. 7-14 are available in

  9. Antisecretory Factor Peptide AF-16 Inhibits the Secreted Autotransporter Toxin-Stimulated Transcellular and Paracellular Passages of Fluid in Cultured Human Enterocyte-Like Cells

    PubMed Central

    Nicolas, Valérie

    2014-01-01

    Both the endogenous antisecretory factor (AF) protein and peptide AF-16, which has a sequence that matches that of the active N-terminal region of AF, inhibit the increase in the epithelial transport of fluid and electrolytes induced by bacterial toxins in animal and ex vivo models. We conducted a study to investigate the inhibitory effect of peptide AF-16 against the increase of transcellular passage and paracellular permeability promoted by the secreted autotransporter toxin (Sat) in a cultured cellular model of the human intestinal epithelial barrier. Peptide AF-16 produced a concentration-dependent inhibition of the Sat-induced increase in the formation of fluid domes, in the mucosal-to-serosal passage of d-[1-14C]mannitol, and in the rearrangements in the distribution and protein expression of the tight junction (TJ)-associated proteins ZO-1 and occludin in cultured human enterocyte-like Caco-2/TC7 cell monolayers. In addition, we show that peptide AF-16 also inhibits the cholera toxin-induced increase of transcellular passage and the Clostridium difficile toxin-induced effects on paracellular permeability and TJ protein organization in Caco-2/TC7 cell monolayers. Treatment of cell monolayers by the lipid raft disorganizer methyl-β-cyclodextrin abolished the inhibitory activity of peptide AF-16 at the transcellular passage level and did not modify the effect of the peptide at the paracellular level. PMID:25534938

  10. Antisecretory factor peptide AF-16 inhibits the secreted autotransporter toxin-stimulated transcellular and paracellular passages of fluid in cultured human enterocyte-like cells.

    PubMed

    Nicolas, Valérie; Liévin-Le Moal, Vanessa

    2015-03-01

    Both the endogenous antisecretory factor (AF) protein and peptide AF-16, which has a sequence that matches that of the active N-terminal region of AF, inhibit the increase in the epithelial transport of fluid and electrolytes induced by bacterial toxins in animal and ex vivo models. We conducted a study to investigate the inhibitory effect of peptide AF-16 against the increase of transcellular passage and paracellular permeability promoted by the secreted autotransporter toxin (Sat) in a cultured cellular model of the human intestinal epithelial barrier. Peptide AF-16 produced a concentration-dependent inhibition of the Sat-induced increase in the formation of fluid domes, in the mucosal-to-serosal passage of D-[1-(14)C]mannitol, and in the rearrangements in the distribution and protein expression of the tight junction (TJ)-associated proteins ZO-1 and occludin in cultured human enterocyte-like Caco-2/TC7 cell monolayers. In addition, we show that peptide AF-16 also inhibits the cholera toxin-induced increase of transcellular passage and the Clostridium difficile toxin-induced effects on paracellular permeability and TJ protein organization in Caco-2/TC7 cell monolayers. Treatment of cell monolayers by the lipid raft disorganizer methyl-β-cyclodextrin abolished the inhibitory activity of peptide AF-16 at the transcellular passage level and did not modify the effect of the peptide at the paracellular level. PMID:25534938

  11. Flavonoid-enriched apple fraction AF4 induces cell cycle arrest, DNA topoisomerase II inhibition, and apoptosis in human liver cancer HepG2 cells.

    PubMed

    Sudan, Sudhanshu; Rupasinghe, H P Vasantha

    2014-01-01

    Apples are a major source of dietary phytochemicals such as flavonoids in the Western diet. Here we report anticancer properties and possible mechanism of action of apple flavonoid-enriched fraction (AF4) isolated from the peels of Northern Spy apples in human hepatocellular carcinoma cells, HepG2. Treatment with AF4 induced cell growth inhibition in HepG2 cells in time- and dose-dependent manner. Concentration of 50 μg/ml (50 μg total monomeric polyphenols/ml) AF4 was sufficient to induce a significant reduction in cell viability within 6 h of treatment (92%, P < 0.05) but had very low toxicity (minimum 4% to maximum 16%) on primary liver and lung cells, which was significantly lower than currently prescribed chemotherapy drug Sorafenib (minimum 29% to maximum 49%, P < 0.05). AF4 induced apoptosis in HepG2 cells within 6 h of treatment via activation of caspase-3. Cell cycle analysis via flow-cytometer showed that AF4 induced G2/M phase arrest. Further, results showed that AF4 acts as a strong DNA topoisomerase II catalytic inhibitor, which may be a plausible reason to drive the cells to apoptosis. Overall, our data suggests that AF4 possesses a significantly stronger antiproliferative and specific action than Sorafenib in vitro and is a potential natural chemotherapy agent for treatment of liver cancer. PMID:25256427

  12. U2AF65 adapts to diverse pre-mRNA splice sites through conformational selection of specific and promiscuous RNA recognition motifs.

    PubMed

    Jenkins, Jermaine L; Agrawal, Anant A; Gupta, Ankit; Green, Michael R; Kielkopf, Clara L

    2013-04-01

    Degenerate splice site sequences mark the intron boundaries of pre-mRNA transcripts in multicellular eukaryotes. The essential pre-mRNA splicing factor U2AF(65) is faced with the paradoxical tasks of accurately targeting polypyrimidine (Py) tracts preceding 3' splice sites while adapting to both cytidine and uridine nucleotides with nearly equivalent frequencies. To understand how U2AF(65) recognizes degenerate Py tracts, we determined six crystal structures of human U2AF(65) bound to cytidine-containing Py tracts. As deoxy-ribose backbones were required for co-crystallization with these Py tracts, we also determined two baseline structures of U2AF(65) bound to the deoxy-uridine counterparts and compared the original, RNA-bound structure. Local structural changes suggest that the N-terminal RNA recognition motif 1 (RRM1) is more promiscuous for cytosine-containing Py tracts than the C-terminal RRM2. These structural differences between the RRMs were reinforced by the specificities of wild-type and site-directed mutant U2AF(65) for region-dependent cytosine- and uracil-containing RNA sites. Small-angle X-ray scattering analyses further demonstrated that Py tract variations select distinct inter-RRM spacings from a pre-existing ensemble of U2AF(65) conformations. Our results highlight both local and global conformational selection as a means for universal 3' splice site recognition by U2AF(65). PMID:23376934

  13. Prevalence and Spectrum of TBX5 Mutation in Patients with Lone Atrial Fibrillation

    PubMed Central

    Wang, Zhan-Cheng; Ji, Wen-Hui; Ruan, Chang-Wu; Liu, Xing-Yuan; Qiu, Xing-Biao; Yuan, Fang; Li, Ruo-Gu; Xu, Ying-Jia; Liu, Xu; Huang, Ru-Tai; Xue, Song; Yang, Yi-Qing

    2016-01-01

    Atrial fibrillation (AF), the most common type of cardiac rhythm disturbance encountered in clinical practice, is associated with substantially increased morbidity and mortality. Aggregating evidence demonstrates that abnormal cardiovascular development is involved in the pathogenesis of AF. A recent study has revealed that the TBX5 gene, which encodes a T-box transcription factor key to cardiovascular development, was associated with AF and atypical Holt-Oram syndrome. However, the prevalence and spectrum of TBX5 mutation in patients with lone AF remain unclear. In this study, the coding regions and splicing junction sites of TBX5 were sequenced in 192 unrelated patients with lone AF and 300 unrelated ethnically-matched healthy individuals used as controls. The causative potential of the identified TBX5 variation was evaluated by MutationTaster and PolyPhen-2. The functional effect of the mutant TBX5 was assayed by using a dual-luciferase reporter assay system. As a result, a novel heterozygous TBX5 mutation, p.H170D, was identified in a patient, with a mutational prevalence of approximately 0.52%. This mutation, which was absent in the 300 control individuals, altered the amino acid completely conserved evolutionarily across species, and was predicted to be disease-causing. Functional deciphers showed that the mutant TBX5 was associated with significantly reduced transcriptional activity when compared with its wild-type counterpart. Furthermore, the mutation significantly decreased the synergistic activation between TBX5 and NKX2-5 or GATA4. The findings expand the mutational spectrum of TBX5 linked to AF and provide new evidence that dysfunctional TBX5 may contribute to lone AF. PMID:26917986

  14. Prospective observational studies of the management and outcomes in patients with atrial fibrillation: A systematic review

    PubMed Central

    Hersi, Ahmad S.; Alsheikh-Ali, Alawi A.; Zubaid, Mohammad; Al Suwaidi, Jassim

    2012-01-01

    Background Atrial fibrillation (AF) is a major global public health problem. Observational studies are necessary to understand patient characteristics, management, and outcomes of this common arrhythmia. Accordingly, our objective was to describe the current status of published prospective observational studies of AF. Methods and results MEDLINE and EMBASE (to June 2012) and reference lists of eligible studies were searched for English-language prospective observational registries of AF (n ⩾ 100 and follow-up ⩾6 months). Two reviewers independently extracted data. Disagreements were resolved by consensus. Eight prospective studies enrolled a total of 17,924 patients with AF (total 41,306 patient-years of exposure; follow-up 11 months to 9.9 years). The majority of subjects were enrolled in Europe (74%) or North America (21%), and 0.3% had rheumatic AF. The most consistently reported comorbidities were diabetes mellitus (range 5–18%), hypertension (39–68%), heart failure (5–58%), and prior stroke (4–17%). Three studies did not report all the variables necessary to calculate the currently recommended stroke risk assessment score, and no study reported all the variables required to calculate a recently validated bleeding risk score. The most consistently reported management features were oral anticoagulation (32–64%) and aspirin (28–61%) use. Calcium channel blockers were less frequently used than other rate controlling agents, and digoxin was most common in the single study from Africa (63%). Total mortality was reported in all studies, while data on stroke/systemic embolism, hospitalizations, and major hemorrhage rates were not always reported. Conclusions Current literature on real-world management of AF is relatively limited with inadequate data to allow detailed comparisons among reports. Data on rheumatic AF and from Africa and the developing world in general are sparse. PMID:24174832

  15. Dot1a-AF9 Complex Mediates Histone H3 Lys-79 Hypermethylation and Repression of ENaCα in an Aldosterone-sensitive Manner*

    PubMed Central

    Zhang, Wenzheng; Xia, Xuefeng; Reisenauer, Mary Rose; Hemenway, Charles S.; Kone, Bruce C.

    2010-01-01

    Aldosterone is a major regulator of epithelial Na+ absorption and acts in large part through induction of the epithelial Na+ channel (ENaC) gene in the renal collecting duct. We previously identified Dot1a as an aldosterone early repressed gene and a repressor of ENaCα transcription through mediating histone H3 Lys-79 methylation associated with the ENaCα promoter. Here, we report a novel aldosterone-signaling network involving AF9, Dot1a, and ENaCα. AF9 and Dot1a interact in vitro and in vivo as evidenced in multiple assays and colocalize in the nuclei of mIMCD3 renal collecting duct cells. Overexpression of AF9 results in hypermethylation of histone H3 Lys-79 at the endogenous ENaCα promoter at most, but not all subregions examined, repression of endogenous ENaCα mRNA expression and acts synergistically with Dot1a to inhibit ENaCα promoter-luciferase constructs. In contrast, RNA interference-mediated knockdown of AF9 causes the opposite effects. Chromatin immunoprecipitation assays reveal that overexpressed FLAG-AF9, endogenous AF9, and Dot1a are each associated with the ENaCα promoter. Aldosterone negatively regulates AF9 expression at both mRNA and protein levels. Thus, Dot1a-AF9 modulates histone H3 Lys-79 methylation at the ENaCα promoter and represses ENaCα transcription in an aldosterone-sensitive manner. This mechanism appears to be more broadly applicable to other aldosterone-regulated genes because overexpression of AF9 alone or in combination with Dot1a inhibited mRNA levels of three other known aldosterone-inducible genes in mIMCD3 cells. PMID:16636056

  16. Allogeneic stem cell transplantation improves the outcome of adults with t(1;19)/E2A-PBX1 and t(4;11)/MLL-AF4 positive B-cell acute lymphoblastic leukemia: results of the prospective multicenter LALA-94 study.

    PubMed

    Vey, N; Thomas, X; Picard, C; Kovascovicz, T; Charin, C; Cayuela, J M; Dombret, H; Dastugue, N; Huguet, F; Bastard, C; Stamatoulas, A; Giollant, M; Tournilhac, O; Macintyre, E; Buzyn, A; Bories, D; Kuentz, M; Dreyfus, F; Delannoy, A; Raynaud, S; Gratecos, N; Bordessoule, D; de Botton, S; Preudhomme, C; Reman, O; Troussard, X; Pigneux, A; Bilhou, C; Vernant, J P; Boucheix, C; Gabert, J

    2006-12-01

    Adult patients with acute lymphoblastic leukemia (ALL) and t(1;19)/E2A-PBX1 or t(4;11)/MLL-AF4 have a poor outcome. We have evaluated the impact of an intensified post-remission therapy using a high-dose chemotherapy course followed by allogeneic or autologous SCT on the outcome of 58 patients with t(1;19)/E2A-PBX1 (E2A group, n=24) or t(4;11)/MLL-AF4 (MLL group, n=34) treated in the LALA-94 multicenter prospective study. Patients in the MLL group had higher WBC counts and more frequent DIC. CR rates achieved by MLL and E2A groups were similar to other B-cell ALL (87, 82 and 86% respectively). While in CR, patients with a donor were assigned to alloSCT (n=22), the remaining patients with were randomized between autoSCT (n=15) or chemotherapy (n=8). Five-year overall survival was 31 and 45% for E2A and MLL groups, respectively. In both groups, DFS was higher in the alloSCT arm as compared to autoSCT and chemotherapy arms. The results of this study show that chemotherapy intensification did not overcome the poor prognosis of adults with t(1;19)/E2A-PBX1. Allogeneic SCT should thus be offered in first CR to patients with t(1;19)/E2A-PBX1 or t(4;11)/MLL-AF4. New therapeutic approaches are needed for patients without donor. PMID:17039234

  17. Altered physiological functions and ion currents in atrial fibroblasts from patients with chronic atrial fibrillation.

    PubMed

    Poulet, Claire; Künzel, Stephan; Büttner, Edgar; Lindner, Diana; Westermann, Dirk; Ravens, Ursula

    2016-02-01

    The contribution of human atrial fibroblasts to cardiac physiology and pathophysiology is poorly understood. Fibroblasts may contribute to arrhythmogenesis through fibrosis, or by directly altering electrical activity in cardiomyocytes. The objective of our study was to uncover phenotypic differences between cells from patients in sinus rhythm (SR) and chronic atrial fibrillation (AF), with special emphasis on electrophysiological properties. We isolated fibroblasts from human right atrial tissue for patch-clamp experiments, proliferation, migration, and differentiation assays, and gene expression profiling. In culture, proliferation and migration of AF fibroblasts were strongly impaired but differentiation into myofibroblasts was increased. This was associated with a higher number of AF fibroblasts expressing functional Nav1.5 channels. Strikingly Na(+) currents were considerably larger in AF cells. Blocking Na(+) channels in culture with tetrodotoxin did not affect proliferation, migration, or differentiation in neither SR nor AF cells. While freshly isolated fibroblasts showed mostly weak rectifier currents, fibroblasts in culture developed outward rectifier K(+) currents of similar amplitude between the SR and AF groups. Adding the K(+) channel blockers tetraethylammonium and 4-aminopyridin in culture reduced current amplitude and inhibited proliferation in the SR group only. Analysis of gene expression revealed significant differences between SR and AF in genes encoding for ion channels, collagen, growth factors, connexins, and cadherins. In conclusion, this study shows that under AF conditions atrial fibroblasts undergo phenotypic changes that are revealed in culture. Future experiments should be performed in situ to understand the nature of those changes and whether they affect cardiac electrical activity. PMID:26811054

  18. Increased risk of atrial fibrillation in end-stage renal disease patients on dialysis

    PubMed Central

    Shen, Cheng-Huang; Zheng, Cai-Mei; Kiu, Kee-Thai; Chen, Hsin-An; Wu, Chia-Chang; Lu, Kuo-Cheng; Hsu, Yung-Ho; Lin, Yuh-Feng; Wang, Yuan-Hung

    2016-01-01

    Abstract End-stage renal disease (ESRD) patients commonly have a higher risk of developing cardiovascular diseases than general population. Chronic kidney disease is an independent risk factor for atrial fibrillation (AF); however, little is known about the AF risk among ESRD patients with various modalities of renal replacement therapy. We used the Taiwan National Health Insurance Research Database to determine the incident AF among peritoneal dialysis (PD) and hemodialysis (HD) patients in Taiwan. Our ESRD cohort include Taiwan National Health Insurance Research Database, we identified 15,947 patients, who started renal replacement therapy between January 1, 2002 and December 31, 2003. From the same data source, 47,841 controls without ESRD (3 subjects for each patient) were identified randomly and frequency matched by gender, age (±1 year), and the year of the study patient's index date for ESRD between January 1, 2002 and December 31, 2003. During the follow-up period (mean duration: 8–10 years), 3428 individuals developed the new-onset AF. The incidence rate ratios for AF were 2.07 (95% confidence interval [CI] = 1.93–2.23) and 1.78 (95% CI = 1.30–2.44) in HD and PD groups, respectively. After we adjusted for age, gender, and comorbidities, the hazard ratios for the AF risk were 1.46 (95% CI = 1.32–1.61) and 1.32 (95% CI = 1.00–1.83) in HD and PD groups, respectively. ESRD patients with a history of certain comorbidities including hypertension, diabetes mellitus, hyperlipidemia, coronary artery disease, heart failure, valvular heart disease, and chronic obstructive pulmonary disease (COPD) have significantly increased risks of AF. This nationwide, population-based study suggests that incidence of AF is increased among dialysis ESRD patients. Furthermore, we have to pay more attention in clinical practice and long-term care for those ESRD patients with a history of certain comorbidities. PMID:27336884

  19. Challenges and Treatment for Stroke Prophylaxis in Patients with Atrial Fibrillation in Mexico: A Review.

    PubMed

    Alcocer, Luis

    2016-06-01

    Atrial fibrillation (AF) is associated with an increased risk of stroke. AF-related strokes cause greater disability and mortality than those in patients without AF, and are associated with a significant clinical and economic burden in Mexico. Antithrombotic therapy reduces stroke risk in patients with AF and is recommended for all patients except those classified as having a low stroke risk. However, its use is suboptimal all around the world; one study showed that only 4 % of Mexican patients with AF who presented with ischemic stroke were in the therapeutic range for anticoagulation. Vitamin K antagonists (VKAs) such as warfarin or acenocoumarin have long been the only oral anticoagulants for stroke prevention in AF. Although effective, VKAs have disadvantages, including the need for regular coagulation monitoring and dose adjustment. Interactions with numerous common medications and foods contribute to the risk of serious bleeding and thrombotic events in VKA-treated patients. Thus novel oral anticoagulants (NOACs), more properly called direct oral anticoagulants (DOACs), such as dabigatran etexilate, rivaroxaban, apixaban, and edoxaban (not available in Mexico), have been developed. These offer the convenience of fixed-dose treatment without the need for monitoring, and have few drug or food interactions. Pivotal phase III trials have demonstrated that these agents are at least as effective as warfarin in preventing stroke and are associated with a reduced risk of intracranial hemorrhage. With apixaban approved in Mexico in April 2013, clinicians now have the choice of three novel DOACs as alternatives to warfarin. However, it is yet to be established which of these agents should be the first choice, and treatment decisions are likely to depend on the individual patient's characteristics. PMID:26923792

  20. Left atrial enlargement is an independent predictor of stroke and systemic embolism in patients with non-valvular atrial fibrillation

    PubMed Central

    Hamatani, Yasuhiro; Ogawa, Hisashi; Takabayashi, Kensuke; Yamashita, Yugo; Takagi, Daisuke; Esato, Masahiro; Chun, Yeong-Hwa; Tsuji, Hikari; Wada, Hiromichi; Hasegawa, Koji; Abe, Mitsuru; Lip, Gregory Y. H.; Akao, Masaharu

    2016-01-01

    Controversy exists regarding whether left atrial enlargement (LAE) is a predictor of stroke/systemic embolism (SE) in atrial fibrillation (AF) patients. The Fushimi AF Registry, a community-based prospective survey, enrolled all AF patients in Fushmi-ku, Japan, from March 2011. Follow-up data and baseline echocardiographic data were available for 2,713 patients by August 2015. We compared backgrounds and incidence of events over a median follow-up of 976.5 days between patients with LAE (left atrial diameter > 45 mm; LAE group) and those without in the Fushimi AF Registry. The LAE group accounted for 39% (n = 1,049) of cohort. The LAE group was older and had longer AF duration, with more prevalent non-paroxysmal AF, higher CHADS2/CHA2DS2-VASc score, and oral anticoagulant (OAC) use. A higher risk of stroke/SE during follow-up in the LAE group was found (entire cohort; hazard ratio (HR): 1.92, 95% confidence interval (CI): 1.40–2.64; p < 0.01; without OAC; HR: 1.97, 95% CI: 1.18–3.25; p < 0.01; with OAC; HR: 1.83, 95% CI: 1.21–2.82; p < 0.01). LAE was independently associated with increased risk of stroke/SE (HR: 1.74, 95% CI: 1.25–2.42; p < 0.01) after adjustment by the components of CHA2DS2-VASc score and OAC use. In conclusion, LAE was an independent predictor of stroke/SE in large community cohort of AF patients. PMID:27485817

  1. Left atrial enlargement is an independent predictor of stroke and systemic embolism in patients with non-valvular atrial fibrillation.

    PubMed

    Hamatani, Yasuhiro; Ogawa, Hisashi; Takabayashi, Kensuke; Yamashita, Yugo; Takagi, Daisuke; Esato, Masahiro; Chun, Yeong-Hwa; Tsuji, Hikari; Wada, Hiromichi; Hasegawa, Koji; Abe, Mitsuru; Lip, Gregory Y H; Akao, Masaharu

    2016-01-01

    Controversy exists regarding whether left atrial enlargement (LAE) is a predictor of stroke/systemic embolism (SE) in atrial fibrillation (AF) patients. The Fushimi AF Registry, a community-based prospective survey, enrolled all AF patients in Fushmi-ku, Japan, from March 2011. Follow-up data and baseline echocardiographic data were available for 2,713 patients by August 2015. We compared backgrounds and incidence of events over a median follow-up of 976.5 days between patients with LAE (left atrial diameter > 45 mm; LAE group) and those without in the Fushimi AF Registry. The LAE group accounted for 39% (n = 1,049) of cohort. The LAE group was older and had longer AF duration, with more prevalent non-paroxysmal AF, higher CHADS2/CHA2DS2-VASc score, and oral anticoagulant (OAC) use. A higher risk of stroke/SE during follow-up in the LAE group was found (entire cohort; hazard ratio (HR): 1.92, 95% confidence interval (CI): 1.40-2.64; p < 0.01; without OAC; HR: 1.97, 95% CI: 1.18-3.25; p < 0.01; with OAC; HR: 1.83, 95% CI: 1.21-2.82; p < 0.01). LAE was independently associated with increased risk of stroke/SE (HR: 1.74, 95% CI: 1.25-2.42; p < 0.01) after adjustment by the components of CHA2DS2-VASc score and OAC use. In conclusion, LAE was an independent predictor of stroke/SE in large community cohort of AF patients. PMID:27485817

  2. Atrial Fibrillation on Intensive Care Unit Admission Independently Increases the Risk of Weaning Failure in Nonheart Failure Mechanically Ventilated Patients in a Medical Intensive Care Unit: A Retrospective Case-Control Study.

