tbuckley/cabot-search huggingface dataset:
Relation Between Modifiable Lifestyle Factors and Lifetime Risk of Heart Failure
Authors: Luc Djoussé
Journal: JAMA (2009)

<h3>Context</h3>The lifetime risk of heart failure at age 40 years is approximately 1 in 5 in the general population; however, little is known about the association between modifiable lifestyle factors and the remaining lifetime risk of heart failure.<h3>Objective</h3>To examine the association between modifiable lifestyle factors and the lifetime risk of heart failure in a large cohort of men.<h3>Design, Setting, and Participants</h3>Prospective cohort study using data from 20 900 men (mean age at baseline, 53.6 years) from the Physicians' Health Study I (1982-2008) who were apparently healthy at baseline. Six modifiable lifestyle factors were assessed: body weight, smoking, exercise, alcohol intake, consumption of breakfast cereals, and consumption of fruits and vegetables.<h3>Main Outcome Measure</h3>Lifetime risk of heart failure.<h3>Results</h3>During a mean follow-up of 22.4 years, 1200 men developed heart failure. Overall, the lifetime risk of heart failure was 13.8% (95% confidence interval [CI], 12.9%-14.7%) at age 40 years. Lifetime risk remained constant in men who survived free of heart failure through age 70 years and reached 10.6% (95% CI, 9.4%-11.7%) at age 80 years. Lifetime risk of heart failure was higher in men with hypertension than in those without hypertension. Healthy lifestyle habits (normal body weight, not smoking, regular exercise, moderate alcohol intake, consumption of breakfast cereals, and consumption of fruits and vegetables) were individually and jointly associated with a lower lifetime risk of heart failure, with the highest risk in men adhering to none of the 6 lifestyle factors (21.2%; 95% CI, 16.8%-25.6%) and the lowest risk in men adhering to 4 or more desirable factors (10.1%; 95% CI, 7.9%-12.3%).<h3>Conclusion</h3>In this cohort of apparently healthy men, adherence to healthy lifestyle factors is associated with a lower lifetime risk of heart failure.
Poster session 2. Signal transduction targets
Authors: A. Nikolakopoulos, D. Kotsirilou, E. Giannopoulou, E. Papadimitriou, T. Makatsoris, H. P. Kalofonos, L. Mavroeidis, H. Sheldon, E. Briasoulis, M. Marselos, P. Pappas, A. Harris, J. C. Lee, J. K. Rho, C. M. Choi, Y. S. Park, H. R. Kim, B. M. Oliva, J. R. Fernandez, Y. Tejeda, S. Astrada, H. E. Garay, O. Reyes, L. Delgado, M. Bollati-Fogolin, M. G. Vallespi, M. I. Acuna, C. Camacho, M. E. Mendoza-Garrido, W. C. Huang, Y. J. Chen, M. C. Yu, Y. L. Wei, M. H. Yeh
Journal: Annals of Oncology (2013)
The Guyana Diabetes and Foot Care Project: A Complex Quality Improvement Intervention to Decrease Diabetes-Related Major Lower Extremity Amputations and Improve Diabetes Care in a Lower-Middle-Income Country
Authors: Julia Lowe, R. Gary Sibbald, Nashwah Y. Taha, Gerald Lebovic, Carlos Martin, Indira Bhoj, Rolinda Kirton, Brian Ostrow
Journal: PLoS Medicine (2015)

Points• Type 2 diabetes is the fourth leading cause of death and affects 15.5% of the adult population in Guyana, South America.• Preintervention, 41.4% of individuals with diabetic foot complications experienced major lower extremity amputation at the national referral hospital.• A complex, interprofessional quality improvement intervention to improve diabetes and foot care was rolled out in two phases between 2008-2013.• We report the experience from this unique nationwide intervention, with a national referral hospital prototype (phase 1) regionalized to six administrative regions in Guyana comprising 89% of the population (phase 2).
Occupational Musculoskeletal Disorders
Authors: V Wright
Journal: Annals of the Rheumatic Diseases (1993)

