Cardiac Calcitropes, Myotropes, and Mitotropes: JACC Review Topic of the Week.

The term "inotrope" is familiar and intimately connected with pharmaceuticals clinically used for treatment of low cardiac output with cardiogenic shock. Traditional inotropic agents exert their effect by modulating calcium signaling in the myocardium. Their use is associated with poor long-term outcomes. Newer molecules in development intend to break from calcium mediation and the associated detrimental long-term effects by targeting distinct mechanisms of action to improve cardiac performance. Thus, "inotropy" does not sufficiently describe the range of potential novel pharmaceutical products. To enhance communication around and evaluation of current, emerging, and potential therapies, this review proposes a novel nuanced and holistic framework to categorize pharmacological agents that improve myocardial performance based on 3 myocardial mechanisms: calcitropes, which alter intracellular calcium concentrations; myotropes, which affect the molecular motor and scaffolding; and mitotropes, which influence energetics. Novel chemical entities can easily be incorporated into this structure, distinguishing themselves based on their mechanisms and clinical outcomes

Historical trends in survival of hospitalized heart failure patients: 2000 versus 1995

BACKGROUND: Population-based secular trends in survival of patients with congestive heart failure (CHF) are central to public health research on the burden of the syndrome. METHODS: Patients 35–79 years old with a CHF discharge code in 1995 or 2000 were identified in 22 Minneapolis-St. Paul hospitals. A sample of the records was abstracted (50% of 1995 records; 38% of 2000 records). A total of 2,257 patients in 1995 and 1,825 patients in 2000 were determined to have had a CHF-related hospitalization. Each patient was followed for one year to ascertain vital status. RESULTS: The risk profile of the 2000 patient cohort was somewhat worse than that of the 1995 cohort in both sex groups, but the distributions of age and left ventricular ejection fraction were similar. Within one year of admission in 2000, 28% of male patients and 27% of female patients have died, compared to 36% and 27% of their counterparts in 1995, respectively. In various Cox regression models the average year effect (2000 vs. 1995) was around 0.75 for men and 0.95 to 1.00 for women. The use of angiotensin converting-enzyme inhibitors and beta-blockers was associated with substantially lower hazard of death during the subsequent year. CONCLUSION: Survival of men who were hospitalized for CHF has improved during the second half of the 1990s. The trend in women was very weak, compatible with little to no change. Documented benefits of angiotensin converting-enzyme inhibitors and beta-blockers were evident in these observational data in both men and women

Endorsement of the CONSORT Statement by High-Impact Medical Journals in China: A Survey of Instructions for Authors and Published Papers

The CONSORT Statement is a reporting guideline for authors when reporting randomized controlled trials (RCTs). It offers a standard way for authors to prepare RCT reports. It has been endorsed by many high-impact medical journals and by international editorial groups. This study was conducted to assess the endorsement of the CONSORT Statement by high-impact medical journals in China by reviewing their instructions for authors.A total of 200 medical journals were selected according to the Chinese Science and Technology Journal Citation Reports, 195 of which publish clinical research papers. Their instructions for authors were reviewed and all texts mentioning the CONSORT Statement or CONSORT extension papers were extracted. Any mention of the Uniform Requirements for Manuscripts Submitted to Biomedical Journals (URM) developed by the International Committee of Medical Journal Editors (ICMJE) or ‘clinical trial registration’ was also extracted. For journals endorsing the CONSORT Statement, their most recently published RCT reports were retrieved and evaluated to assess whether the journals have followed what the CONSORT Statement required. Out of the 195 medical journals publishing clinical research papers, only six (6/195, 3.08%) mentioned ‘CONSORT’ in their instructions for authors; out of the 200 medical journals surveyed, only 14 (14/200, 7.00%) mentioned ‘ICMJE’ or ‘URM’ in their instructions for authors, and another five journals stated in their instructions for authors that clinical trials should have trial registration numbers and that priority would be given to clinical trials which had been registered. Among the 62 RCT reports published in the six journals endorsing the CONSORT Statement, 20 (20/62, 32.26%) contained flow diagrams and only three (3/62, 4.84%) provided trial registration information.Medical journals in China endorsing either the CONSORT Statement or the ICMJE's URM constituted a small percentage of the total; all of these journals used ambiguous language regarding what was expected of authors

An annotated bibliography of C.J. van der Klaauw with notes on the impact of his work

Van der Klaauw was a professor of Descriptive Zoology in the period 1934–1958. This paper presents a concise annotated overview of his publications. In his work three main topics can be recognized: comparative anatomy of the mammalian auditory region, theoretical studies about ecology and ecological morphology, and vertebrate functional morphology. In particular van der Klaauw developed new concepts on functional morphology, based upon a holistic approach. A series of studies in functional morphology of Vertebrates by his students is added. An overview of recent morphological and theoretical studies show that this new approach had a long lasting impact in studies of functional morphology

A Systematic Review of Mosquito Coils and Passive Emanators: Defining Recommendations for Spatial Repellency Testing Methodologies.