    PubMed

    Tseng, Yen-Han; Ko, Hsin-Kuo; Tseng, Yen-Chiang; Lin, Yi-Hsuan; Kou, Yu Ru

    2016-05-01

    Atrial fibrillation (AF) is one of the most frequent arrhythmias in clinical practice. Previous studies have reported the influence of AF on patients with heart failure (HF). The effect of AF on the non-HF critically ill patients in a medical intensive care unit (ICU) remains largely unclear. The study aimed to investigate the impact of AF presenting on ICU admission on the weaning outcome of non-HF mechanically ventilated patients in a medical ICU.A retrospective observational case-control study was conducted over a 1-year period in a medical ICU at Taipei Veterans General Hospital, a tertiary medical center in north Taiwan. Non-HF mechanically ventilated patients who were successful in their spontaneous breathing trial and underwent ventilator discontinuation were enrolled. The primary outcome measure was the ventilator status after the first episode of ventilator discontinuation.A total of 285 non-HF patients enrolled were divided into AF (n = 62) and non-AF (n = 223) groups. Compared with the non-AF patients, the AF patients were significantly associated with old age (P = 0.002), a higher rate of acute respiratory distress syndrome causing respiratory failure (P = 0.015), a higher percentage of sepsis before liberation from mechanical ventilation (MV) (P = 0.004), and a higher serum level of blood urea nitrogen on the day of liberation from MV (P = 0.003). Multivariate logistic regression analysis demonstrated that AF independently increased the risk of weaning failure [adjusted odds ratio (AOR), 3.268; 95% confidence interval (CI), 1.254-8.517; P = 0.015]. Furthermore, the AF patients were found to be independently associated with a high rate of ventilator dependence (log rank test, P = 0.026), prolonged total ventilator use (AOR, 1.979; 95% CI, 1.032-3.794; P = 0.040), increased length of ICU stay (AOR, 2.256; 95% CI, 1.049-4.849; P = 0.037), increased length of hospital stay (AOR, 2.921; 95% CI, 1.363-6.260; P = 0

  3. Perturbative magnetoresistance technique used to investigate FM/AF coupled bilayers

    NASA Astrophysics Data System (ADS)

    Oliveira, Alexandre; da Costa, Ricardo; Melo, Abner; Chesman, Carlos

    2014-03-01

    In this study we introduced modifications to a collinear four probe magnetoresistance set-up in order to measure magnetic properties that can only be sensed by techniques based on magnetization perturbation. In addition to the applied DC magnetic field (Hdc) , in magnetoresistance experiments, a small and quasi-static alternating magnetic field (hac, less than 10 Oe and around 800 Hz) is applied perpendicularly, both parallel to the sample plane. Due to Zeeman interaction, hac drives sample magnetization to oscillate slightly around its equilibrium position. Although we apply only DC current (few mA), the detected voltage carries DC and AC components. The DC voltage component provides information on magnetoresistance (MR) and the AC component is called perturbative magnetoresistance (PMR). We successfully demonstrated that the PMR signal is proportional to the first derivative of resistance with respect to hac. Using this technique and a phenomenological model that takes into account the relevant free energy terms of FM/AF coupled bilayers, we were able to study reversible and irreversible magnetization rotation processes in these magnetic systems. With respect to magnetic anisotropy, we investigated rotatable anisotropy, proposed by McMichael et al and Geshev et al. Financial support: CNPq, FAPERN and CAPES (Brazilian agencies).

  4. Bisphenol AF may cause testosterone reduction by directly affecting testis function in adult male rats.

    PubMed

    Feng, Yixing; Yin, Jie; Jiao, Zhihao; Shi, Jiachen; Li, Ming; Shao, Bing

    2012-06-01

    Although in vitro studies have indicated that Bisphenol AF (BPAF) might be a more dangerous endocrine disruptor than Bisphenol A (BPA), no information on reproductive toxicity in animals is available. In this study, the effects of BPAF exposure on the testis and the related mechanisms of toxicity were investigated. Sprague-Dawley (SD) male rats were exposed to BPAF (0, 2, 10, 50 and 200 mg/kg/d) for 14 days. Total cholesterol levels in serum were decreased in rats given a dose of 50 and 200 mg/kg/d. BPAF concentration in the testes increased with increasing doses of BPAF. Reduced serum testosterone and increased luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were observed in rats in the higher dose groups. Furthermore, BPAF exposure resulted in a dramatic decline in genes and protein involved in cholesterol biosynthesis, transport and steroid biosynthesis. Similarly, the testicular mRNA levels of inhibin B, estrogen receptor (ERα) and luteinizing hormone receptor (LHR) also decreased in rats given a dosage of 200 mg/kg/d BPAF. Together, these data demonstrate that BPAF-induced inhibition of testosterone production primarily resulted from the alteration of genes and proteins in the testosterone biosynthesis pathway. PMID:22504055

  5. Neurotoxic effects of bisphenol AF on calcium-induced ROS and MAPKs.

    PubMed

    Lee, Soyoung; Kim, Yoo Kyeong; Shin, Tae-Yong; Kim, Sang-Hyun

    2013-04-01

    Bisphenol AF (BPAF), a newly introduced chemical structurally related to bisphenol A, is used extensively in fluoroelastomers and polyesters, and has been known to induce estrogen-dependent responses. However, the toxicity of BPAF is largely unknown except for its endocrine-related effects. In this study, we investigated the neurotoxicity of BPAF and underlying mechanisms of action using hippocampal cell line (HT-22) and mouse primary neuronal cells. We found that BPAF induced apoptosis in both HT-22 and primary neuronal cells. In order to clarify the underlying mechanisms of BPAF-induced apoptosis, various signaling molecules were evaluated. BPAF increased the level of intracellular calcium, followed by the generation of reactive oxygen species (ROS). BPAF upregulated the phosphorylation of mitogen-activated protein kinase: extracellular signal-regulated kinase, p38 and c-Jun N-terminal kinase (JNK), and nuclear translocation of nuclear factor-κB. Using specific inhibitors, we confirmed that calcium, ROS, p38, and JNK mediated the BPAF-induced apoptosis. In addition, BPAF inhibited microglial activation in a microglia/neuroblastoma coculture model by the reduction of nitric oxide production. We found that BPAF interrupted the normal physiologic functions of microglia at non-toxic levels. Taken together, our results suggest that BPAF, the substitute of BPA, also have neurotoxic properties. PMID:22996013

  6. Detection of a Light Echo from the Otherwise Normal SN 2007af

    NASA Astrophysics Data System (ADS)

    Drozdov, D.; Leising, M. D.; Milne, P. A.; Pearcy, J.; Riess, A. G.; Macri, L. M.; Bryngelson, G. L.; Garnavich, P. M.

    2015-05-01

    We present the discovery of a light echo from SN 2007af, a normal Type Ia supernova (SN Ia) in NGC 5584. Hubble Space Telescope images taken three years post explosion reveal two separate echoes: an outer echo and an extended central region, which we propose to be an inner echo for which details are unresolved. Multiple images were obtained in the F160W, F350LP, F555W, and F814W using the Wide Field Camera 3. If the outer echo is produced by an interstellar dust sheet perpendicular to the line of sight, it is located ∼800 pc in front of the SN. The dust for the inner echo is 0.45 pc \\lt d\\lt 90 pc away from the SN. The inner echo color is consistent with typical interstellar dust wavelength-dependent scattering cross-sections, while the outer echo is redder than predicted. Both dust sheets, if in the foreground, are optically thin for scattering, and the outer echo sheet thickness is consistent with the inferred extinction from peak brightness. Whether the inner echo is from interstellar or circumstellar dust is ambiguous. Overall, the echo characteristics are quite similar to previously observed SN Ia echoes.

  7. Penarines A-F, (nor-)sesquiterpene carboxylic acids from Hygrophorus penarius (Basidiomycetes).

    PubMed

    Otto, Alexander; Porzel, Andrea; Schmidt, Jürgen; Wessjohann, Ludger; Arnold, Norbert

    2014-12-01

    Five sesquiterpene carboxylic acids (1-5) and one nor-sesquiterpene carboxylic acid (6) of the very rare ventricosane type, named penarines A-F, were isolated from fruiting bodies of the basidiomycete Hygrophorus penarius (Hygrophoraceae). This is the first report of (nor)-sesquiterpenes isolated from basidiocarps of the family Hygrophoraceae. Their structures were elucidated on the basis of extensive 1D ((1)H, (13)C) and 2D (HSQC, HMBC, COSY, ROESY) NMR spectroscopic analyses as well as high-resolution mass spectrometry studies. Additionally, the only known member of this rare type of sesquiterpenes, ventricos-7(13)-ene (7), could be identified via headspace GC-MS analysis in a fruiting body of H. penarius. Compounds 1-6 were devoid of remarkable antifungal activity against Cladosporium cucumerinum. Additionally, the cytotoxic activities of compounds 1 and 2 were evaluated against the human prostate cancer cell line PC-3 and the colon cancer cell line HT-29 showing no significant cytotoxic activity. PMID:25269661

  8. Chemically peculiar A/F stars in open clusters of the Milky Way

    NASA Astrophysics Data System (ADS)

    Gebran, M.; Monier, R.

    2010-12-01

    Abundance anomalies have been determined at the surface of many field and open cluster A and F dwarfs. These abundance anomalies are most likely caused by microscopic diffusion at work within the stable envelopes of A stars. However diffusion can be counteracted by several other mixing processes such as convection, rotational mixing and mass loss. We present a short review of the surface abundance patterns of A/F stars in the Pleiades (100 Myr), Coma Berenices (450 Myr) and Hyades (650 Myr) open clusters. Real star-to-star variations of the abundances were found for several chemical elements in the A dwarfs in these clusters. The derived abundances are then compared to evolutionary models from the Montreal group. These comparisons strongly suggest the occurence of hydrodynamical processes at play within the radiative zones of these stars and hindering the effects of microscopic diffusion (mixing processes/mass loss). In the frame of Gaia mission, simulations are presented that predict the number of A stars and open clusters that Gaia will observe in the Galaxy.

  9. INTERPRETATION OF AT-LINE SPECTRA FROM AFS-2 BATCH #3 FERROUS SULFAMATE TREATMENT

    SciTech Connect

    Kyser, E.; O'Rourke, P.

    2013-12-10

    Spectra from the “at-line” spectrometer were obtained during the ferrous sulfamate (FS) valence adjustment step of AFS-2 Batch #3 on 9/18/2013. These spectra were analyzed by mathematical principal component regression (PCR) techniques to evaluate the effectiveness of this treatment. Despite the complications from Pu(IV), we conclude that all Pu(VI) was consumed during the FS treatment, and that by the end of the treatment, about 85% was as Pu(IV) and about 15% was as Pu(III). Due to the concerns about the “odd” shape of the Pu(IV) peak and the possibility of this behavior being observed in the future, a follow-up sample was sent to SRNL to investigate this further. Analysis of this sample confirmed the previous results and concluded that it “odd” shape was due to an intermediate acid concentration. Since the spectral evidence shows complete reduction of Pu(VI) we conclude that it is appropriate to proceed with processing of this the batch of feed solution for HB-Line including the complexation of the fluoride with aluminum nitrate.

  10. High temperature dielectric properties of Apical, Kapton, Peek, Teflon AF, and Upilex polymers

    NASA Technical Reports Server (NTRS)

    Hammoud, A. N.; Baumann, E. D.; Overton, E.; Myers, I. T.; Suthar, J. L.; Khachen, W.; Laghari, J. R.

    1992-01-01

    Reliable lightweight systems capable of providing electrical power at the magawatt level are a requirement for future manned space exploration missions. This can be achieved by the development of high temperature insulating materials which are not only capable of surviving the hostile space environment but can contribute to reducing the mass and weight of the heat rejection system. In this work, Apical, Upilex, Kapton, Teflon AF, and Peek polymers are characterized for AC and DC dielectric breakdown in air and in silicone oil at temperatures up to 250 C. The materials are also tested in terms of their dielectric constant and dissipation factor at high temperatures with an electrical stress of 60 Hz, 200 V/mil present. The effects of thermal aging on the properties of the films are determined after 15 hours of exposure to 200 and 250 C, each. The results obtained are discussed and conclusions are made concerning the suitability of these dielectrics for use in capacitors and cable insulations in high temperature environments.

  11. The Detection of a Light Echo from Type Ia SN 2007af in NGC 5584

    NASA Astrophysics Data System (ADS)

    Drozdov, Dina; Leising, M. D.; Milne, P.; Riess, A. G.

    2013-06-01

    We report the discovery of a light echo (LE) at t ~1000 days past maximum from the normal Type Ia supernova (SNe Ia) SN 2007af in the spiral galaxy NGC 5584. The presence of a LE is supported by photometric data and analysis of the images acquired during the Cepheid campaign using the Hubble Space Telescope (HST) Wide Field Camera 3 (Riess et al. 2011). The F350 and F555 images show a distinct ring-like structure with an additional central source. The images, taken months apart, show an evolution of the ring structure, which is consistent with a growing light echo in time. We find an angular radius of the outer echo to be ~0.29'' - 0.36''. Using the Cepheid distance to NGC 5584 of 24 Mpc, we find the dust illuminated by the light echo to be at a distance ~800 pc from the supernova. This rare discovery adds to the select few light echoes found in Type Ia SNe: SN 1572, SN 1991T, SN 1995E, SN 1998bu, and SN 2006X. Light echoes are powerful tools that probe the environment around supernovae, determine dust properties and characteristics, and could provide constraints on the progenitors, which are not fully understood for SN Ia.

  12. Advances in catheter ablation: atrial fibrillation ablation in patients with mitral mechanical prosthetic valve.

    PubMed

    Santangeli, Pasquale; Di Biase, Luigi; Bai, Rong; Horton, Rodney; Burkhardt, J David; Sanchez, Javier; Price, Justin; Natale, Andrea

    2012-11-01

    Atrial fibrillation (AF) is common in patients with mitral valve replacement (MVR). Treatment of AF in these subjects is challenging, as the arrhythmia is often refractory to antiarrhythmic drug therapy. Radiofrequency catheter ablation (RFCA) is usually avoided or delayed in patients with MVR due to the higher perceived risks and difficulty of left atrial catheter manipulation in the presence of a mechanical valve. Over the last few years, several investigators have reported the feasibility and safety of RFCA of AF in patients with MVR. Five case-control studies have evaluated the feasibility and safety of RFCA of AF or perimitral flutter (PMFL) in patients with MVR. Overall, a total of 178 patients with MVR have been included (21 undergoing ablation of only PMFL), and have been compared with a matched control group of 285 patients. Total procedural duration (weighted mean difference [WMD] = +24.5 min, 95% confidence interval [CI] +10.2 min to +38.8 min, P = 0.001), and fluoroscopy time (WMD = +13.5 min, 95% CI +3.7 min to +23.4 min, P = 0.007) were longer in the MVR group. After a mean follow-up of 11.5 ± 8.6 months, 64 (36%) patients in the MVR group experienced recurrence of AF/PMFL, as compared to 73 (26%) patients in the control group, accounting for a trend toward an increased rate of recurrences in patients with MVR (odds ratio [OR] = 1.66, 95% CI 0.99 to 2.78, P = 0.053). Periprocedural complications occurred in 10 (5.6%) patients in the MVR group, and in 8 (2.8%) patients in the control group (OR = 2.01, 95% CI 0.56 to 7.15, P = 0.28). In conclusion, a quantitative analysis of the available evidence supports a trend toward a worse arrhythmia-free survival and a higher absolute rate of periprocedural complications in patients with MVR undergoing RFCA of AF or PMFL, as compared to a matched control group without mitral valve disease. These data would encourage the adoption of RFCA of AF in MVR patients mostly by more experienced Institutions. PMID:23003204

  13. Hematopoietic stem cell transplantation for pediatric mature B-cell acute lymphoblastic leukemia with non-L3 morphology and MLL-AF9 gene fusion: three case reports and review of the literature.

    PubMed

    Sarashina, Takeo; Iwabuchi, Haruko; Miyagawa, Naoyuki; Sekimizu, Masahiro; Yokosuka, Tomoko; Fukuda, Kunio; Hamanoue, Satoshi; Iwasaki, Fuminori; Goto, Shoko; Shiomi, Masae; Imai, Chihaya; Goto, Hiroaki

    2016-07-01

    Mature B-cell acute lymphoblastic leukemia (B-ALL) is typically associated with French-American-British (FAB)-L3 morphology and MYC gene rearrangement. However, rare cases of mature B-ALL with non-L3 morphology and MLL-AF9 fusion have been reported, and such cases are characterized by a rapid and aggressive clinical course. We here report three such cases of pediatric mature B-ALL in female patients respectively aged 15 months, 4 years, and 4 months. Bone marrow smears at diagnosis showed FAB-L1 morphology in all patients. Immunophenotypically, they were positive for cluster of differentiation (CD)10, CD19, CD20 (or CD22), Human Leukocyte Antigen-DR, and surface immunoglobulin λ. No evidence of MYC rearrangement was detected in any of the cases by fluorescent in situ hybridization (FISH) analysis. However, MLL rearrangement was detected by FISH, and MLL-AF9 fusion was confirmed by reverse transcriptase-polymerase chain reaction. All patients achieved complete remission after conventional chemotherapy and subsequently underwent hematopoietic stem cell transplantation as high-risk ALL; patient 3 for infantile ALL with MLL rearrangement and the others for ALL with MLL rearrangement and hyperleukocytosis (white blood cell count at diagnosis >50 × 10(9)/L). At the latest follow-up for each case (12-98 months post-transplantation), complete remission was maintained. Moreover, we discuss the clinical, genetic, and immunophenotypic features of this rare disease. PMID:27084248

  14. Human PSENEN and U2AF1L4 genes are concertedly regulated by a genuine bidirectional promoter.

    PubMed

    Didych, D A; Shamsutdinov, M F; Smirnov, N A; Akopov, S B; Monastyrskaya, G S; Uspenskaya, N Y; Nikolaev, L G; Sverdlov, E D

    2013-02-15

    Head-to-head genes with a short distance between their transcription start sites may constitute up to 10% of all genes in the genomes of various species. It was hypothesized that this intergenic space may represent bidirectional promoters which are able to initiate transcription of both genes, but the true bidirectionality was proved only for a few of them. We present experimental evidence that, according to several criteria, a 269 bp region located between the PSENEN and U2AF1L4 human genes is a genuine bidirectional promoter regulating a concerted divergent transcription of these genes. Concerted transcription of PSENEN and U2AF1L4 can be necessary for regulation of T-cell activity. PMID:23246698

  15. AF4 uses the SL1 components of RNAP1 machinery to initiate MLL fusion- and AEP-dependent transcription.

    PubMed

    Okuda, Hiroshi; Kanai, Akinori; Ito, Shinji; Matsui, Hirotaka; Yokoyama, Akihiko

    2015-01-01

    Gene rearrangements generate MLL fusion genes, which can lead to aggressive leukemia. In most cases, MLL fuses with a gene encoding a component of the AEP (AF4 family/ENL family/P-TEFb) coactivator complex. MLL-AEP fusion proteins constitutively activate their target genes to immortalize haematopoietic progenitors. Here we show that AEP and MLL-AEP fusion proteins activate transcription through selectivity factor 1 (SL1), a core component of the pre-initiation complex (PIC) of RNA polymerase I (RNAP1). The pSER domain of AF4 family proteins associates with SL1 on chromatin and loads TATA-binding protein (TBP) onto the promoter to initiate RNA polymerase II (RNAP2)-dependent transcription. These results reveal a previously unknown transcription initiation mechanism involving AEP and a role for SL1 as a TBP-loading factor in RNAP2-dependent gene activation. PMID:26593443

  16. Birth order in transgendered males from Polynesia: a quantitative study of Samoan fa'afāfine.

    PubMed

    Poasa, Kris H; Blanchard, Ray; Zucker, Kenneth J

    2004-01-01

    In previous research, a late birth order has been shown to be a characteristic of Western homosexual transsexual men. To date, however, it is not clear if a late birth order is specific to Western transsexuals or may be a characteristic of non-Western transgendered males as well. We quantified birth order in a sample of 13 transgendered males known as fa'afāfine from Samoa. On average, the fa'afāfine were late born, both with regard to number of older brothers and number of older sisters, although the effect appeared to be somewhat stronger with regard to number of older brothers. We consider possible interpretations of the late birth order effect, along with recommendations for further research to identify common mechanisms that might underlie transgenderism across different cultural groups. PMID:14660290

  17. How are patients with atrial fibrillation approached and informed about their risk profile and available therapies in Europe? Results of the European Heart Rhythm Association Survey.

    PubMed

    Potpara, Tatjana S; Pison, Laurent; Larsen, Torben B; Estner, Heidi; Madrid, Antonio; Blomström-Lundqvist, Carina

    2015-03-01

    This European Heart Rhythm (EHRA) Scientific Initiatives Committee EP Wire Survey aimed at exploring the common practices in approaching patients with atrial fibrillation (AF) and informing them about their risk profiles and available therapies in Europe. In the majority of 53 responding centres, patients were seen by cardiologists (86.8%) or arrhythmologists (64.2%). First- and follow-up visits most commonly lasted 21-30 and 11-20 min (41.5 and 69.8% of centres, respectively). In most centres (80.2%) stroke and bleeding risk had the highest priority for discussion with AF patients; 50.9% of centres had a structured patient education programme for stroke prevention. Individual patient stroke risk was assessed at every visit in 69.2% of the centres; 46.1% of centres had a hospital-based anticoagulation clinic. Information about non-vitamin K oral anticoagulants (NOACs) was communicated to all AF patients eligible for oral anticoagulation (38.5% of centres) or to warfarin-naive/unstable patients (42.3%). Only two centres (3.8%) had a structured NOAC adherence follow-up programme; in eight centres (15.4%) patients were requested to sign the statement they have been informed about the risks of non-adherence to NOAC therapy, and three centres (5.8%) had a patient education programme. Patient preferences were of the highest relevance regarding oral anticoagulation and AF ablation (64.7 and 49.0% of centres, respectively). This EP Wire Survey shows that in Europe considerable amount of time and resources are used in daily clinical practice to inform AF patients about their risk profile and available therapies. However, a diversity of strategies used across the European hospitals was noted, and further research is needed to better define optimal strategies for informing AF patients about their risk profile and treatment options. PMID:25722478

  18. Comparative expression profiles of microRNA in left and right atrial appendages from patients with rheumatic mitral valve disease exhibiting sinus rhythm or atrial fibrillation

    PubMed Central

    2014-01-01

    Background The atrial fibrillation (AF) associated microRNAs (miRNAs) were found in the right atrium (RA) and left atrium (LA) from patients with rheumatic mitral valve disease (RMVD). However, most studies only focus on the RA; and the potential differences of AF-associated miRNAs between the RA and LA are still unknown. The aim of this study was to perform miRNA expression profiles analysis to compare the potential differences of AF-associated miRNAs in the right atrial appendages (RAA) and left atrial appendages (LAA) from RMVD patients. Methods Samples tissues from the RAA and LAA were obtained from 18 RMVD patients (10 with AF) during mitral valve replacement surgery. From these tissues, miRNA expression profiles were created and analyzed using a human miRNA microarray. Then, the results were validated using qRT-PCR analysis for 12 selected miRNAs. Finally, potential targets of 10 validated miRNAs were predicted and their functions and potential pathways were analyzed using the miRFocus database. Results In RAA, 65 AF-associated miRNAs were found and significantly dysregulated (i.e. 28 miRNAs were up-regulated and 37 were down-regulated). In LAA, 42 AF-associated miRNAs were found and significantly dysregulated (i.e. 22 miRNAs were up-regulated and 20 were down-regulated). Among these AF-associated miRNAs, 23 of them were found in both RAA and LAA, 45 of them were found only in RAA, and 19 of them were found only in LAA. Finally, 10 AF-associated miRNAs validated by qRT-PCR were similarly distributed in RAA and LAA; 3 were found in both RAA and LAA, 5 were found only in RAA, and 2 were found only in LAA. Potential miRNA targets and molecular pathways were identified. Conclusions We have found the different distributions of AF-associated miRNAs in the RAA and LAA from RMVD patients. This may reflect different miRNA mechanisms in AF between the RA and LA. These findings may provide new insights into the underlying mechanisms of AF in RMVD patients. PMID:24708751

  19. Distinct binding determinants for 9-cis retinoic acid are located within AF-2 of retinoic acid receptor alpha.

    PubMed Central

    Tate, B F; Allenby, G; Janocha, R; Kazmer, S; Speck, J; Sturzenbecker, L J; Abarzúa, P; Levin, A A; Grippo, J F

