tbuckley/cabot-search huggingface dataset:
Abstract 18513: CXCl16 Promotes Ly6Chigh Monocyte/Macrophage Infiltration and Impairs Cardiac Function After Acute Myocardial Infarction
Authors: Jing Zhang, Taotao Li, Youcai Ma, Junmeng Zhang, Jie Du
Journal: Circulation (2016)

Objective: CXCL16 has been implicated in the pathogenesis of atherosclerosis, but the function of CXCL16 in myocardial infarction (MI) is unknown. This research examines the effects of CXCL16 in myocardial infarcted mice. Methods and results: MI was induced in 8 to 12 week-old male mice (C57BL/6 background) by permanent coronary ligation of the left anterior descending artery (LAD). The expression of CXCL16 was increased in the heart of mice after MI on day 1. Compared to WT mice, CXCL16 knockout (CXCL16 KO) mice showed improved cardiac function by echocardiography and attenuated infarct size by Masson trichrome staining on 14 days after MI. FACS analysis of cardiac tissue of mice on 3 days after MI showed an increased infiltration of CD45+CD11b+F4/80+ monocytes/macrophages, including Ly6Chigh monocytes/macrophages and Ly6Clow monocytes/macrophages. Q-PCR analysis demonstrated that TNFα and IL1β were highly expressed in Ly6Chigh monocytes/macrophages, while IL4 and TGFβ were highly expressed in Ly6Clow mo...
Correlation of Synaptic Inputs in the Visual Cortex of Awake, Behaving Mice
Authors: Sergio Arroyo, Corbett Bennett, Shaul Hestrin
Journal: Neuron (2018)

Highlights•Vm correlations in V1 depend on behavioral state but not tuning similarity•Visual stimulation reduces low-frequency and generates high-frequency Vm coherence•Inhibition lags excitation by ∼5 ms during correlated Vm fluctuations•Neurons activate in a conserved sequence across stimulus and behavioral statesSummaryThe subthreshold mechanisms that underlie neuronal correlations in awake animals are poorly understood. Here, we perform dual whole-cell recordings in the visual cortex (V1) of awake mice to investigate membrane potential (Vm) correlations between upper-layer sensory neurons. We find that the membrane potentials of neighboring neurons display large, correlated fluctuations during quiet wakefulness, including pairs of cells with disparate tuning properties. These fluctuations are driven by correlated barrages of excitation followed closely by inhibition (∼5-ms lag). During visual stimulation, low-frequency activity is diminished, and coherent high-frequency oscillations appear, even for non-preferred stimuli. These oscillations are generated by alternating excitatory and inhibitory inputs at a similar lag. The temporal sequence of depolarization for pairs of neurons is conserved during both spontaneous- and visually-evoked activity, suggesting a stereotyped flow of activation that may function to produce temporally precise "windows of opportunity" for additional synaptic inputs.
Coupling the Circadian Clock to Homeostasis: The Role of Period in Timing Physiology
Authors: Pureum Kim, Henrik Oster, Hendrik Lehnert, Sebastian M Schmid, Nicole Salamat, Johanna L Barclay, Erik Maronde, Warrick Inder, Oliver Rawashdeh
Journal: Endocrine Reviews (2018)

A plethora of physiological processes show stable and synchronized daily oscillations that are either driven or modulated by biological clocks. A circadian pacemaker located in the suprachiasmatic nucleus of the ventral hypothalamus coordinates 24-hour oscillations of central and peripheral physiology with the environment. The circadian clockwork involved in driving rhythmic physiology is composed of various clock genes that are interlocked via a complex feedback loop to generate precise yet plastic oscillations of ∼24 hours. This review focuses on the specific role of the core clockwork gene Period1 and its paralogs on intra-oscillator and extra-oscillator functions, including, but not limited to, hippocampus-dependent processes, cardiovascular function, appetite control, as well as glucose and lipid homeostasis. Alterations in Period gene function have been implicated in a wide range of physical and mental disorders. At the same time, a variety of conditions including metabolic disorders also impact clock gene expression, resulting in circadian disruptions, which in turn often exacerbates the disease state.
Abstract 17428: Impact of Asymptomatic Cerebral Microbleeds or Lacunar Infarction on Clinical Outcome in Patients With Coronary Artery Disease (CAD) Requiring Percutaneous Coronary Intervention
Authors: Seiji Hokimoto, Noriaki Tabata, Tomonori Akasaka, Kenji Sakamoto, Kenichi Tsujita, Eiichiro Yamamoto, Megumi Yamamuro, Daisuke Sueta, Koichi Kaikita, Sunao Kojima, Hisao Ogawa
Journal: Circulation (2015)

