tbuckley/cabot-search huggingface dataset:
Abstract 3495: Obesity and Development of New Atrial Fibrillation in the Women’s Health Study
Authors: Usha B Tedrow, David Conen, Bruce A Koplan, JoAnn E Manson, Julie E Buring, Christine M Albert
Journal: Circulation (2007)

Obesity and atrial fibrillation (AF) are increasing public health problems, especially among women. Overweight and obesity (as defined by WHO criteria) have been previously associated with incident AF in existing cohorts; however, relatively few women with AF were included. We sought to further characterize the risk of incident AF over the entire range of body mass index (BMI) in a large prospective cohort of women enrolled in the Women’s Health Study. Women included in this analysis provided information on BMI and were free of cardiovascular disease and AF at baseline. Among the 38,807 women, 1022 incident AF cases were reported (9.8 +/− 1.2 person-years of AF). Compared with women not reporting AF, those who developed AF were older (58.8 +/− 8.0 vs 54.4 +/− 6.9 years), had higher BMI (27.2 +/− 5.7 vs 26.0 +/−5.0 kg/m2), and were more often diabetic (4.3% vs 2.5%), hypertensive (41.5% vs 2.5%), and hyperlipidemic (35.4% vs 29.1%), p &lt; 0.0001 for each comparison. Continuous BMI was associated with AF in age-adjusted (HR 1.05; 95%CI, 1.04 –1.06) and multivariable Cox proportional hazards models controlling for age, diabetes, hypertension, hyperlipidemia, smoking, and physical activity (HR = 1.04; 95%CI, 1.03–1.05, p &lt; 0.0001). When BMI was divided into 7 pre-specified categories, risk of AF was significantly increased among those with a BMI &gt; 30 (see graph). Compared with women with BMI &lt; 21, women with BMI &gt; 35 were at 1.90-fold (95%CI, 1.42–2.55) increased risk of AF even after controlling for the listed obesity-associated comorbidities. Conclusion: These prospective data suggest a nonlinear relationship between BMI and risk of AF, with significant risk above a BMI threshold of 30 kg/m2.
A Recombinant Human scFv Anti-Rh(D) Antibody With Multiple Valences Using a C-Terminal Fragment of C4-Binding Protein
Authors: M. Tonye Libyh, D. Goossens, S. Oudin, N. Gupta, X. Dervillez, G. Juszczak, P. Cornillet, F. Bougy, B. Reveil, F. Philbert, T. Tabary, D. Klatzmann, P. Rouger, J.H.M. Cohen
Journal: Blood (1997)
Pharmacogenetics of Paclitaxel in the Treatment of Ovarian Cancer – a Pilot Study in Preparation of Individualized Chemotherapy
Authors: Henrik Green, Peter Söderkvist, Per Rosenberg, Rajaa A. Mirghani, Per Rymark, Elisabeth Åvall-Lundqvist, Curt Peterson
Journal: Clinical Cancer Research (2007)

Pharmacogenetics of Paclitaxel in the Treatment of Ovarian Cancer – a Pilot Study in Preparation of Individualized Chemotherapy
Soundings: The European Leisure Time Directive
Authors: James Owen Drife
Journal: BMJ (2001)

The European Working Time Directive, currently causing chaos in the NHS, puts a 48 hour limit on the working week. This is difficult for doctors as most of us warm up only after 48 hours. Indeed, we are starting to panic about how to fill the other 120. Fortunately, help is at hand in the form of the European Leisure Time Directive.

Research has shown that leisure is beneficial to health and therefore, like seat belts, it is being made compulsory. This is not as easy as it sounds. Academics, for example, are paid to think but if they do so beyond the limit, their employer will incur financial penalties. The traditional decerebrant, alcohol, is also unhealthy, so universities are introducing intensive tenpin bowling and snooker.

Unlike the Working Time Directive, which puts doctors on a par with shelf stackers, the European Leisure Time Directive (ELTD) treats medicine as a special case. It also acknowledges that Britain is not like other countries, leisurewise.

Britain's favourite relaxation is watching television drama. Nowadays this consists entirely of psychologically damaged people being aggressive to one another. As doctors spend much of their time listening to psychologically damaged people being aggressive, soap operas—particularly EastEnders—will not count as medical leisure activity (MLA) under European law.

The country's second leisure activity is eating out. This raises problems of definition as working meals become more common. The ELTD requires the buffet to be weighed before and after a meal and the difference divided by the number of doctors present. A working breakfast is defined as up to 75g of croissant, 100g of muesli or 50g of yoghurt per head.