    1994-01-01

    Retinoids exert their physiological action by interacting with two families of nuclear receptors, the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs), which regulate gene expression by forming transcriptionally active heterodimeric RAR/RXR or homodimeric RXR/RXR complexes on DNA. Retinoid receptor activity resides in several regions, including the DNA and ligand binding domains, a dimerization interface, and both a ligand-independent (AF-1) and a ligand-dependent (AF-2) transactivation function. While 9-cis retinoic acid (RA) alone is the cognate ligand for the RXRs, both 9-cis RA and all-trans RA (t-RA) compete for binding with high affinity to the RARs. This latter observation suggested to us that the two isomers may interact with a common binding site. Here we report that RAR alpha has two distinct but overlapping binding sites for 9-cis RA and t-RA. Truncation of a human RAR alpha to 419 amino acids yields a receptor that binds both t-RA and 9-cis RA with high affinity, but truncation to amino acid 404 yields a mutant receptor that binds only t-RA with high affinity. Remarkably, this region also defines a C-terminal boundary for AF-2, as addition of amino acids 405 to 419 restores receptor-mediated gene activity to a truncated human RAR alpha lacking this region. It is interesting to speculate that binding of retinoid stereoisomers to unique sites within an RAR may function with AF-2 to cause differential activation of retinoid-responsive gene pathways. Images PMID:8139538

  20. AF-353, a novel, potent and orally bioavailable P2X3/P2X2/3 receptor antagonist

    PubMed Central

    Gever, Joel R; Soto, Rothschild; Henningsen, Robert A; Martin, Renee S; Hackos, David H; Panicker, Sandip; Rubas, Werner; Oglesby, Ian B; Dillon, Michael P; Milla, Marcos E; Burnstock, Geoffrey; Ford, Anthony PDW

    2010-01-01

    Background and purpose: Purinoceptors containing the P2X3 subunit (P2X3 homotrimeric and P2X2/3 heterotrimeric) are members of the P2X family of ion channels gated by ATP and may participate in primary afferent sensitization in a variety of pain-related diseases. The current work describes the in vitro pharmacological characteristics of AF-353, a novel, orally bioavailable, highly potent and selective P2X3/P2X2/3 receptor antagonist. Experimental approach: The antagonistic potencies (pIC50) of AF-353 for rat and human P2X3 and human P2X2/3 receptors were determined using methods of radioligand binding, intracellular calcium flux and whole cell voltage-clamp electrophysiology. Key results: The pIC50 estimates for these receptors ranged from 7.3 to 8.5, while concentrations 300-fold higher had little or no effect on other P2X channels or on an assortment of receptors, enzymes and transporter proteins. In contrast to A-317491 and TNP-ATP, competition binding and intracellular calcium flux experiments suggested that AF-353 inhibits activation by ATP in a non-competitive fashion. Favourable pharmacokinetic parameters were observed in rat, with good oral bioavailability (%F = 32.9), reasonable half-life (t1/2 = 1.63 h) and plasma-free fraction (98.2% protein bound). Conclusions and implications: The combination of a favourable pharmacokinetic profile with the antagonist potency and selectivity for P2X3 and P2X2/3 receptors suggests that AF-353 is an excellent in vivo tool compound for study of these channels in animal models and demonstrates the feasibility of identifying and optimizing molecules into potential clinical candidates, and, ultimately, into a novel class of therapeutics for the treatment of pain-related disorders. PMID:20590629

  1. The M2 selective antagonist AF-DX 116 shows high affinity for muscarine receptors in bovine tracheal membranes.

    PubMed

    Roffel, A F; in't Hout, W G; de Zeeuw, R A; Zaagsma, J

    1987-05-01

    We have characterized the muscarine receptors in bovine tracheal and left ventricular membranes using 3H-dexetimide/pirenzepine and 3H-dexetimide/AF-DX 116 competition studies. Pirenzepine exhibited low (M2) affinity binding to both preparations; Kd was 590 nM in left ventricle and 463 nM in trachea. AF-DX 116 exhibited high (M2) affinity binding to left ventricle (Kd = 95.6 nM); in tracheal membranes it bound with high (M2) affinity (Kd = 40.7 nM) to 74% of the receptors and with low (M3) affinity (Kd = 2.26 microM) to 26% of the receptors. It is concluded that bovine tracheal muscle membranes contain a heterogeneous population of muscarine binding sites, the majority having M2 (heart) subtype characteristics and being located on the smooth muscle membranes; a minority having M3 (exocrine gland) subtype characteristics and presumed to be located in submucosal glands. This is the first report of high affinity binding of AF-DX 116 to non-cardiac peripheral muscarine receptors. PMID:3614390

  2. Mll-AF4 Confers Enhanced Self-Renewal and Lymphoid Potential during a Restricted Window in Development.

    PubMed

    Barrett, Neil A; Malouf, Camille; Kapeni, Chrysa; Bacon, Wendi A; Giotopoulos, George; Jacobsen, Sten Eirik W; Huntly, Brian J; Ottersbach, Katrin

    2016-07-26

    MLL-AF4+ infant B cell acute lymphoblastic leukemia is characterized by an early onset and dismal survival. It initiates before birth, and very little is known about the early stages of the disease's development. Using a conditional Mll-AF4-expressing mouse model in which fusion expression is targeted to the earliest definitive hematopoietic cells generated in the mouse embryo, we demonstrate that Mll-AF4 imparts enhanced B lymphoid potential and increases repopulation and self-renewal capacity during a putative pre-leukemic state. This occurs between embryonic days 12 and 14 and manifests itself most strongly in the lymphoid-primed multipotent progenitor population, thus pointing to a window of opportunity and a potential cell of origin. However, this state alone is insufficient to generate disease, with the mice succumbing to B cell lymphomas only after a long latency. Future analysis of the molecular details of this pre-leukemic state will shed light on additional events required for progression to acute leukemia. PMID:27396339

  3. The SRB recovery ship Liberty Star reenters the Hangar AF area at CCAS with a spent SRB used on STS-

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Seen carrying a spent solid rocket booster (SRB) from the STS-87 launch on Nov. 19 is the solid rocket booster recovery ship Liberty Star as it reenters the Hangar AF area at Cape Canaveral Air Station. Hangar AF is a building originally used for Project Mercury, the first U.S. manned space program. The SRBs are the largest solid propellant motors ever flown and the first designed for reuse. After a Shuttle is launched, the SRBs are jettisoned at two minutes, seven seconds into the flight. At six minutes and 44 seconds after liftoff, the spent SRBs, weighing about 165,000 lb., have slowed their descent speed to about 62 mph and splashdown takes place in a predetermined area. They are retrieved from the Atlantic Ocean by special recovery vessels and returned for refurbishment and eventual reuse on future Shuttle flights. Once at Hangar AF, the SRBs are unloaded onto a hoisting slip and mobile gantry cranes lift them onto tracked dollies where they are safed and undergo their first washing.

  4. Essential role of PR-domain protein MDS1-EVI1 in MLL-AF9 leukemia

    PubMed Central

    Owens, Kristina; Hatem, Layla; Glass, Carolyn H.; Karuppaiah, Kannan; Camargo, Fernando

    2013-01-01

    A subgroup of leukemogenic mixed-lineage leukemia (MLL) fusion proteins (MFPs) including MLL-AF9 activates the Mecom locus and exhibits extremely poor clinical prognosis. Mecom encodes EVI1 and MDS1-EVI1 (ME) proteins via alternative transcription start sites; these differ by the presence of a PRDI-BF1-RIZ1 (PR) domain with histone methyltransferase activity in the ME isoform. Using an ME-deficient mouse, we show that ME is required for MLL-AF9–induced transformation both in vitro and in vivo. And, although Nup98-HOXA9, MEIS1-HOXA9, and E2A-Hlf could transform ME-deficient cells, both MLL-AF9 and MLL-ENL were ineffective, indicating that the ME requirement is specific to MLL fusion leukemia. Further, we show that the PR domain is essential for MFP-induced transformation. These studies clearly indicate an essential role of PR-domain protein ME in MFP leukemia, suggesting that ME may be a novel target for therapeutic intervention for this group of leukemias. PMID:24021671

  5. Comparison of beta blocker and digoxin alone and in combination for management of patients with atrial fibrillation and heart failure.

    PubMed

    Fauchier, Laurent; Grimard, Caroline; Pierre, Bertrand; Nonin, Emilie; Gorin, Laurent; Rauzy, Bruno; Cosnay, Pierre; Babuty, Dominique; Charbonnier, Bernard

    2009-01-15

    In patients with atrial fibrillation (AF) and heart failure (HF), beta blockers and digoxin reduce the ventricular rate, but controversy exists concerning how these drugs affect prognosis in this setting. This study compared the effects of beta blocker and digoxin on mortality in patients with both AF and HF. In a single-center institution, patients with AF and HF seen between January 2000 and January 2004 were identified and followed until September 2007. Of 1,269 consecutive patients with both AF and HF, 260 were treated with a beta blocker alone, 189 with beta blocker plus digoxin, 402 with digoxin alone, and 418 without beta blocker or digoxin (control group). During a follow-up of 881+/-859 days, 247 patients died. Compared with the control group, treatment with beta blocker was associated with a decreased mortality (relative risk=0.58, 95% confidence interval 0.40 to 0.85, p=0.005 for beta blocker alone and 0.59, 95% confidence interval 0.40 to 0.87, p=0.008 for beta blocker plus digoxin). By contrast, treatment with digoxin alone was not associated with a better survival (relative risk=0.97, 95% confidence interval 0.73 to 1.30, p=NS). Results remained significant after adjustment for potential confounders and similar when we considered, separately, HF with permanent or nonpermanent AF, presence or absence of coronary disease, and patients with decreased or preserved systolic function. In conclusion, in unselected patients with AF and HF, treatments with beta blocker alone or with beta blocker plus digoxin are associated with a similar decrease in the risk of death. Digoxin alone is associated with a worse survival chance, similar to that of patients without any rate control treatment. PMID:19121446

  6. The relationship between D-dimer level and the development of atrial fibrillation in patients with systolic heart failure.

    PubMed

    Zorlu, Ali; Akkaya, Emre; Altay, Hakan; Bektasoglu, Gokhan; Turkdogan, Kenan Ahmet; Sincer, Isa; Vuruskan, Ertan; Cınar, Ziynet; Tandogan, Izzet; Yilmaz, Mehmet Birhan

    2012-05-01

    Heart failure (HF) is one of the most common and leading cause of death worldwide. Clinical trials provide evidence that the development of atrial fibrillation (AF) is a marker of poor prognosis in patients with HF. Furthermore, elevated D-dimer level is associated with increased cardiovascular mortality independent of AF in HF patients. We investigated whether plasma D-dimer levels in patients with hospitalized systolic HF could predict development of AF. A total of 150 consecutive patients with sinus rhythm who admitted to the emergency department with hospitalized systolic HF were evaluated. All hospitalized patients were obtained D-dimer levels within the first 24 h following admission. Atrial fibrillation developed in 31 (20.7%) patients during follow-up period of 6.3 ± 5 months. Patients who developed atrial fibrillation had significantly increased levels of D-dimer [608 (339-1,022) ng/ml versus 1,100 (608-2,599) ng/ml, P = 0.001]. Optimal cut-off level of D-dimer to predict development of AF was found to be >792 ng/ml. D-dimer >792 ng/ml, right ventricular dilatation, age, systolic pulmonary pressure, left atrium size, moderate to severe tricuspid regurgitation, and beta blocker usage were found to have prognostic significance in univariate analysis. In multivariate Cox proportional-hazards model, D-dimer levels >792 ng/ml (HR = 3.019, P = 0.006), and right ventricular dilatation (HR = 8.676, P = 0.003) were associated with an increased risk of new-onset AF. In conclusion, D-dimer could predict development of AF in patients with hospitalized systolic HF. PMID:22139027

  7. Effects of IKur blocker MK-0448 on human right atrial action potentials from patients in sinus rhythm and in permanent atrial fibrillation

    PubMed Central

    Loose, Simone; Mueller, Judith; Wettwer, Erich; Knaut, Michael; Ford, John; Milnes, James; Ravens, Ursula

    2014-01-01

    Selective blockers of the Kv1.5 channel have been developed for the treatment of atrial fibrillation (AF), but little is known how these atrial-selective drugs affect human action potentials (APs). Therefore we have investigated the Kv1.5 blocker MK-0448 (N-{6-[(1S)-1-(4-fluorophenyl)-2,2-di(pyridin-3-yl)ethyl]pyridin-2-yl}methanesulfon- amide) in right atrial trabeculae from patients in sinus rhythm (SR), permanent AF (>6 months), and intermittent AF. MK-0448 blocked Kv1.5 current in an expression system and concentration-dependently elevated the plateau phase of atrial APs. In SR preparations stimulated at 1 Hz, MK-0448 (3 μM) shortened action potential duration at 90% of repolarization (APD90) and effective refractory period (ERP), but in permanent AF preparations, MK-0448 prolonged APD90 and ERP. The effects of MK-0448 in intermittent AF resembled those in SR preparations. Block of IKs is probably more prominent in AF because of reduced repolarization reserve due to AF-induced remodeling. PMID:24624083

  8. Outcome of patients with atrial fibrillation after intravenous thrombolysis for cerebral ischaemia.

    PubMed

    Padjen, Visnja; Bodenant, Marie; Jovanovic, Dejana R; Ponchelle-Dequatre, Nelly; Novakovic, Novak; Cordonnier, Charlotte; Beslac-Bumbasirevic, Ljiljana; Leys, Didier

    2013-12-01

    The question of whether i.v. rt-PA is beneficial in patients with ischaemic stroke and atrial fibrillation (AF) remains unresolved. Our objective was to evaluate the outcome of patients with AF who received i.v. rt-PA for stroke in the registries of Lille (France) and Belgrade (Serbia). End-points were poor outcome [modified Rankin Scale (mRS) 3-6], and symptomatic haemorrhagic transformation (sHT) according to ECASS3. Of 734 consecutive patients, 155 (21.2 %) had AF. The unadjusted comparison found patients with AF to be 12 years older, more likely to be women, to have hypertension, and baseline INR > 1.2, and less likely to be smokers. They had higher baseline NIHSS scores, diastolic blood pressure, and serum glucose concentrations, and lower platelet counts. They did not differ for sHT (5.8 vs. 5.5 %; p = 0.893), but they more frequently had poor outcomes (52.3 vs. 35.2 %; p < 0.001) and death (21.9 vs. 9.0 %; p < 0.001). The only independent predictor of sHT was baseline NIHSS (adjOR 1.05 per 1 point increase; 95 % CI 1.01-1.10). Independent variables associated with poor outcome were age (adjOR 1.04 for 1 year increase; 95 % CI 1.03-1.06), baseline NIHSS (adjOR 1.17 per 1 point increase; 95 % CI 1.13-1.21), and sHT (adjOR 47.6; 95 % CI 10.2-250) but not AF. In patients treated with i.v. rt-PA for cerebral ischaemia, those with AF have worse outcomes because they are older and have more severe strokes at admission. This result suggests that we should focus on prevention and research of more aggressive strategies at the acute stage. PMID:24068372

  9. Pattern Analysis of Acute Mucosal Reactions in Patients With Head and Neck Cancer Treated With Conventional and Accelerated Irradiation

    SciTech Connect

    Wygoda, Andrzej Maciejewski, Boguslaw; Skladowski, Krzysztof; Hutnik, Marcin; Pilecki, Boleslaw; Golen, Maria; Rutkowski, Tomasz

    2009-02-01

    Purpose: To evaluate severity of acute mucosal reactions (AMR) caused by conventional (CF) and accelerated fractionation (AF) regimens using a modified Dische system and to analyze differences in incidence and severity of AMR according to frequency and regularity of scoring. Methods and Materials: Sixty-six consecutive patients (33 CF, 33 AF) with head and neck cancer irradiated with 5 fractions in 5 days per week (CF) or with 7 fractions in 7 days (AF) to a total dose of 70 Gy. A modified Dische system was used for daily quantitation of AMR during radiotherapy until complete healing. Results: Confluent mucositis (CM) was noted in 79% of patients in the CF group and 85% in the AF group. In 24% of the CF group and 18% of the AF group the CM presented a wave-like pattern. In 55% of CF and 67% of AF a classic triphasic pattern was noted. In 12 patients acute reactions did not transgress the level of spotted mucositis. The present study clearly shows that quantitation of the incidence and severity of acute mucosal effects strongly depends on frequent and regular scoring. A significant difference in the incidence of CM between the CF and AF groups was noted, mainly in weeks 4-6 of irradiation. When once-weekly irregular instead of daily scoring was evaluated, the incidence of CM was underestimated by approximately 20-36%. Conclusions: Acute mucosal reactions occur as a complex of morphologic and functional disorders with individual intensity, even among patients treated with the same fractionation regimen. In some cases they present a 'wave-like' pattern during irradiation. Therefore, precise quantitation of acute effects requires regular and frequent scoring.

  10. Practical and clinical considerations in assessing patients with atrial fibrillation for switching to non-vitamin K antagonist oral anticoagulants in primary care

    PubMed Central

    Guimarães, Patrícia O; Kaatz, Scott; Lopes, Renato D

    2015-01-01

    Atrial fibrillation (AF) is an important risk factor for thromboembolic events, and anticoagulation therapy can reduce this risk. Vitamin K antagonists (VKAs), such as warfarin, have been used for decades in patients with AF for stroke prevention. Currently, non-VKA oral anticoagulants (NOACs) are approved and available for non-valvular AF patients who are at increased risk of stroke. These agents are safe and effective and have important advantages over VKAs, such as significant reduction in intracranial hemorrhage and no need for routine laboratory monitoring. Thus, should all VKA-treated patients be switched to a NOAC? The aims of this article are: 1) to review the advantages of NOACs over VKAs; 2) to identify the group of patients who most benefit from receiving a NOAC and, therefore, are higher priority to be switched from VKAs; and 3) to provide clinical and practical guidance on how to switch patients safely from VKAs to NOACs. PMID:26379443

  11. Patients with atrial fibrillation undergoing percutaneous coronary intervention: current concepts and concerns: part II.

    PubMed

    Dzeshka, Mikhail S; Brown, Richard A; Lip, Gregory Y H

    2015-01-01

    Atrial fibrillation (AF) and coronary artery disease (CAD) often present concomitantly. Given the increased risk of thrombotic complications with either of them but different pathogenesis of clot formation, combined antithrombotic therapy is necessary in patients developing acute coronary syndrome and/or undergoing percutaneous coronary intervention (PCI). Different antithrombotic regimens in this group of patients have been summarized and discussed earlier. Triple therapy remains the treatment of choice in these patients despite the increased risk of hemorrhagic complications. Given the absence of evidence from randomized controlled trials, balancing the risk of stroke and stent thrombosis against the risk of major bleeding is a challenge. Precise stroke and bleeding risk assessment is an essential part of the decision making process regarding antithrombotic management. Continuing the discussion of current concepts and concerns of antithrombotic management in AF patients undergoing PCI, we emphasize the importance of various strategies to reduce bleeding in the modern era, namely, radial access combined with careful selection of a P2Y₁₂ receptor inhibitor, use of newer drug-eluting stents, and uninterrupted anticoagulation for patients undergoing procedures. We also focus on the role of the non-vitamin K oral anticoagulants (novel oral anticoagulants, eg, dabigatran, rivaroxaban, apixaban, and edoxaban) which are increasingly used for stroke prevention in AF. Finally, recent recommendations on the management of antithrombotic therapy in AF patients presenting with acute coronary syndrome and/or undergoing PCI as well as ongoing clinical trials and future directions are highlighted. PMID:25534093

  12. Detection of early bronchial cancer by autofluorescence: results in patients with H&N cancer

    NASA Astrophysics Data System (ADS)

    Gabrecht, Tanja; Radu, Alexandre; Zellweger, Matthieu; Lovisa, Blaise; Goujon, Didier; Grosjean, Pierre; van den Bergh, Hubert; Monnier, Philippe; Wagnières, Georges

    2007-07-01

    Head and neck (H&N) cancer patients have a high incidence of second primary tumours in the tracheobronchial tree. Diagnostic autofluorescence bronchoscopy (DAFE) has shown promising results in the detection of early neoplastic and pre-neoplastic changes in the bronchi. We have investigated the medical impact of DAFE in a population of H&N cancer patients. The bronchoscopies were performed using a modified commercially available DAFE system. Endoscopic imaging of the tissue autofluorescence (AF) was combined with an online image analysis procedure allowing to discriminate between true and false positive results. White light (WL) bronchoscopy was performed as a control. Twenty-one patients with high lung cancer risk factors underwent WL and AF bronchoscopy with this improved system. Forty-one biopsies were taken on macroscopicall suspicious (WL or AF positive) sites. Seven patients were found to have second primary tumours in the bronchi. The sensitivity for the detection of these early lesions with the DAFE was 1.6 times larger than the sensitivity of WL bronchoscopy only. The positive predictive value (PPV) for AF is 79% (33% for WL alone). The PPV of both methods together is 100%. DAFE proved to be efficient for the detection of second primary lesions in H&N cancer patients and can be used as a simple addition to pre-operative work-up or follow-up in this patient population.