Background: Patients with coronary artery disease (CAD) are often complicated with cerebrovascular disease (CVD). Although there are many reports on the relation between stoke with symptomatic signs and CAD, there are few studies on cerebral microbleeds or lacunar infarction without symptomatic signs. The aim was to examine the prevalence of cerebral microbleeds or lacunar infarction without symptoms and clinical outcome in CAD patients. Methods: Among 1,091 consecutive CAD patients who required percutaneous coronary intervention (PCI), patients with non-lacunar infarction more severe than lacunar infarction or old cerebral hemorrhage by computed tomography (CT) or magnetic resonance imaging (MRI) were excluded. We analyzed CAD patients with cerebral microbleeds or lacunar infarction without overt neurological signs (ML group; n=98, 71males) compared with patients without cerebral findings of CT or MRI and stroke history as control (N group; n=762, 525males). Clinical endpoints were cardiovascular death, myocardial infarction (MI), stroke, unstable angina and urgent revascularization. Results: ML group had a high age (72.9±9.6 vs. 69.2±10.8ys; P=0.001), high incidence of diabetes mellitus (58.2 vs. 47.2%; P=0.042), peripheral artery disease (21.4 vs. 11.5%; P=0.005), and renal dysfunction (49.0 vs. 37.3%; P=0.025), and high levels of fibrinogen (435 vs. 402mg/dl; P=0.005), and high brachial-ankle pulse wave velocity (1975 vs. 1786cm/sec; P=0.001) compared with N group. Cardiovascular event rate was significantly higher in ML group than in N group (11.2 vs. 4.7%, P=0.008). Details in clinical outcome were as follows: cardiovascular death (ML group vs. N group, 0 vs. 0.9%; P=0.341), MI (1.0 vs. 0.5%; P=0.544), stroke (4.1 vs.0.7%; P=0.002), unstable angina (5.1 vs. 2.5%; P=0.140), revascularization (2.0 vs. 0.7%; P=0.498), respectively. Multiple regression analysis identified findings of microbleeds or lacunar infarction as a predictor of clinical events (OR, 2.830; 95%CI, 1.328-6.031; P=0.007). Conclusions: There was high incidence of brain MRI or CT findings without symptom in CAD patients. We should pay attention to the asymptomatic patients with microbleeds or lacunar infarction irrespective of overt previous stroke.
Abstract 16580: Safety and Efficacy of Cryoballoon Ablation in Patients With Congestive Heart Failure
Authors: Roger Tseng, Muhanad Al-Zubaidi, Alexander Homer, Kelly DanCanay, Wilber Su
Journal: Circulation (2015)

Background: Irrigated radiofrequency ablation of atrial fibrillation (AF) is challenging in patient with severe systolic congestive heart failure due to large fluid load. The use of cryoballoon ablation in patients with low ejection fraction (EF) and NYHA class II-IV congestive heart failure has not been well described, and may benefit from the lack of fluid bolus and restoration of sinus rhythm. Method: To evaluate the efficacy and safety of cryoballoon ablation for systolic heart failure patients with atrial fibrillation (AF). Single center retrospective review of 832 patients with AF ablation using Arctic Front Advance Cryoballoon (Medtronic, Minneapolis, MN) was performed, and 188 patients has EF less than 35% (24 paroxysmal, 122 persistent, and 42 long-standing persistent, average EF 28%) was analyzed. Procedural tolerance, complications, and impact on congestive heart failure were reviewed over a 12 months follow up. Results: All 188 patients (Average age 68, LA size 5.8 cm) with systolic CHF and atrial fibrillation underwent successful pulmonary vein (PV) isolation and extra-pulmonary vein lesions sets applied using cryoballoon. Non-irrigated radiofrequency ablation was used in (22%) for cavo-tricuspid isthmus flutter ablation. Acute procedural success rate was 100% with length of hospitalization of 1.1 days. Average procedural time was 2.6 hours, and fluid infusion of 0.3 liters, no significant complications was noted. Atrial fibrillation burden was monitored by implantable pacemaker or defibrillator in 118 of 188 patients (63%), and others were monitoring via wearable looping recorders every 3 months. Significant AF burden (&lt;10% atrial high rate burden) was observed in over 67% of the patients, and improvement CHF symptoms were reported in all of the patients with reduction of atrial fibrillation burden. Conclusions: Cryoballoon of AF in systolic CHF population is well tolerated with high procedural success rate and low complication rate. Significant clinical improvement of CHF class was observed in patient with reduction of atrial fibrillation burden. Ongoing collection of data is needed to quantify long-term benefit.
Double-Blind Randomized Clinical Trial of Prazosin for Alcohol Use Disorder
Authors: Tracy L. Simpson, Andrew J. Saxon, Cynthia Stappenbeck, Carol A. Malte, Robert Lyons, Dana Tell, Steven P. Millard, Murray Raskind
Journal: American Journal of Psychiatry (2018)