Our third relaxation is sport. The gym is classed as MLA although it involves more calorific output than work. Boxing and tae kwon do are acceptable MLA for geriatricians but not for casualty officers, for whom they are normal working activities. Coarse fishing involves sitting around for long periods staring into space and waiting for the chance to do something, so it does not count as MLA for NHS surgeons in winter.

Fourth is complaining about the state of the NHS. The ELTD recognises reality and allows this as leisure activity for doctors as for everyone else.
Abstract 3908: Interaction between C-Reactive Protein and Complement Inhibitor Factor H and Risk of Myocardial Infarction. The Rotterdam Study.
Authors: Isabella Kardys, Moniek P de Maat, Caroline C Klaver, Dominiek D Despriet, Andre G Uitterlinden, Albert Hofman, Paulus T de Jong, Jacqueline C Witteman
Journal: Circulation (2006)

The Rsch Institute for Diseases in the Elderly(RIDE) supported this study (grant 948 – 00 – 016) Background Complement inhibitor factor H (CFH) is an important regulator of the alternative compleme...
Is medical school selection discriminatory?
Authors: K. Abbasi
Journal: BMJ (1998)

Papers p 1111 Education and debate p 1149 

Being white, female, an academic high achiever, and singleminded can have its drawbacks, but when it comes to selection for United Kingdom medical schools, no one's better placed. At least that's the message from the analysis by McManus of the anonymised data on selection released this week (p 1111).1 The key findings show, surprisingly, that women are more likely to gain entry to medical schools, but candidates from ethnic minorities remain disadvantaged. Concerns about the selection procedure have long inspired calls for a code of practice.2



Differences exist between ethnic minority groups. Caribbeans are less disadvantaged than Africans. Indians are less disadvantaged than Bangladeshis or Pakistanis. While wide confidence intervals hint that some of these differences may not be real, it is undeniable—and suspicions are confirmed—that overall ethnic minorities are disadvantaged. Sceptics will argue that this analysis by McManus doesn't take into account data on predicted A level grades (which were not made available to him but which selectors rely on heavily), but previous work …
Abstract 9256: Overexpression of C-Terminal Domain of Talin-1 Enhances Survival, Migration, and Differentiation of Human Cardiac Stem Cells
Authors: Umesh Sharma, Jia-Qiang He, Duc M Vu, Xian-Liang Tang, Gregg Rokosh, Roberto Bolli
Journal: Circulation (2011)

Background: Cardiac stem cells (CSCs) have emerged as a promising therapy for cardiac repair after acute MI. Talin-1 is a key downstream signaling mediator of integrins. The C-terminal part of the talin rod, talin C, contains binding sites and regulatory elements that convey essential aspects of talin function in cells. In this study, we aimed to investigate the role of talin C in the survival and migration of CSCs and their differentiation into adult cardiomyocytes. Methods: Utilizing a baculovirus-mediated protein expression system in mammals (BacMam), we overexpressed talin C in c-kit-positive CSCs isolated from human right atrial appendages. In a TNF-α -treated cell culture system, we examined the survival of talin C-expressing CSCs by measuring LDH release. Adhesion of CSCs to fibronectin was measured by colorimetric Azur dye assay. Cell migration at baseline and with high glucose (HG) was studied by in vitro scratch assay. Differentiation of CSCs to adult cardiomyocytes was measured by flow cytometry using troponin I as cardiac lineage marker. Results: Overexpressed talin C was localized to intracellular adhesion complexes and actin filaments. Overexpression of talin C inhibited TNF-α-induced cytotoxicity of CSCs (optical density: TNF-α, 0.713±0.11; TNF-α+talin C, 0.33±0.02, P&lt;0.001, N=10, each group). Talin C overexpression prevented HG-induced loss of cell adhesion (optical density: HG, 0.92±0.07; HG+talin C, 1.05±0.046; p=0.04, N=8, each group), and enhanced CSC migration (migration index: HG, 15.34±2.7; HG+talin C, 34±4.7; p=0.03, N=3-4, each group). Furthermore, talin C overexpression increased the commitment of CSCs to a cardiac lineage (% of troponin-I positivity: control, 66.13±4.07; talin C, 80.53±1.79; p=0.05). Conclusions: This study demonstrates a novel role for talin C in mediating i) increased CSC survival in a high pro-inflammatory environment, ii) increased CSC migration in HG cell growth environment, and 3 iii) enhanced commitment of CSCs to a cardiac lineage in vitro. These findings suggest that talin C enhancement may improve CSC survival, homing and differentiation after transplantation.
Abstract 1642: Feeding a Western Diet to LDL Receptor Null Mice Causes Inflammatory Changes in the Glomerulus, which are Ameliorated by D-4F an Apolipoprotein A-I Mimetic
Authors: Georgette Buga, Ashkan Hakhamian, Joy S Frank, Giuliano Mottino, Srinivasa T Reddy, Mohamad Navab, GM Ananthramiah, Alan M Fogelman
Journal: Circulation (2006)