  13. SERMs have substance-specific effects on bone, and these effects are mediated via ERαAF-1 in female mice.

    PubMed

    Börjesson, Anna E; Farman, Helen H; Movérare-Skrtic, Sofia; Engdahl, Cecilia; Antal, Maria Cristina; Koskela, Antti; Tuukkanen, Juha; Carlsten, Hans; Krust, Andrée; Chambon, Pierre; Sjögren, Klara; Lagerquist, Marie K; Windahl, Sara H; Ohlsson, Claes

    2016-06-01

    The bone-sparing effect of estrogens is mediated primarily via estrogen receptor (ER)α, which stimulates gene transcription through activation function (AF)-1 and AF-2. The role of ERαAF-1 for the estradiol (E2) effects is tissue specific. The selective ER modulators (SERMs) raloxifene (Ral), lasofoxifene (Las), and bazedoxifene (Bza) can be used to treat postmenopausal osteoporosis. They all reduce the risk for vertebral fractures, whereas Las and partly Bza, but not Ral, reduce the risk for nonvertebral fractures. Here, we have compared the tissue specificity of Ral, Las, and Bza and evaluated the role of ERαAF-1 for the effects of these SERMs, with an emphasis on bone parameters. We treated ovariectomized (OVX) wild-type (WT) mice and OVX mice lacking ERαAF-1 (ERαAF-1(0)) with E2, Ral, Las, or Bza. All three SERMs increased trabecular bone mass in the axial skeleton. In the appendicular skeleton, only Las increased the trabecular bone volume/tissue volume and trabecular number, whereas both Ral and Las increased the cortical bone thickness and strength. However, Ral also increased cortical porosity. The three SERMs had only a minor effect on uterine weight. Notably, all evaluated effects of these SERMs were absent in ovx ERαAF-1(0) mice. In conclusion, all SERMs had similar effects on axial bone mass. However, the SERMs had slightly different effects on the appendicular skeleton since only Las increased the trabecular bone mass and only Ral increased the cortical porosity. Importantly, all SERM effects require a functional ERαAF-1 in female mice. These results could lead to development of more specific treatments for osteoporosis. PMID:27048997

  14. Hazard identification and risk characterization of bisphenols A, F and AF to aquatic organisms.

    PubMed

    Tišler, Tatjana; Krel, Alja; Gerželj, Urška; Erjavec, Boštjan; Dolenc, Marija Sollner; Pintar, Albin

    2016-05-01

    Production of bisphenol A (BPA) analogues such as bisphenol F (BPF) and bisphenol AF (BPAF) has recently increased, due to clear evidence of adverse effects of BPA on humans and wildlife. Bisphenols (BPs) have already been released into aquatic environment without previous available information about potential adverse effects of BPs and their potential risk to aquatic ecosystems. In this study, lethal and sublethal effects of BPF and BPAF to bacteria, algae, crustacea and fish embryos were investigated and the results were compared to the adverse effects obtained for BPA. We found that BPAF was the most toxic compound to Daphnia magna, Danio rerio and Desmodesmus subspicatus; the lowest 72 h EC50 (median effective concentration) and 21 d NOEC (no observed effect concentration) values were determined at 2.2 mg/L regarding zebrafish hatching success and 0.23 mg/L of BPAF obtained for growth and reproduction of water fleas, respectively. In most cases, BPA was more toxic to D. magna, D. rerio and D. subspicatus in comparison to BPF, but pigmentation of zebrafish embryos after 48 h of exposure and reproduction of water fleas after 21-day D. magna reproductive test exposure to BPF were much more impaired. Risk quotients (measured environmental concentration/21 d NOEC) showed that BPA, BPF and BPAF are recently not chronically hazardous to the survival, reproduction and growth of water fleas in surface waters. On the other hand, we importantly show that currently present BPAF concentrations in surface waters could cause a potential ecological risk to aquatic organisms. In the near future, higher concentrations of BPF and BPAF in surface waters are anticipated and for this reason further testing using test systems with various aquatic species and endpoints are needed to provide additional information about toxic impacts of BPF and BPAF on aquatic biota. PMID:26957022

  15. Biotransformation of Bisphenol AF to Its Major Glucuronide Metabolite Reduces Estrogenic Activity

    PubMed Central

    Yin, Jie; Zhang, Jing; Feng, Yixing; Shao, Bing

    2013-01-01

    Bisphenol AF (BPAF), an endocrine disrupting chemical, can induce estrogenic activity through binding to estrogen receptor (ER). However, the metabolism of BPAF in vivo and the estrogenic activity of its metabolites remain unknown. In the present study, we identified four metabolites including BPAF diglucuronide, BPAF glucuronide (BPAF-G), BPAF glucuronide dehydrated and BPAF sulfate in the urine of Sprague-Dawley (SD) rats. BPAF-G was further characterized by nuclear magnetic resonance (NMR). After treatment with a single dose of BPAF, BPAF was metabolized rapidly to BPAF-G, as detected in the plasma of SD rats. Biotransformation of BPAF to BPAF-G was confirmed with human liver microsomes (HLM), and Vmax of glucuronidation for HLM was 11.6 nmol/min/mg. We also found that BPAF glucuronidation could be mediated through several human recombinant UDP-glucuronosyltransferases (UGTs) including UGT1A1, UGT1A3, UGT1A8, UGT1A9, UGT2B4, UGT2B7, UGT2B15 and UGT2B17, among which UGT2B7 showed the highest efficiency of glucuronidation. To explain the biological function of BPAF biotransformation, the estrogenic activities of BPAF and BPAF-G were evaluated in ER-positive breast cancer T47D and MCF7 cells. BPAF significantly stimulates ER-regulated gene expression and cell proliferation at the dose of 100 nM and 1 μM in breast cancer cells. However, BPAF-G did not show any induction of estrogenic activity at the same dosages, implying that formation of BPAF-G is a potential host defense mechanism against BPAF. Based on our study, biotransformation of BPAF to BPAF-G can eliminate BPAF-induced estrogenic activity, which is therefore considered as reducing the potential threat to human beings. PMID:24349450

  16. Biotransformation of bisphenol AF to its major glucuronide metabolite reduces estrogenic activity.

    PubMed

    Li, Ming; Yang, Yunjia; Yang, Yi; Yin, Jie; Zhang, Jing; Feng, Yixing; Shao, Bing

    2013-01-01

    Bisphenol AF (BPAF), an endocrine disrupting chemical, can induce estrogenic activity through binding to estrogen receptor (ER). However, the metabolism of BPAF in vivo and the estrogenic activity of its metabolites remain unknown. In the present study, we identified four metabolites including BPAF diglucuronide, BPAF glucuronide (BPAF-G), BPAF glucuronide dehydrated and BPAF sulfate in the urine of Sprague-Dawley (SD) rats. BPAF-G was further characterized by nuclear magnetic resonance (NMR). After treatment with a single dose of BPAF, BPAF was metabolized rapidly to BPAF-G, as detected in the plasma of SD rats. Biotransformation of BPAF to BPAF-G was confirmed with human liver microsomes (HLM), and Vmax of glucuronidation for HLM was 11.6 nmol/min/mg. We also found that BPAF glucuronidation could be mediated through several human recombinant UDP-glucuronosyltransferases (UGTs) including UGT1A1, UGT1A3, UGT1A8, UGT1A9, UGT2B4, UGT2B7, UGT2B15 and UGT2B17, among which UGT2B7 showed the highest efficiency of glucuronidation. To explain the biological function of BPAF biotransformation, the estrogenic activities of BPAF and BPAF-G were evaluated in ER-positive breast cancer T47D and MCF7 cells. BPAF significantly stimulates ER-regulated gene expression and cell proliferation at the dose of 100 nM and 1 μM in breast cancer cells. However, BPAF-G did not show any induction of estrogenic activity at the same dosages, implying that formation of BPAF-G is a potential host defense mechanism against BPAF. Based on our study, biotransformation of BPAF to BPAF-G can eliminate BPAF-induced estrogenic activity, which is therefore considered as reducing the potential threat to human beings. PMID:24349450

  17. Thyroid Disruption in Zebrafish Larvae by Short-Term Exposure to Bisphenol AF

    PubMed Central

    Tang, Tianle; Yang, Yang; Chen, Yawen; Tang, Wenhao; Wang, Fuqiang; Diao, Xiaoping

    2015-01-01

    Bisphenol AF (BPAF) is extensively used as a raw material in industry, resulting in its widespread distribution in the aqueous environment. However, the effect of BPAF on the hypothalamic-pituitary-thyroidal (HPT) axis remains unknown. For elucidating the disruptive effects of BPAF on thyroid function and expression of the representative genes along the HPT axis in zebrafish (Danio rerio) embryos, whole-body total 3,3′,5-triiodothyronine (TT3), total 3,5,3′,5′-tetraiodothyronine (TT4), free 3,3′,5-triiodothyronine (FT3) and free 3,5,3′,5′-tetraiodothyronine (FT4) levels were examined following 168 h post-fertilization exposure to different BPAF concentrations (0, 5, 50 and 500 μg/L). The results showed that whole-body TT3, TT4, FT3 and FT4 contents decreased significantly with the BPAF treatment, indicating an endocrine disruption of thyroid. The expression of thyroid-stimulating hormone-β and thyroglobulin genes increased after exposing to 50 μg/L BPAF in seven-day-old larvae. The expressions of thyronine deiodinases type 1, type 2 and transthyretin mRNAs were also significantly up-regulated, which were possibly associated with a deterioration of thyroid function. However, slc5a5 gene transcription was significantly down-regulated at 50 μg/L and 500 μg/L BPAF exposure. Furthermore, trα and trβ genes were down-regulated transcriptionally after BPAF exposure. It demonstrates that BPAF exposure triggered thyroid endocrine toxicity by altering the whole-body contents of thyroid hormones and changing the transcription of the genes involved in the HPT axis in zebrafish larvae. PMID:26501309

  18. Thyroid Disruption in Zebrafish Larvae by Short-Term Exposure to Bisphenol AF.

    PubMed

    Tang, Tianle; Yang, Yang; Chen, Yawen; Tang, Wenhao; Wang, Fuqiang; Diao, Xiaoping

    2015-10-01

    Bisphenol AF (BPAF) is extensively used as a raw material in industry, resulting in its widespread distribution in the aqueous environment. However, the effect of BPAF on the hypothalamic-pituitary-thyroidal (HPT) axis remains unknown. For elucidating the disruptive effects of BPAF on thyroid function and expression of the representative genes along the HPT axis in zebrafish (Danio rerio) embryos, whole-body total 3,3',5-triiodothyronine (TT3), total 3,5,3',5'-tetraiodothyronine (TT4), free 3,3',5-triiodothyronine (FT3) and free 3,5,3',5'-tetraiodothyronine (FT4) levels were examined following 168 h post-fertilization exposure to different BPAF concentrations (0, 5, 50 and 500 μg/L). The results showed that whole-body TT3, TT4, FT3 and FT4 contents decreased significantly with the BPAF treatment, indicating an endocrine disruption of thyroid. The expression of thyroid-stimulating hormone-β and thyroglobulin genes increased after exposing to 50 μg/L BPAF in seven-day-old larvae. The expressions of thyronine deiodinases type 1, type 2 and transthyretin mRNAs were also significantly up-regulated, which were possibly associated with a deterioration of thyroid function. However, slc5a5 gene transcription was significantly down-regulated at 50 μg/L and 500 μg/L BPAF exposure. Furthermore, trα and trβ genes were down-regulated transcriptionally after BPAF exposure. It demonstrates that BPAF exposure triggered thyroid endocrine toxicity by altering the whole-body contents of thyroid hormones and changing the transcription of the genes involved in the HPT axis in zebrafish larvae. PMID:26501309

  19. The action of neuropeptide AF on passive avoidance learning. Involvement of neurotransmitters.

    PubMed

    Palotai, Miklós; Telegdy, Gyula; Bagosi, Zsolt; Jászberényi, Miklós

    2016-01-01

    Neuropeptide AF (NPAF) is an amidated octadecapeptide, which is member of the RFamide peptide family. NPAF is encoded by the farp-1 gene and acts through the G protein coupled NPFF-1 and NPFF-2 receptors. NPAF is involved in several physiological functions of the central nervous system, however we have little evidence about the involvement of NPAF in learning and memory. Therefore, the aim of the present study was to investigate the action of NPAF on consolidation of memory in a passive avoidance learning paradigm in mice. We have also investigated the underlying neurotransmissions and the action of NPAF on β-amyloid-induced memory impairment. Accordingly, mice were pretreated with a nonselective muscarinic acetylcholine receptor antagonist, atropine, a non-selective 5-HT2 serotonergic receptor antagonist, cyproheptadine, a mixed 5-HT1/5-HT2 serotonergic receptor antagonist, methysergide, a D2, D3, D4 dopamine receptor antagonist, haloperidol, a non-selective opioid receptor antagonist, naloxone, a nitric oxide synthase inhibitor, nitro-l-arginine, a α1/α2β-adrenergic receptor antagonist, prazosin, a nonselective β-adrenergic receptor antagonist, propranolol or β-amyloid 25-35 in combination with NPAF administration. Our results demonstrate for the first time that NPAF improves the consolidation of passive avoidance learning. This effect is mediated through muscarinic cholinergic, 5HT1- and 5HT2-serotoninergic, dopaminergic, nitrergic and α- and β-adrenergic neurotransmissions, but not by opioid transmission, since atropine, cyproheptadine, methysergide, haloperidol, nitro-l-arginine, prazosin and propranolol reversed the action of NPAF, whereas naloxone was ineffective. The present study also shows that NPAF reverses the β-amyloid 25-35-induced memory impairment. PMID:26639667

  20. Neuropeptide AF induces anxiety-like and antidepressant-like behavior in mice.

    PubMed

    Palotai, Miklós; Telegdy, Gyula; Tanaka, Masaru; Bagosi, Zsolt; Jászberényi, Miklós

    2014-11-01

    Little is known about the action of neuropeptide AF (NPAF) on anxiety and depression. Only our previous study provides evidence that NPAF induces anxiety-like behavior in rats. Therefore, the aim of the present study was to investigate the action of NPAF on depression-like behavior and the underlying neurotransmissions in mice. In order to determine whether there are species differences between rats and mice, we have investigated the action of NPAF on anxiety-like behavior in mice as well. A modified forced swimming test (mFST) and an elevated plus maze test (EPMT) were used to investigate the depression and anxiety-related behaviors, respectively. Mice were treated with NPAF 30min prior to the tests. In the mFST, the animals were pretreated with a non-selective muscarinic acetylcholine receptor antagonist, atropine, a non-selective 5-HT2 serotonergic receptor antagonist, cyproheptadine, a mixed 5-HT1/5-HT2 serotonergic receptor antagonist, methysergide, a D2/D3/D4 dopamine receptor antagonist, haloperidol, a α1/α2β-adrenergic receptor antagonist, prazosin or a non-selective β-adrenergic receptor antagonist, propranolol 30min before the NPAF administration. In the mFST, NPAF decreased the immobility time and increased the climbing and swimming times. This action was reversed completely by methysergide and partially by atropine, whereas cyproheptadine, haloperidol, prazosin and propranolol were ineffective. In the EPMT, NPAF decreased the time spent in the arms (open/open+closed). Our results demonstrate that NPAF induces anti-depressant-like behavior in mice, which is mediated, at least in part, through 5HT2-serotonergic and muscarinic cholinergic neurotransmissions. In addition, the NPAF-induced anxiety is species-independent, since it develops also in mice. PMID:25116251

  1. Use of novel oral anticoagulants for patients with atrial fibrillation: systematic review and clinical implications.

    PubMed

    Albert, Nancy M

    2014-01-01

    Atrial fibrillation (AF), a common arrhythmia, increases the risk of ischemic stroke. Stroke and bleeding scores for patients with AF can help to stratify risk and determine the need for antithrombotic therapy, for which warfarin has been the gold standard. Although highly effective, warfarin has several limitations that can lead to its underuse. Data from randomized, Phase III clinical trials of the novel oral anticoagulants, dabigatran, a direct thrombin inhibitor, and rivaroxaban and apixaban, both factor Xa inhibitors, indicate these drugs are at least noninferior to warfarin for the prevention of stroke and systemic embolism. They are easier to administer, and have an equivalent or lower risk of bleeding versus warfarin. A better understanding of the risks and benefits of the novel oral anticoagulants, and their use in clinical practice, will prepare clinicians to anticipate and address educational and clinical needs of AF patients and their families, and promote evidence-based prescription of appropriate and safe anticoagulation therapy. PMID:24373340

  2. Letter to the Editor: H-1, C-13 and N-15 Assignments for the Archaeglobus fulgidis Protein AF2095.

    SciTech Connect

    Powers, Robert; Acton, Thomas; Chiang, Yiwen; Rajan, Paranji K.; Cort, John R.; Kennedy, Michael A.; Liu, Jinfeng; Ma, LiChung; Rost, Burkhard; Montelione, Gaetano

    2004-09-01

    The Human genome project promises to provide an unprecedented wealth of information on cell biology, development, evolution and physiology. Translating this immense increase in genomic information into advances in medicine and human health requires a concerted effort to explore and investigate the structure and molecular activity for the vast amount of proteins in the Human proteome that lack any such explicit experimental information. Structural genomics is providing a means to determine the molecular and cellular function of these proteins by characterizing the complete range of protein folds (Montelione, 2001). By annotating sequence information with a protein structure, it is sometimes possible to decipher the biochemical activity of hypothetical proteins from structural similarity and the conservation of spatial arrangement of active site residues. Homology can often be inferred by structural similarity even in the absence of recognizable sequence similarity, and can sometimes be used to identify functional relationships between distantly related proteins. Determining an experimental structure for each protein in a proteome is currently impractical because of the significant time commitment and resources required by X-ray and NMR. Therefore, the current paradigm of structural genomics is to determine a representative structure for each cluster of homologous protein domain sequences that lack similarity to a protein domain with a known structure. In this manner, comparative modeling using a single experimental structure can provide approximate but useful 3D structural information for an entire protein domain family. The Northeast Structural Genomics Consortium (NESG; www.nesg.org) is a pilot project funded by the National Institutes of Health Protein Structure Initiative, focusing on proteins from eukaryotic model organisms including humans. The thermophillic archaea Archaeglobus fulgidis AF2095 protein is an example of a protein of unknown biological function

  3. Role of Platelets in Thromboembolism in Patients with Atrial Fibrillation.

    PubMed

    Gosk-Bierska, Izabela; Wasilewska, Marta; Wysokiński, Waldemar

    2016-01-01

    Thromboembolic complications of atrial fibrillation (AF) are a major cause of morbidity and mortality but the mechanism of its process remain poorly understood. There are many as yet unanswered questions surrounding the increased thrombotic tendency in AF. One of the crucial questions is what determines the fact that a thrombus remains in the left atrium in situ in some patients, while in others it breaks off and leads to embolic complications. Recent studies indicated an important role of platelets in the left atrial's thrombus formation and suggest that the embolic potential of left atrial thromboses depends on the involvement of platelets in the process of fibrin stabilization rather than aggregation. New methods for investigating platelets function, such as the analysis of transcription activity of RNA coming from platelets contained in thrombi formed in AF, creates an opportunity for studying populations of platelets that are directly involved in homeostatic clot formation. In this paper we present current opinions on the participation of platelets in the pathogenesis of thromboembolism in patients with AF. PMID:26935511

  4. [Effect of down-regulating mll-af9 gene expression on proliferation of acute monocytic leukemia cell line THP-1].

    PubMed

    Li, Lei; Zhang, Ai-Hua; Liu, Ling-Bo; Bi, Lan; Wang, Li; Zhao, Ya-Jie; Zou, Ping

    2008-04-01

    This study was aimed to investigate the effect of small interfering RNA (siRNA) on the expression of mll-af9 oncogene and the proliferation of human acute monocytic leukemia cell line THP-1. One group of siRNA was designed targeting mll-af9 mRNA and finally obtained by chemosynthesis. Then the obtained siRNA was transfected into cultured human acute monocytic leukemia cell line THP-1 by lipofectamine. Flow cytometry was used to detect siRNA transfection efficiency. The level of mll-af9 mRNA expression was analyzed by reverse transcription polymerase chain reaction (RT-PCR). The cell proliferation rate was assayed by MTT. The change of cell cycles and apoptosis rate was detected by flow cytometry. The results showed that the siRNA transfection efficiency was 69.1%+/-1.8%. The level of mll-af9 mRNA expression was significantly inhibited in siRNA-transfected cells as compared with the controls. mll-af9-targeted siRNA inhibited the proliferation of THP-1 cells and induced cell apoptosis effectively after transfection. The percentage of G0/G1 phase cells significantly increased in siRNA-transfected cells in comparion with the control cells, but the percentage of S phase cells significantly decreased. It is concluded that the mll-af9-targeted siRNA can effectively inhibit the proliferation of human acute monocytic leukemia cell line THP-1. PMID:18426643

  5. Complexity Generation in Fungal Peptidyl Alkaloid Biosynthesis: Oxidation of Fumiquinazoline A to the Heptacyclic Hemiaminal Fumiquinazoline C by the Flavoenzyme Af12070 from Aspergillus fumigatus†

    PubMed Central

    Ames, Brian D.; Haynes, Stuart W.; Gao, Xue; Evans, Bradley S; Kelleher, Neil L.; Tang, Yi; Walsh, Christopher T.

    2011-01-01

    The human pathogen Aspergillus fumigatus makes a series of fumiquinazoline (FQ) peptidyl alkaloids of increasing scaffold complexity using L-Trp, two equivalents of L-Ala, and the non-proteinogenic amino acid anthranilate as building blocks. The FQ gene cluster encodes two nonribosomal peptide synthetases (NRPS) and two flavoproteins. The trimodular NRPS Af12080 assembles FQF (the first level of complexity) while the next two enzymes, Af12060 and Af12050, act in tandem in an oxidative annulation sequence to couple alanine to the indole side chain of FQF to yield the imidazolindolone-containing FQA. In this study we show that the fourth enzyme, the mono-covalent flavoprotein Af12070, introduces a third layer of scaffold complexity by converting FQA to the spirohemiaminal FQC, presumably by catalyzing the formation of a transient imine within the pyrazinone ring (and therefore acting in an unprecedented manner as an FAD-dependent amide oxidase). FQC subsequently converts non-enzymatically to the known cyclic aminal FQD. We also investigated the effect of substrate structure on Af12070 activity and subsequent cyclization with a variety of FQA analogues, including an FQA diastereomer (2′-epi-FQA) which is an intermediate in the fungal biosynthesis of the tremorgenic tryptoquialanine. 2′-epi-FQA is processed by Af12070 to epi-FQD, not epi-FQC, illustrating that the delicate balance in product cyclization regiochemistry can be perturbed by a remote stereochemical center. PMID:21899262

  6. Influence of cytochrome c on apoptosis induced by Anagrapha (Syngrapha) falcifera multiple nuclear polyhedrosis virus (AfMNPV) in insect Spodoptera litura cells.

    PubMed

    Liu, Lijun; Peng, Jianxin; Liu, Kaiyu; Yang, Hong; Li, Yi; Hong, Huazhu

    2007-09-01

    We investigated the influence of cytochrome c on apoptosis induced by Anagrapha (Syngrapha) falcifera multiple nuclear polyhedrosis virus (AfMNPV). Microscopic observation revealed that infection of SL-1 cells with AfMNPV resulted in apoptosis, displaying apoptotic bodies in fluorescent-stained nuclei of AfMNPV-infected SL-1cells. Western blot analysis demonstrated that AfMNPV-induced apoptosis in insect SL-1 cells was significantly inhibited by cyclosporin A which blocked a translocation of cytochrome c from the mitochondria to the cytosol. As determined by using AC-DEVD-AFC as substrate, the activity of caspase-3 in AfMNPV-induced cells was detected as early as 4h post infection, gradually increased with time extension, and reached a highest level after 16h of infection. However, activity of caspase-3 in apoptotic cells decreased in the presence of cyclosporin A (30microM), indicating that activation of caspase-3 in SfaMNPV-induced cells was dependent on the release of cytochrome c from the mitochondria. In addition, cyclosporin A could markedly inhibit mitochondrial transmembrane potential (DeltaPsim) disruption in undergoing apoptotic cells. These data indicate that cytochrome c plays a key role in AfMNPV-induced apoptosis in S. litura cells and may be required for caspase activation during the induction of apoptosis. PMID:17478109

  7. Impact of deteriorated calcium-phosphate homeostasis on amputation-free survival after endovascular revascularization in patients with critical limb ischemia on hemodialysis.