Current medications for alcohol use disorder do not target brain noradrenergic pathways. Theoretical and preclinical evidence suggests that noradrenergic circuits may be involved in alcohol reinforcement and relapse. After a positive pilot study, the authors tested the α-1 adrenergic receptor antagonist prazosin to treat alcohol use disorder in a larger sample.Ninety-two participants with alcohol use disorder but without posttraumatic stress disorder were randomly assigned to receive prazosin or placebo in a 12-week double-blind study. Medication was titrated to a target dosing schedule of 4 mg in the morning, 4 mg in the afternoon, and 8 mg at bedtime by the end of week 2. The behavioral platform was medical management. Participants provided daily data on alcohol consumption. Generalized linear mixed-effects models were used to examine the impact of prazosin compared with placebo on number of drinks per week, number of drinking days per week, and number of heavy drinking days per week.Eighty participants completed the titration period and were included in the primary analyses. There was a significant interaction between condition and week for both number of drinks and number of heavy drinking days, such that the rate of drinking and the probability of heavy drinking showed a greater decrease over time for participants in the prazosin condition compared with those in the placebo condition. Participants in the prazosin condition were more likely to report drowsiness and edema than participants in the placebo condition.Prazosin holds promise as a harm-reduction pharmacologic treatment for alcohol use disorder and deserves further evaluation by independent research groups.
Abstract 14879: Impact of Vascular Function and Genotyping on Platelet Activation and Cardiovascular Outcome in Patients After Percutaneous Coronary Intervention Receiving Clopidogrel: Two Pieces of the Puzzle of Clopidogrel Resistance
Authors: Gerasimos Siasos, Dimitris Tousoulis, Stamatios Kioufis, Evangelos Oikonomou, Marina Zaromitidou, Konstantinos Maniatis, Eleni Kokkou, Antigoni Miliou, Panagiotis Tourikis, Manolis Vavuranakis, Christodoulos Stefanadis
Journal: Circulation (2013)

Background: Individual platelet response to antiplatelet therapy depends on genetic, cellular and clinical factors. CYP2C19 and P2Y12 receptor polymorphisms are implicated in platelet response to a...
Abstract 15438: Serum Proprotein Convertase Subtilisin/Kexin Type 9 Levels Are Not Increased by Plant Stanol Ester Consumption
Authors: Piia Simonen, Ulf-Håkan Stenman, Helena Gylling
Journal: Circulation (2014)

Introduction: Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a critical role in regulating cholesterol metabolism mainly by binding to LDL receptors targeting them for degradation. Statins, inhibitors of cholesterol synthesis, increase the serum PCSK9 concentration limiting the potential of statins to reduce LDL cholesterol (C) concentration, whereas ezetimibe, an inhibitor of cholesterol absorption, has ambiguous effects on circulating PCSK9 levels. Plant stanols lower LDL-C by inhibiting cholesterol absorption, but their effect on serum PCSK9 concentration is not known. Hypothesis: We assessed the hypothesis that consumption of plant stanol esters lowers LDL-C without increasing circulating PCSK9 levels. Methods: Ninety-two normo- and mildly hypercholesterolemic subjects, 35 men and 57 women (mean age 50.8±1.0 (SE) years) were randomly divided into plant stanol ester (STANOL) (n=46) and control (n=46) groups. They consumed spread enriched with (STANOL group) and without (control group) plant stanol (3g /d) ester in a double-blind intervention for six months. Serum lipids and lipoproteins were analysed enzymatically and serum PCSK9 concentration was quantitated with Quantikine Elisa Immunoassay at baseline and after the intervention. Results: At baseline, serum PCSK9 levels correlated positively with LDL-C in the whole study population. Serum total, LDL-C and non-HDL-C concentrations, similar between the study groups at baseline, declined by 7%,10%, and 11% at the end of the intervention in the STANOL group compared with the control group (p&lt; 0.001, for all). The baseline serum PCSK9 concentrations were similar between the groups (STANOL 284±16 ng/ml, controls 273±16 ng/ml, ns). At the end of the intervention, serum PCSK9 concentrations were unchanged from baseline in both groups and did not differ between the groups (STANOL 293 ±15 ng/ml, controls 309±16 ng/ml, ns). Conclusion: In conclusion, plant stanol ester consumption does not affect the circulating PCSK9 concentration. Thus, plant stanols provide an efficient dietary means to lower LDL-C concentration without interfering with the LDL receptor-mediated cellular cholesterol uptake and removal.
Molecular Assay Testing to Rule Out Tuberculosis—Be That Early Adopter
Authors: Max Salfinger
Journal: JAMA Internal Medicine (2018)