Background-  Feeding a Western diet to LDL receptor null mice results in hyperlipidemia, atherosclerosis, and endothelial dysfunction. Atheroslcerosis and endothelial dysfunction have been shown to be improved by oral administration of the apoA-I mimetic D-4F without altering hyperlipidemia. We asked if hyperlipidemia in this mouse model would result in renal glomerular changes and if D-4F would mitigate these changes.   Methods and Results-  Female LDL receptor null mice were fed a Western diet for 6 to 8 weeks with D-4F (n =10) or the inactive control peptide, scrambled D-4F (ScD-4F) (n =10) added to their drinking water at 300 μg/mL. Kidneys were removed and the cellularity of the glomeruli and the ratio of the glomerulus to Bowman’s capsule (a measure of glomerular proliferation) were determined. Glomerular monocyte chemoattractant protein-1 (MCP-1) was quantified with Image Pro Plus software. Plasma lipids and lipoproteins were also determined and blood pressure was measured by the tail cuff method. The mice that received the inactive control peptide ScD-4F compared to D-4F had significantly more cells per glomerulus (62.8±1.9 cells per glomerulus for ScD-4F  versus  37.2±0.8 for D-4F; p versus  0.82±0.01 for D-4F; p versus  5.03±2.6 for D-4F; p   Conclusion-  Feeding a Western diet to LDL receptor null mice induces glomerular inflammation which is ameliorated by the apoA-I mimetic peptide D-4F without altering plasma lipids or blood pressure.
Abstract 392: Loss of SHP Protects LDLRKO from Diet-induced Hypercholesterolemia
Authors: Helen B Hartman, KehDih Lai, Mark J Evans
Journal: Circulation (2007)

CYP7A1 encodes the rate limiting enzyme for the conversion of cholesterol to bile acids. Several studies have demonstrated that elevated expression of CYP7A1 confers protection from hypercholesterolemia. CYP7A1 expression is regulated by two nuclear receptors, farnesoid X receptor (FXR) and small heterodimer (SHP). Here we demonstrate that although FXR −/ − and SHP −/ − mice have similarly elevated levels of CYP7A1, FXR −/ − mice have elevated serum cholesterol and triglyceride levels and serum markers of hepatic inflammation whereas the SHP −/ − mice do not. This suggestion of a beneficial lipid effect of the loss of SHP was confirmed in a cholesterol/cholic acid diet model, in which SHP −/ − mice were strongly protected form diet-induced hypercholesterolemia and hepatic inflammation. To examine the effects of the loss of SHP in a model relevant to human dyslipidemia, we generated LDLR −/ − SHP −/ − mice. The LDLR −/ − SHP −/ − mice were highly resistant to Western diet-induced elevation in serum VLDL and LDL cholesterol levels and had significantly increased levels of HDL cholesterol as compared to LDLR −/ − mice fed the Western diet. Further, hepatic inflammatory gene expression induced by the Western diet was abolished in the LDLR −/ − SHP −/ − mice. Surprisingly, the LDLR −/ − and LDLR −/ − SHP −/ − mice had nearly identical elevations in hepatic cholesterol content and repression of cholesterol regulated genes such as HMG CoA synthase and PCSK9. CYP7A1 expression was induced 10-fold by Western in the LDLR −/ − SHP −/ − mice but not in the LDLR −/ − . The Western diet induction of CYP7A1 expression in the LDLR −/ − SHP −/ − mice as compared to the LDLR −/ − (containing an intact FXR/SHP negative pathway to modulate CYP7A1 expression) may provide a basis for the protection of LDLR −/ − SHP −/ − mice, and suggests potential utility of SHP antagonists in dyslipidemia.
The new WPA Section on Stigma and Mental Disorders.
Authors: Heather Stuart
Journal: World Psychiatry (2005)

The WPA, through its Global Program to Fight Stigma and Discrimination because of Schizophrenia, has identified stigma as a major challenge. Stigma creates a cycle of discrimination and social exclusion for those who suffer from a mental disorder, as well as all of those who are associated with them. More so than the illness itself, stigma is the single most important barrier to the quality of life of people with mental disorders, their family members, and friends. It is also a major impediment to mental health reform and service development.

The majority of people with mental illnesses are now treated in the community, where negative public opinions can have significant consequences, ranging from human rights violations to discriminatory unemployment and housing practices, as well as diminished self-esteem. Stigma, and the expectation of stigma, can also produce disruptions in family relationships and reduce normal interactions.