<h3>ABSTRACT</h3> Understanding the major drivers that influence soil bacterial and fungal communities is essential to mitigate the impacts of human activity on vulnerable ecosystems, like those found on the Galápagos Islands. Located ~1000 km off the coast of Ecuador, the volcanically formed islands are situated within distinct oceanic currents, which provide seasonal weather patterns and unique microclimates within small spatial scales across the islands. Although much is known about the impacts of human activity, such as climate change and invasive plant species, on above ground biodiversity of the Galápagos Islands, little is known about the resident soil microbial communities and the drivers that shape these communities. Here, our goal was to investigate the bacterial and fungal communities found in soil located in three distinct microclimates: Mirador (arid), Cerro Alto (semi-arid), and El Junco (humid), and associated with native and invasive plant types. At each site, we collected soil at three depths (rhizosphere, 5 cm, and 15 cm) associated with the invasive plant, <i>Psidium guajava</i> (guava), and native plant types. We determined that the sampling location (microclimate) was the strongest driver of both bacterial and fungal communities (74 and 38%, respectively), with additional minor but significant impacts from plant type and soil depth. This study highlights the continued need to explore microbial communities across diverse environments and demonstrates the weight of different abiotic and biotic factors impacting soil microbial communities across San Cristóbal Island in the Galápagos archipelago. <h3>IMPORTANCE/SIGNIFICANCE</h3> Human activity such as climate change, pollution, introduction of invasive species, and deforestation, poses a huge threat to biodiverse environments. Soil microbiota are an essential component to maintaining healthy ecosystems. However, a greater understanding of factors that alter these microbial communities is needed in order to find ways to mitigate and reverse the impacts imposed by human activity. The Galápagos Islands are a unique real-world laboratory, in that the islands’ biogeography and physical locations in the Pacific Ocean provide distinct microclimates within small geographic distances. Harnessing these distinct environments allowed us to investigate the influence of microclimates, soil depth, and vegetation cover on bacterial and fungal community composition.
The Epidemiological Approach
Authors: Mark Hohenberg
Journal: Journal of the Royal Society of Medicine (2004)

Modern medicine is founded on epidemiological concepts but epidemiology itself tends to be unpopular with medical students. Despite efforts to brighten the teaching, many students still find the subject tedious and hard to grasp. For these, I recommend The Epidemiological Approach, which Professor Wald originally wrote for students in his own school (Barts). Its small size belies the wide-ranging content, and the style of writing is engaging. All the major areas of epidemiology are covered—from study design to birth and death patterns—and his explanations of concepts such as relative risk, likelihood ratio and prevalence are coupled with easy-to-follow examples and advice on how to calculate as well as interpret them. Statistical analysis of raw data is dealt with briefly but broadly. The subject matter even includes death certification—a task feared by many a new house officer. With its focus on the basics, its perfect balance of information and its readability The Epidemiological Approach is a book that no medical student should be without.
Relapse and Relapse Prevention
Authors: Thomas H. Brandon, Jennifer Irvin Vidrine, Erika B. Litvin
Journal: Annual Review of Clinical Psychology (2007)

Most psychological disorders and problem behaviors are characterized by very high rates of postremittance relapse. Thus, advances in the long-term efficacy of psychological interventions require understanding the causes and processes of relapse, with the ultimate goal of developing strategies that reduce the probability of relapse. Existing psychological theory and interventions relevant to relapse and relapse prevention (RP) are reviewed, with a focus on addictive behaviors. The past two decades have produced increased attention toward the relapse problem and important advances in the conceptualization of relapse (i.e., as a process rather than a discrete event). Further progress will require the translation of basic theory into applied theory, the development of integrative theories of relapse, and the design and testing of theory-based, multimodal RP interventions.
Activator Protein-2 Overexpression Accounts for Increased Insulin Receptor Expression in Human Breast Cancer
Authors: Francesco Paonessa, Daniela Foti, Vanessa Costa, Eusebio Chiefari, Giuseppe Brunetti, Francesco Leone, Francesco Luciano, Frank Wu, Amy S. Lee, Elio Gulletta, Alfredo Fusco, Antonio Brunetti
Journal: Cancer Research (2006)

