tbuckley/cabot-search huggingface dataset:
Abstract 354: ZnT-1 Expression in the Human Atria and New Insights on its Activity as an Inhibitor of L-type Calcium Channels
Authors: Yoram Etzion, Shiri Kolt, Ofer Beharier, Amir Ganiel, Buzaglo Liat, Aryeh Shalev, Victor Novack, Gideon Sahar, Amos Katz, Arie Moran
Journal: Circulation (2007)

BACKGROUND : Recent findings indicate that the membranous protein ZnT-1 acts as an inhibitor of L-type calcium channels (LTCC). However, no direct interaction between ZnT-1 and the LTCC α 1 C subunit was demonstrated. Recently, we found that atrial tachypacing in rats augments the expression of ZnT-1 in conjunction with AERP reduction. Therefore, we postulated that ZnT-1 may play a role in atrial tachycardia remodeling of patients with AF. In this study, we assessed the atrial expression of ZnT-1 in humans with AF or sinus rhythm (SR). In addition, in order to explore the mechanism of action of ZnT-1 we used heterologous expression system, and tested the possibility that ZnT-1 interacts with the β-subunit of the LTCC. METHODS AND RESULTS : From 39 patients (27 in SR and 12 in AF) undergoing open heart surgery, we collected right atrial appendage tissue. The expression of ZnT-1 was analyzed. β-actin served as an internal loading control and data was compared to a rat standard (STD). Overall, AF patients (n = 12) had median ZnT-1/β-actin of 1.80 STD (inter-quartile range 1.26 to 2.85) vs. 0.73 STD (0.24 to 1.64) in the SR group (p = 0.002). Multivariate analysis determined that AF and increased BMI are the only independent variables associated with higher levels of ZnT-1. In Xenopus oocytes, the absence of the β-subunit prevented the inhibition of LTCC activity by ZnT-1 (127 ± 43nA and 153 ± 39nA for control and ZnT-1 containing oocytes, respectively, p&gt;0.5, n = 8). In addition, ZnT-1 failed to inhibit the current when the α-subunit was truncated in the part essential for the interaction with the β subunit (2037 ± 300nA and 1938 ± 341nA for control and ZnT-1 containing oocytes, respectively, p&gt;0.5, n = 3). Direct interaction between ZnT-1 and the LTCC β-subunit was demonstrated by co-immunoprecipitation of ZnT-1-myc and the β-subunit, using anti-myc antibodies (n = 3) CONCLUSIONS : This work provides first evidence for an increased ZnT-1 expression in patients with AF and marks it as a putative missing link in the development of atrial electrical remodeling. An interaction of the LTCC β-subunit and the ZnT-1 plays a role in the molecular mechanism by which ZnT-1 inhibits the LTCC.
Abstract 17458: Use of Galectin-3 to Create a Simplified Heart Failure Rehospitalization Risk Model
Authors: Priya Kansal, Rudolph A de Boer, Christopher R deFilippi, Hanna Gaggin, Pieter Muntendam, Aram Adourian, Dirk J van Veldhuisen, James L Januzzi, Sanjiv J Shah
Journal: Circulation (2012)

Introduction: Heart failure (HF) patients are at high risk for short-term rehospitalization and death but there are no simple risk models for the prediction of these outcomes. We hypothesized that ...
Abstract 5221: Plasma Levels of Tetrahydrobiopterin and Endothelial Function Were Improved by Fenofibrate Treatment in Patients With Hypertriglyceridemia
Authors: Li Y He, Shan Liu, Jie M Mao, Xin H Feng, Jie L Feng, Guang Wang
Journal: Circulation (2009)