Therefore, stigma and its consequences pose major obstacles to recovery and promote psychiatric disability. A new WPA Section on Stigma and Mental Disorders has been established on an ad hoc basis, under the co-chairmanship of Wolfgang Fleischhacker (Austria) and Heather Stuart (Canada), awaiting final approval at the World Congress in Cairo. The Section will engage in activities designed to reduce stigma and discrimination because of mental disorders and improve social inclusion for people with mental illness and their families.

More specifically, the Section will: a) disseminate information about stigma and discrimination because of mental disorders through academic and technical publications, and through symposia and courses offered at WPA regional meetings and congresses; b) advance scientific knowledge about stigma through collaborative research and evaluation; c) provide training opportunities to support the development of effective programs to fight stigma and discrimination because of mental disorders.

Any individuals who are interested in becoming members of this Section are invited to contact the Section Secretary, Richard Warner, at moc.evresupmoc@renraW kciD, including a brief note on their recent activities in this area as well as complete contact information.
Abstract 1476: Different Role Of Shp2 Mutants In Cardiomyocyte Hypertrophy In Noonan/leopard Syndrome Spectrum
Authors: Jun Narita, Shigetoyo Kogaki, Hidekazu Ishida, Hiroaki Ichimori, Toshiki Uchikawa, Sayaka Nasuno, Yoko Okada, Yoko Yoshida, Keiichi Ozono
Journal: Circulation (2008)
Abstract 18433: A Novel Intracellular Isoform of Matrix Metalloproteinase-2 Activates Innate Immunity and Leads to Cardiac Failure
Authors: David H Lovett, Rajeev Mahimkar, Elena Maklashina, Gary Cecchini, Joel S Karliner
Journal: Circulation (2011)

Modulation of cardiac structure and function by matrix metalloproteinases (MMP) is an area of intense interest. Experimental and clinical evidence has pinpointed a critical role for a specific enzyme, MMP-2, in ventricular remodeling and systolic failure. Transgenic expression of active 68 kDa MMP-2 yields multiple defects, including systolic failure and mitochondrial dysfunction. We hypothesized that an additional intracellular isoform of MMP-2 must exist that initiates mitochondrial dysfunction and inflammation. Western blots of mitochondria from ageing mice and a transgenic model of atherogenesis revealed a smaller 65 kDa MMP-2 isoform. Cardiomyoblast cells subjected to transient inhibition of oxidative phosphorylation also generated the mitochondrial 65 kDa MMP-2 isoform. MMP-2 contains three in-frame methionines in the N-terminus, each with a Kozak sequence supporting translational initiation. The 65 kDa MMP-2 isoform is an N-terminal truncation variant generated by alternative translational start site selection at M 77 , thereby deleting the signal sequence and the inhibitory prodomain: thus the 65 kDa MMP-2 is intracellular and enzymatically active. A portion of the 65 kDa MMP-2 localizes in the mitochondrial intramembranous space, triggers mitochondria-to-nuclear stress signaling and actvitates NF-κB and NFAT. Microarray analysis showed that 65 kDa MMP-2 induces a restricted innate immune response transcriptome, including viral stress response genes (OAS1, IFIT, PRKRA), the crucial innate immunity transcription factor IRF7, chemokines and pro-apoptosis genes. Cardiac-specific transgenic expression of the truncated MMP-2 isoform induced progressive cardiomyocyte and ventricular hypertrophy, followed by mononuclear inflammatory cell infiltration and cardiomyocyte apoptosis, as predicted from the microarray results. Functionally, the transgenics showed cardiomyocyte hypertrophy, contractile defects, systolic failure and enhanced injury following ex vivo ischemia/reperfusion. Conclusion: a novel intracellular isoform of MMP-2 is generated by acute or chronic oxidative stress, initiates inflammatory signaling and drives cardiomyocyte apoptosis, features directly relevant to clinical cardiac disease.
Abstract 3127: Pulmonary Valve Replacement in Tetralogy of Fallot: Impact on Survival and Freedom from Ventricular Tachycardia
Authors: David M Harrild, Tal Geva, Frank Pigula, Frank Cecchin, Charles I Berul, Kimberlee Gauvreau, Edward P Walsh
Journal: Circulation (2007)