Mosquito coils, vaporizer mats and emanators confer protection against mosquito bites through the spatial action of emanated vapor or airborne pyrethroid particles. These products dominate the pest control market; therefore, it is vital to characterize mosquito responses elicited by the chemical actives and their potential for disease prevention. The aim of this review was to determine effects of mosquito coils and emanators on mosquito responses that reduce human-vector contact and to propose scientific consensus on terminologies and methodologies used for evaluation of product formats that could contain spatial chemical actives, including indoor residual spraying (IRS), long lasting insecticide treated nets (LLINs) and insecticide treated materials (ITMs). PubMed, (National Centre for Biotechnology Information (NCBI), U.S. National Library of Medicine, NIH), MEDLINE, LILAC, Cochrane library, IBECS and Armed Forces Pest Management Board Literature Retrieval System search engines were used to identify studies of pyrethroid based coils and emanators with key-words "Mosquito coils" "Mosquito emanators" and "Spatial repellents". It was concluded that there is need to improve statistical reporting of studies, and reach consensus in the methodologies and terminologies used through standardized testing guidelines. Despite differing evaluation methodologies, data showed that coils and emanators induce mortality, deterrence, repellency as well as reduce the ability of mosquitoes to feed on humans. Available data on efficacy outdoors, dose-response relationships and effective distance of coils and emanators is inadequate for developing a target product profile (TPP), which will be required for such chemicals before optimized implementation can occur for maximum benefits in disease control

The SOS Pilot Study: a RCT of routine oxygen supplementation early after acute stroke—effect on recovery of neurological function at one week

Mild hypoxia is common after stroke and associated with poor long-term outcome. Oxygen supplementation could prevent hypoxia and improve recovery. A previous study of routine oxygen supplementation showed no significant benefit at 7 and 12 months. This pilot study reports the effects of routine oxygen supplementation for 72 hours on oxygen saturation and neurological outcomes at 1 week after a stroke

Transfusion of red cells in hematopoietic stem cell transplantation (TRIST): study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Insight regarding transfusion practices in Hematopoietic Stem cell Transplantation (HSCT) are lacking and the impact of red cell transfusion in this high risk group on outcomes following HSCT are not well appreciated. Red blood cell transfusion can be life-saving, however, liberal use of transfusion in critically ill patients failed to demonstrate significant clinical benefit. A large number of other observational studies have also demonstrated an association between red blood cell transfusions and increased morbidity such as infections and multi organ failure as well as increased mortality. The role of red cell transfusion on the clinical outcomes observed in patients undergoing HSCT remains poorly understood and a prospective randomized study of transfusion is required to gain insight and knowledge on best transfusion practices in this high risk population.</p> <p>Methods</p> <p>This report describes the design and methodological issues of a randomized pilot study evaluating red cell transfusion triggers in the setting of Hematopoietic Stem Cell Transplantation. This study has been funded by a peer review grant from the Canadian Blood Services and is registered on Clinicaltrials.gov NCT01237639.</p> <p>Results</p> <p>In 3 Canadian centres, 100 patients undergoing Hematopoietic Stem Cell Transplantation will be randomized to either a restrictive (target hemoglobin of 70-90 g/L) or liberal (target hemoglobin of 90-110 g/L) red cell transfusion strategy, based daily hemoglobin values up to 100 days post-transplant. The study will stratify participants by centre and type of transplant. The primary goal is to demonstrate study feasibility and we will collect clinical outcomes on 1) Transfusion Requirements, 2) Transplant Related Mortality, 3) Maximum grade of acute Graft versus Host Disease, 4) Veno-occlusive Disease, 5) Serious Infections, 6) Bearman Toxicity Score, 7) Bleeding, 8) Quality of Life, 9) Number of Hospitalizations and 10) Number of Intensive Care Unit (ICU) Admissions.</p> <p>Conclusion</p> <p>Upon completion, this pilot trial will provide preliminary insight into red cell transfusion practice and its influence in hematopoietic stem cell transplant outcomes. The results of this trial will inform the conduct of a larger study.</p

Impact of patient characteristics, education and knowledge on emergency room visits in patients with asthma and COPD: a descriptive and correlative study