    PubMed

    Hioki, Hirofumi; Miyashita, Yusuke; Shiraki, Tatsuya; Iida, Osamu; Uematsu, Masaaki; Miura, Takashi; Ebisawa, Souichirou; Ikeda, Uichi

    2016-04-01

    Patients on hemodialysis (HD) have abnormalities of calcium-phosphate (CaP) homeostasis and high CaP product contributes to atherosclerosis pathogenesis and adverse events. Patients on HD with critical limb ischemia (CLI) are at risk for major amputation and death because of advanced systemic atherosclerotic disease. The aim of this study was to evaluate the relationship between CaP product and amputation-free survival (AFS) in CLI after endovascular treatment (EVT). We retrospectively analyzed 221 CLI patients on HD. In Kaplan-Meier analysis, AFS was significantly lower in patients with CaP product ⩾ 55 mg(2)/dL(2) compared to those with CaP product <55 mg(2)/dL(2) (54.3% vs 78.5%, p = 0.002). However, neither serum phosphate nor calcium levels were individually associated with AFS. In multivariate analysis, CaP product ⩾ 55 mg(2)/dL(2) was an independent predictor for AFS in CLI patients on HD (hazard ratio, 3.03; 95% confidence interval, 1.78-5.15; p-value < 0.001). We concluded abnormal CaP homeostasis was associated with lower AFS after EVT in CLI patients on HD, and can serve for their risk stratification. PMID:26681436

  8. Attitudes toward anticoagulant treatment among nonvalvular atrial fibrillation patients at high risk of stroke and low risk of bleed

    PubMed Central

    Crivera, Concetta; Nelson, Winnie W; Schein, Jeff R; Witt, Edward A

    2016-01-01

    Background Atrial fibrillation (AF) is associated with an increased risk of stroke. Anticoagulant (AC) therapies are effective at treating AF, but carry with them an increased risk of bleed. Research suggests that a large proportion of AF patients who have high risk of stroke and low risk of bleeding are not currently receiving AC treatment. The goal of this study was to understand the reasons why these patients do not engage in this potentially life-saving treatment. Method Through a self-report online survey, using validated instruments, 1,184 US adults who self-reported a diagnosis of AF were screened for the risk of stroke and bleed. Of these patients, 230 (19.4%) were at high risk of stroke, low risk of bleed, and not currently using an AC treatment, and were asked follow-up questions to assess their reasons for nontreatment, attitudes toward treatment, and attitudes toward dosing regimens. Results The most common reasons patients stopped AC treatment were concerns regarding bleeding (27.8%) and other medical concerns (26.6%), whereas the most common reason cited for not being prescribed an AC in the first place was the use of antiplatelet therapy as an alternative (57.1%). In both cases, potentially erroneous decisions regarding perceived stoke and/or bleeding risk were also a factor. Finally, the largest factors regarding attitudes toward treatment and dosing regimen were instructions from an authority figure (eg, physician, pharmacist) and ease of use, respectively. Conclusion Results suggest that many AF patients who are at high risk of stroke but at low risk of bleed may not be receiving AC due to potentially inaccurate beliefs about risk. This study also found that AF patients place trust in physicians above other factors such as cost when making treatment decisions. Increased education of patients by physicians on the risks and benefits may be a simple strategy to improve outcomes. PMID:27274206

  9. Patient Outcomes According to Adherence to Treatment Guidelines for Rhythm Control of Atrial Fibrillation

    PubMed Central

    Qin, Dingxin; Leef, George; Alam, Mian Bilal; Rattan, Rohit; Munir, Mohamad Bilal; Patel, Divyang; Khattak, Furqan; Vaghasia, Nishit; Adelstein, Evan; Jain, Sandeep K.; Saba, Samir

    2015-01-01

    Background Although guidelines for antiarrhythmic drug therapy in atrial fibrillation (AF) were published in 2006, it remains uncertain whether adherence to these guidelines affects patient outcomes. Methods and Results We retrospectively evaluated the records of 5976 consecutive AF patients who were prescribed at least 1 antiarrhythmic drug between 2006 and 2013. Patients with 1 or more prescribed antiarrhythmic drugs that did not comply with guideline recommendations comprised the non–guideline‐directed group (=2920); the remainder constituted the guideline‐directed group (=3056). Time to events was assessed using the survival analysis method and adjusted for covariates using Cox regression. Rates of adherence to the guidelines increased significantly with a higher degree of prescriber specialization in arrhythmias (49%, 55%, and 60% for primary care physicians, general cardiologists, and cardiac electrophysiologists, respectively, P=0.001) for the first prescribed antiarrhythmic drug. Compared to the non–guideline‐directed group, the guideline‐directed group had higher rates of heart failure, but lower baseline CHADS2‐VASc scores (P<0.001) and lower rates of coronary artery disease, valvular disease, hypertension, hyperlipidemia, pulmonary disease, and renal insufficiency (P<0.05 for all). During 45±26 months follow‐up, the guideline‐directed group had a lower risk of AF recurrence (hazard ratio=0.86, 95% CI=0.80 to 0.93), fewer hospital admissions for AF (hazard ratio=0.87, 95% CI=0.79 to 0.97), and fewer procedures for recurrent AF, including electrical cardioversion, pacemaker implantation, and atrioventricular nodal ablation (P<0.01 for all). The mortality and stroke risks were similar between the groups. Conclusions Adherence to published guidelines in the antiarrhythmic management of AF is associated with improved patient outcomes. PMID:25845930

  10. Early Experience Using a Left Atrial Appendage Occlusion Device in Patients with Atrial Fibrillation

    PubMed Central

    Kim, Yung Ly; Joung, Boyoung; On, Young Keun; Shim, Chi Young; Lee, Moon Hyoung; Kim, Young-Hoon

    2012-01-01

    Purpose Atrial fibrillation (AF) is one of the major risk factors for ischemic stroke, and 90% of thromboembolisms in these patients arise from the left atrial appendage (LAA). Recently, it has been documented that an LAA occlusion device (OD) is not inferior to warfarin therapy, and that it reduces mortality and risk of stroke in patients with AF. Materials and Methods We implanted LAA-ODs in 5 Korean patients (all male, 59.8±7.3 years old) with long-standing persistent AF or permanent AF via a percutaneous trans-septal approach. Results 1) The major reasons for LAA-OD implantation were high risk of recurrent stroke (80%), labile international neutralizing ratio with hemorrhage (60%), and 3/5 (60%) patients had a past history of failed cardioversion for rhythm control. 2) The mean LA size was 51.3±5.0 mm and LAA size was 25.1×30.1 mm. We implanted the LAA-OD (28.8±3.4 mm device) successfully in all 5 patients with no complications. 3) After eight weeks of anticoagulation, all patients switched from warfarin to anti-platelet agent after confirmation of successful LAA occlusion by trans-esophageal echocardiography. Conclusion We report on our early experience with LAA-OD deployment in patients with 1) persistent or permanent AF who cannot tolerate anticoagulation despite significant risk of ischemic stroke, or 2) recurrent stroke in patients who are unable to maintain sinus rhythm. PMID:22187236

  11. Clinical impact of quantitative left atrial vortex flow analysis in patients with atrial fibrillation: a comparison with invasive left atrial voltage mapping.

    PubMed

    Lee, Jung Myung; Hong, Geu-Ru; Pak, Hui-Nam; Shim, Chi Young; Houle, Helene; Vannan, Mani A; Kim, Minji; Chung, Namsik

    2015-08-01

    Recently, left atrial (LA) vortex flow analysis using contrast transesophageal echocardiography (TEE) has been shown to be feasible and has demonstrated significant differences in vortex flow morphology and pulsatility between normal subjects and patients with atrial fibrillation (AF). However, the relationship between LA vortex flow and electrophysiological properties and the clinical significance of LA vortex flow are unknown. The aims of this study were (1) to compare LA vortex flow parameters with LA voltage and (2) to assess the predictive value of LA vortex flow parameters for the recurrence of AF after radiofrequency catheter ablation (RFCA). Thirty-nine patients with symptomatic non-valvular AF underwent contrast TEE before undergoing RFCA for AF. Quantitative LA vortex flow parameters were analyzed by Omega flow (Siemens Medical Solution, Mountain View, CA, USA). The morphology and pulsatility of LA vortex flow were compared with electrophysiologic parameters that were measured invasively. Hemodynamic, electrophysiological, and vortex flow parameters were compared between patients with and without early recurrence of AF after RFCA. Morphologic parameters, including LA vortex depth, length, width, and sphericity index were not associated with LA voltage or hemodynamic parameters. The relative strength (RS), which represents the pulsatility power of LA, was positively correlated with LA voltage (R = 0.53, p = 0.01) and LA appendage flow velocity (R = 0.73, p < 0.001) and negatively correlated with LA volume index (R = -0.56, p < 0.001). Patients with recurrent AF after RFCA showed significantly lower RS (1.7 ± 0.2 vs 1.9 ± 0.4, p = 0.048) and LA voltage (0.9 ± 0.7 vs 1.7 ± 0.8, p = 0.004) than patients without AF recurrence. In the relatively small LA dimension group (LA volume index ≤ 33 ml/m(2)), RS was significantly lower (2.1 ± 0.3 vs 1.7 ± 0.1, p = 0.029) in patients with the recurrent AF. Quantitative LA vortex flow analysis, especially RS

  12. Activated KRAS Cooperates with MLL-AF4 to Promote Extramedullary Engraftment and Migration of Cord Blood CD34+ HSPC But Is Insufficient to Initiate Leukemia.

    PubMed

    Prieto, Cristina; Stam, Ronald W; Agraz-Doblas, Antonio; Ballerini, Paola; Camos, Mireia; Castaño, Julio; Marschalek, Rolf; Bursen, Aldeheid; Varela, Ignacio; Bueno, Clara; Menendez, Pablo

    2016-04-15

    The MLL-AF4 (MA4) fusion gene is the genetic hallmark of an aggressive infant pro-B-acute lymphoblastic leukemia (B-ALL). Our understanding of MA4-mediated transformation is very limited. Whole-genome sequencing studies revealed a silent mutational landscape, which contradicts the aggressive clinical outcome of this hematologic malignancy. Only RAS mutations were recurrently detected in patients and found to be associated with poorer outcome. The absence of MA4-driven B-ALL models further questions whether MA4 acts as a single oncogenic driver or requires cooperating mutations to manifest a malignant phenotype. We explored whether KRAS activation cooperates with MA4 to initiate leukemia in cord blood-derived CD34(+) hematopoietic stem/progenitor cells (HSPC). Clonogenic and differentiation/proliferation assays demonstrated that KRAS activation does not cooperate with MA4 to immortalize CD34(+) HSPCs. Intrabone marrow transplantation into immunodeficient mice further showed that MA4 and KRAS(G12V) alone or in combination enhanced hematopoietic repopulation without impairing myeloid-lymphoid differentiation, and that mutated KRAS did not cooperate with MA4 to initiate leukemia. However, KRAS activation enhanced extramedullary hematopoiesis of MA4-expressing cell lines and CD34(+) HSPCs that was associated with leukocytosis and central nervous system infiltration, both hallmarks of infant t(4;11)(+) B-ALL. Transcriptional profiling of MA4-expressing patients supported a cell migration gene signature underlying the mutant KRAS-mediated phenotype. Collectively, our findings demonstrate that KRAS affects the homeostasis of MA4-expressing HSPCs, suggesting that KRAS activation in MA4(+) B-ALL is important for tumor maintenance rather than initiation. Cancer Res; 76(8); 2478-89. ©2016 AACR. PMID:26837759

  13. Incidence and Severity of Coronary Artery Disease in Patients with Atrial Fibrillation Undergoing First-Time Coronary Angiography

    PubMed Central

    Kralev, Stefan; Schneider, Kathrin; Lang, Siegfried; Süselbeck, Tim; Borggrefe, Martin

    2011-01-01

    Background In standard reference sources, the incidence of coronary artery disease (CAD) in patients with atrial fibrillation (AF) ranged between 24 and 46.5%. Since then, the incidence of cardiovascular risk factors (CRF) has increased and modern treatment strategies (“pill in the pocket”) are only applicable to patients without structural heart disease. The aim of this study was to investigate the incidence and severity of CAD in patients with AF. Methods From January 2005 until December 2009, we included 261 consecutive patients admitted to hospital with paroxysmal, persistent or permanent AF in this prospective study. All patients underwent coronary angiography and the Framingham risk score (FRS) was calculated. Patients with previously diagnosed or previously excluded CAD were excluded. Results The overall incidence of CAD in patients presenting with AF was 34%; in patients >70 years, the incidence of CAD was 41%. The incidence of patients undergoing a percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) was 21%. Patients with CAD were older (73±8 years vs 68±10 years, p = 0.001), had significantly more frequent hypercholesterolemia (60% vs 30%, p<0.001), were more frequent smokers (26% vs 13%, p = 0.017) and suffered from angina more often (37% vs 2%, p<0.001). There was a significant linear trend among the FRS categories in percentage and the prevalence of CAD and PCI/CABG (p<0.0001). Conclusions The overall incidence of CAD in patients presenting with AF was relatively high at 34%; the incidence of PCI/CABG was 21%. Based upon increasing CRF in the western world, we recommend a careful investigation respecting the FRS to either definitely exclude or establish an early diagnosis of CAD – which could contribute to an early and safe therapeutic strategy considering type Ic antiarrhythmics and oral anticoagulation. PMID:21957469

  14. Effectiveness of brain natriuretic peptide in predicting postoperative atrial fibrillation in patients undergoing non-cardiac thoracic surgery.

    PubMed

    Toufektzian, Levon; Zisis, Charalambos; Balaka, Christina; Roussakis, Antonios

    2015-05-01

    A best evidence topic was written according to a structured protocol. The question addressed was whether plasma brain natriuretic peptide (BNP) levels could effectively predict the occurrence of postoperative atrial fibrillation (AF) in patients undergoing non-cardiac thoracic surgery. A total of 14 papers were identified using the reported search, of which 5 represented the best evidence to answer the clinical question. The authors, date, journal, country, study type, population, outcomes and key results are tabulated. All studies were prospective observational, and all reported a significant association between BNP and N-terminal (NT)-proBNP plasma levels measured in the immediate preoperative period and the incidence of postoperative AF in patients undergoing either anatomical lung resections or oesophagectomy. One study reported a cut-off value of 30 pg/ml above which significantly more patients suffered from postoperative AF (P < 0.0001), while another one reported that this value could predict postoperative AF with a sensitivity of 77% and a specificity of 93%. Another study reported that patients with NT-proBNP levels of 113 pg/ml or above had an 8-fold increased risk of developing postoperative AF. These findings support that BNP or NT-proBNP levels, especially when determined during the preoperative period, if increased, are able to identify patients at risk for the development of postoperative AF after anatomical major lung resection or oesophagectomy. The same does not seem to be true for lesser lung resections. These high-risk patients might have a particular benefit from the administration of prophylactic antiarrhythmic therapy. PMID:25630332

  15. Exposure to Bisphenol AF disrupts sex hormone levels and vitellogenin expression in zebrafish.

    PubMed

    Yang, Xiaoxi; Liu, Yuchen; Li, Jia; Chen, Minjie; Peng, Di; Liang, Yong; Song, Maoyong; Zhang, Jie; Jiang, Guibin

    2016-03-01

    Bisphenol AF (BPAF) is widely used in food-contact products, electronic devices, and as a cross-linking reagent in fluoroelastomers. There are growing concerns about its toxicity and endocrine-disrupting effects based on its structural similarity with bisphenol A (BPA). The endocrine-disrupting effects of BPAF were studied by exposing 2-month-old zebrafish to 0, 0.05, 0.25, or 1 mg/L BPAF for 28 days and evaluating the effect on growth, histopathology, hormone levels, enzyme activity, and gene expression. The overall fitness was not significantly affected. There were no apparent alterations in the gills and intestine tissues of both sexes after BPAF exposure. However, exposure to 1 mg/L BPAF caused damage to the liver in the male fish, characterized by hepatocellular swelling and vacuolation. There was no obvious effect in the liver of female fish, suggesting that the hepatic toxicity of BPAF is gender dependent. Gonadal examination indicated that exposure to 1 mg/L BPAF caused induction of acellular areas in the testis and retardation of oocyte development in the ovary. BPAF exposure increased free triiodothyronine levels of females in a dose-dependent manner. In males, the testosterone levels decreased in a concentration-dependent manner. In contrast, estradiol levels increased in a concentration-dependent manner and were significantly higher in males exposed to 1 mg/L BPAF compared with the controls. In females, 0.05 and 0.25 mg/L BPAF caused an increase in testosterone levels. Furthermore, the estradiol levels increased in females exposed to 0.05 and 1 mg/L. We observed an upregulation of hepatic vitellogenin in both sexes and significantly higher levels in males exposed to 1 mg/L BPAF and females exposed to 0.25 mg/L BPAF, suggesting that BPAF has an estrogenic activity. Our results indicate that BPAF is an endocrine-disrupting chemical that exerts reproductive toxicity and estrogenic effects on zebrafish. PMID:25213402

  16. Underuse of anticoagulation in patients with atrial fibrillation.

    PubMed

    Vallakati, Ajay; Lewis, William R

    2016-01-01

    Atrial fibrillation (AF) is a major risk factor for ischemic stroke. Guidelines recommend anticoagulation for patients with intermediate and high stroke risk (CHA2DS2-VASc score ≥ 2). Underuse of anticoagulants among eligible patients remains a persistent problem. Evidence demonstrates that the psychology of the fear of causing harm (omission bias) results in physicians' hesitancy to initiate anticoagulation and an inaccurate estimation of stroke risk. The American Heart Association (AHA) initiated the Get With The Guidelines-AFIB (GWTG-AFIB) module in June 2013 to enhance guideline adherence for treatment and management of AF. Better quality of care for AF patients can be provided by increasing adherence to anticoagulation guidelines and improving patient compliance with anticoagulation therapy through education and established protocols. Nonvitamin K antagonist oral anticoagulants may facilitate better patient adherence due to ease of administration and reduced monitoring burden. In this review, we discuss the reasons for underuse, omission bias contributing to underuse, and different strategies to address this issue. PMID:26666288

  17. Cost Analysis of Periprocedural Imaging in Patients Undergoing Catheter Ablation for Atrial Fibrillation

    PubMed Central

    Pokorney, Sean D.; Hammill, Bradley G.; Qualls, Laura G.; Steinberg, Benjamin A.; Curtis, Lesley H.; Piccini, Jonathan P.

    2014-01-01

    Cardiovascular imaging is an important part of procedural planning and safety for catheter ablation of atrial fibrillation (AF). However, the costs of imaging surrounding catheter ablation of AF have not been described. Medicare fee-for-service data were used to evaluate Medicare expenditures before, during, and after catheter ablation for AF from July 2007 to December 2009. Among 11,525 patients who underwent catheter ablation for AF, the mean overall expenditure on the day of the procedure was $14,455 (SD $7,441). The mean imaging expenditure in the periprocedural period, which included the 30 days before the catheter ablation and the day of the ablation itself, was $884 (SD $455). Periprocedural imaging expenditures varied by the imaging strategy used, ranging from a mean of $557 (SD $269) for patients with electroanatomic mapping only to $1,234 (SD $461) for patients with electroanatomic mapping, transesophageal echocardiogram, and computed tomography or magnetic resonance imaging. Mean patient-level imaging expenditures varied by provider (mean $872, SD $249). Periprocedural imaging expenditures also varied by patient risk, with mean expenditures of $862 (SD $444) for patients with a CHADS2 score of ≥2 compared with $907 (SD $466) for CHADS2 score <2 (p <0.001). In conclusion, peri-procedural imaging accounts for approximately 6% of mean Medicare expenditures for catheter ablation of AF. The expenditures for periprocedural imaging vary both at the patient and at the provider level and they are inversely related to stroke risk by CHADS2 score. PMID:24952929

  18. Photometric properties for selected algol-type binaries. VIII. The triple systems DI Peg and AF Gem revisited

    SciTech Connect

    Yang, Yuan-Gui; Li, Shu-Zheng; Yang, Ying E-mail: yangyg@chnu.edu.cn

    2014-06-01

    New extensive photometry for two triple binary stars, DI Peg and AF Gem, was performed from 2012 October to 2013 January, with two small telescopes at Xinglong station (XLs) of NAOC. From new multi-color observations and previously published ones in literature, the photometric models were (re)deduced using the updated Wilson-Devinney code. The results indicated that the low third lights exist in two classic Algol-type binaries, whose fill-out factors for the more massive components are f{sub p} = 78.2(± 0.4)% for DI Peg, and f{sub p} = 69.0(± 0.3)% for AF Gem, respectively. Through analyzing the O–C curves, the orbital periods for two binaries change in the complicated mode. The period of DI Peg possibly appears to show two light-time orbits, whose modulated periods are P {sub 3} = 54.6(± 0.5) yr and P {sub 4} = 23.0(± 0.6) yr, respectively. The inferred minimum masses for the inner and outer sub-stellar companions are M {sub in} = 0.095 M {sub ☉} and M {sub out} = 0.170 M {sub ☉}, respectively. Therefore, DI Peg may be a quadruple star. The orbital period of AF Gem appears to show a continuous period decrease or a cyclic variation; the latter may be preferable. The cyclic oscillation, with a period of 120.3(± 2.5) yr, may be attributed to the light-time effect due to the third body. This kind of additional companion may extract angular momentum from the central system, which may play a key role in the evolution of the binary.

  19. Catalytic soman scavenging by Y337A/F338A acetylcholinesterase mutant assisted with novel site-directed aldoximes

    PubMed Central

    Kovarik, Zrinka; Hrvat, Nikolina Maček; Katalinić, Maja; Sit, Rakesh K.; Paradyse, Alexander; Žunec, Suzana; Musilek, Kamil; Fokin, Valery V.; Taylor, Palmer; Radić, Zoran

    2016-01-01

    Exposure to the nerve agent soman is difficult to treat due to the rapid dealkylation of soman-acetylcholinesterase (AChE) conjugate known as aging. Oxime antidotes commonly used to reactivate organophosphate inhibited AChE are ineffective against soman, while the efficacy of the recommended nerve agent bioscavenger butyrylcholinesterase is limited by strictly stoichiometric scavenging. To overcome this limitation, we tested ex vivo, in human blood, and in vivo, in soman exposed mice, the capacity of aging-resistant human AChE mutant Y337A/F338A in combination with oxime HI-6 to act as a catalytic bioscavenger of soman. HI-6 was previously shown in vitro to efficiently reactivate this mutant upon soman, as well as VX, cyclosarin, sarin and paraoxon inhibition. We here demonstrate that ex vivo, in whole human blood, 1 μM soman was detoxified within 30 minutes when supplemented with 0.5 μM Y337A/F338A AChE and 100 μM HI-6. This combination was further tested in vivo. Catalytic scavenging of soman in mice improved the therapeutic outcome and resulted in the delayed onset of toxicity symptoms. Furthermore, in a preliminary in vitro screen we identified an even more efficacious oxime than HI-6, in a series of forty-two pyridinium aldoximes, and five imidazole 2-aldoxime N-propyl pyridinium derivatives. One of the later imidazole aldoximes, RS-170B, was a 2–3 –fold more effective reactivator of Y337A/F338A AChE than HI-6 due to the smaller imidazole ring, as indicated by computational molecular models, that affords a more productive angle of nucleophilic attack. PMID:25835984

  20. Photometric Properties for Selected Algol-type Binaries. VIII. The Triple Systems DI Peg and AF Gem Revisited

    NASA Astrophysics Data System (ADS)

    Yang, Yuan-Gui; Yang, Ying; Li, Shu-Zheng

    2014-06-01

    New extensive photometry for two triple binary stars, DI Peg and AF Gem, was performed from 2012 October to 2013 January, with two small telescopes at Xinglong station (XLs) of NAOC. From new multi-color observations and previously published ones in literature, the photometric models were (re)deduced using the updated Wilson-Devinney code. The results indicated that the low third lights exist in two classic Algol-type binaries, whose fill-out factors for the more massive components are fp = 78.2(± 0.4)% for DI Peg, and fp = 69.0(± 0.3)% for AF Gem, respectively. Through analyzing the O-C curves, the orbital periods for two binaries change in the complicated mode. The period of DI Peg possibly appears to show two light-time orbits, whose modulated periods are P 3 = 54.6(± 0.5) yr and P 4 = 23.0(± 0.6) yr, respectively. The inferred minimum masses for the inner and outer sub-stellar companions are M in = 0.095 M ⊙ and M out = 0.170 M ⊙, respectively. Therefore, DI Peg may be a quadruple star. The orbital period of AF Gem appears to show a continuous period decrease or a cyclic variation; the latter may be preferable. The cyclic oscillation, with a period of 120.3(± 2.5) yr, may be attributed to the light-time effect due to the third body. This kind of additional companion may extract angular momentum from the central system, which may play a key role in the evolution of the binary.

  1. The ultraviolet-bright, slowly declining transient PS1-11af as a partial tidal disruption event

    SciTech Connect

    Chornock, R.; Berger, E.; Zauderer, B. A.; Kamble, A.; Soderberg, A. M.; Czekala, I.; Dittmann, J.; Drout, M.; Foley, R. J.; Fong, W.; Kirshner, R. P.; Lunnan, R.; Marion, G. H.; Narayan, G.; Gezari, S.; Rest, A.; Riess, A. G.; Chomiuk, L.; Huber, M. E.; Lawrence, A.; and others

    2014-01-01

    We present the Pan-STARRS1 discovery of the long-lived and blue transient PS1-11af, which was also detected by Galaxy Evolution Explorer with coordinated observations in the near-ultraviolet (NUV) band. PS1-11af is associated with the nucleus of an early type galaxy at redshift z = 0.4046 that exhibits no evidence for star formation or active galactic nucleus activity. Four epochs of spectroscopy reveal a pair of transient broad absorption features in the UV on otherwise featureless spectra. Despite the superficial similarity of these features to P-Cygni absorptions of supernovae (SNe), we conclude that PS1-11af is not consistent with the properties of known types of SNe. Blackbody fits to the spectral energy distribution are inconsistent with the cooling, expanding ejecta of a SN, and the velocities of the absorption features are too high to represent material in homologous expansion near a SN photosphere. However, the constant blue colors and slow evolution of the luminosity are similar to previous optically selected tidal disruption events (TDEs). The shape of the optical light curve is consistent with models for TDEs, but the minimum accreted mass necessary to power the observed luminosity is only ∼0.002 M {sub ☉}, which points to a partial disruption model. A full disruption model predicts higher bolometric luminosities, which would require most of the radiation to be emitted in a separate component at high energies where we lack observations. In addition, the observed temperature is lower than that predicted by pure accretion disk models for TDEs and requires reprocessing to a constant, lower temperature. Three deep non-detections in the radio with the Very Large Array over the first two years after the event set strict limits on the production of any relativistic outflow comparable to Swift J1644+57, even if off-axis.

