Subclinical thyroid dysfunction and the risk of heart failure events: an individual participant data analysis from 6 prospective cohorts.

BACKGROUND: American College of Cardiology/American Heart Association guidelines for the diagnosis and management of heart failure recommend investigating exacerbating conditions such as thyroid dysfunction, but without specifying the impact of different thyroid-stimulation hormone (TSH) levels. Limited prospective data exist on the association between subclinical thyroid dysfunction and heart failure events. METHODS AND RESULTS: We performed a pooled analysis of individual participant data using all available prospective cohorts with thyroid function tests and subsequent follow-up of heart failure events. Individual data on 25 390 participants with 216 248 person-years of follow-up were supplied from 6 prospective cohorts in the United States and Europe. Euthyroidism was defined as TSH of 0.45 to 4.49 mIU/L, subclinical hypothyroidism as TSH of 4.5 to 19.9 mIU/L, and subclinical hyperthyroidism as TSH <0.45 mIU/L, the last two with normal free thyroxine levels. Among 25 390 participants, 2068 (8.1%) had subclinical hypothyroidism and 648 (2.6%) had subclinical hyperthyroidism. In age- and sex-adjusted analyses, risks of heart failure events were increased with both higher and lower TSH levels (P for quadratic pattern <0.01); the hazard ratio was 1.01 (95% confidence interval, 0.81-1.26) for TSH of 4.5 to 6.9 mIU/L, 1.65 (95% confidence interval, 0.84-3.23) for TSH of 7.0 to 9.9 mIU/L, 1.86 (95% confidence interval, 1.27-2.72) for TSH of 10.0 to 19.9 mIU/L (P for trend <0.01) and 1.31 (95% confidence interval, 0.88-1.95) for TSH of 0.10 to 0.44 mIU/L and 1.94 (95% confidence interval, 1.01-3.72) for TSH <0.10 mIU/L (P for trend=0.047). Risks remained similar after adjustment for cardiovascular risk factors. CONCLUSION: Risks of heart failure events were increased with both higher and lower TSH levels, particularly for TSH ≥10 and <0.10 mIU/L.

American Library Association, twenty-fifth annual conference, Niagara Falls, June 22-27, 1903. --

A history of Niagara Falls, including the Programme for the Conference.

Conditional transgenic expression of fibroblast growth factor 9 in the adult mouse heart reduces heart failure mortality after myocardial infarction

BACKGROUND: Fibroblast growth factor 9 (FGF9) is secreted from bone marrow cells, which have been shown to improve systolic function after myocardial infarction (MI) in a clinical trial. FGF9 promotes cardiac vascularization during embryonic development but is only weakly expressed in the adult heart. METHODS AND RESULTS: We used a tetracycline-responsive binary transgene system based on the α-myosin heavy chain promoter to test whether conditional expression of FGF9 in the adult myocardium supports adaptation after MI. In sham-operated mice, transgenic FGF9 stimulated left ventricular hypertrophy with microvessel expansion and preserved systolic and diastolic function. After coronary artery ligation, transgenic FGF9 enhanced hypertrophy of the noninfarcted left ventricular myocardium with increased microvessel density, reduced interstitial fibrosis, attenuated fetal gene expression, and improved systolic function. Heart failure mortality after MI was markedly reduced by transgenic FGF9, whereas rupture rates were not affected. Adenoviral FGF9 gene transfer after MI similarly promoted left ventricular hypertrophy with improved systolic function and reduced heart failure mortality. Mechanistically, FGF9 stimulated proliferation and network formation of endothelial cells but induced no direct hypertrophic effects in neonatal or adult rat cardiomyocytes in vitro. FGF9-stimulated endothelial cell supernatants, however, induced cardiomyocyte hypertrophy via paracrine release of bone morphogenetic protein 6. In accord with this observation, expression of bone morphogenetic protein 6 and phosphorylation of its downstream targets SMAD1/5 were increased in the myocardium of FGF9 transgenic mice. CONCLUSIONS: Conditional expression of FGF9 promotes myocardial vascularization and hypertrophy with enhanced systolic function and reduced heart failure mortality after MI. These observations suggest a previously unrecognized therapeutic potential for FGF9 after MI.

