tbuckley/cabot-search huggingface dataset:
Abstract 5765: 9p21 Genetic Variant and Benefit From Intensive Statin Therapy After an Acute Coronary Syndrome
Authors: Jessica L Mega, Olga A Iakoubova, James J Devlin, Jie Qin, Christopher P Cannon, Eugene Braunwald, Marc S Sabatine
Journal: Circulation (2009)

Background Genetic variation at 9p21 has been associated with a greater risk of MI. The relationship of this locus to risk of recurrent coronary events in patients with ACS and to benefit from intensive statin therapy is unknown. Methods We studied 2029 pts in PROVE IT-TIMI 22, a trial of intensive (atorvastatin 80 mg/d) vs moderate (pravastatin 40 mg/d) statin therapy after recent ACS. Cox regression was used to assess risk of recurrent coronary events associated with 9p21 rs1333049 “C” allele adjusting for clinical risk factors and to test for an interaction between statin therapy and rs1333049, as well as KIF6 719Arg, a gene variant previously shown to be associated with clinical benefit of statins. Results Among those treated with moderate statin therapy, the adj HR for CHD/MI over 2 yrs was 1.35 (95% CI 0.80 –2.28) for carriers (75% of pts) vs non-carriers. Benefit from intensive vs moderate statin therapy was significantly greater among rs1333049 “C” allele carriers than non-carriers (Fig ). In a multilocus model, both rs1333049 and KIF6 variants modified statin therapy (P interaction 0.035 &amp; 0.029), and a particularly large benefit of intensive statin therapy was seen in carriers of both variants (HR 0.32, 95% CI 0.17– 0.59, P&lt;0.0001). Conclusion The rs1333049 variant at 9p21 is associated with a trend towards increased risk of recurrent CHD/MI in patients who receive moderate statin therapy following an ACS, consistent with the risk seen for MI in population studies. Carriers of the rs1333049 “C” and the KIF6 719Arg variants appear to receive significantly greater benefit from intensive versus moderate statin therapy. Further study of these pharmacogenetic interactions is warranted.
Book: The Challenge for Primary Care
Authors: Martin Marshall
Journal: BMJ (2004)

Primary care might not be the sexiest part of the NHS, but it is essential if the health service is to function effectively. Each day over 95% of the contacts that patients make with the NHS take place in primary care. Most of these are dealt with without any input from the hospital sector. Primary care services are cost effective, most of them are of high quality, and we know that patients rate them highly. Why then do so many frontline primary care professionals feel demoralised and fearful of the future? Perhaps it is because people working at the sharp end find it difficult to see beyond the stresses and strains of their current work and to understand the big picture of primary care's current and future role in the health system.​system.




Figure 1



Nigel Starey

Radcliffe Medical Press, £35, pp 240 ISBN 1 85775 569 3

Rating: ★★




This book, written by someone with experience as a clinician, a manager, and a policy adviser, tries to help. Starey adopts an appropriately broad perspective on primary care, moving beyond the traditional domination of general practice to examine the contributions of a wide variety of different stakeholders. He explores the history of primary care in the United Kingdom and its impact on current paradigms, structures, and processes. Using this historical perspective he examines trends and extrapolates from them to predict the future.

Aided by the technique of scenario planning, Starey describes two possible paths down which primary care might go: one is market led and focuses on the demands of individual consumers, the other is a collectivist model that is planned and regulated. Starey argues passionately against vested professional interests and the traditional reactive approach of many people working in primary care. He is an advocate of “whole systems” thinking—of understanding how these systems work as well as how they are structured.