Abstract Various studies have shown that the insulin receptor (IR) is increased in most human breast cancers, and both ligand-dependent malignant transformation and increased cell growth occur in cultured breast cells overexpressing the IR. However, although numerous in vivo and in vitro observations have indicated an important contributory role for the IR in breast cancer cell biology, the molecular mechanisms accounting for increased IR expression in breast tumors have not previously been elucidated. Herein, we did immunoblot analyses of nuclear protein from cultured breast cancer cells and normal and tumoral tissues from breast cancer patients combined with promoter studies by using a series of human wild-type and mutant IR promoter constructs. We provide evidence that IR overexpression in breast cancer is dependent on the assembly of a transcriptionally active multiprotein-DNA complex, which includes the high-mobility group A1 (HMGA1) protein, the developmentally regulated activator protein-2 (AP-2) transcription factor and the ubiquitously expressed transcription factor Sp1. In cultured breast cancer cells and human breast cancer specimens, the expression of AP-2 was significantly higher than that observed in cells and tissues derived from normal breast, and this overexpression paralleled the increase in IR expression. However, AP-2 DNA-binding activity was undetectable with the IR gene promoter, suggesting that transactivation of this gene by AP-2 might occur indirectly through physical and functional cooperation with HMGA1 and Sp1. Our findings support this hypothesis and suggest that in affected individuals, hyperactivation of the AP-2 gene through the overexpression of IR may play a key role in breast carcinogenesis. (Cancer Res 2006; 66(10): 5085-93)
TGF-β Mediates Homing of Bone Marrow–Derived Human Mesenchymal Stem Cells to Glioma Stem Cells
Authors: Naoki Shinojima, Anwar Hossain, Tatsuya Takezaki, Juan Fueyo, Joy Gumin, Feng Gao, Felix Nwajei, Frank C. Marini, Michael Andreeff, Jun-Ichi Kuratsu, Frederick F. Lang
Journal: Cancer Research (2013)

Abstract Although studies have suggested that bone marrow human mesenchymal stem cells (BM-hMSC) may be used as delivery vehicles for cancer therapy, it remains unclear whether BM-hMSCs are capable of targeting cancer stem cells, including glioma stem cells (GSC), which are the tumor-initiating cells responsible for treatment failures. Using standard glioma models, we identify TGF-β as a tumor factor that attracts BM-hMSCs via TGF-β receptors (TGFβR) on BM-hMSCs. Using human and rat GSCs, we then show for the first time that intravascularly administered BM-hMSCs home to GSC-xenografts that express TGF-β. In therapeutic studies, we show that BM-hMSCs carrying the oncolytic adenovirus Delta-24-RGD prolonged the survival of TGF-β–secreting GSC xenografts and that the efficacy of this strategy can be abrogated by inhibition of TGFβR on BM-hMSCs. These findings reveal the TGF-β/TGFβR axis as a mediator of the tropism of BM-hMSCs for GSCs and suggest that TGF-β predicts patients in whom BM-hMSC delivery will be effective. Cancer Res; 73(7); 2333–44. ©2012 AACR.
Brain Natriuretic Peptide as a Predictor of Adverse Outcome in Patients With Pulmonary Embolism
Authors: M. ten Wolde, I.I. Tulevski, J.W.M. Mulder, M. Söhne, F. Boomsma, B.J.M. Mulder, H.R. Büller
Journal: Circulation (2003)

Despite effective treatment with anticoagulants, 2% to 7% of patients with pulmonary embolism will die as a result of their disease.We examined in 110 consecutive patients with pulmonary embolism whether plasma brain natriuretic peptide (BNP), a novel marker of (right) ventricular dysfunction, is a predictor of fatal pulmonary embolism. The relationship between BNP concentration measured at presentation and clinical outcome was assessed by comparing the proportion of outcome events among tertiles. Positive and negative predictive values of BNP levels in the highest and lowest tertiles were calculated. The risk of death related to pulmonary embolism if the BNP level is >21.7 pmol/L is 17% (95% CI, 6% to 33%). The negative predictive value for uneventful outcome of a BNP value <21.7 pmol/L is 99% (95% CI, 93% to 100%).This is the first study to show that plasma BNP levels seem to predict adverse outcome in patients with acute pulmonary embolism.
Direct selection and phage display of a Gram-positive secretome
Authors: Dragana Jankovic, Michael A Collett, Mark W Lubbers, Jasna Rakonjac
Journal: Genome biology (2007)

Abstract Surface, secreted and transmembrane protein-encoding open reading frames, collectively the secretome, can be identified in bacterial genome sequences using bioinformatics. However, functional analysis of translated secretomes is possible only if many secretome proteins are expressed and purified individually. We have now developed and applied a phage display system for direct selection, identification, expression and purification of bacterial secretome proteins.
Cytosolic Heat Shock Protein 60, Apoptosis, and Myocardial Injury
Authors: S.R. Kirchhoff, S. Gupta, A.A. Knowlton
Journal: Circulation (2002)