  2. Single-Unit Activity during Natural Vision: Diversity, Consistency, and Spatial Sensitivity among AF Face Patch Neurons

    PubMed Central

    Russ, Brian E.; Elnaiem, Heba D.; Kurnikova, Anastasia I.; Leopold, David A.

    2015-01-01

    Several visual areas within the STS of the macaque brain respond strongly to faces and other biological stimuli. Determining the principles that govern neural responses in this region has proven challenging, due in part to the inherently complex stimulus domain of dynamic biological stimuli that are not captured by an easily parameterized stimulus set. Here we investigated neural responses in one fMRI-defined face patch in the anterior fundus (AF) of the STS while macaques freely view complex videos rich with natural social content. Longitudinal single-unit recordings allowed for the accumulation of each neuron's responses to repeated video presentations across sessions. We found that individual neurons, while diverse in their response patterns, were consistently and deterministically driven by the video content. We used principal component analysis to compute a family of eigenneurons, which summarized 24% of the shared population activity in the first two components. We found that the most prominent component of AF activity reflected an interaction between visible body region and scene layout. Close-up shots of faces elicited the strongest neural responses, whereas far away shots of faces or close-up shots of hindquarters elicited weak or inhibitory responses. Sensitivity to the apparent proximity of faces was also observed in gamma band local field potential. This category-selective sensitivity to spatial scale, together with the known exchange of anatomical projections of this area with regions involved in visuospatial analysis, suggests that the AF face patch may be specialized in aspects of face perception that pertain to the layout of a social scene. PMID:25855170

  3. Three enzymatically active neurotoxins of Clostridium botulinum strain Af84: BoNT/A2, /F4, and /F5.

    PubMed

    Kalb, Suzanne R; Baudys, Jakub; Smith, Theresa J; Smith, Leonard A; Barr, John R

    2014-04-01

    Botulinum neurotoxins (BoNTs) are produced by various species of clostridia and are potent neurotoxins which cause the disease botulism, by cleaving proteins needed for successful nerve transmission. There are currently seven confirmed serotypes of BoNTs, labeled A-G, and toxin-producing clostridia typically only produce one serotype of BoNT. There are a few strains (bivalent strains) which are known to produce more than one serotype of BoNT, producing either both BoNT/A and /B, BoNT/A and /F, or BoNT/B and /F, designated as Ab, Ba, Af, or Bf. Recently, it was reported that Clostridium botulinum strain Af84 has three neurotoxin gene clusters: bont/A2, bont/F4, and bont/F5. This was the first report of a clostridial organism containing more than two neurotoxin gene clusters. Using a mass spectrometry based proteomics approach, we report here that all three neurotoxins, BoNT/A2, /F4, and /F5, are produced by C. botulinum Af84. Label free MS(E) quantification of the three toxins indicated that toxin composition is 88% BoNT/A2, 1% BoNT/F4, and 11% BoNT/F5. The enzymatic activity of all three neurotoxins was assessed by examining the enzymatic activity of the neurotoxins upon peptide substrates, which mimic the toxins' natural targets, and monitoring cleavage of the substrates by mass spectrometry. We determined that all three neurotoxins are enzymatically active. This is the first report of three enzymatically active neurotoxins produced in a single strain of Clostridium botulinum. PMID:24605815

  4. AFS-2 FLOWSHEET MODIFICATIONS TO ADDRESS THE INGROWTH OF PU(VI) DURING METAL DISSOLUTION

    SciTech Connect

    Crapse, K.; Rudisill, T.; O'Rourke, P.; Kyser, E.

    2014-07-02

    In support of the Alternate Feed Stock Two (AFS-2) PuO{sub 2} production campaign, Savannah River National Laboratory (SRNL) conducted a series of experiments concluding that dissolving Pu metal at 95°C using a 6–10 M HNO{sub 3} solution containing 0.05–0.2 M KF and 0–2 g/L B could reduce the oxidation of Pu(IV) to Pu(VI) as compared to dissolving Pu metal under the same conditions but at or near the boiling temperature. This flowsheet was demonstrated by conducting Pu metal dissolutions at 95°C to ensure that PuO{sub 2} solids were not formed during the dissolution. These dissolution parameters can be used for dissolving both Aqueous Polishing (AP) and MOX Process (MP) specification materials. Preceding the studies reported herein, two batches of Pu metal were dissolved in the H-Canyon 6.1D dissolver to prepare feed solution for the AFS-2 PuO{sub 2} production campaign. While in storage, UV-visible spectra obtained from an at-line spectrophotometer indicated the presence of Pu(VI). Analysis of the solutions also showed the presence of Fe, Ni, and Cr. Oxidation of Pu(IV) produced during metal dissolution to Pu(VI) is a concern for anion exchange purification. Anion exchange requires Pu in the +4 oxidation state for formation of the anionic plutonium(IV) hexanitrato complex which absorbs onto the resin. The presence of Pu(VI) in the anion feed solution would require a valence adjustment step to prevent losses. In addition, the presence of Cr(VI) would result in absorption of chromate ion onto the resin and could limit the purification of Pu from Cr which may challenge the purity specification of the final PuO{sub 2} product. Initial experiments were performed to quantify the rate of oxidation of Pu(IV) to Pu(VI) (presumed to be facilitated by Cr(VI)) as functions of the HNO{sub 3} concentration and temperature in simulated dissolution solutions containing Cr, Fe, and Ni. In these simulated Pu dissolutions studies, lowering the temperature from near boiling

  5. New Oral Anticoagulants vs Vitamin K Antagonists: Benefits for Health-Related Quality of Life in Patients with Atrial Fibrillation

    PubMed Central

    Alegret, Josep M.; Viñolas, Xavier; Arias, Miguel A.; Martínez-Rubio, Antoni; Rebollo, Pablo; Ràfols, Carles; Martínez-Sande, José L.

    2014-01-01

    New oral anticoagulants (NOAC) have demonstrated their efficacy as an alternative to vitamin K antagonists (VKA) in the prophylaxis of cardioembolic events in patients with atrial fibrillation (AF). However, evidence on the benefits of NOAC in health-related quality of life (HRQoL) is lacking.We evaluated changes in HRQoL related to oral anticoagulation therapy employing a specific questionnaire in a cohort of 416 patients with AF undergoing electrical cardioversion. In terms of HRQoL, we observed a progressive adaptation to treatment with VKA; satisfaction with NOAC remained constant. Older age, higher left ventricular ejection fraction and NOAC were associated with better HRQoL. PMID:24843316

  6. New oral anticoagulants vs vitamin K antagonists: benefits for health-related quality of life in patients with atrial fibrillation.

    PubMed

    Alegret, Josep M; Viñolas, Xavier; Arias, Miguel A; Martínez-Rubio, Antoni; Rebollo, Pablo; Ràfols, Carles; Martínez-Sande, José L

    2014-01-01

    New oral anticoagulants (NOAC) have demonstrated their efficacy as an alternative to vitamin K antagonists (VKA) in the prophylaxis of cardioembolic events in patients with atrial fibrillation (AF). However, evidence on the benefits of NOAC in health-related quality of life (HRQoL) is lacking.We evaluated changes in HRQoL related to oral anticoagulation therapy employing a specific questionnaire in a cohort of 416 patients with AF undergoing electrical cardioversion. In terms of HRQoL, we observed a progressive adaptation to treatment with VKA; satisfaction with NOAC remained constant. Older age, higher left ventricular ejection fraction and NOAC were associated with better HRQoL. PMID:24843316

  7. Terraced copper growth deposited onto Teflon AF1600 by the excimer laser irradiation of Cu(hfac)TMVS

    SciTech Connect

    Popovici, D.; Piyakis, K.; Sacher, E.; Meunier, M.

    1996-12-31

    The authors are studying the feasibility of constructing Cu/fluoropolymer multilayer devices, in an effort to reduce both metal R and insulator C, a necessary condition in VLSI and GSI microelectronic applications. The laser chemical vapor deposition (LCVD) of the organometallic precursor Cu(hfac)TMVS (hexafluoroacetylacetonate)(trimethylvinylsilane) is used to grow copper films on a Teflon AF1600 substrate. Exposure to excimer laser radiation at 248 nm results in a terraced copper growth. A simple model, based on interference effects in the Teflon and copper layers, is presented to account for this structure.

  8. The AFFORD Clinical Decision Aid To Identify Emergency Department Patients With Atrial Fibrillation At Low Risk For 30-Day Adverse Events

    PubMed Central

    Barrett, Tyler W.; Storrow, Alan B.; Jenkins, Cathy A.; Abraham, Robert L.; Liu, Dandan; Miller, Karen F.; Moser, Kelly M.; Russ, Stephan; Roden, Dan M.; Harrell, Frank E.; Darbar, Dawood

    2015-01-01

    There is wide variation in the management of emergency department (ED) patients with atrial fibrillation (AF). We aimed to derive and internally validate the first prospective, ED-based clinical decision aid to identify patients with AF at low risk for 30-day adverse events. We performed a prospective cohort study at a university-affiliated, tertiary-care, ED. Patients were enrolled from June 9, 2010 to February 28, 2013 and followed for 30 days. We enrolled a convenience sample of ED patients presenting with symptomatic AF. Candidate predictors were based on ED data available in the first two hours. The decision aid was derived using model approximation (preconditioning) followed by strong bootstrap internal validation. We utilized an ordinal outcome hierarchy defined as the incidence of the most severe adverse event within 30 days of the ED evaluation. Of 497 patients enrolled, stroke and AF-related death occurred in 13 (3%) and 4 (<1%) patients, respectively. The decision aid included the following: age, triage vitals (systolic blood pressure, temperature, respiratory rate, oxygen saturation, supplemental oxygen requirement); medical history (heart failure, home sotalol use, prior percutaneous coronary intervention, electrical cardioversion, cardiac ablation, frequency of AF symptoms); ED data (2 hour heart rate, chest radiograph results, hemoglobin, creatinine, and brain natriuretic peptide). The decision aid’s c-statistic in predicting any 30-day adverse event was 0.7 (95% CI, 0.65, 0.76). In conclusion, among ED patients with AF, AFFORD provides the first evidence based decision aid for identifying patients who are at low risk for 30-day adverse events and candidates for safe discharge. PMID:25633190

  9. Prevalence and Clinical Significance of Sterile Intra-amniotic Inflammation in Patients with Preterm Labor and Intact Membranes

    PubMed Central

    Romero, Roberto; Miranda, Jezid; Chaiworapongsa, Tinnakorn; Korzeniewski, Steven J.; Chaemsaithong, Piya; Gotsch, Francesca; Dong, Zhong; Ahmed, Ahmed I.; Yoon, Bo Hyun; Hassan, Sonia S.; Kim, Chong J.; Yeo, Lami

    2014-01-01

    Problem Inflammation and infection play a major role in preterm birth. The purpose of this study was to: 1) determine the prevalence and clinical significance of sterile intra-amniotic inflammation; and 2) examine the relationship between amniotic fluid (AF) concentrations of high mobility group box-1 (HMGB1) and the interval from amniocentesis-to-delivery in patients with sterile intra-amniotic inflammation. Method of Study AF samples obtained from 135 women with preterm labor and intact membranes were analyzed using cultivation techniques as well as broad-range PCR and mass spectrometry (PCR/ESI-MS). Sterile intra-amniotic inflammation was defined when patients with negative AF cultures and without evidence of microbial footprints had intra-amniotic inflammation (AF interleukin-6 ≥ 2.6 ng/mL). Results 1) The frequency of sterile intra-amniotic inflammation was significantly greater than that of microbial-associated intra-amniotic inflammation [26% (35/135) vs. 11% (15/135); (p=0.005)]; 2) patients with sterile intra-amniotic inflammation delivered at comparable gestational ages, had similar rates of acute placental inflammation and adverse neonatal outcomes as patients with microbial-associated intra-amniotic inflammation; and 3) patients with sterile intra-amniotic inflammation and high AF concentrations of HMGB1 (≥ 8.55 ng/mL) delivered earlier than those with low AF concentrations of HMGB1 (p=0.02). Conclusions 1) sterile intra-amniotic inflammation is more frequent than microbial-associated intra-amniotic inflammation; and 2) we propose that danger signals participate in sterile intra-amniotic inflammation in the setting of preterm labor. PMID:25078709

  10. The Cox-maze IV procedure for lone atrial fibrillation: a single center experience in 100 consecutive patients

    PubMed Central

    Weimar, Timo; Bailey, Marci S.; Watanabe, Yoshiyuki; Marin, Donna; Maniar, Hersh S.; Schuessler, Richard B.

    2015-01-01

    Purpose The Cox-maze III procedure (CMP) has achieved high success rates for the surgical treatment of atrial fibrillation (AF). In 2002, our group introduced a simplified CMP, in which most incisions were replaced with linear lines of ablation using bipolar radiofrequency and cryoenergy. This operation, termed the CMP-IV, has significantly shortened operative times and allowed for a minimally invasive approach. This report evaluates our results in 100 consecutive patients undergoing a stand-alone CMP-IV. Methods Data were collected prospectively on 100 patients (mean age, 56±10 years) who underwent a CMP-IV from January 2002 through May 2010. All patients were available for follow-up with a mean follow-up of 17±10 months. Electrocardiograms or 24-h Holter monitorings were obtained at 6, 12, and 24 months. Data were analyzed using a longitudinal database containing over 380 variables. Results Thirty-one percent of patients had paroxysmal AF, with the remainder having persistent (6%) or longstanding persistent AF (63%). The mean preoperative duration of AF was 7.4±6.7 years. The mean left atrial diameter was 4.7±1.1 cm. In this group, 40 patients had failed with a mean of 2.6±1.3 catheter ablations. Mean aortic cross-clamp time was 41±13 min. There was one postoperative mortality. Postoperative freedom from AF was 93%, 90%, and 90% at 6, 12, and 24 months, respectively. Freedom from AF off antiarrhythmic medication was 82%, 82%, and 84% at 6, 12, and 24 months, respectively. Conclusion The less invasive CMP-IV has a high single procedure success rate, even with improved follow-up and stricter definitions of failure. PMID:21340516

  11. Electrocardiogram PR Interval Is a Surrogate Marker to Predict New Occurrence of Atrial Fibrillation in Patients with Frequent Premature Atrial Contractions.

    PubMed

    Chun, Kwang Jin; Hwang, Jin Kyung; Choi, So Ra; Park, Seung-Jung; On, Young Keun; Kim, June Soo; Park, Kyoung-Min

    2016-04-01

    The clinical significance of prolonged PR interval has not been evaluated in patients with frequent premature atrial contractions (PACs). We investigated whether prolonged PR interval could predict new occurrence of atrial fibrillation (AF) in patients with frequent PACs. We retrospectively analyzed 684 patients with frequent PACs (> 100 PACs/day) who performed repeated 24-hour Holter monitoring. Prolonged PR interval was defined as longer than 200 msec. Among 684 patients, 626 patients had normal PR intervals (group A) and 58 patients had prolonged PR intervals (group B). After a mean follow-up of 59.3 months, 14 patients (24.1%) in group B developed AF compared to 50 patients (8.0%) in group A (P < 0.001). Cox regression analysis showed that prolonged PR interval (hazard ratio [HR], 1.950; 95% CI, 1.029-3.698; P = 0.041), age (HR, 1.033; 95% CI, 1.006-1.060; P = 0.015), and left atrial (LA) dimension (HR, 1.061; 95% CI, 1.012-1.112; P = 0.015) were associated with AF occurrence. Prolonged PR interval, advanced age, and enlarged LA dimension are independent risk factors of AF occurrence in patients with frequent PACs. PMID:27051234

  12. Electrocardiogram PR Interval Is a Surrogate Marker to Predict New Occurrence of Atrial Fibrillation in Patients with Frequent Premature Atrial Contractions

    PubMed Central

    Hwang, Jin Kyung; Choi, So Ra; Park, Seung-Jung; Kim, June Soo

    2016-01-01

    The clinical significance of prolonged PR interval has not been evaluated in patients with frequent premature atrial contractions (PACs). We investigated whether prolonged PR interval could predict new occurrence of atrial fibrillation (AF) in patients with frequent PACs. We retrospectively analyzed 684 patients with frequent PACs (> 100 PACs/day) who performed repeated 24-hour Holter monitoring. Prolonged PR interval was defined as longer than 200 msec. Among 684 patients, 626 patients had normal PR intervals (group A) and 58 patients had prolonged PR intervals (group B). After a mean follow-up of 59.3 months, 14 patients (24.1%) in group B developed AF compared to 50 patients (8.0%) in group A (P < 0.001). Cox regression analysis showed that prolonged PR interval (hazard ratio [HR], 1.950; 95% CI, 1.029–3.698; P = 0.041), age (HR, 1.033; 95% CI, 1.006–1.060; P = 0.015), and left atrial (LA) dimension (HR, 1.061; 95% CI, 1.012–1.112; P = 0.015) were associated with AF occurrence. Prolonged PR interval, advanced age, and enlarged LA dimension are independent risk factors of AF occurrence in patients with frequent PACs. PMID:27051234

  13. The relationship between HbA1c & atrial fibrillation after off-pump coronary artery bypass surgery in diabetic patients

    PubMed Central

    Surer, Suleyman; Seren, Mustafa; Saydam, Onur; Bulut, Ali; Kiziltepe, Ugursay

    2016-01-01

    Objective: Diabetes mellitus is recognized as a risk factor for mortality and morbidity after coronary bypass grafting. We aimed to determine the association between preoperative hemoglobin HbA1c and AF after isolated off-pump coronary bypass grafting (OPCAB). Methods: The seventy-two diabetic patients undergoing isolated off-pump coronary bypass grafting were retrospectively analyzed for AF. They were divided into; Low (4.8–5.4%), Medium (5.5–8%) and High (8.1–11.5%) groups. The three groups were compared with respect to demographic, echocardiographic, intraoperative and postoperative clinical characteristics correlation. Results: Three patients died during postoperative period. AF occurred in 12 patients (16.6%) after surgery. The incidence of postoperative AF was 15.3% in the lower, 4.4% middle and 57.1% upper group. There was statistically significant correlation between preoperative HbA1C and preoperative stroke, preoperative MI history, Left atrial (LA) size, preoperative levosimendan, preoperative clopidogrel, postoperative AF, postoperative dopamine and dobutamine use, IABP, duration of extubation time, 24-hour chest tube drainage, duration of ICU and hospital mortality. Univariate logistic regression analysis showed significant correlation between postoperative AF and variables like preoperative HbA1c levels, LVEF<30%, history of preoperative MI, preoperative use of levosimendan, preoperative use of clopidogrel, postoperative dopamine, dobutamine adrenaline use, left atrium size, 24-hour chest tube drainage and length of stay in the intensive care unit. Conclusion: Preoperative HbA1c levels could predict the occurrence of postoperative AF in diabetic patients and may entail to administer protective strategies. PMID:27022346

  14. Atg5-dependent autophagy contributes to the development of acute myeloid leukemia in an MLL-AF9-driven mouse model.

    PubMed

    Liu, Qiang; Chen, Longgui; Atkinson, Jennifer M; Claxton, David F; Wang, Hong-Gang

    2016-01-01

    Acute myeloid leukemia (AML) is a hierarchical hematopoietic malignancy originating from leukemic stem cells (LSCs). Autophagy is a lysosomal degradation pathway that is hypothesized to be important for the maintenance of AML as well as contribute to chemotherapy response. Here we employ a mouse model of AML expressing the fusion oncogene MLL-AF9 and explore the effects of Atg5 deletion, a key autophagy protein, on the malignant transformation and progression of AML. Consistent with a transient decrease in colony-forming potential in vitro, the in vivo deletion of Atg5 in MLL-AF9-transduced bone marrow cells during primary transplantation prolonged the survival of recipient mice, suggesting that autophagy has a role in MLL-AF9-driven leukemia initiation. In contrast, deletion of Atg5 in malignant AML cells during secondary transplantation did not influence the survival or chemotherapeutic response of leukemic mice. Interestingly, autophagy was found to be involved in the survival of differentiated myeloid cells originating from MLL-AF9-driven LSCs. Taken together, our data suggest that Atg5-dependent autophagy may contribute to the development but not chemotherapy sensitivity of murine AML induced by MLL-AF9. PMID:27607576

  15. The transactivation domain AF-2 but not the DNA-binding domain of the estrogen receptor is required to inhibit differentiation of avian erythroid progenitors.

    PubMed

    von Lindern, M; Boer, L; Wessely, O; Parker, M; Beug, H

    1998-02-01

    Earlier work demonstrated that an activated estrogen receptor (ER) is required for long-term self-renewal of c-ErbB-expressing avian erythroid progenitors. Here, we demonstrate that activation of the ER does not only arrest or retard differentiation of early progenitors but that it affects erythroid differentiation at all stages of erythroid maturation. A search for genes whose expression is affected by the ER showed that the 17beta-estradiol-activated receptor suppressed the differentiation-associated up-regulation of Gata-1, SCL-1, and globin genes in partially mature cells. In the same cells, the expression of carbonic anhydrase II (CAII) and histone H5 was enhanced. This led to premature expression of CAII, a possible explanation for the toxic effects of overexpressed ER. Repression specifically required the transactivation domain AF-2, but neither an intact DNA-binding domain (DBD) nor the AF-1 domain. The transcriptional activation of CAII, however, required both an intact AF-2 and a functional DBD. The requirement for the AF-2, but not the DBD, suggested that the ER may compete with other nuclear hormone receptors for transcriptional coactivators that bind AF-2, a domain well conserved within this family of transcription factors. We show, however, that this model does not apply for the most likely candidate, the avian thyroid hormone receptor. PMID:9482667

  16. Induction of apoptosis in MCF-7 cells by the hemagglutinin-neuraminidase glycoprotein of Newcastle disease virus Malaysian strain AF2240.