Background : Pulmonary regurgitation (PR) in repaired tetralogy of Fallot (TOF) is associated with right ventricular (RV) dilation and dysfunction as well as arrhythmia. Pulmonary valve replacement (PVR) may prevent the development of these late complications. This retrospective study tests the hypothesis that PVR improves survival and freedom from ventricular tachycardia (VT) in patients with TOF. Methods : Enrolled patients had TOF with PVR for RV dilation from PR. Referral for PVR was largely based on symptoms. Controls (TOF patients with RV dilation but no PVR ), were matched by age (± 2 years) and QRS duration (± 30 msec). There were 77 case/control pairs. Pairs did not differ significantly for age, repair type, decade of TOF repair, age at TOF repair, or presence of pre-PVR VT. Primary outcome events were death and VT. Events were recorded only if they occurred while both case/control were actively followed. Total duration of post-PVR follow-up was 172 patient years per group (median 1.4y, 0.01 – 13.2). PVRs were performed between 1990 and 2005 at median age 21y (6 –57). Results: The change in QRS duration did not differ significantly between the two groups (p = 0.43). Other results are summarized in the table and figure below. Conclusion: In this cohort of patients with repaired TOF, late PVR for symptomatic PR/RV dilation did not lead to reduced incidence of VT and/or death.
Abstract 2422: Calcification within the Advanced Human Carotid Atherosclerotic Plaque is Associated with Intraplaque Hemorrhage: A Magnetic Resonance Imaging and Histology Investigation
Authors: Minako Oikawa, Chun Yuan, Hunter Underhill, Baocheng Chu, Wei Yu, Marina S Ferguson, Thomas S Hatsukami
Journal: Circulation (2006)

Purpose: There is a lack of consensus regarding the significance of calcification in the atherosclerotic carotid plaque. While some studies suggest calcification is a stabilizing factor, others hav...
Abstract 796: Reduction of Cardiac Calsequestrin Increases Sarcoplasmic Reticulum Ca <sup>2+</sup> -Leak Independent of Luminal Ca <sup>2+</sup> and Triggers Ventricular Arrhythmias in Mice
Authors: Nagesh Chopra, Prince J Kannankeril, Tao Yang, Thinn Hlaing, Izabela A Holinstat, Kristen Ettensohn, Karl Pfeifer, Brandy Akin, Larry R Jones, Clara Franzini-Armstrong, Bjorn C Knollmann
Journal: Circulation (2007)

Deletion of cardiac calsequestrin (Casq2) causes VT in mice akin to CASQ2 mutations. However, other sarcoplasmic reticulum (SR) proteins (triadin-1/junctin) are also reduced in homozygous ( Casq2 &amp; minus;/− ) mice and may contribute to their arrhythmia phenotype. Furthermore, it is unknown if Casq2 regulates SR Ca 2+ -release directly or indirectly by buffering SR luminal Ca 2+ . To address both questions, we examined heterozygous ( Casq2 +/ − ) mice with a 25% reduction in Casq2, but no decrease in other SR proteins. Results: Casq2 +/ − mice (n=35) challenged with isoproterenol displayed 3-fold higher rates of ventricular ectopy than Casq2 +/+ mice (n=31; p&lt;0.05). Programmed stimulation induced significantly more VT in Casq2 + / − mice. Field-stimulated Ca 2+ transients, cell shortening, L-type Ca 2+ current and SR volume were not different between the 2 groups. However, in presence of isoproterenol, SR Ca 2+ leak was significantly higher in Casq2 + / − myocytes ( Casq2 +/− 0.18±0.02 F ratio vs Casq2 +/+ 0.11±0.01 F ratio , n=57, 60; p=0.01), resulting in a significantly higher rate of spontaneous SR Ca 2+ -releases/triggered beats ( Casq2 +/− 0.38±0.07 vs Casq2 +/+ 0.12±0.06, n=47, 34; p=0.007). Luminal SR Ca 2+ was not significantly different between the 2 groups. However, on plotting SR Ca 2+ leak as a function of luminal SR Ca 2+, leak remained significantly higher in Casq2 +/− myocytes (figure ). Conclusion: Even modest reductions in Casq2 increase SR Ca 2+ leak and cause VT susceptibility under stress, which could explain increased risk for VT in CASQ2 +/− mutations. The underlying mechanism is likely the direct modulation of SR Ca 2+ -release by Casq2 rather than decreased Ca 2+ buffering in the SR lumen.
Abstract 2685: “Exercise Prestriction” in Long QT Syndrome: Impact of Genotype on Repolarization Reserve
Authors: Raymond W Sy, Ishvinder Chattha, Matthew Bennett, Lorne J Gula, Allan C Skanes, Raymond Yee, George J Klein, Andrew D Krahn
Journal: Circulation (2009)

Introduction Strict exercise restriction for patients with Long QT syndrome (LQTS) is recommended in current guidelines. However, LQTS has a variable genotype and phenotype, such that this recommen...