At times the style is evangelistic, and Starey seems to accept uncritically the political dogma that dominates current policy. The book is peppered with generalisations and unsubstantiated assertions that are justified on the grounds that the author wants to “provoke the reader.” Most disappointingly, Starey focuses more on the public health model of general practice than on the biographical model. His view that the main responsibility of the primary care system is to deliver social justice seems to me to miss the point. Unless those responsible for reform of primary care understand the most basic of human needs—the desire for a one to one therapeutic relationship between a patient and a trusted health professional—then the oft cited commitment to a health system led by primary care will remain nothing more than an empty promise.
A Randomized Comparison of Platinum Chromium-Based Everolimus-Eluting Stents Versus Cobalt Chromium-Based Zotarolimus-Eluting Stents in All-Comers Receiving Percutaneous Coronary Intervention
Authors: Kyung Woo Park, Si-Hyuck Kang, Hyun-Jae Kang, Bon-Kwon Koo, Byoung-Eun Park, Kwang Soo Cha, Jay Young Rhew, Hui-Kyoung Jeon, Eun-Seok Shin, Ju Hyeon Oh, Myung-Ho Jeong, Sanghyun Kim, Kyung-Kuk Hwang, Jung-Han Yoon, Sung Yun Lee, Tae-Ho Park, Keon Woong Moon, Hyuck-Moon Kwon, Seung-Ho Hur, Jae-Kean Ryu, Bong-Ryul Lee, Yong Whi Park, In-Ho Chae, Hyo-Soo Kim
Journal: Journal of the American College of Cardiology (2014)
MODULATION OF THE CYCLOOXYGENASE PATHWAY IS ASSOCIATED WITH EFFICACY IN A RANDOMIZED PHASE II TRIAL OF ERLOTINIB AND CELECOXIB OR PLACEBO IN ADVANCED NON-SMALL CELL LUNG CANCER (NSCLC)
Authors: Michael C Fishbein, Brian Gardner, Ginder L Milne, Marianna Koczywas, Mihaela Cristea, Jonathan E Dowell, Hejing Wang, Robert A Figlin, Robert M Elashoff, Steven M Dubinett, Karen L Reckamp
Journal: Journal of Thoracic Oncology (2013)
The results of a nurse-led nicotine dependence therapy as a part of interdisciplinary rehabilitation in Iceland
Authors: Jonina Sigurgeirsdottir, Gudbjorg Petursdottir, Torunn Gudmundsdottir, Aldis Jonsdottir, Ingibjorg Eydis Ingimarsdottir
Journal: European Respiratory Journal (2014)

The study aims to assess the results of a nicotine dependence therapy provided at a rehabilitation centre in Iceland for patients with lung, heart, pain, psychiatric, obesity, rheumatoid and central nervous system diseases. A study conducted 2000-2002 revealed that 34,8% of the participants were smokefree all 12 months of follow-up and 52,2% were smokefree at the point of 12 months9 contact (Sigurgeirsdottir, 2004). The therapy 2011-2013 was the same, and in concordance with the clinical guidelines of the Icelandic Directorate of Health (2009) unless that it did not contain Nicotine replacement: personal consultation, weekly support group, weekly interdisciplinary education, and personal support as needed. Telephone follow-up every second month for one year. Data collection started 1.1.2011 and follow-up completed 18.02.2014. The population was all patients using tobacco when they started rehabiliation and the final sample was 119 participants.  The most common medical diagnoses of participants were COPD (51), anxiety or depression disorder (18), atherosclerotic or other heart disease (16), and pain or arthritis (15). Other diagnoses were less common.  Adult smoking prevalence in Iceland (18-67 years) is 13,8% (Icelandic Directorate of Health, 2012). Depressive patients and alcohol dependent seem to have specially hard time to master nicotine dependency (Kapson and Haaga, 2010). Sigurgeirsdottir9s study (2004) suggests that the therapy described above is useful for lung patients in rehabilitation. Here is an opportunity to compare the results according to medical diagnosis and reveal if there is a difference in the mastery of the dependency between patient groups.
Diffuse Large B-Cell Lymphoma (DLBCL) Patients Failing Second-Line R-DHAP Or R-ICE Chemotherapy Included In The Coral Study
Authors: Eric Van Den Neste, Christian Gisselbrecht, Norbert Schmitz, Nicolas Mounier, Devinder S Gill, David Linch FMedSci, Marek Trneny, Noel Milpied, John Radford, Nicolas Ketterer, Ofer Shpilberg, Ulrich Dührsen, David Ma, Josette Brière, Catherine Thieblemont, Gilles Andre Salles, Craig H. Moskowitz, Bertram Glass
Journal: Blood (2013)
Abstract 722: High Reproducibility of Serial Adenosine Single Photon Tomography Myocardial Perfusion Studies: A Quantitative Analysis from the ADVANCE 2 Study
Authors: John J Mahmarian, Ami E Iskandrian, Manuel D Cerqueira, Lemuel A Moye, Gregory S Thomas, Timothy M Bateman, Robert C Hendel, Ann W Olmsted
Journal: Circulation (2008)
Abstract 16096: Snf1-Related Kinase Inhibits Cell Proliferation Through Upregulated Calcyclin Binding Protein and Reduced Beta-Catenin Signaling
Authors: Amy K Rines, Michael A Burke, Richard Fernandez, Hossein Ardehali
Journal: Circulation (2011)