    PubMed

    Ghrici, Mohamed; El Zowalaty, Mohamed; Omar, Abdul Rahman; Ideris, Aini

    2013-09-01

    Newcastle disease virus (NDV) exerts its naturally occurring oncolysis possibly through the induction of apoptosis. We hypothesized that the binding of the virus to the cell via the hemagglutinin-neuraminidase (HN) glycoprotein may be sufficient to not only induce apoptosis but to induce a higher apoptosis level than the parental NDV AF2240 virus. NDV AF2240 induction of apoptosis in MCF-7 human breast cancer cells was analyzed and quantified. In addition, the complete HN gene of NDV strain AF2240 was amplified, sequenced and cloned into the pDisplay eukaryotic expression vector. HN gene expression was first detected at the cell surface membrane of the transfected MCF-7 cells. HN induction of apoptosis in transfected MCF-7 cells was analyzed and quantified. The expression of the HN gene alone was able to induce apoptosis in MCF-7 cells but it was a less potent apoptosis inducer compared to the parental NDV AF2240 strain. In conclusion, the NDV AF2240 strain is a more suitable antitumor candidate agent than its recombinant HN gene unless the latter is further improved by additional modifications. PMID:23807159

  17. Determinants of Left Atrial Appendage Volume in Stroke Patients without Chronic Atrial Fibrillation

    PubMed Central

    Taina, Mikko; Sipola, Petri; Muuronen, Antti; Hedman, Marja; Mustonen, Pirjo; Kantanen, Anne-Mari; Jäkälä, Pekka; Vanninen, Ritva

    2014-01-01

    Background Left atrial appendage (LAA) volume has been shown to be increased in patients with acute cryptogenic stroke. Atrial fibrillation (AF) is a well-recognized risk factor but it is not the only one associated with LAA enlargement. The aim of the study was to clarify the multifactorial etiology of LAA enlargement in cardiogenic stroke/TIA patients without AF. Methods Altogether 149 patients with suspected cardioembolic stroke/TIA (47 females; mean age 61 years) underwent cardiac CT. Diagnosed AF on admittance was an exclusion criteria but 24-hour Holter ambulatory ECG revealed paroxysmal AF (PAF) in 20 patients. Body surface area adjusted LAA volume was evaluated. Eighteen different variables were registered including general characteristics, definite and potential causal risk factors for ischemic stroke/TIA, clinical echoparameters and CT based cardiac volumetric and adipose tissue measurements. A stepwise linear regression analysis was performed to achieve a model adjusted for the number of predictors of LAA volume increase. Results In linear regression analysis, the best model accounted for 30% of the variability in LAA volume, including PAF (19%) and enlarged left atrial volume (6%), enlarged left ventricle end-systolic diameter (3%) and decreased pericardial adipose tissue (2%). No multi-colinearity between variables was observed. In addition to PAF, no other definitive or potential causal risk factors could account for the LAA volume in these patients. Conclusions LAA volume increase seems to be poorly associated with currently known stroke/TIA risk factors, except for AF. Targeting more comprehensive ECG monitoring for stroke patients with increased LAA volume should be considered. PMID:24595515

  18. Appropriate Use of Antithrombotic Medication in Canadian Patients With Nonvalvular Atrial Fibrillation.

    PubMed

    Bell, Alan D; Gross, Peter; Heffernan, Michael; Deschaintre, Yan; Roux, Jean-Francois; Purdham, Daniel M; Shuaib, Ashfaq

    2016-04-01

    This national chart audit of 7,019 patients with nonvalvular atrial fibrillation (AF) from 735 primary care physician practices sought to examine the management of Canadian patients with AF through an evidence-based, guideline-recommended approach. The appropriate use of oral anticoagulants (OACs) in this patient population and the potential factors guiding OAC choice were examined. Suboptimal dosing was seen. In patients on warfarin, 30.9% had not achieved a time in therapeutic range (TTR) in excess of 65% and, despite current Canadian guideline recommendations, were continued on warfarin rather than one of the novel OACs. In patients who received no antithrombotic therapy, 65.5% met criteria for treatment with an OAC. In addition, 62.8% of patients who were treated with acetylsalicylic acid monotherapy met guideline criteria for the use of an OAC. In those patients treated with an OAC, 24.8% were not on the recommended dose based on the product monograph or, if on warfarin, had a TTR <65%. Of the patients on novel OACs (NOACs), 7.4% of patients were underdosed, whereas overdosing was seen in 4.3%. Factors that may have contributed to dosing outside recommendations included underestimation of stroke risk, overestimation of bleed risk, compliance concerns, and lack of provincial reimbursement. In conclusion, significant correctable gaps remain in optimal treatment for stroke prevention in AF. PMID:26879070

  19. [Simultaneous determination of arsanilic, nitarsone and roxarsone residues in foods of animal origin by ASE-LC-AFS].

    PubMed

    Xiao, Ya-Bing; Zhang, Man; Wen, Hua-Wei

    2014-04-01

    A method for simultaneous determination of arsanilic, nitarsone and roxarsone (ROX) residues in foods of animal origin was developed by accelerated solvent extraction-liquid chromatography-atomic fluorescence spectrometry (ASE-LC-AFS). The ultrasound centrifugation extraction and accelerated solvent extraction were compared, and the accelerated solvent extraction conditions, namely the proportion of the extraction solvent, the extraction temperature, extraction time and extraction times, were optimized. The operating conditions of LC-AFS and the mobile phase were optimized. Under the optimal conditions, the calibration curves for ASA , NIT and ROX were linear over the concentration range of 0-2.0 mg x L(-1) and their correlation coefficients were 0.999 2-0.999 8. The detection limits of ASA, NIT and ROX were 2.4, 7.4 and 4.1 microg x L(-1) respectively. The average recoveries of ASA, NIT and ROX from two samples spiked at three levels of 0.5, 2, 5 mg x kg(-1) were in the ranges of 87.1%-93.2%, 85.2%-93.9%, and 84.2%-93.7% with RSDs of 1.4%-4.6%, 1.2%-4.2%, and 1.1%-4.5%, respectively. This method possesses the merits of convenience and good repeatability, and is a feasible method for analysis of ASA, NIT and ROX in foods of animal origin. PMID:25007637

  20. Speciation of antimony in airborne particulate matter using ultrasound probe fast extraction and analysis by HPLC-HG-AFS.

    PubMed

    Bellido-Martín, A; Gómez-Ariza, J L; Smichowsky, P; Sánchez-Rodas, D

    2009-09-01

    A fast extraction procedure has been developed for Sb(III) and Sb(V) oxoanions speciation in airborne particulate matter samples. Different extraction media (diammonium tartrate, hidroxilammonium clorhidrate, citric acid+ascorbic acid, phosphoric acid and citrate solutions) were tried, with assistance of an ultrasonic probe. The operation power and time of extraction were also optimized. The higher extraction recoveries were obtained with a 100 mmol L(-1) hidroxilammonium clorhidrate aqueous solution assisted by the ultrasound probe operated at 50 W during 3 min. The extracts were analyzed by HPLC-HG-AFS. The chromatographic separation of Sb(III) and Sb(V) was also optimized using diammonium tartrate and phthalic acid as mobile phases. The separation of both Sb species was performed in less than 3 min under isocratic conditions, using a 200 mmol L(-1) diammonium tartrate solution. The proposed extraction procedure and the HPLC-HG-AFS instrumental coupling have been successfully applied to airborne particulate matter samples, with high Sb content, collected in heavy traffic streets from Buenos Aires (Argentina). The results showed the presence of both Sb species at similar concentrations in the ng m(-3) level. The extraction yield was higher than 90% for all the analyzed samples. PMID:19699393

  1. Linear quadratic game and non-cooperative predictive methods for potential application to modelling driver-AFS interactive steering control

    NASA Astrophysics Data System (ADS)

    Na, Xiaoxiang; Cole, David J.

    2013-02-01

    This paper is concerned with the modelling of strategic interactions between the human driver and the vehicle active front steering (AFS) controller in a path-following task where the two controllers hold different target paths. The work is aimed at extending the use of mathematical models in representing driver steering behaviour in complicated driving situations. Two game theoretic approaches, namely linear quadratic game and non-cooperative model predictive control (non-cooperative MPC), are used for developing the driver-AFS interactive steering control model. For each approach, the open-loop Nash steering control solution is derived; the influences of the path-following weights, preview and control horizons, driver time delay and arm neuromuscular system (NMS) dynamics are investigated, and the CPU time consumed is recorded. It is found that the two approaches give identical time histories as well as control gains, while the non-cooperative MPC method uses much less CPU time. Specifically, it is observed that the introduction of weight on the integral of vehicle lateral displacement error helps to eliminate the steady-state path-following error; the increase in preview horizon and NMS natural frequency and the decline in time delay and NMS damping ratio improve the path-following accuracy.

  2. Comparison of the ferromagnetic Blume-Emery-Griffiths model and the AF spin-1 longitudinal Ising model at low temperature

    NASA Astrophysics Data System (ADS)

    Thomaz, M. T.; Corrêa Silva, E. V.

    2016-03-01

    We derive the exact Helmholtz free energy (HFE) of the standard and staggered one-dimensional Blume-Emery-Griffiths (BEG) model in the presence of an external longitudinal magnetic field. We discuss in detail the thermodynamic behavior of the ferromagnetic version of the model, which exhibits magnetic field-dependent plateaux in the z-component of its magnetization at low temperatures. We also study the behavior of its specific heat and entropy, both per site, at finite temperature. The degeneracy of the ground state, at T=0, along the lines that separate distinct phases in the phase diagram of the ferromagnetic BEG model is calculated, extending the study of the phase diagram of the spin-1 antiferromagnetic (AF) Ising model in S.M. de Souza and M.T. Thomaz, J. Magn. and Magn. Mater. 354 (2014) 205 [5]. We explore the implications of the equality of phase diagrams, at T=0, of the ferromagnetic BEG model with K/|J| = - 2 and of the spin-1 AF Ising model for D/|J| > 1/2.

  3. L17A/F19A Substitutions Augment the α-Helicity of β-Amyloid Peptide Discordant Segment

    PubMed Central

    Wang, Chih-Ching; Chen, Yi-Ru; Chang, Chi-Fon; Shiao, Ming-Shi; Chen, Yi-Cheng; Lin, Ta-Hsien

    2016-01-01

    β-amyloid peptide (Aβ) aggregation has been thought to be associated with the pathogenesis of Alzheimer’s disease. Recently, we showed that L17A/F19A substitutions may increase the structural stability of wild-type and Arctic-type Aβ40 and decrease the rates of structural conversion and fibril formation. However, the underlying mechanism for the increase of structural stability as a result of the alanine substitutions remained elusive. In this study, we apply nuclear magnetic resonance and circular dichroism spectroscopies to characterize the Aβ40 structure, demonstrating that L17A/F19A substitutions can augment the α-helicity of the residues located in the α/β-discordant segment (resides 15 to 23) of both wild-type and Arctic-type Aβ40. These results provide a structural basis to link the α-helicity of the α/β-discordant segment with the conformational conversion propensity of Aβ. PMID:27104649

  4. [Perioperative Management of Lung Cancer Patients with atrial fibrillation being treated by antiplatelet or anticoagulant therapy].

    PubMed

    Ishikawa, Shinya; Kasai, Yoshitaka; Matsuura, Natsumi; Tarumi, Shintaro; Nakano, Jun; Okuda, Masaya; Goto, Masashi; Ryu, Dagu; Go, Tetsuhiko; Yokomise, Hiroyasu

    2015-04-01

    In an aging society, the high incidence of surgery for the patients with ischemic heart disease(IHD)or atrial fibrillation(Af) under antiplatelet or anticoagulant therapy is a great problem. Interruption of antiplatelet or anticoagulant oral agents in the perioperative period may increase the risk of coronary or cerebral events. We retrospectively reviewed the surgical outcomes for lung cancer patients with IHD or Af. We reviewed 135 patients with lung cancer(41~88 years;97 men) who had preoperative oral administration of antiplatelet or anticoagulant drugs for IHD or Af between 2005 and 2012 at 2 centers, and analyzed retrospectively the perioperative medications and complications. IHD, Af and vasospastic angina(VSA) were complicated in 94, 33 and 8 patients, respectively. Drugeluted and bare-metal stents had been placed in 18 and 19 patients. Oral agents were aspirin in 68 patients, ticlopidine in 10 patients, clopidogrel in 15 patients and warfarin in 25 patients. These agents were stopped 2 to 60 days before surgery. Perioperative heparinization was performed in 22 patients. Oral agents were restarted after confirmation of hemostasis and no need for further invasive treatment. The surgical procedures were lobectomy in 88 patients, segmentectomy in 19 and partial resection in 25. There were no hemorrhagic or thromboembolic complications in a perioperative period except 1 case of pulmonary hemorrhage and 1 case of cerebral infarction. No perioperative hospital death was documented. Short-term interruption of antiplatelet or anticoagulant drugs before lung cancer surgery and heparinization was acceptable from the view of perioperative outcomes. PMID:25836998

  5. Atrial premature beats in patients with focal atrial fibrillation: incidence at baseline and impact of provocative maneuvers.

    PubMed

    Ventura, Rodolfo; Weiss, Christian; Willems, Stephan; Sturm, Nina; Klemm, Hanno; Meinertz, Thomas

    2002-10-01

    This study evaluated the incidence of atrial premature beats (APBs) and the impact of various provocative maneuvers in patients with focally initiated AF. Fifty patients (39 men, 57 +/- 0.4 years) with focally initiated, paroxysmal AF underwent Holter recording and a standardized protocol of provocative maneuvers: vagomechanical stimulation, adenosine 12 mg i.v., esmolol 500 ng/kg i.v., orciprenaline i.v. 5 mg/50 mL saline 0.9%, and atropine 0.01 mg/kg i.v. A surface ECG was recorded for 20 minutes at baseline and following each part of the protocol. High focal activity was defined as > or = 1 APB/minute. During Holter ECG, 29 (58%) patients had an amount of < 200 APBs, 12 (24%) patients < 700 > or = 200, and 9 (18%) patients > or = 700 APBs. Less than 1 hour of high focal activity was observed in 34 (68%) of the 50 patients. Before starting provocative maneuvers 15 (30%) patients had high focal activity whereas 35 (70%) presented < 1 APB/minute. In 29 (58%) patients APBs increased by > or = 1/min during provocative maneuvers: by vagomechanical stimulation in 11 patients, after adenosine in 15, esmolol in 12, orciprenaline in 15, and after atropine in 9 patients. In all patients with > or = 1 APB/min at baseline, focal activity decreased or disappeared during some single provocative maneuvers. AF occurred in eight patients under provocative maneuvers. No predictive factors of a successful provocative maneuver were detected with regard to the baseline patients characteristics and Holter results. In conclusion, patients with focally initiated AF have a low incidence of spontaneous APBs. Various provocative maneuvers successfully increase APBs in more than half of the patients; orciprenaline had the highest efficacy. Some provocative maneuvers may suppress APBs in the setting of high focal activity at baseline. PMID:12418745

  6. Case Report: Atrial Fibrillation After Intravenous Administration of Iodinated Contrast Medium in a Patient With Hepatocellular Carcinoma.

    PubMed

    Maimone, Sergio; Filomia, Roberto; Saitta, Carlo; Raimondo, Giovanni; Squadrito, Giovanni

    2015-09-01

    We describe the case of a 73-year-old woman with liver cirrhosis and hepatocellular carcinoma (HCC) who developed 2 distinct episodes of paroxystic atrial fibrillation (AF) each of which occurred 1 to 4 hours after iodine medium contrast-enhanced computed tomography. Sinus rhythm was restored by amiodarone therapy after the first AF episode and by electrical cardioversion after the second one. A careful clinical, biochemical, and instrumental examination showed that the patient had subclinical hyperthyroidism and moderate mitral insufficiency with mild atrial enlargement.Thus, the coexistence of both subclinical disthyroidism and of cardiac anatomical alterations may have predisposed the patient to AF that in fact occurred when exogenous iodine administration triggered a hyperthyroidism status. PMID:26334896

  7. Case Report: Atrial Fibrillation After Intravenous Administration of Iodinated Contrast Medium in a Patient With Hepatocellular Carcinoma

    PubMed Central

    Maimone, Sergio; Filomia, Roberto; Saitta, Carlo; Raimondo, Giovanni; Squadrito, Giovanni

    2015-01-01

    Abstract We describe the case of a 73-year-old woman with liver cirrhosis and hepatocellular carcinoma (HCC) who developed 2 distinct episodes of paroxystic atrial fibrillation (AF) each of which occurred 1 to 4 hours after iodine medium contrast-enhanced computed tomography. Sinus rhythm was restored by amiodarone therapy after the first AF episode and by electrical cardioversion after the second one. A careful clinical, biochemical, and instrumental examination showed that the patient had subclinical hyperthyroidism and moderate mitral insufficiency with mild atrial enlargement. Thus, the coexistence of both subclinical disthyroidism and of cardiac anatomical alterations may have predisposed the patient to AF that in fact occurred when exogenous iodine administration triggered a hyperthyroidism status. PMID:26334896

  8. Gene signatures of postoperative atrial fibrillation in atrial tissue after coronary artery bypass grafting surgery in patients receiving β-blockers.

    PubMed

    Kertai, Miklos D; Qi, Wenjing; Li, Yi-Ju; Lombard, Frederick W; Liu, Yutao; Smith, Michael P; Stafford-Smith, Mark; Newman, Mark F; Milano, Carmelo A; Mathew, Joseph P; Podgoreanu, Mihai V

    2016-03-01

    Atrial tissue gene expression profiling may help to determine how differentially expressed genes in the human atrium before cardiopulmonary bypass (CPB) are related to subsequent biologic pathway activation patterns, and whether specific expression profiles are associated with an increased risk for postoperative atrial fibrillation (AF) or altered response to β-blocker (BB) therapy after coronary artery bypass grafting (CABG) surgery. Right atrial appendage (RAA) samples were collected from 45 patients who were receiving perioperative BB treatment, and underwent CABG surgery. The isolated RNA samples were used for microarray gene expression analysis, to identify probes that were expressed differently in patients with and without postoperative AF. Gene expression analysis was performed to identify probes that were expressed differently in patients with and without postoperative AF. Gene set enrichment analysis (GSEA) was performed to determine how sets of genes might be systematically altered in patients with postoperative AF. Of the 45 patients studied, genomic DNA from 42 patients was used for target sequencing of 66 candidate genes potentially associated with AF, and 2,144 single-nucleotide polymorphisms (SNPs) were identified. We then performed expression quantitative trait loci (eQTL) analysis to determine the correlation between SNPs identified in the genotyped patients, and RAA expression. Probes that met a false discovery rate<0.25 were selected for eQTL analysis. Of the 17,678 gene expression probes analyzed, 2 probes met our prespecified significance threshold of false discovery rate<0.25. The most significant probe corresponded to vesicular overexpressed in cancer - prosurvival protein 1 gene (VOPP1; 1.83 fold change; P=3.47×10(-7)), and was up-regulated in patients with postoperative AF, whereas the second most significant probe, which corresponded to the LOC389286 gene (0.49 fold change; P=1.54×10(-5)), was down-regulated in patients with

  9. Oral anticoagulant therapy for stroke prevention in patients with atrial fibrillation undergoing ablation: results from the First European Snapshot Survey on Procedural Routines for Atrial Fibrillation Ablation (ESS-PRAFA).

    PubMed

    Potpara, Tatjana S; Larsen, Torben B; Deharo, Jean Claude; Rossvoll, Ole; Dagres, Nikolaos; Todd, Derick; Pison, Laurent; Proclemer, Alessandro; Purefellner, Helmut; Blomström-Lundqvist, Carina

    2015-06-01

    The European Snapshot Survey on Procedural Routines in Atrial Fibrillation Ablation (ESS-PRAFA) is a prospective, multicentre snapshot survey of patients undergoing atrial fibrillation (AF) ablation, conducted to collect patient-based data on current clinical practices in AF ablation in context of the latest AF Guidelines and contemporary oral anticoagulant therapies. The EP Research Network Centres were asked to prospectively enrol consecutive patients during a 6-week period (September/October 2014). Data were collected via the web-based case report form. We present the results pertinent to the use of antithrombotic therapies. Thirteen countries prospectively enrolled 455 eligible consecutive patients [mean age 59 ± 10.8 years, 131 (28.8%) females]. The mean CHA2DS2-VASc score was 1.12 ± 1.06 [137 patients (30.1%) had a score of ≥2]. Before ablation, 443 patients (97.4%) were on anticoagulant therapy [143 (31.4%) on non-vitamin K antagonist oral anticoagulants (NOACs) and 264 (58.0%) on vitamin K antagonists (VKAs)]. Of the latter, 79.7% underwent ablation without VKA interruption, whilst a variety of strategies were used in patients taking NOAC. After ablation, most patients (89.3%) continued the same anticoagulant as before, and 2 (0.4%) were not prescribed any anticoagulation. At discharge, 280 patients (62.2%) were advised oral anticoagulation for a limited period of mean 3.8 ± 2.2 months. On multivariate analysis, CHA2DS2-VASc, AF duration, prior VKA use, and estimated AF ablation success were significantly associated with the decision on short-term anticoagulation. Our results show the increasing use of NOAC in patients undergoing AF ablation and emphasize the need for more information to guide the periprocedural use of both NOACs and VKAs in real-world setting. PMID:26023177

  10. Intravenous heparin dosing strategy in hospitalized patients with atrial dysrhythmias.

    PubMed

    Roswell, Robert O; Greet, Brian; Shah, Sunny; Bernard, Samuel; Milin, Alexandra; Lobach, Iryna; Guo, Yu; Radford, Martha J; Berger, Jeffrey S

    2016-08-01

    Patients with non-valvular atrial fibrillation (AF) have an elevated stroke risk that is 2-7 times greater than in those without AF. Intravenous unfractionated heparin (UFH) is commonly used for hospitalized patients with atrial fibrillation and atrial flutter (AFL) to prevent stroke. Dosing strategies exist for intravenous anticoagulation in patients with acute coronary syndromes and venous thromboembolic diseases, but there are no data to guide providers on a dosing strategy for intravenous anticoagulation in patients with AF/AFL. 996 hospitalized patients with AF/AFL on UFH were evaluated. Bolus dosing and initial infusion rates of UFH were recorded along with rates of stroke, thromboemobolic events, and bleeding events as defined by the International Society on Thrombosis and Haemostasis criteria. Among 226 patients included in the analysis, 76 bleeding events occurred. Using linear regression analysis, initial rates of heparin infusion ranging from 9.7 to 11.8 units/kilogram/hour (U/kg/h) resulted in activated partial thromboplastin times that were within therapeutic range. The median initial infusion rate in patients with bleeding was 13.3 U/kg/h, while in those without bleeding it was 11.4 U/kg/h; p = 0.012. An initial infusion rate >11.0 U/kg/h yielded an OR 1.95 (1.06-3.59); p = 0.03 for any bleeding event. Using IV heparin boluses neither increased the probability of attaining a therapeutic aPTT (56.1 vs 56.3 %; p = 0.99) nor did it significantly increase bleeding events in the study (35.7 vs 31.3 %; p = 0.48). The results suggest that higher initial rates of heparin are associated with increased bleeding risk. From this dataset, initial heparin infusion rates of 9.7-11.0 U/kg/h without a bolus can result in therapeutic levels of anticoagulation in hospitalized patients with AF/AFL without increasing the risk of bleeding. PMID:26951166

  11. Analysis of 16 cystic fibrosis mutations in Mexican patients

    SciTech Connect

    Villalobos-Torres, C.; Rojas-Martinez, A.; Barrera-Saldana, H.A.

    1997-04-14

    We carried out molecular analysis of 80 chromosomes from 40 unrelated Mexican patients with a diagnosis of cystic fibrosis. The study was performed in two PCR steps: a preliminary one to identify mutation AF508, the most frequent cause of cystic fibrosis worldwide, and the second a reverse dot-blot with allele-specific oligonucleotide probes to detect 15 additional common mutations in the Caucasian population. A frequency of 45% for AF508 was found, making it the most common in our sample of Mexican patients. Another five mutations (G542X, 3849 + 10 kb C{r_arrow}T, N1303K, S549N, and 621 + 1 G{r_arrow}T) were detected, and these accounted for 11.25%. The remaining mutations (43.75%) were undetectable with the methodology used. 20 refs., 2 tabs.

  12. Extensive ameloblastic fibroma of the mandibula in a female adult patient: A case report with a follow-up of 3 years

    PubMed Central

    Tozoglu, Sinan; Hatipoglu, Mukerrem; Aytekin, Zeliha; Gurer, Elif Inanc

    2016-01-01

    Ameloblastic fibroma (AF) is rare benign odontogenic tumour which usually occurs in the first two decades of life. It can occur either the mandible or maxilla but it is most frequently found in the posterior region of the mandible. Treatment of AF in usual is a conservative approach, such as enucleation and curettage but the aggressive lesions require a radical approach. A more radical approach should be considered in older patients who have likely high recurrence tendency. This report describes a case of AF in a 38-year-old female patient identified during a routine radiographic exam. Tomographic examination through three-dimensional reconstruction indicated vestibular fenestration of the cortical bone, with involvement of lingual cortical bone as the lession extended to the posterior region. We removed the tumor under local anesthesia. In this case patient has continued to be followed frequently and has been disease-free for 3 years. PMID:27011753

  13. Differential ligand-dependent interactions between the AF-2 activating domain of nuclear receptors and the putative transcriptional intermediary factors mSUG1 and TIF1.