Background: Endothelial nitric oxide synthase (eNOS) catalytic activity becomes “uncoupled” when tetrahydrobiopterin (BH 4 ) is limiting or absent which causes the endothelial function to be impaird. The objective of our study was to investigate the effects of peroxisome proliferator-activated receptor α (PPAR α ) agonists fenofibrate on plasma levels of nitric oxide (NO) and BH 4 and endothelial function in patients with hypertriglyceridemia. Methods and results: Sixty patients with hypertriglyceridemia were randomly divided into treatment group and the control group. The treatment group (mean follow-up was 145±51 days) was treated with lifestyle changes and fenofibrate 200mg/d; the control group was treated with lifestyle changes only. At the end of the follow-up, plasma NO (99.09±35.51 μ mol/L vs.121.98±53.27 μ mol/L, P &lt; 0.05) and BH 4 (1.48±0.79pmol/mL vs. 2.16±1.50pmol/mL, P &lt; 0.05) levels were elevated and plasma homocysteine (Hcy) levels were elevated by 50.1% ( P &lt; 0.001) compared with the baseline, coronary flow reserve which reflected coronary endothelial function were improved (2.89±0.78 vs. 3.14±0.67, P &lt; 0.05). Fenofibrate could elevate the plasma BH 4 levels (1.39±0.77 pmol/mL vs. 2.31±1.70 pmol/mL, P &lt; 0.01) in patients whose baseline Hcy ≤ 15 μ mol/L; but could not change the plasma BH 4 levels (1.71±0.83 pmol/mL vs. 1.73±0.58 pmol/mL, P &gt; 0.05) in patients whose baseline Hcy &gt; 15 μ mol/L. Furthermore, fenofibrate could elevate plasma BH 4 levels only in patients whose Hcy levels ≤15 μ mol/L at baseline and at the end of follow-up (1.27±0.78 pmol/mL vs. 2.47±2.07 pmol/mL, P &lt; 0.05), and couldn’t change plasma BH 4 levels in patients whose Hcy levels &gt; 15 μ mol/L at baseline and at the end of follow-up(1.68±0.87 pmol/mL vs. 1.76±0.61 pmol/mL, P &gt; 0.05). Conclusion: Fenofibrate can improve endothelial function in patients with hypertriglyceridemia which might relate to the increased expression of NO and BH 4 by fenofibrate. Fenofibrate might inhibit the effects of Hcy in decreasing BH 4 and impairing of the endothelial function, and elevated Hcy might partially inhibit the effects of fenofibrate in increasing BH 4 and improving the vascular endothelial function.
Abstract 1812: More CPR with the New Guidelines. Does it Impact VF Termination by Defibrillation Shocks?
Authors: Olivier Hersan, Daniel Jost, Isabelle L Banville, Franck Calamai, David Fontaine, David Lallement, Fred W Chapman, Rob G Walker, Herve Degrange, Claude Fuilla
Journal: Circulation (2007)

The 2005 resuscitation Guidelines emphasize reducing interruptions of cardiopulmonary resuscitation (CPR) and provide changes to the CPR and defibrillation protocols for automated external defibrillator (AED) use. We investigated whether the differences between Guidelines 2000 and 2005 resuscitation protocols influence the ventricular fibrillation (VF) termination rate of AED shocks during out-of-hospital cardiac arrest. Methods: As part of a clinical trial, VF cardiac arrest patients treated by firefighters were prospectively randomized to treatment protocols consistent with Guidelines 2000 (CONTROL) or Guidelines 2005 (STUDY). The STUDY protocol removed stacked shocks and post-shock pulse checks. It featured 1 minute of CPR before the 1st shock, and CPR between rhythm analysis and shock delivery. All AEDs delivered escalating biphasic shocks beginning at 200J. We reviewed AED electronic records to evaluate VF termination for all shocks within the first 8 minutes of treatment. Successful defibrillation was defined per Guidelines 2005 as termination of VF for &gt; 5seconds. A sample size of 400 shocks per group was prospectively chosen for statistical power to detect an 8% difference in VF termination rate. Results: As expected, the STUDY protocol resulted in more prompted CPR time, more actual CPR delivered, and fewer shocks during the first 8 minutes of treatment. The VF termination rate did not differ between the two groups (85% CONTROL vs. 87% STUDY). The proportions of patients with ventricular complexes (24% vs. 27%), in asystole (61% vs. 60%), or remaining in a shockable rhythm (15% vs. 13%) at 5 seconds were also not different between the CONTROL and STUDY groups, respectively. Conclusion: Despite a reduction in CPR hands-off time, VF termination effectiveness of biphasic shocks is similar for Guidelines 2000 and Guidelines 2005 cardiac arrest treatment protocols.
The molecular and pathway characterization of patients with metastatic castration resistant prostate cancer (mCRPC) refractory to therapy with abiraterone acetate or enzalutamide: Preliminary results from the SU2C/PCF/AACR West Coast Prostate Cancer Dream Team (WCDT).
Authors: Eric Jay Small, Jack Youngren, Tomasz M. Beer, Charles J. Ryan, George Thomas, Nader Pourmand, Robert Evan Reiter, Joshi J. Alumkal, Joshua M. Stuart, Christopher P. Evans, Martin Edwin Gleave, Kim N. Chi, Alex Toschi, Adam Foye, Primo Lara, Owen Witte
Journal: Journal of Clinical Oncology (2014)