Introduction: Snf1-related kinase (SNRK) is a mammalian serine-threonine kinase with sequence similarity to the AMP-activated kinase alpha subunit. SNRK localizes to the cytoplasm and nucleus, howe...
Abstract 12233: Gender Differences in Outcomes After Cardiac Resynchronization Therapy: A Systematic Review, and Meta Analysis of Prospective Studies With Meta-Regression
Authors: Parikshit S Sharma, Dipti S Pancholy, Tejas Patel, David J Callans, Samir B Pancholy
Journal: Circulation (2013)

Background: Gender related differences in outcome have been observed in cardiac resynchronization therapy (CRT) patients, although the literature has conflicting reports. Methods: After comprehensi...
Evidence for Skeletal Resistance to Parathyroid Hormone in Magnesium Deficiency
Authors: Jeffrey J. Freitag, Kevin J. Martin, Mary B. Conrades, Ezequiel Bellorin-Font, Steven Teitelbaum, Saulo Klahr, Eduardo Slatopolsky
Journal: Journal of Clinical Investigation (1979)

Hypocalcemia during magnesium (Mg) depletion has been well described, but the precise mechanism(s) responsible for its occurrence is not yet fully understood. The hypocalcemia has been ascribed to decreased parathyroid hormone (PTH) secretion as well as skeletal resistance to PTH. Whereas the former is well established, controversy exists as to whether or not Mg depletion results in skeletal resistance to PTH. These studies examine the skeletal response to PTH in normal dogs and dogs fed a Mg-free diet for 4-6 mo. Isolated tibia from normal (serum Mg 1.83±0.1 mg/100 ml) and experimental dogs (serum Mg 1.34±0.15 mg/100 ml) were perfused with Krebs-Henseleit buffer during a constant infusion of 3 ng/ml of synthetic bovine PTH 1-34 (syn b-PTH 1-34). The arteriovenous (A-V) difference for immunoreactive PTH (iPTH) across seven normal bones was 37.5±3%. In contrast, the A-V difference for iPTH was markedly depressed to 10.1±1% across seven bones from Mg-depleted dogs. These findings correlated well with a biological effect (cyclic AMP [cAMP] production) of syn b-PTH 1-34 on bone. In control bones, cAMP production rose from a basal level of 5.8±0.2 to 17.5±0.7 pmol/min after syn b-PTH 1-34 infusion. In experimental bones, basal cAMP production was significantly lower than in controls, 4.5±0.1 pmol/min, and increased to only 7.1±0.4 pmol/min after syn b-PTH 1-34 infusion. Even when PTH concentrations were increased to 20 ng/ml, cAMP production by experimental bones was lower than in control bones perfused with 3 ng/ml. Histological examination of bones from Mg-deficient dogs showed a picture compatible with skeletal inactivity. These studies demonstrate decreased uptake of iPTH and diminished cAMP production by bone, which indicates skeletal resistance to PTH in chronic Mg deficiency.
A novel complex comprising BRaf, PKCϵ and S6K2 mediates the pro-survival effects of FGF-2 in small cell lung cancer cells
Authors: Michael Seckl, Olivier Pardo, Neil Sebire, Frances Bowen, Ivan Gout, Richard Marias, Julian Downward
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