    PubMed Central

    vom Baur, E; Zechel, C; Heery, D; Heine, M J; Garnier, J M; Vivat, V; Le Douarin, B; Gronemeyer, H; Chambon, P; Losson, R

    1996-01-01

    Using a yeast two-hybrid system we report the isolation of a novel mouse protein, mSUG1, that interacts with retinoic acid receptor alpha (RAR alpha) both in yeast cells and in vitro in a ligand- and AF-2 activating domain (AF-2 AD)-dependent manner and show that it is a structural and functional homologue of the essential yeast protein SUG1. mSUG1 also efficiently interacts with other nuclear receptors, including oestrogen (ER), thyroid hormone (TR), Vitamin D3 (VDR) and retinoid X (RXR) receptors. By comparing the interaction properties of these receptors with mSUG1 and TIF1, we demonstrate that: (i) RXR alpha efficiently interacts with TIF1, but not with mSUG1, whereas TR alpha interacts much more efficiently with mSUG1 than with TIF1, and RAR alpha, VDR and ER efficiently interact with mSUG1 and TIF1; (ii) the amphipathic alpha-helix core of the AF-2 AD is differentially involved in interactions of RAR alpha with mSUG1 and TIF1; (iii) the AF-2 AD cores of RAR alpha and ER are similarly involved in their interaction with TIF1, but not with mSUG1. Thus, the interaction interfaces between the different receptors and either mSUG1 or TIF1 may vary depending on the nature of the receptor and the putative mediator of its AF-2 function. We discuss the possibility that mSUG1 and TIF1 may mediate the transcriptional activity of the AF-2 of nuclear receptors through different mechanisms. Images PMID:8598193

  14. Role of 20-HETE in the impaired myogenic and TGF responses of the Af-Art of Dahl salt-sensitive rats.

    PubMed

    Ge, Ying; Murphy, Sydney R; Fan, Fan; Williams, Jan Michael; Falck, John R; Liu, Ruisheng; Roman, Richard J

    2014-09-01

    The present study examined whether 20-HETE production is reduced in the renal vasculature and whether this impairs myogenic or tubuloglomerular feedback (TGF) responses of the afferent arteriole (Af-Art). The production of 20-HETE was 73% lower in renal microvessels of Dahl salt-sensitive rats (SS) rats than in SS.5(BN) rats, in which chromosome 5 from the Brown Norway (BN) rat containing the CYP4A genes was transferred into the SS genetic background. The luminal diameter of the Af-Art decreased by 14.7 ± 1.5% in SS.5(BN) rats when the perfusion pressure was increased from 60 to 120 mmHg, but it remained unaltered in SS rats. Administration of an adenosine type 1 receptor agonist (CCPA, 1 μM) reduced the diameter of the Af-Art in the SS.5(BN) rats by 44 ± 2%, whereas the diameter of the Af-Art of SS rats was unaltered. Autoregulation of renal blood flow (RBF) and glomerular capillary pressure (PGC) was significantly impaired in SS rats but was intact in SS.5(BN) rats. Administration of a 20-HETE synthesis inhibitor, HET0016 (1 μM), completely blocked the myogenic and adenosine responses in the Af-Art and autoregulation of RBF and PGC in SS.5(BN) rats, but it had no effect in SS rats. These data indicate that a deficiency in the formation of 20-HETE in renal microvessels impairs the reactivity of the Af-Art of SS rats and likely contributes to the development of hypertension induced renal injury. PMID:25007877

  15. Differential Estrogenic Actions of Endocrine-Disrupting Chemicals Bisphenol A, Bisphenol AF, and Zearalenone through Estrogen Receptor α and β in Vitro

    PubMed Central

    Li, Yin; Burns, Katherine A.; Arao, Yukitomo; Luh, Colin J.

    2012-01-01

    Background: Endocrine-disrupting chemicals (EDCs) are widely found in the environment. Estrogen-like activity is attributed to EDCs, such as bisphenol A (BPA), bisphenol AF (BPAF), and zearalenone (Zea), but mechanisms of action and diversity of effects are poorly understood. Objectives: We used in vitro models to evaluate the mechanistic actions of BPA, BPAF, and Zea on estrogen receptor (ER) α and ERβ. Methods: We used three human cell lines (Ishikawa, HeLa, and HepG2) representing three cell types to evaluate the estrogen promoter activity of BPA, BPAF, and Zea on ERα and ERβ. Ishikawa/ERα stable cells were used to determine changes in estrogen response element (ERE)-mediated target gene expression or rapid action-mediated effects. Results: The three EDCs showed strong estrogenic activity as agonists for ERα in a dose-dependent manner. At lower concentrations, BPA acted as an antagonist for ERα in Ishikawa cells and BPAF acted as an antagonist for ERβ in HeLa cells, whereas Zea was only a partial antagonist for ERα. ERE-mediated activation by BPA and BPAF was via the AF-2 function of ERα, but Zea activated via both the AF-1 and AF-2 functions. Endogenous ERα target genes and rapid signaling via the p44/42 MAPK pathway were activated by BPA, BPAF, and Zea. Conclusion: BPA and BPAF can function as EDCs by acting as cell type–specific agonists (≥ 10 nM) or antagonists (≤ 10 nM) for ERα and ERβ. Zea had strong estrogenic activity and activated both the AF-1 and AF-2 functions of ERα. In addition, all three compounds induced the rapid action-mediated response for ERα. PMID:22494775

  16. Resident Physicians Choices of Anticoagulation for Stroke Prevention in Patients With Nonvalvular Atrial Fibrillation.

    PubMed

    Oqab, Zardasht; McIntyre, William F; Quinn, Kieran L; Lamb, Tyler; Quadros, Kenneth; Yazdan-Ashoori, Payam; van Oosten, Erik; Chu, Karen; Lamba, Jasmine; Barake, Walid; Mohajer, Kiarash; Marr, Jeffrey N; Baranchuk, Adrian

    2016-06-01

    Atrial fibrillation (AF) is a common cardiac arrhythmia and is associated with an increased risk of ischemic stroke. The aim of this study was to identify practice patterns of Canadian resident physicians pertaining to stroke prevention in nonvalvular AF according to the Canadian Cardiovascular Society guidelines. A Web-based survey consisting of 16 multiple-choice questions was distributed to 11 academic centres. Questions involved identification of risks of stroke, bleeding, and selection of appropriate therapy in clinical scenarios that involve a patient with AF with a Congestive Heart Failure, Hypertension, Age, Diabetes, Stroke/Transient Ischemic Attack (CHADS2) score of 3 and no absolute contraindications to anticoagulation. There were 1014 total respondents, of whom 570 were internal, 247 family, 137 emergency medicine, and 60 adult cardiology residents. For a patient with a new diagnosis of AF, warfarin was chosen by 80.3%, novel oral anticoagulants (NOACs) by 60.3%, and acetylsalicylic acid (ASA) by 7.2% of residents. To a patient with a history of gastrointestinal bleed during ASA treatment, warfarin was recommended by 75.1%, NOACs by 36.1%, ASA by 12.1%, and 4% were unsure. For a patient with a history of an intracranial bleed, warfarin was recommended by 38.8%, NOACs by 23%, ASA by 24.8%, and 18.2% were unsure. For a patient taking warfarin who had a labile international normalized ratio, 89% would switch to a NOAC and 29.5% would continue warfarin. This study revealed that, across a wide sampling of disciplines and centres, resident physician choices of anticoagulation in nonvalvular AF differ significantly from contemporary Canadian Cardiovascular Society guidelines. PMID:26652126

  17. Heterogeneity of the M1 muscarinic receptor subtype between peripheral lung and cerebral cortex demonstrated by the selective antagonist AF-DX 116

    SciTech Connect

    Bloom, J.W.; Halonen, M.; Seaver, N.A.; Yamamura, H.I.

    1987-07-27

    Recent studies have demonstrated that the majority of muscarinic receptors in rabbit peripheral lung homogenates bind pirenzepine with high affinity (putative M1 subtype). In experiments of AF-DX 116 inhibiting (TH)(-)quinuclidinyl benzilate or (TH)pirenzepine, the authors found similar inhibitory constants for AF-DX 116 binding in rat heart and rabbit peripheral lung that were 4-fold smaller (i.e. of higher affinity) than the inhibitory constant for rat cerebral cortex. This results demonstrates heterogeneity of the M1 muscarinic receptor subtype between peripheral lung and cerebral cortex. 20 references, 1 figure, 2 tables.

  18. Validation of a simplified method to determine left atrial volume by computed tomography in patients with atrial fibrillation.

    PubMed

    Hof, Irene; Arbab-Zadeh, Armin; Dong, Jun; Scherr, Daniel; Chilukuri, Karuna; Calkins, Hugh

    2008-12-01

    The success of catheter ablation of atrial fibrillation (AF) is highly dependent on a preprocedural assessment of the size and shape of the left atrium. The most precise method to determine left atrial (LA) volume using computed tomography requires manually tracing the LA area of each cross-sectional image. This is a labor-intensive and time-consuming technique. The purpose of this study was to compare LA volume derived using the "gold-standard" multiple-slice technique with LA volume estimated using 3 orthogonal LA dimensions in patients with AF. The patient population was composed of 100 patients referred for catheter ablation of AF (87 men, mean age 57 +/- 12 years). AF was paroxysmal in 49 patients and persistent in 51. Each patient underwent computed tomography before catheter ablation, and LA volume was measured using the 2 methods. The mean LA volume measured using the multiple-slice technique was 136 +/- 46 ml. According to the simpler estimation approach, the mean LA volume was 112 +/- 41 ml. A close correlation was noted between atrial volumes determined using the 2 methods (r = 0.91, p <0.001). There was a mean underestimation of LA volume by the estimation technique of 17 +/- 13%. In conclusion, the results of this study reveal that LA volume determined using an estimation approach correlates closely with true LA volume as determined using the gold-standard multiple-slice approach. This estimation approach underestimates true LA volume by approximately 20%. PMID:19026316

  19. Increased risk of atrial fibrillation in end-stage renal disease patients on dialysis: A nationwide, population-based study in Taiwan.

    PubMed

    Shen, Cheng-Huang; Zheng, Cai-Mei; Kiu, Kee-Thai; Chen, Hsin-An; Wu, Chia-Chang; Lu, Kuo-Cheng; Hsu, Yung-Ho; Lin, Yuh-Feng; Wang, Yuan-Hung

    2016-06-01

    End-stage renal disease (ESRD) patients commonly have a higher risk of developing cardiovascular diseases than general population. Chronic kidney disease is an independent risk factor for atrial fibrillation (AF); however, little is known about the AF risk among ESRD patients with various modalities of renal replacement therapy. We used the Taiwan National Health Insurance Research Database to determine the incident AF among peritoneal dialysis (PD) and hemodialysis (HD) patients in Taiwan.Our ESRD cohort include Taiwan National Health Insurance Research Database, we identified 15,947 patients, who started renal replacement therapy between January 1, 2002 and December 31, 2003. From the same data source, 47,841 controls without ESRD (3 subjects for each patient) were identified randomly and frequency matched by gender, age (±1 year), and the year of the study patient's index date for ESRD between January 1, 2002 and December 31, 2003.During the follow-up period (mean duration: 8-10 years), 3428 individuals developed the new-onset AF. The incidence rate ratios for AF were 2.07 (95% confidence interval [CI] = 1.93-2.23) and 1.78 (95% CI = 1.30-2.44) in HD and PD groups, respectively. After we adjusted for age, gender, and comorbidities, the hazard ratios for the AF risk were 1.46 (95% CI = 1.32-1.61) and 1.32 (95% CI = 1.00-1.83) in HD and PD groups, respectively. ESRD patients with a history of certain comorbidities including hypertension, diabetes mellitus, hyperlipidemia, coronary artery disease, heart failure, valvular heart disease, and chronic obstructive pulmonary disease (COPD) have significantly increased risks of AF.This nationwide, population-based study suggests that incidence of AF is increased among dialysis ESRD patients. Furthermore, we have to pay more attention in clinical practice and long-term care for those ESRD patients with a history of certain comorbidities. PMID:27336884

  20. Atrial Fibrillation in Patients with Transient Ischemic Attack in Accordance with the Tissue-Based Definition

    PubMed Central

    Scheef, Björn; Al-Khaled, Mohamed

    2016-01-01

    Background Transient ischemic attack (TIA) management requires a cardiac evaluation with a Holter electrocardiogram (ECG), preferably a long-term (24 h) electrocardiogram (LT-ECG), to detect atrial fibrillation (AF), which places patients at higher risk of cerebrovascular events. The aim of this study was to determine the frequency of AF using ECG and LT-ECG in patients with tissue-based TIA. Methods During a three-year period (starting in 2011), all consecutive patients with tissue-based TIA (no evidence of infarction by brain imaging) were included and prospectively evaluated. Results Of 861 patients (mean age, 70 ± 13 years; 49.7% women), 854 patients (99.2%) had an ECG at admission, and 338 patients (39.3%) underwent 24-h LT-ECG monitoring during hospitalization. Patients who underwent LT-ECG monitoring were significantly younger (68 vs. 71 years; P=0.001) and experienced longer symptom duration (143 vs. 79 minutes; P=0.024) compared with those who did not. Furthermore, they had lower rates of unilateral weakness (32% vs. 39%; P=0.034) and previous strokes (18% vs. 26%; P=0.007). The LT-ECG investigation was also associated with longer hospitalization (7.9 vs. 5.7 days; P<0.001). A total of 77 patients (8.9%) exhibited AF on the ECG at admission. The LT-ECG revealed AF among seven patients (2.1%); five of these received a new treatment with oral anticoagulation based on the LT-ECG findings. Using the logistic regression, the presence of AF was associated with the following: age over 65 years (odds ratio [OR], 20.6; 95% confidence interval [CI], 2.8–152; P=0.003), hypertension (OR, 3.1; 95% CI: 1–8.9; P=0.041) and increased glucose level >6.05 mmol/L) on admission (OR, 1.9; 95% CI: 1–3.5; P=0.036). Conclusion Cardiac evaluation with LT-ECG appears to increase the rate of detected AF and may lead to a change in secondary prophylaxis in patients with tissue-based TIA.

  1. Quantitative Tissue‐Tracking Cardiac Magnetic Resonance (CMR) of Left Atrial Deformation and the Risk of Stroke in Patients With Atrial Fibrillation

    PubMed Central

    Inoue, Yuko Y.; Alissa, Abdullah; Khurram, Irfan M.; Fukumoto, Kotaro; Habibi, Mohammadali; Venkatesh, Bharath A.; Zimmerman, Stefan L.; Nazarian, Saman; Berger, Ronald D.; Calkins, Hugh; Lima, Joao A.; Ashikaga, Hiroshi

    2015-01-01

    Background Recent evidence suggests that left atrial (LA) dysfunction may be mechanistically contributing to cerebrovascular events in patients with atrial fibrillation (AF). We investigated the association between regional LA function and a prior history of stroke during sinus rhythm in patients referred for catheter ablation of AF. Methods and Results A total of 169 patients (59±10 years, 74% male, 29% persistent AF) with a history of AF in sinus rhythm at the time of pre‐ablation cardiac magnetic resonance (CMR) were analyzed. The LA volume, emptying fraction, strain (S), and strain rate (SR) were assessed by tissue‐tracking cardiac magnetic resonance. The patients with a history of stroke or transient ischemic attack (n=18) had greater LA volumes (Vmax and Vmin; P=0.02 and P<0.001, respectively), lower LA total emptying fraction (P<0.001), lower LA maximum and pre‐atrial contraction strains (Smax and SpreA; P<0.001 and P=0.01, respectively), and lower absolute values of LA SR during left ventricular (LV) systole and early diastole (SRs and SRe; P=0.005 and 0.03, respectively) than those without stroke/transient ischemic attack (n=151). Multivariable analysis demonstrated that the LA reservoir function, including total emptying fraction, Smax, and SRs, was associated with stroke/transient ischemic attack (odds ratio 0.94, 0.91, and 0.17; P=0.03, 0.02, and 0.04, respectively) after adjusting for the CHA2DS2‐VASc score and LA Vmin. Conclusions Depressed LA reservoir function assessed by tissue‐tracking cardiac magnetic resonance is significantly associated with a prior history of stroke/transient ischemic attack in patients with AF. Our findings suggest that assessment of LA reservoir function can improve the risk stratification of cerebrovascular events in AF patients. PMID:25917441

  2. Expression of E1AF/PEA3, an Ets-related transcription factor in human non-small-cell lung cancers: its relevance in cell motility and invasion.

    PubMed

    Hiroumi, H; Dosaka-Akita, H; Yoshida, K; Shindoh, M; Ohbuchi, T; Fujinaga, K; Nishimura, M

    2001-09-01

    Cell invasion and metastasis characterize the malignant potential of non-small-cell lung cancers (NSCLCs). We have previously reported that E1AF, a member of the Ets-related transcription factor family, confers invasive phenotype on breast cancer and oral squamous-cell carcinoma cell lines. In our study, we analyzed the E1AF expression in cell lines and resected tumors of NSCLCs by Northern blot and in situ hybridization analyses and found that 15 of 17 cell lines and 12 of 19 tumors expressed E1AF mRNA while normal lung tissue and concomitant normal cells within tumors did not. To examine the biologic importance of E1AF in NSCLCs, we introduced the E1AF gene into VMRC-LCD and NCI-H226, NSCLC cell lines lacking E1AF expression, and examined cell motility and invasion activities. E1AF-transfected VMRC-LCD cells showed increased cell motility that was 2-fold that of parental and vector-transfected control cells (p < 0.01), and both cell motility and invasion were increased 1.6-fold in NCI-H226 (p < 0.01). Furthermore, hepatocyte growth factor (HGF), which is one of the most effective cell-scattering factors, stimulated the motile and invasive activities in E1AF-transfected VMRC-LCD and NCI-H226 cells but not in their parental or vector-transfected control cells. Ets-1 mRNA expression was found in E1AF-transfected VMRC-LCD cells but not in parental or vector-transfected cells. HGF further induced expression of the Ets-1 and urokinase-type plasminogen activator (uPA) genes specifically in E1AF-transfected cells. These findings suggest that E1AF plays a substantial role in the cell motility and invasion of NSCLCs. PMID:11519038

  3. Prognostic role of left atrial strain and its combination index with transmitral E-wave velocity in patients with atrial fibrillation

    PubMed Central

    Hsu, Po-Chao; Lee, Wen-Hsien; Chu, Chun-Yuan; Lee, Hung-Hao; Lee, Chee-Siong; Yen, Hsueh-Wei; Lin, Tsung-Hsien; Voon, Wen-Chol; Lai, Wen-Ter; Sheu, Sheng-Hsiung; Su, Ho-Ming

    2016-01-01

    Left atrial (LA) strain can reflect LA remodeling and is reduced in atrial fibrillation (AF) patients with prior stroke. This study sought to examine the ability of LA strain in predicting subsequent stroke event in AF and also evaluated whether E/LA strain could predict cardiovascular (CV) events in these patients. In 190 persistent AF patients, we performed comprehensive echocardiography with assessment of LA strain. There were 69 CV events including 19 CV death, 32 hospitalizations for heart failure, 3 myocardial infarctions, and 15 strokes during an average follow-up of 29 months. Multivariate analysis showed old age, chronic heart failure, increased left ventricular (LV) mass index, and increased E/LA strain were associated with CV events and decreased LA strain was associated with subsequent stroke event. The addition of E/LA strain and LA strain to a model containing CHA2DS2-VASc score and LV function significantly improved the values in predicting CV events and subsequent stroke event, respectively. In conclusion, E/LA strain and LA strain were respectively useful in predicting CV events and subsequent stroke event in AF. E/LA strain and LA strain could provide incremental values for CV outcome and subsequent stroke outcome prediction over conventional clinical and echocardiographic parameters in AF, respectively. PMID:26833057

  4. Evidence for plasticity in white-matter tracts of patients with chronic Broca's aphasia undergoing intense intonation-based speech therapy.

    PubMed

    Schlaug, Gottfried; Marchina, Sarah; Norton, Andrea

    2009-07-01

    Recovery from aphasia can be achieved through recruitment of either perilesional brain regions in the affected hemisphere or homologous language regions in the nonlesional hemisphere. For patients with large left-hemisphere lesions, recovery through the right hemisphere may be the only possible path. The right-hemisphere regions most likely to play a role in this recovery process are the superior temporal lobe (important for auditory feedback control), premotor regions/posterior inferior frontal gyrus (important for planning and sequencing of motor actions and for auditory-motor mapping), and the primary motor cortex (important for execution of vocal motor actions). These regions are connected reciprocally via a major fiber tract called the arcuate fasciculus (AF), however, this tract is not as well developed in the right hemisphere as it is in the dominant left. We tested whether an intonation-based speech therapy (i.e., melodic intonation therapy [MIT]), which is typically administered in an intense fashion with 75-80 daily therapy sessions, would lead to changes in white-matter tracts, particularly the AF. Using diffusion tensor imaging (DTI), we found a significant increase in the number of AF fibers and AF volume comparing post- with pretreatment assessments in six patients that could not be attributed to scan-to-scan variability. This suggests that intense, long-term MIT leads to remodeling of the right AF and may provide an explanation for the sustained therapy effects that were seen in these six patients. PMID:19673813

  5. The Effect of Catheter Ablation on Left Atrial Size and Function for Patients with Atrial Fibrillation: An Updated Meta-Analysis

    PubMed Central

    Xiong, Bin; Li, Dan; Wang, Jianling; Gyawali, Laxman; Jing, Jinjin; Su, Li

    2015-01-01

    Background Catheter ablation (CA) for atrial fibrillation (AF) is now an important therapeutic modality for patients with AF. However, data regarding changes in left atrial (LA) function after CA have indicated conflicting results depending on the AF types, follow-up period, and the analytical imaging tools. The objective of this review was to analyze the effect of CA on the LA size and function for patients with AF. Methods We searched for studies regarding LA size and function pre- and post-ablation in PubMed, Embase, the Cochrane Library, and Web of Knowledge through May 2014. LA function was measured by LA ejective fraction (LAEF), LA active ejective fraction (LAAEF), or both. Total and subgroup analyses were implemented using Cochrane Review Manager Version 5.2. Weighted mean differences with 95% confidence intervals were used to express the results of continuous outcomes using fixed or random effect models. I2 was used to calculate heterogeneity. To assess publication bias, Egger’s test and Begg’s funnel plot were performed using Stata 12.0. Results Twenty-five studies (2040 enrolled patients) were selected for this meta-analysis. The LA diameter (LAD), maximum LA volume, and minimal LA volume were significantly decreased post-ablation, as compared with those at a pre-ablation visit. Compared with the pre-ablation outcomes, we found no significant differences in LAEF/LAAEF at a post-ablation follow-up. Decreases in LA volume and LAEF remained significant post-ablation for paroxysmal AF (PAF); however, the LAEF was insignificant changes in persistent AF (PeAF). Heterogeneity was significant in spite which individual study was excluded. A publication bias was not found. In a meta-regression analysis, we did not find any factor that contributed to the heterogeneity. Conclusion With CA, LA volumes and LAD were decreased significantly in patients with AF; LAEF was not significant changes in patients with PeAF but decreased in those with PAF. PMID:26147984

  6. Warfarin treatment among Finnish patients with atrial fibrillation: retrospective registry study based on primary healthcare data

    PubMed Central

    Hallinen, Taru; Soini, Erkki J; Asseburg, Christian; Kuosmanen, Pekka; Laakkonen, Ari

    2014-01-01

    Objective To assess the frequency of warfarin use, the achieved international normalised ratio (INR) balance among warfarin users and the primary healthcare outpatient costs of patients with atrial fibrillation (AF). Design Retrospective, non-interventional registry study. Setting Primary healthcare. Participants All patients with AF (n=2746) treated in one Finnish health centre between October 2010 and March 2012. Methods Data on healthcare resource use, warfarin use, individually defined target INR range and INR test results were collected from the primary healthcare database for patients with AF diagnosis. The analysed dataset consisted of a 1-year follow-up. Warfarin treatment balance was estimated with the proportion of time spent in the therapeutic INR range (TTR). The cost of used healthcare resources was valued separately with national and service provider unit costs to estimate the total outpatient treatment costs. The factors potentially impacting the treatment costs were assessed with a generalised linear regression model. Results Approximately 50% of the p