79 Background: Progressive metastatic castration resistant prostate cancer (mCRPC) has historically been challenging to biopsy and characterize on a molecular basis because of its bone tropism. Since mechanisms of resistance to androgen signaling inhibitors such as enzalutamide or abiraterone are not fully understood, both an unbiased and a targeted assessment of the molecular landscape of these patients is required. Methods: Patients (pts) with mCRPC undergo biopsy at one of five West Coast Prostate Cancer Dream Team (WCDT) clinical sites, using a uniform biopsy protocol, following central radiologic review. Tissue is both frozen, and formalin fixed/paraffin embedded (FFPE). Frozen tissue undergoes laser capture microdissection (LCM) for RNA seq, DNA seq, and array comparative genomic hybridization (aCGH). An RNA seq process was developed that allows using extremely small quantities of RNA (approximately 1 ng). FFPE tissue undergoes a CLIA-certified assessment of a 37-gene mutational panel, FISH for AR, and IHC for PTEN. Peripheral blood is collected for miRNA, immune responses, and CTC analysis including aCGH. Pathway assessment integrating clinical, RNA seq, DNA seq, aCGH data is undertaken using PARADIGM analysis. Results: Thirty six of 300 planned mCRPC pts have undergone a metastasis biopsy: 17 from bone, eight from liver, one from lung, and 10 from distant lymph nodes. Tumor is present in around 75% of the frozen specimens. To date, LCM has been undertaken in 11 samples, with RNA seq done in six, DNA whole exome seq in one, aCGH in four. FFPE tissue has been evaluated by mutational panel sequencing (n=9), FISH for AR (n=11), and IHC for PTEN (n=13). CTC have been isolated in 33 pts. aCGH has been successfully undertaken in paired CTC and biopsy specimens. Expression data from patients with full RNA sequencing have been analyzed by PARADIGM, with top disrupted pathways identified. Conclusions: Biopsies of mCRPC, including from bony sites, can be undertaken and used for molecular and pathway analysis. Sufficient tissue for unbiased and targeted assessment can be obtained. Linkage of results from these studies to the clinical characteristics of these patients will reveal important insights into mechanisms of resistance.
Traditional Beer Consumption and the Iron Status of Spouse Pairs From a Rural Community in Zimbabwe
Authors: Victor M. Moyo, Innocent T. Gangaidzo, Z.A.R. Gomo, Hlosukwazi Khumalo, Thokozile Saungweme, C.F. Kiire, Tracey Rouault, Victor R. Gordeuk
Journal: Blood (1997)
Abstract 3687: Assessment of Endothelial Function in the Forearm with Blood Oxygen Level-Dependent Magnetic Resonance Imaging
Authors: Matthias Voehringer, Yichun Sun, Jordin D Green, Todd J Anderson, Matthias G Friedrich
Journal: Circulation (2008)

Background: Blood Oxygen Level-Dependent Magnetic Resonance Imaging (BOLD-MRI) sensitively detects changes of blood flow, blood volume, and oxygenation. Objective: To assess endothelial function wi...
Abstract 1361: Leukocyte Antigen-Related Phosphatase Regulates Insulin Sensitivity by Interaction with Snapin
Authors: Aleksandr E Vendrov, Igor Tchivilev, Xi-Lin Niu, Juxiang Li, Marschall S Runge, Nageswara R Madamanchi
Journal: Circulation (2008)