2522 

Patients with small cell lung cancer (SCLC) die because of chemoresistance. We have previously shown that fibroblast growth factor-2 (FGF-2) increases the translation and thereby the expression of antiapoptotic proteins, XIAP and Bcl-XL and triggers chemoresistance in SCLC cells. Here we show that these effects are mediated through the formation of a specific multi-protein complex comprising B-Raf, PKCϵ and S6K2. S6K1, Raf-1 and other PKC isoforms do not form similar complexes. RNAi-mediated downregulation of B-Raf, PKCϵ or S6K2 abolishes FGF-2-mediated survival. In contrast, over-expression of PKCϵ increases XIAP and Bcl-XL levels and chemoresistance in SCLC cells. In a tetracycline-inducible system, increased S6K2 kinase activity triggers upregulation of XIAP, Bcl-XL and pro-survival effects. However, increased S6K1 kinase activity has no such effect. The prosurvival effects of this complex were also seen in HEK293 cells. Moreover, RNAi mediated knockdown of B-Raf, PKCϵ and S6K2 but not S6K1 impaired clonogenic growth of breast and non-small cell lung cancer cells. Thus, S6K2 but not S6K1 mediates pro-survival/chemoresistance signalling. Intriguingly, the immunohistochemical expression levels of S6K2 in lung cancer biopsy specimens appeared to correlate with subsequent resistance to therapy. In conclusion, this FGF-2-mediated pathway may predict chemoresistance and provide new targets for novel therapeutics.
Inferior Vena Cava Filter and Recurrent Pulmonary Embolism—Reply
Authors: Patrick Mismetti, Silvy Laporte, Guy Meyer
Journal: JAMA (2015)

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Suppression of EZH2 Prevents the Shift of Osteoporotic MSC Fate to Adipocyte and Enhances Bone Formation During Osteoporosis
Authors: Huan Jing, Li Liao, Yulin An, Xiaoxia Su, Shiyu Liu, Yi Shuai, Xinjing Zhang, Yan Jin
Journal: Molecular Therapy (2015)