Probiotic administration attenuates myocardial hypertrophy and heart failure following myocardial infarction in the rat

Background—Probiotics are extensively used to promote gastrointestinal health and emerging evidence suggests that their beneficial properties can extend beyond the local environment of the gut. Here, we determined whether oral probiotic administration can alter the progression of post-infarction heart failure. Methods and Results—Rats were subjected to six weeks of sustained coronary artery occlusion and administered the probiotic Lactobacillus rhamnosus GR-1 or placebo in the drinking water ad libitum. Culture and 16s rRNA sequencing showed no evidence of GR-1 colonization or a significant shift in the composition of the cecal microbiome. However, animals administered GR-1 exhibited a significant attenuation of left ventricular hypertrophy based on tissue weight assessment as well as gene expression of atrial natriuretic peptide. Moreover, these animals demonstrated improved hemodynamic parameters reflecting both improved systolic and diastolic left ventricular function. Serial echocardiography revealed significantly improved left ventricular parameters throughout the six week follow-up period including a marked preservation of left ventricular ejection fraction as well as fractional shortening. Beneficial effects of GR-1 were still evident in those animals in which GR-1 was withdrawn at four weeks suggesting persistence of the GR-1 effects following cessation of therapy. Investigation of mechanisms showed a significant increase in the leptin to adiponectin plasma concentration ratio in rats subjected to coronary ligation which was abrogated by GR-1. Metabonomic analysis showed differences between sham control and coronary artery ligated hearts particularly with respect to preservation of myocardial taurine levels. Conclusions—The study suggests that probiotics offer promise as a potential therapy for the attenuation of heart failure.

Inflame my heart (by p38-MAPK).

Although many studies have explored the stimuli which promote hypertrophic growth or death in cardiac myocytes and the signaling pathways which they activate, the mechanisms by which these pathways promote the pathophysiological responses are still obscure. The mitogen-activated protein kinase (MAPK) cascades (in which MAPKs are phosphorylated and activated by upstream MAPK kinases [MKKs] which are, in turn, phosphorylated and activated by MKK kinases [MKKKs]) were identified in the early- to mid-1990s as potentially key regulatory pathways in cardiac myocyte pathophysiology.1,2 The principal MAPKs investigated in cardiac myocytes are the extracellular signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinases (JNKs), and p38-MAPKs. ERK1/2 are potently activated by hypertrophic stimuli, whereas JNKs and p38-MAPKs are potently activated by cellular stresses (eg, oxidative stress). However, there is cross-talk such that JNKs and p38-MAPKs are activated by hypertrophic stimuli and ERK1/2 are activated by cellular stresses, and the contribution of each pathway to the overall cardiac myocyte response is not entirely clear. MAPKs phosphorylate a number of known transcription factors to alter their transactivating activities thus, presumably, influencing gene expression to elicit the cellular response.3 Nevertheless, the immediate consequences (ie, the transcription factors which are phosphorylated) and downstream consequences (ie, genes with altered expression) of MAPK signaling in the heart or specifically in cardiac myocytes are still largely unknown. To start to address this issue for the p38-MAPK pathway in the (rat) heart (Figure), Tenhunen et al4 directly injected adenoviruses encoding wild-type (WT) p38-MAPKα together …

Obesity, a worldwide epidemic related to heart disease and stroke: group IV prevention/treatment

Obesity is a worldwide problem, not just an issue for industrialized nations. Therefore, we need to examine opportunities for prevention and treatment from a global perspective.

Association between surgical indications, operative risk, and clinical outcome in infective endocarditis: a prospective study from the International Collaboration on Endocarditis.

Use of surgery for the treatment of infective endocarditis (IE) as related to surgical indications and operative risk for mortality has not been well defined.

Depression is a risk factor for incident coronary heart disease in women: an 18-year longitudinal study

BACKGROUND: According to a recent position paper by the American Heart Association, it remains unclear whether depression is a risk factor for incident Coronary Heart Disease (CHD). We assessed whether a depressive disorder independently predicts 18-year incident CHD in women. METHOD: A prospective longitudinal study of 860 women enrolled in the Geelong Osteoporosis Study (1993-2011) was conducted. Participants were derived from an age-stratified, representative sample of women (20-94 years) randomly selected from electoral rolls in South-Eastern Australia. The exposure was a diagnosis of a depressive disorder using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders. Outcomes data were collected from hospital medical records: (1) Primary outcome: a composite measure of cardiac death, non-fatal Myocardial Infarction or coronary intervention. (2) Secondary outcome: any cardiac event (un/stable angina, cardiac event not otherwise defined) occurring over the study period. RESULTS: Seven participants were excluded based on CHD history. Eighty-three participants (9.6%) recorded ≥1 cardiac event over the study period; 47 had a diagnosis that met criteria for inclusion in the primary analysis. Baseline depression predicted 18-year incidence, adjusting for (1) anxiety (adj. OR:2.39; 95% CIs:1.19-4.82), plus (2) typical risk factors (adj. OR:3.22; 95% CIs:1.45-6.93), plus (3) atypical risk factors (adj. OR:3.28; 95% CIs:1.36-7.90). This relationship held when including all cardiac events. No relationship was observed between depression and recurrent cardiac events. CONCLUSION: The results of this study support the contention that depression is an independent risk factor for CHD incidence in women. Moreover, the strength of association between depression and CHD incidence was of a greater magnitude than any typical and atypical risk factor.

