bluuebunny/crossref_metadata_2025 huggingface dataset:
The influence of optimal medical treatment on the ‘obesity paradox’, body mass index and long-term mortality in patients treated with percutaneous coronary intervention: a prospective cohort study
Authors: Schenkeveld Lisanne , Magro Michael , Oemrawsingh Rohit M , Lenzen Mattie , de Jaegere Peter , van Geuns Robert-Jan , Serruys Patrick W , van Domburg Ron T
Published: February 2012

Objective

To assess whether the obesity paradox persists in the long term and to study the effect of optimal medical treatment on this phenomenon.

Design

A retrospective cohort study.

Setting

A tertiary care centre in Rotterdam.

Participants

From January 2000 to December 2005, 6332 patients undergoing percutaneous coronary intervention for coronary artery disease were categorised into underweight (body mass index (BMI)<18.5), normal (18.5–24.9), overweight (25–29.9) and obese (>30).

Primary outcome measure

Mortality.

Secondary outcome measures

Cardiac death and non-fatal myocardial infarction.

Results

Optimal medical treatment was more common in obese patients as compared with normal weight patients (85% vs 76%; p<0.001). At a mean of 6.1 years, overweight and obese patients had a lower risk of all-cause mortality (HR: 0.75, 95% CI 0.66 to 0.86 and HR: 0.72, 95% CI 0.60 to 0.87, respectively). After adjusting for OMT in the multivariate analysis, BMI did not remain an independent predictor of long-term mortality (HR: 0.90, 95% CI 0.72 to 1.12 and HR: 1.07, 95% CI: 0.80 to 1.43, respectively).

Conclusion

BMI is inversely related to long-term mortality in patients treated with percutaneous coronary intervention. Patients with a normal BMI are on suboptimal medical treatment when compared with those with a high BMI. A more optimal medical treatment in the obese group may explain the observed improved outcome in these patients.
Surveillance of unplanned return to the operating theatre in neurosurgery combined with a mortality–morbidity conference: results of a pilot survey
Authors: Marini Hélène , Merle Véronique , Derrey Stéphane , Lebaron Christine , Josset Valérie , Langlois Olivier , Gilles Baray Marie , Frébourg Noëlle , Proust François , Czernichow Pierre
Published: February 2012

Background

Unplanned return to the operating theatre (UROT) is a useful trigger tool that could be used to identify surgical adverse events (SAEs). The present study describes the feasibility of SAE surveillance in neurosurgical patients, based on UROT identification, completed with SAE analysis at a morbidity–mortality conference (MMC) meeting.

Method

For consecutive patients who underwent a neurosurgical procedure between 1 November 2008 and 30 April 2009, return to the operating theatre (ROT) was identified based on the hospital information system associated to prospective payment (HISPP). ROT was classified as planned or unplanned and UROT was further classified as related to the natural history of the disease or related to an adverse event (AE-UROT). MMC meetings were organised to discuss results of UROT surveillance and to analyse AE-UROT.

Results

1006 neurosurgical procedures were included in the surveillance. HISSP identified 152 ROTs, with 73 UROTs related to an SAE (7.3% (5.7% to 9.0%)): infectious SAE (n=24, 2.4% (1.5% to 3.5%)), haemorrhagic SAE (n=23, 2.3% (1.5% to 3.4%)), other cause SAE (n=26, 2.8% (1.9% to 4.0%)), and infectious and other cause SAE (n=2, 0.2% (0.0% to 0.7%)). Identification of AE-UROT through HISSP required a 4 h/month time frame. Eight UROTs related to SAE cases were discussed during MMC meetings, leading to the identification of non-conforming care processes and practical improvement actions.

Conclusion

UROT related to SAE surveillance in neurosurgical patients was considered feasible. The association of surveillance and MMCs allowed staff to concentrate on the analysis of most frequent or most severe AEs and was a practical and useful tool to stimulate improvement. The impact on healthcare quality of SAE surveillance associated with MMC warrants further research.
Attitudes towards infection prevention and control: an interview study with nursing students and nurse mentors
Authors: Ward Deborah Jane
Published: February 2012

Background

Despite both national and international recommendations for good practice in infection prevention and control (IPC), compliance can be low. Several reasons for this have been identified, including staff attitudes. There is little literature on how these attitudes are perceived by nursing students learning in clinical placements, and this study was undertaken to explore perceptions of both nursing students and their mentors in relation to attitudes towards IPC.