During osteoporosis, the shift of mesenchymal stem cell (MSC) lineage commitment to adipocyte leads to the imbalance between bone mass and fat, which increases the risk of fracture. The Enhancer of Zeste homology 2 (EZH2), which methylates histone H3 on lysine 27 (H3K27me3), controls MSC cell lineage commitment. However, whether EZH2 is related to osteoporosis remains elusive. In our study, we found EZH2 expression was significantly increased in osteoporotic MSCs. EZH2 directly increased H3K27me3 levels on promoters of Wnt1, Wnt6, and Wnt10a to silence Wnt gene transcription. The inhibition of Wnt/β-catenin signaling shifted MSC cell lineage commitment to adipocyte. Knockdown of EZH2 by lentivirus-expressing shRNA rescued the abnormal fate of osteoporotic MSC. By employing the H3K27me3 inhibitor DZNep, we effectively derepressed Wnt signaling and improved osteogenic differentiation of osteoporotic MSCs in vitro. Furthermore, in vivo administration of DZNep successfully increased bone formation and repressed excessive bone marrow fat formation in osteoporotic mice. Noteworthy, DZNep treatment persistently enhanced osteogenic differentiation of endogenous MSCs. In conclusion, our study demonstrated that redundant EZH2 shifted MSC cell lineage commitment to adipocyte, which contributed to the development of osteoporosis. We also provided EZH2 as a novel therapeutic target for improving bone formation during osteoporosis. During osteoporosis, the shift of mesenchymal stem cell (MSC) lineage commitment to adipocyte leads to the imbalance between bone mass and fat, which increases the risk of fracture. The Enhancer of Zeste homology 2 (EZH2), which methylates histone H3 on lysine 27 (H3K27me3), controls MSC cell lineage commitment. However, whether EZH2 is related to osteoporosis remains elusive. In our study, we found EZH2 expression was significantly increased in osteoporotic MSCs. EZH2 directly increased H3K27me3 levels on promoters of Wnt1, Wnt6, and Wnt10a to silence Wnt gene transcription. The inhibition of Wnt/β-catenin signaling shifted MSC cell lineage commitment to adipocyte. Knockdown of EZH2 by lentivirus-expressing shRNA rescued the abnormal fate of osteoporotic MSC. By employing the H3K27me3 inhibitor DZNep, we effectively derepressed Wnt signaling and improved osteogenic differentiation of osteoporotic MSCs in vitro. Furthermore, in vivo administration of DZNep successfully increased bone formation and repressed excessive bone marrow fat formation in osteoporotic mice. Noteworthy, DZNep treatment persistently enhanced osteogenic differentiation of endogenous MSCs. In conclusion, our study demonstrated that redundant EZH2 shifted MSC cell lineage commitment to adipocyte, which contributed to the development of osteoporosis. We also provided EZH2 as a novel therapeutic target for improving bone formation during osteoporosis.
Retained in HIV Care But Not on Antiretroviral Treatment: A Qualitative Patient-Provider Dyadic Study
Authors: Katerina A. Christopoulos, Susan Olender, Andrea M. Lopez, Helen-Maria Lekas, Jessica Jaiswal, Will Mellman, Elvin Geng, Kimberly A. Koester
Journal: PLoS Medicine (2015)

Background Patients retained in HIV care but not on antiretroviral therapy (ART) represent an important part of the HIV care cascade in the United States. Even in an era of more tolerable and efficacious ART, decision making in regards to ART offer and uptake remains complex and calls for exploration of both patient and provider perspectives. We sought to understand reasons for lack of ART usage in patients meeting the Health Resources Services Administration definition of retention as well as what motivated HIV primary care appointment attendance in the absence of ART. Methods and Findings We conducted a qualitative study consisting of 70 in-depth interviews with ART-naïve and ART-experienced patients off ART and their primary care providers in two urban safety-net HIV clinics in San Francisco and New York. Twenty patients and their providers were interviewed separately at baseline, and 15 dyads were interviewed again after at least 3 mo and another clinic visit in order to understand any ART use in the interim. We applied dyadic analysis to our data. Nearly all patients were willing to consider ART, and 40% of the sample went on ART, citing education on newer antiretroviral drugs, acceptance of HIV diagnosis, social support, and increased confidence in their ability to adhere as facilitators. However, the strength of the provider recommendation of ART played an important role. Many patients had internalized messages from providers that their health was too good to warrant ART. In addition, providers, while demonstrating patient-centered care through sensitivity to patients experiencing psychosocial instability, frequently muted the offer of ART, at times unintentionally. In the absence of ART, lab monitoring, provider relationships, access to social services, opiate pain medications, and acute symptoms motivated care. The main limitations of this study were that treatment as prevention was not explored in depth and that participants were recruited from academic HIV clinics in the US, making the findings most generalizable to this setting. Conclusions Provider communication with regard to ART is a key focus for further exploration and intervention in order to increase ART uptake for those retained in HIV care.
功能性消化不良的规范治疗——中国消化不良诊治指南解读(二)
Authors: 李延青
Journal: BMJ (2008)