Several protein tyrosine phosphatases including leukocyte antigen-related (LAR) phosphatase have been implicated in insulin resistance, which is a risk factor for atherosclerosis. We showed previously that LAR negatively regulates insulin-like growth factor-1 (IGF1) signaling in vascular smooth muscle cells (VSMC) leading to increased proliferation and migration. Absence of LAR also enhanced neointima formation in response to arterial injury in mice. However, the role of LAR-modulated signaling in the development of insulin resistance has not been elucidated. Here, we investigated the function of LAR in regulating glucose uptake and insulin sensitivity. We identified snapin, a SNARE-associated protein involved in glucose transporter Glut4 vesicle fusion with plasma membrane, as a LAR-interacting protein using a yeast two-hybrid screen. IGF1-induced serine phosphorylation of snapin, its translocation to membrane and association with SNARE complex were enhanced in VSMC lacking LAR. Similarly, PI3K-PDK1-PKCζ signaling pathway was more active in LAR-/- cells after IGF1 treatment. This resulted in enhanced Glut4 activation, its membrane translocation and association with snapin. Glut4 membrane translocation and association with snapin after IGF1 treatment were impaired in snapin+/− VSMC. IGF1 treatment also increased serine phosphorylation of GSK3 β in LAR−/− VSMC leading to increased activation of glycogen synthase. Consistent with this, enhanced glucose uptake was observed in LAR−/− VSMC compared to wild-type cells after IGF1 treatment. Basal and IGF1-induced glucose uptake were significantly lower in snapin+/− VSMC than in wild-type cells. Snapin+/− mice had higher levels of blood glucose, lower quantitative insulin sensitivity check index (QUICKI) and impaired response to insulin in insulin tolerance test (ITT) compared to wild-type mice. Decrease of QUICKI and impairment of IIT were more pronounced in snapin+/− mice fed a high-fat diet. In addition, Doppler ultrasonography indicated increased arterial stiffness in snapin+/− mice. Together, these data indicate that LAR negatively regulates snapin phosphorylation which in turn affects glucose uptake leading to the development of insulin resistance and vascular pathology.
Machine that combines radiotherapy with MRI scanner will undergo trials next year:
Authors: Nigel Hawkes
Journal: BMJ (2015)

The Royal Marsden Hospital in London will take delivery early next year of a machine that combines radiotherapy with real time imaging using a magnetic resonance imaging (MRI) scanner.

Tumours can move quite perceptibly on a daily or even hourly basis, making precise targeting of the x ray beam difficult. The MR Linac, which is being developed in a collaboration between its manufacturers and medical centres around the world, aims to get around this difficulty by combining imaging with treatment, so that the x ray beam can be tailored to the tumour to deliver the radiation dose where it …
Abstract 120: Early Defibrillation Benefit in Patients Wearing a Wearable Defibrillator
Authors: Jo Ann M Glad, Stephen J Szymkiewicz
Journal: Circulation (2010)

Background: Early defibrillation through public access to defibrillation has been met with some success (e.g., casinos) in treating sudden cardiac arrest (SCA) but is limited by the need for a witn...
Soundings: Gulliver and bmj.com
Authors: Imre Loefler
Journal: BMJ (2004)

Suppose that Jonathan Swift published Gulliver's Travels in the BMJ. Within hours the rapid responses have begun to appear.

The first one anticipates Thackeray, in whose judgment the book was “Filthy in word, filthy in thoughts, furious, raging, and obscene.” Moral outrage is followed by the scoffing of seafarers, geographers, and meteorologists pointing out that the tale is mere fantasy.

An engineer submits his calculations, according to which 1500 horses 4 inches high could not have drawn the carriage on to which Gulliver was fastened.

The human rights movement condemns the author for making fun of Lilliputians, people who were disadvantaged in growth. A rapid responder uses the words “dwarf” and “unnatural.”

Hell breaks loose. For two days rapid responders are hurling insults at each other. The World Federation of Acromegalics protests, claming that the description of the people of Brobdingnag is insulting to them. The animal welfare people deplore the mention of a cage.

Before long, rapid responders begin to refer to the Bible, some of them misquoting it and most of them interpreting it liberally.