Background — Heat shock proteins (HSPs) are well known for their ability to “protect” the structure and function of native macromolecules, particularly as they traffic across membranes. Considering the role of key mitochondrial proteins in apoptosis and the known antiapoptotic effects of HSP27 and HSP72, we postulated that HSP60, primarily a mitochondrial protein, also exerts an antiapoptotic effect. Methods and Results — To test this hypothesis, we used an antisense phosphorothioate oligonucleotide to effect a 50% reduction in the levels of HSP60 in cardiac myocytes, a cell type that has abundant mitochondria. The induced decrease in HSP60 precipitated apoptosis, as manifested by the release of cytochrome c, activation of caspase 3, and induction of DNA fragmentation. Antisense treatment was associated with an increase in bax and a decrease in bcl-2 secondary to increased synthesis of bax and degradation of bcl-2. A control oligonucleotide had no effect on these measurements. We further demonstrated that cytosolic HSP60 forms a macromolecular complex with bax and bak in vitro suggesting that complex formation with HSP60 may block the ability of bax and bak to effect apoptosis in vivo. Lastly, we show that as cytosolic (nonmitochondrial) HSP60 decreases, a small unbound fraction of bax appears and that the amount of bax associated with the mitochondria and cell membranes increases. Conclusions — These results support a key antiapoptotic role for cytosolic HSP60. To our knowledge, this is the first report suggesting that interactions of HSP60 with bax and/or bak regulate apoptosis.
Low-Dose Dietary Phytoestrogen Abrogates Tamoxifen-Associated Mammary Tumor Prevention
Authors: Bolin Liu, Susan Edgerton, Xiaohe Yang, Aeree Kim, Dalia Ordonez-Ercan, Terza Mason, Kathy Alvarez, Christine McKimmey, Naxin Liu, Ann Thor
Journal: Cancer Research (2005)

Wild-type erbB-2/neu transgenic mice were used to study the interactions between tamoxifen and dietary phytoestrogens (or isoflavones) by dose and form in vivo. Mice were randomized to one of four dietary formulas and implanted with an 8-week continuous-release tamoxifen or placebo pellet at 8 weeks of age. In placebo-treated mice, soy meal diet (but not diets supplemented with low-dose or high-dose isoflavones or a casein diet) resulted in prolongation of tumor latency. In tamoxifen-treated mice fed the soy meal, casein, or high-dose isoflavone enriched diets, the majority (>80%) showed no tumor formation by 60 weeks of age. Of the mice that developed tumors, latency was significantly prolonged. In tamoxifen-treated mice fed the low-dose isoflavone enriched diet, a much higher rate of mammary tumor development (>50%; P < 0.002) and a shorter tumor latency were observed. In vitro studies of human and mouse mammary tumor cell lines confirm that low doses of genistein, co-administered with tamoxifen, promote cell proliferation. This is in contrast to tamoxifen alone or tamoxifen with higher doses of genistein that are growth inhibitory. In summary, low-dose dietary isoflavones abrogated tamoxifen-associated mammary tumor prevention in vivo. These interactions are supported by in vitro data from human and mouse mammary tumor cell lines. These dose-associated interactions likely have relevance to the human use of tamoxifen for prevention or treatment of breast cancer.
Short-lived Plasmablasts and Long-lived Plasma Cells Contribute to Chronic Humoral Autoimmunity in NZB/W Mice
Authors: Bimba F. Hoyer, Katrin Moser, Anja E. Hauser, Anette Peddinghaus, Caroline Voigt, Dan Eilat, Andreas Radbruch, Falk Hiepe, Rudolf A. Manz
Journal: The Journal of Experimental Medicine (2004)

The current view holds that chronic autoimmune diseases are driven by the continuous activation of autoreactive B and T lymphocytes. However, despite the use of potent immunosuppressive drugs designed to interfere with this activation the production of autoantibodies often persists and contributes to progression of the immunopathology. In the present study, we analyzed the life span of (auto)antibody-secreting cells in the spleens of NZB × NZW F1 (NZB/W) mice, a murine model of systemic lupus erythematosus. The number of splenic ASCs increased in mice aged 1–5 mo and became stable thereafter. Less than 60% of the splenic (auto)antibody-secreting cells were short-lived plasmablasts, whereas 40% were nondividing, long-lived plasma cells with a half-life of &amp;gt;6 mo. In NZB/W mice and D42 Ig heavy chain knock-in mice, a fraction of DNA-specific plasma cells were also long-lived. Although antiproliferative immunosuppressive therapy depleted short-lived plasmablasts, long-lived plasma cells survived and continued to produce (auto)antibodies. Thus, long-lived, autoreactive plasma cells are a relevant target for researchers aiming to develop curative therapies for autoimmune diseases.
The ASCI, the spring meetings, and growing up in academic medicine: a personal perspective
Authors: Anthony S. Fauci
Journal: Journal of Clinical Investigation (2008)