按照功能性胃肠病罗马Ⅲ标准，消化不良（dyspepsia）的定义为：一组表现为上腹部疼痛或烧灼感、餐后上腹饱胀和早饱感的症候群，可伴有食欲不振、嗳气、恶心和呕吐。从病因上可以分为器质性消化不良（organic dyspepsia，OD）和功能性消化不良（functional dyspepsia，FD）。目前国内对消化不良的诊治存在相当程度的不规范，尤其是功能性消化不良患者的诊治。针对这种情况，中华医学会消化病分会胃肠动力组制定了《中国消化不良的诊治指南（2007，大连）》，
Abstract 15397: Enhanced AKAP12/GRAVIN Expression Leads to Myocardial Injury by Disrupting Angiogenic Signals Related to HSP/Thioredoxin-1/VEGF Cascade in Type I Diabetic Rats
Authors: Vaithinathan Selvaraju, Sumanth C Suresh, Mahesh Thirunavukkarasu, J.Alexander Palesty, Juan A Sanchez, Nilanjana Maulik
Journal: Circulation (2014)

Background: Our earlier studies showed that AKAP12 and Thioredoxin-Interacting Protein (TXNIP) interfere with HSPA12B-induced angiogenic signaling in rat myocardium. HSPA12B appears to play an essential role in myocardial angiogenesis, which is impaired during diabetes. This study explores the impact of HSPA12B overexpression on heart function, neovascularization, and downstream target proteins, AKAP12, Thioredoxin-1 (Trx-1) and VEGF, in non-diabetic and diabetic animals following myocardial infarction (MI). Methods: Rats were divided into 6 groups: 1) Non-Diabetic Sham (NDS), 2) Non-Diabetic LacZ MI (NDLZMI), 3) Non-Diabetic HSPA12B MI (NDHSPMI), 4) Diabetic Sham (DS), 5) Diabetic LacZ MI (DLZMI), 6) Diabetic HSPA12B MI (DHSPMI). Ad.LacZ/Ad.HSPA12B was administered intramyocardially at 4 sites around the infarct border zone in NDLZMI/DiaLZMI or NDHSPMI/DiaHSPMI animals immediately after permanent LAD ligation. Results: Co-immunoprecipitation followed by immunoblot analysis showed significant increase in HSPA12B/AKAP12 association in diabetic group suggesting that diabetes impairs HSPA12B availability triggering impairment of angiogenesis. This result was also confirmed by docking analysis (insilico models). Trx-1 activity (1.73 fold) along with HSPA12B and VEGF expression was increased in DHSPMI and NDHSPMI compared to respective controls. Both AKAP12 (1.31 fold) and TXNIP (2.22 fold) appeared to be down-regulated in HSPA12B-treated groups compared to controls. Echocardiography demonstrated increased fractional shortening and ejection fraction 4 weeks post-MI in DHSPMI-treated rats compared to DLZMI. Increased capillary and arteriolar density in DHSPMI compared to DLZMI was obesrved by morphometric analysis. In addition Picrosirius red staining documented decreased fibrosis in DHSPMI vs. DLZMI myocardium. Conclusion: Therefore overexpression of HSPA12B enhances neovascularization and cardiac function following MI in diabetic animals by down-regulating Trx-1/TXNIP and HSPA12B/AKAP12 association, resulting in increased HSPA12B, Trx-1 and VEGF. These findings support a role for HSPA12B gene therapy in mitigating the morbid expression of ischemic heart disease in the setting of diabetes.
Social capital
Authors: T. Welsh, M. Pringle
Journal: BMJ (2001)

In today's British health service the experiences of patients and the insights of doctors and nurses1 highlight demoralisation and fragmentation. The solution lies in correcting years of underinvestment, but the nature of that investment must be appropriate: new buildings and staff are not enough.

Public policy experts such as Robert Putnam (who recently ran a seminar at 10 Downing Street2) argue that any complex organisation uses three forms of “capital”—physical, human, and social.3–5 All three have been run down in the NHS since 1948 and are addressed in the NHS Plan for England.6 The planned increase in spending on health and the proposed expansion in staffing, with increased emphasis on good employment practices, may …