Rules of origin in economic integration agreements signed by countries belonging to the Latin American Integration Association

This article refers to rules of origin included in the main Economic Integration Agreements signed by members of the Latin American Integration Association (LAIA). Issues relating to trade facilitation and reduction of transaction costs of international trade in goods are also discussed.The author is on the staff of the International Trade and Integration Division of ECLAC.

Odontological assistance to Down Syndrome patients having congenital heart malformations

In this study the authors present the frequency and types of congenital heart malformations (CHM) among Down Syndrome (DS) patients emphasizing the prevention of infectious endocarditis (IE) with appropriate antibiotic prophylaxis (ABP). Out of 390 DS patients, 312 (80%) were considered free from any CHM. 78 (20%) presented some CHM; from these 11,54% (n=9) have more than one CHM; ABP to prevent IE was recommended for 41,03% (n=32). Ventricular septal defect was the most frequent CHM (20,51%, n=16). Dentists must know about the patients’ cardiologic diagnosis before a treatment that could cause bleeding, because they have to administer antibiotics to prevent IE. Although some CHM doesn’t need ABP, according to the protocol of the American Heart Association, there are systemic conditions in DS that are relevant to the prescription of antibiotics.

What Business Reference Librarians Need to Know about Intellectual Property: Presentations sponsored by the Patent and Trademark Depository Library Association (PTDLA) at the American Library Association Annual Conference, New Orleans, June 25, 2006

Presentations sponsored by the Patent and Trademark Depository Library Association (PTDLA) at the American Library Association Annual Conference, New Orleans, June 25, 2006 Speaker #1: Nan Myers Associate Professor; Government Documents, Patents and Trademarks Librarian Wichita State University, Wichita, KS Title: Intellectual Property Roundup: Copyright, Trademarks, Trade Secrets, and Patents Abstract: This presentation provides a capsule overview of the distinctive coverage of the four types of intellectual property – What they are, why they are important, how to get them, what they cost, how long they last. Emphasis will be on what questions patrons ask most, along with the answers! Includes coverage of the mission of Patent & Trademark Depository Libraries (PTDLs) and other sources of business information outside of libraries, such as Small Business Development Centers. Speaker #2: Jan Comfort Government Information Reference Librarian Clemson University, Clemson, SC Title: Patents as a Source of Competitive Intelligence Information Abstract: Large corporations often have R&D departments, or large numbers of staff whose jobs are to monitor the activities of their competitors. This presentation will review strategies that small business owners can employ to do their own competitive intelligence analysis. The focus will be on features of the patent database that is available free of charge on the USPTO website, as well as commercial databases available at many public and academic libraries across the country. Speaker #3: Virginia Baldwin Professor; Engineering Librarian University of Nebraska-Lincoln, Lincoln, NE Title: Mining Online Patent Data for Business Information Abstract: The United States Patent and Trademark Office (USPTO) website and websites of international databases contains information about granted patents and patent applications and the technologies they represent. Statistical information about patents, their technologies, geographical information, and patenting entities are compiled and available as reports on the USPTO website. Other valuable information from these websites can be obtained using data mining techniques. This presentation will provide the keys to opening these resources and obtaining valuable data. Speaker #4: Donna Hopkins Engineering Librarian Renssalaer Polytechnic Institute, Troy, NY Title: Searching the USPTO Trademark Database for Wordmarks and Logos Abstract: This presentation provides an overview of wordmark searching in www.uspto.gov, followed by a review of the techniques of searching for non-word US trademarks using codes from the Design Search Code Manual. These codes are used in an electronic search, either on the uspto website or on CASSIS DVDs. The search is sometimes supplemented by consulting the Official Gazette. A specific example of using a section of the codes for searching is included. Similar searches on the Madrid Express database of WIPO, using the Vienna Classification, will also be briefly described.