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Abstract 18888: Functional and Molecular Characteristics of the Latent Atrial Pacemaker Clusters in Explanted Human Hearts
Authors: Ning Li, Brian J Hansen, Thomas A Csepe, Laura Jayne, Jichao Zhao, Brandon Moore, Robert S Higgins, Raul Weiss, Ahmet Kilic, Michael R Rosen, Peter J Mohler, Brandon J Biesiadecki, Paul M Janssen, Vadim V Fedorov
Journal: Circulation (2014)

Introduction: Enhanced atrial latent pacemaker (LAP) activity may play an important role in triggering atrial arrhythmias including atrial fibrillation in patients with heart failure. However, func...
Abstract P219: Kidney Measures and Future Risk of Abdominal Aortic Aneurysm: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Kunihiro Matsushita, Lucia Kwak, Shoshana Ballew, Morgan Grams, Elizabeth Selvin, Aaron Folsom, Josef Coresh, Weihong Tang
Journal: Circulation (2016)

Introduction: Abdominal aortic aneurysm (AAA) is considered a subtype of atherosclerotic disease, but its risk factor profile is somewhat different than other atherosclerotic disease subtypes. For example, prior studies have demonstrated a null or even inverse association between diabetes and AAA. Chronic kidney disease (CKD) is a known risk factor for cardiovascular outcomes, but its association with AAA has not been explicitly investigated. Methods: We studied 10,722 participants (aged 53-75 years) without clinical history of AAA who attended the ARIC Study fourth visit (1996-98). Cox regression models were used to quantify the association of two key CKD measures—estimated glomerular filtration rate [eGFR] based on serum creatinine and cystatin C and urine albumin-to-creatinine ratio [ACR]—with incidence of AAA-related hospitalizations or deaths (ICD-9 codes: 38.44, 39.71, 441.3, 441.4, or 441.02). Results: During a median follow-up of 14 years, there were 350 cases of AAA (incidence rate 2.5 per 1000 person-years). Both low eGFR and high ACR were associated with increased risk of clinical AAA independently of each other and potential confounders, with a slightly sharper risk gradient for ACR compared to eGFR (Table). We also confirmed an inverse association between diabetes and AAA in our study, although ACR was a significant positive risk factor for AAA risk in both those with and without diabetes. By contrast, low eGFR was associated with AAA risk only in those without diabetes. Conclusion: Both eGFR and ACR were independently associated with increased risk of clinical AAA in the community, suggesting potential usefulness of CKD to identify persons at high risk of AAA beyond traditional atherosclerotic risk factors.
Involvement of acetyl-CoA-producing enzymes in the deterioration of the functional potential of adipose-derived multipotent cells from subjects with metabolic syndrome
Authors: Wilfredo Oliva-Olivera, Said Lhamyani, Leticia Coín-Aragüez, Juan Alcaide-Torres, Fernando Cardona, Rajaa El Bekay, Francisco J Tinahones
Journal: Metabolism (2018)
Stateless: the Rohingya refugees one year on
Authors: Declan Murphy
Journal: BMJ (2018)

Dalila Mahdawi/MSF

In the past year nearly a million people have fled northern Rakhine province in Myanmar for the safety of neighbouring Bangladesh. Around 900 000 of the refugees are now enduring cramped and unhygienic lives in camps, such as Balukhali, left, in Cox’s Bazar. The coastal town has become the world’s largest refugee camp.