One responder expands upon the subaquatic sexual attack of the young Yahoo female and discusses the positions in which the two would have been joined were it not that upon Gulliver's frightened roaring the nag came galloping and chased her away.

By the fifth day the row about what is and is not natural has been revived, the electronic debate has become global, and there is lively participation of people from the former colonies.

So far there is one lonely voice who suspects that the writer may have had his tongue “deeply in his cheek,” but on the fifth day a Dominican is wondering why doctors do not appreciate irony and a New Yorker recognises the style of Swift.

Swift alerts his circle of friends so that they do not miss the comedy. He reiterates his conviction: Aristotle was wrong in assuming that the human is a rational animal; while homo is capable of rationality, it eschews the use of this faculty most of the time.

There is one single syllable rapid response that remains ignored by the respondents but gives the good dean food for thought: this is the word “eh?”
The impact of obstructive sleep apnea on glucose regulation and liver injury in nondiabetic men
Authors: Qian Xiaosen, Liu Yi
Journal: European Respiratory Journal (2011)

Objective:  We explored the effect of Obstructive sleep apnea syndrome (OSAS) on glucose regulation and liver injury in nondiabetic men.   Research design and methods:  We enrolled 49 non diabetic men of the OSAS patients without concomitant diseases/medications based on overnight polysomnography and blood tests. We measured fasting serum glucose (FPG), fasting insulin (FIS), C-reactive protein (CRP), liver enzymes such as alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) and calculated new homeostasis model assessment estimates of insulin resistance (HOMA2-IR), insulin sensitivity (HOMA2-IS) and pancreatic beta-cell function (HOMA2-B).   Results:  Median fasting insulin level, HOMA2-IS, and HOMA2-IR of the severe OSAS group were significantly higher than those of the other OSAS subgroups and controls. No significant differences were observed for FPG and HOMA2-B. CRP levels were significantly correlated with BMI, with AHI, with minimum SpO2, with HOMA2-IR and with LDH during sleep. Both levels of ALT and LDH were significantly positively correlated with insulin and HOMA2-IR ( p  =0.001 respectively). Significant elevations in HOMA2-IR ( p =0.001), fasting serum insulin ( p =0.001), levels of CRP ( p =0.024) levels of ALT ( p =0.040) and levels of LDH ( p =0.047) and significant reductions in HOMA2-IS ( p =0.002) were found in subjects with AHI>15/h compared to those with AHI   Conclusions:  We demonstrated that OSAS contribute to the development of insulin resistance and liver injury. Insulin resistance may be the first key effect of OSAS on glucose regulation. Insulin resistance may be the pathophysiologic basis of liver injury in OSAS.
Pulmonary tuberculosis in two remand prisons (SIZOs) in St Petersburg, Russia
Authors: T Lobacheva, V Sazhin, E Vdovichenko, J Giesecke
Journal: Eurosurveillance (2005)

The tuberculosis (TB) situation in the Russian penitentiary system has received much attention. We performed a descriptive epidemiological study of TB in two St Petersburg remand prisons (SIZOs). The medical databases of the TB divisions in these prisons were searched for all diagnosed cases of TB from 1 January 2000 to 31 December 2002. The main diagnostic method was chest x ray. The total number of reported TB cases in these two remand prisons during this three-year period was 876. Out of these, 432 were diagnosed at entry to prison, and 444 developed the disease during incarceration, with the proportion diagnosed during incarceration increasing over time. The majority of cases were aged under 30 years. TB incidence in Russian remand prisons is still very high and needs to be monitored closely.
Abstract 5625: One-year Mortality in Patients With Troponin I Elevation in an Acute Ischemic Cerebrovascular Event in the Absence of an Acute Coronary Syndrome or Pulmonary Edema
Authors: Bhaskar Purushottam, Steven Amanullah, Jongoh Kim, Aman Amanullah
Journal: Circulation (2009)