For many young physician-scientists, the American Society for Clinical Investigation spring meetings are the backdrop to their initiation into academic medicine. Membership in the ASCI is a high honor and represents one’s maturation and accomplishment in clinical research. The ASCI continues to provide this meeting forum for young investigators who aspire to emulate their idols and mentors just as I did in 1969 when I attended the spring meetings in Atlantic City for the first time.
Interferon-γ Induces Major Histocompatibility Class II Transactivator (CIITA), Which Mediates Collagen Repression and Major Histocompatibility Class II Activation by Human Aortic Smooth Muscle Cells
Authors: Giovanna Butticè, Janice Miller, Lin Wang, Barbara D. Smith
Journal: Circulation Research (2006)

Chronic inflammation in atherosclerosis is responsible for plaque instability through alterations in extracellular matrix. Previously, we demonstrated that major histocompatibility class II (MHC II) transactivator (CIITA) in a complex with regulatory factor for X box 5 (RFX5) is a crucial protein mediating interferon (IFN)-γ–induced repression of collagen type I gene transcription in fibroblasts. This article demonstrates that, in smooth muscle cells (SMCs), IFN-γ dramatically increases the expression of CIITA isoforms III and IV, with no increase in expression of CIITA isoform I. Expression of CIITA III and IV correlates with decreased collagen type I and increased MHC II gene expression. Exogenous expression of CIITA I, III, and IV, in transiently transfected SMCs, represses collagen type I promoters ( COL1A1 and COL1A2 ) and activates MHC II promoter. Levels of CIITA and RFX5 increase in the nucleus of cells treated with IFN-γ. Moreover, simvastatin lowers the IFN-γ–induced expression of RFX5 and MHC II in addition to repressing collagen expression. However, simvastatin does not block the IFN-γ–induced expression of CIITA III and IV, suggesting a CIITA-independent mechanism. This first demonstration that RFX5 and CIITA isoforms are expressed in SMCs after IFN-γ stimulation suggest that CIITA could be a key factor in plaque stability in atherosclerosis.
STUDIES ON UROBILIN PHYSIOLOGY AND PATHOLOGY
Authors: Philip D. McMaster, Robert Elman
Journal: The Journal of Experimental Medicine (1926)

Experimental infection of the intubated and previously sterile biliary tract of the dog with particles of the stools leads to a formation of urobilin from the bilirubin of the bile as it flows through the ducts. No urobilinuria occurs, however, unless temporary biliary obstruction is produced, or the liver parenchyma injured. Then urobilinuria develops, despite the fact that no bile is reaching the intestine and, by corollary, no urobilin being formed there. Cholangitic urobilinuria, as one may term the phenomenon just described, to distinguish it from the urobilinuria having origin in pigment absorbed from within the intestine, is far more pronounced in animals possessing a healthy gall bladder than in those with a pathological gall bladder or with one prevented from functioning by severance of the cystic duct. These facts suggest that there may be an active absorption of urobilin from the normal gall bladder. There can be no doubt that the pigment is absorbed from within the bile ducts. There is no evidence whatever to justify the belief that urobilin is ever formed through the action of liver parenchyma. There may conceivably be an intralobular formation of the pigment consequent upon the activity of bacteria within the liver tissue, though such a happening has yet to be demonstrated.
Challenges and strategies: The immune responses in gene therapy
Authors: Hai‐sheng Zhou, De‐pei Liu, Chih‐chuan Liang
Journal: Medicinal Research Reviews (2004)

The host immune responses, including T lymphocytes mediated immune response and humoral immune responses are the important parts of the challenges in gene therapy. There are some potential immunostimulants in gene delivery systems, such as viral and non-viral vectors. Viral gene products, transgene products, viral proteins derived from viral particles required by dead-end infection, and CpG DNA in plasmid may play important roles in inducing the host immune responses when foreign genes are transferred into the targeted tissues. The immune responses should lead to many problems in gene therapy: transient expression of therapeutic gene, non-efficient re-administration of the same vectors, and severe side-effects in clinical trials. Although RNAi may act as gene therapeutic agent for suppression of specific gene expression, little attention has been given to the potential non-specific effects that might be induced. It was reported that small interfering RNAs (siRNAs) can induce the host interferon response following transfected to mammalian cells. Facing these challenges, a number of studies have been focused on taking measures to solve them, such as immunosuppression, selection of different administration routes and dose of the vectors, using the tissue-specific promoters and modifying the vectors.