Since the exodus of the Rohingya people began, Medecins Sans Frontieres …
Abstract P143: Potential Dietary Impact of Adding Potassium Chloride to Foods as a Sodium Reduction Technique
Authors: Leo van Buren, Mariska Dotsch-Klerk, Rachel S Newson
Journal: Circulation (2016)

Introduction: High sodium intake increases the risk of developing cardiovascular disease, which is particularly concerning as globally sodium intake is too high. The food industry is engaged in the reformulation of products towards a reduced sodium chloride content, however this is challenging to do so while maintaining good preservation, texture and taste properties. To ensure that consumers repeatedly use lower salt products it is important that reformulation is done well. One leading method to achieve sodium reduction is partial replacement of sodium chloride by potassium chloride. Potassium chloride is a good salt replacer as it adds to the salty taste and independently has positive health benefits. However, if the replacement of sodium chloride by potassium chloride widens, it is important to understand the potential health and safety implications of this. Therefore, we evaluated in a population-based survey the current intake of sodium and potassium, the key contributing food groups to both minerals in the diet and the potential impact of different reformulation scenarios. Methods: Intake data was obtained from the Dutch National Food Consumption Survey (2007-2010). Sodium and potassium intake were calculated with NEVO values. Reformulation scenarios were calculated where products were theoretically reformulated to: 1) attain a dietary intake of sodium of 2000mg/day, and 2) where removed sodium chloride was replaced by various potassium chloride levels, based on acceptable sensorial limits. Results: Of the Dutch population 33% were compliant with the Daily Recommended Intakes for sodium (3,510mg/day). Main contributing food groups to sodium were: bread, processed meat and cheese, which accounted for 53% of intake. For potassium: milk products, beverages, potato/rice/pasta, and fresh meat, which accounted for 50% of intake. In the first reformulation scenario where all sodium chloride was replaced by potassium chloride, potassium intake compliance increased to 67%. The second scenario based on sensorial limits resulted in an increase incompliance of 5%. In all reformulations replacement of sodium by potassium did not exceed safety recommendations on added potassium. Conclusions: Sodium intake in the Dutch population is above recommendations and potassium is below. Replacement of sodium chloride by potassium chloride, particularly in key contributing products, according to the current targets would result in better compliance to potassium recommendations (3,510mg/day), but would not exceed EFSA safety recommendations. Based on the intake data and reformulation scenarios, potassium chloride presents as a valuable, safe replacer for sodium chloride in processed foods with a high salt content.
Abstract P163: Coffee Consumption and Risk of Heart Failure in the Physicians’ Health Study
Authors: Vijaykumar Bodar, Jiaying Chen, Howard Sesso, MIchael Gaziano, Luc Djousse
Journal: Circulation (2018)

Background: Coffee consumption is highly prevalent in the United States (US). While previous studies have reported a positive association of coffee consumption with hypertension (HTN) and coronary artery disease, only a few studies have examined the association of coffee consumption with risk of heart failure. Hence, we sought to examine the relation between coffee consumption and risk of heart failure among male physicians. Hypothesis: We hypothesized that coffee consumption is inversely associated with the risk of heart failure. Method: We prospectively studied 20,433 middle-aged and older men from The Physicians’ Health Study. Coffee consumption was assessed using a semi-quantitative food frequency questionnaire. The incidence of heart failure was assessed using annual questionnaires and validated in a subsample using review of medical records. We used Cox Proportional hazard model to compute the hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) across categories of coffee and calorie adjusted caffeine intake, and cubic spline to estimate nonlinear trend. Results: The average age was 66.4 years. During a mean follow-up of 9.3 years, a total of 901 new cases of heart failure were reported. In a Cox model adjusting for age, diabetes, smoking, atrial fibrillation, exercise, and alcohol intake, the HRs (95% CIs) of heart failure were 1.0(reference), 0.89(0.67-1.20), 1.27(1.00-1.62), 0.99 (0.80 - 1.22), 1.19 (0.99- 1.43), and 1.37 (1.05 - 1.80) for coffee consumption of almost never, &lt;=1 cup/week, 2-6cups/week, 1cup/day, 2-3cups/day, and 4+cups/day, respectively; P for nonlinear trend = 0.02. In a secondary analysis, higher caffeine intake was associated with a higher risk of heart failure, with Multivariable HRs (95% CIs) from the lowest to the highest quintile of dietary caffeine were 1.00(reference), 1.10 (0.90-1.35), 1.00 (0.81-1.25), 1.17 (0.95-1.45), and 1.25 (1.00-1.56), respectively; P for nonlinear trend = 0.06. Conclusion: Heavy (+4 cups/day), but not light to moderate, coffee consumption is associated with a higher risk of heart failure.