<p>Abstract</p> <p>Background</p> <p>Asthma and COPD are major health problems and an extensive burden for the patient and the health care system. Patient education has been recommended, but the influence on knowledge and health outcomes is not fully examined. Our aims were to compare patient characteristics, education and knowledge in patients who had an emergency room (ER) visit, to explore factors related to disease knowledge, and to investigate patient characteristics, patient education and knowledge in relation to further ER visits over a 12 month period.</p> <p>Methods</p> <p>Eighty-four patients with asthma and 52 with COPD, who had had an ER visit, were included. They were interviewed by telephone 4 to 6 weeks after the ER visit and followed for a year.</p> <p>Results</p> <p>Patients with COPD were older, more sedentary, had had more ER visits the previous year, and had more co morbidity than patients with asthma. About 80% of the patients had received information from health professionals or participated in education/rehabilitation, but a minority (< 20%) reported that their knowledge about how to handle the disease was good. Patients with "good knowledge" were younger, were more likely to have asthma diagnose, and had a higher educational background (p < 0.05). Sixty-seven percent of the patients with COPD had repeated ER visits during the following year versus 42% in asthma (p < 0.05) (adjusted HRR: 1.73 (1.03-2.90)). Patients who had had ER visits the year before inclusion had a higher risk of ER visits the following year (adjusted HRR: 3.83 (1.99-7.38)). There were no significant differences regarding patient education and knowledge between the group with and without further ER visits after adjusting for sex, diagnose, age, and educational background.</p> <p>Conclusion</p> <p>Patients with asthma had a better self reported knowledge of disease management and were less likely to have new exacerbations than patients with COPD. Reported level of knowledge was, however, in it self not a predictor of exacerbations. This indicates that information is not sufficient to reduce the burden of disease. Patient education focused on self-management and behavioral change should be emphasized.</p

Critical Early Roles for col27a1a and col27a1b in Zebrafish Notochord Morphogenesis, Vertebral Mineralization and Post-embryonic Axial Growth

Fibrillar collagens are well known for their links to human diseases, with which all have been associated except for the two most recently identified fibrillar collagens, type XXIV collagen and type XXVII collagen. To assess functions and potential disease phenotypes of type XXVII collagen, we examined its roles in zebrafish embryonic and post-embryonic development.We identified two type XXVII collagen genes in zebrafish, col27a1a and col27a1b. Both col27a1a and col27a1b were expressed in notochord and cartilage in the embryo and early larva. To determine sites of type XXVII collagen function, col27a1a and col27a1b were knocked down using morpholino antisense oligonucleotides. Knockdown of col27a1a singly or in conjunction with col27a1b resulted in curvature of the notochord at early stages and formation of scoliotic curves as well as dysmorphic vertebrae at later stages. These defects were accompanied by abnormal distributions of cells and protein localization in the notochord, as visualized by transmission electron microscopy, as well as delayed vertebral mineralization as detected histologically.Together, our findings indicate a key role for type XXVII collagen in notochord morphogenesis and axial skeletogenesis and suggest a possible human disease phenotype

Characterization of BTBD1 and BTBD2, two similar BTB-domain-containing Kelch-like proteins that interact with Topoisomerase I

BACKGROUND: Two-hybrid screening for proteins that interact with the core domain of human topoisomerase I identified two novel proteins, BTBD1 and BTBD2, which share 80% amino acid identities. RESULTS: The interactions were confirmed by co-precipitation assays demonstrating the physical interaction of BTBD1 and BTBD2 with 100 kDa topoisomerase I from HeLa cells. Deletion mapping using two-hybrid and GST-pulldown assays demonstrated that less than the C-terminal half of BTBD1 is sufficient for binding topoisomerase I. The topoisomerase I sequences sufficient to bind BTBD2 were mapped to residues 215 to 329. BTBD2 with an epitope tag localized to cytoplasmic bodies. Using truncated versions that direct BTBD2 and TOP1 to the same cellular compartment, either the nucleus or the cytoplasm, co-localization was demonstrated in co-transfected Hela cells. The supercoil relaxation and DNA cleavage activities of topoisomerase I in vitro were affected little or none by co-incubation with BTBD2. Northern analysis revealed only a single sized mRNA for each BTBD1 and BTBD2 in all human tissues tested. Characterization of BTBD2 mRNA revealed a 255 nucleotide 90% GC-rich region predicted to encode the N-terminus. BTBD1 and BTBD2 are widely if not ubiquitously expressed in human tissues, and have two paralogs as well as putative orthologs in C. elegans and D. melanogaster. CONCLUSIONS: BTBD1 and BTBD2 belong to a small family of uncharacterized proteins that appear to be specific to animals. Epitope-tagged BTBD2 localized to cytoplasmic bodies. The characterization of BTBD1 and BTBD2 and their interaction with TOP1 is underway