Introduction: Troponin (TnI) elevation in patients with an acute ischemic cerebrovascular event (AICVE) has a poor prognosis and is often thought to be secondary to cardiac failure {(left ventricular ejection fraction (EF) &lt; 55%} or renal failure (creatinine &gt;1.3 mg/dL). However, the prognosis is not well defined in the absence of cardiac or renal failure. Hypothesis: We hypothesize that patients with an elevated TnI (≥0.08 mcg/L) in an AICVE have an increased risk of one-year mortality, even in the absence of cardiac or renal failure. Methods: Three hundred consecutive patients who were admitted with an acute ischemic stroke or a transient ischemic attack in the absence of an acute coronary syndrome or pulmonary edema from january 2004 to january 2006 were studied. Hazard ratios for all-cause mortality were determined using multivariate Cox Proportional hazards analysis employing multiple variables between patients with and without TnI elevation. Results: The final cohort consisted of 207 patients with a mean age 70 ± 14 years, 62% were females. There was a 33% occurrence of TnI elevation among the entire group of 207 patients (Gr. A) and a 20% occurrence among patients, who had a normal EF(≥ 55%) and a creatinine ≤ 1.3mg/dL (Gr. B, n=91). The one-year mortality was significantly higher in patients with TnI elevation (58% in Gr. A; 42% in Gr. B) as compared to the patients without TnI elevation (20% in Gr. A; 11% in Gr. B). Conclusions: The presence of TnI elevation in patients with an AICVE is a significant independent multivariate predictor of one-year mortality in the presence or absence of cardiac or renal failure. It may be plausible that a recent silent myocardial infarction or other neurohormonal mechanisms may cause troponin elevation apart from cardiac or renal failure in the setting of an AICVE. TnI elevation and one-year mortality
Abstract 5854: Serial Assessment of Pulsatile and Non-Pulsatile Left Ventricular Assist Devices on Left Ventricular Unloading
Authors: Robert S George, Magdi H Yacoub, Carole Webb, Christopher Bowles, Robert Dean, Mike Hedger, Giles Dreyfus, Asghar Khaghani, Emma J Birks
Journal: Circulation (2008)

Pulsatile and continuous flow left ventricular assist device (LVAD)s combined with pharmacological agents have been used to bridge patients with end-stage dilated cardiomyopathy (DCM) to recovery. The aim of this study was to compare the effects of pulsatile versus continuous flow LVADs on left ventricular (LV) unloading. Unloading was assessed by echocardiography at 1, 3 and 6 months in 50 non-ischaemic DCM patients with LVADs. 29 patients received a pulsatile volume displacement pump (HeartMate XVE (HM I group); Thoratec Corp.) and 21 patients received a continuous-flow rotary pump (HeartMate II (HM II group); Thoratec Corp.). Parameters measured included end-systolic and end-diastolic diameters (ESD and EDD) and ejection fraction (EF). There was no difference in pre-implantation data between the two groups. At 1 month post device implantation, HM I patients showed significantly greater LV unloading compared to HM II patients (ESD 30.6±10, EDD 44±9.7, EF 64.8±14.5 vs 41.5±10.7, 50.9±9.7, 45.5±15.9, respectively), but there was no difference in LV unloading at 3 or 6 months (table 1 ). In the patients recovered with HM I (n=16) there was a lower ESD and higher EF compared to those with HM II (n=7) at 1 month. No difference was seen at 3 or 6 months (table 2 ). HM I XVE provided a better degree of LV unloading compared to HM II at 1 month of LVAD support. At three and six months of LVAD support both devices provided an equivalent degree of LV unloading. Table 1. Comparison of LV unloading between HM I and HM II patients. Table 2. Comparison of LV unloading between HM I and HM II recovered patients
经济视点：向配给制发展（2）
Authors: Cam, Donaldson, Angela, Bate, Peter, Brambleby, Howard, Waldner, 郑嵘
Journal: BMJ (2010)

经济学的角度 经济学家一般都建议由市场来配给商品。但是我们知道市场机制在卫生领域表现不佳。虽然认识到这一点，但建立公立医疗保障制度并不能解决资源稀缺的问题。为了让公立医疗保障制度可持续发展，防止倒退到以市场为基础的制度，我们需要清醒过来，通过认清资源稀缺的现状并管理好稀缺资源来进行配给。管理稀缺资源需要做两件事。