Methods

Qualitative study involving semi-structured interviews with 31 nursing students and 32 nurse mentors recruited from one large university and one large NHS Trust in the North of England.

Results

Nursing students generally perceived a negative attitude towards IPC from qualified staff and identified that it was considered to be an additional workload burden as opposed to an integral aspect of patient safety and quality care. Mentors identified more positive attitudes within their areas and organisation, but their comments did not always reflect this. Mentors were more of the opinion that staff attitudes could affect student practice and learning than were students.

Discussion

Nurses in practice need to be more aware of how their attitudes towards IPC can be perceived by nursing students and the possible consequences of this for student learning and practice. Staff need to work towards identifying barriers to good infection prevention practice and ways to overcome these.
The ins and outs of change of shift handoffs between nurses: a communication challenge
Authors: Carroll John S , Williams Michele , Gallivan Theresa M
Published: February 2012

Background

Communication breakdowns have been identified as a source of problems in complex work settings such as hospital-based healthcare.

Methods

The authors conducted a multi-method study of change of shift handoffs between nurses, including interviews, survey, audio taping and direct observation of handoffs, posthandoff questionnaires, and archival coding of clinical records.

Results

The authors found considerable variability across units, nurses and, surprisingly, roles. Incoming and outgoing nurses had different expectations for a good handoff: incoming nurses wanted a conversation with questions and eye contact, whereas outgoing nurses wanted to tell their story without interruptions. More experienced nurses abbreviated their reports when incoming nurses knew the patient, but the incoming nurses responded with a large number of questions, creating a contest for control. Nurses' ratings did not correspond to expert ratings of information adequacy, suggesting that nurses consider other functions of handoffs beyond information processing, such as social interaction and learning.

Discussion

These results suggest that variability across roles as information provider versus receiver and experience level (as well as across individual and organisational contexts) are reasons why improvement efforts directed at standardising and improving handoffs have been challenging in nursing and in other healthcare professions as well.
What is the incidence of major adverse cardiac events in emergency department chest pain patients with a normal ECG, Thrombolysis in Myocardial Infarction score of zero and initial troponin ≤99th centile: an observational study?
Authors: Kelly Anne-Maree
Published: February 2012

Objective

To determine the rate of major adverse cardiac events (MACE) in patients assessed in an emergency department (ED) for chest pain with a non-ischaemic ECG, Thrombolysis in Myocardial Infarction (TIMI) score of 0 and initial troponin I (TnI) ≤99th centile.

Methods

This was a sub-study of a prospective observational study of adult patients with potentially cardiac chest pain who underwent evaluation for acute coronary syndrome in an urban teaching hospital. Adult patients with non-traumatic chest pain were eligible for inclusion. Those with ECG evidence of acute ischaemia or an alternative diagnosis were excluded. Data collected included demographic, clinical, ECG, biomarker and outcome data. Low risk was defined as a TIMI risk score of 0 and initial TnI ≤99th centile. Primary outcome of interest was defined as MACE within 7 days. MACE included death, cardiac arrest, revascularisation, cardiogenic shock, arrhythmia, and prevalent (cause of presentation) and incident (occurring within the follow-up period) myocardial infarction (MI). Analysis was by descriptive and clinical performance analyses.

Results

651 patients were studied of whom 215 met the low risk criteria. There was one MACE in this group (0.47%, 95% CI 0.08% to 2.6%)—a revascularisation within 7 days without prevalent MI. Negative predictive value of low risk classification was 99.5% (95% CI 97% to 100%) at both 7 and 30 days. Negative likelihood ratio, weighted by prevalence, was 0.005 at both intervals.

Conclusion

Risk stratification for early discharge based on ECG, TIMI score of 0 and presentation TnI ≤99th centile appears to identify a group at very low risk of MACE. Research to prospectively validate this is warranted.
Critical care in emergency department: massive haemorrhage in trauma
Authors: Mahambrey Tushar , Pendry Katherine , Nee Alexandra , Bonney Samantha , Nee Patrick A
Published: February 2012

Inadequate resuscitation of major haemorrhage is an important cause of avoidable death in severely injured patients. Early recognition of blood loss, control of bleeding and restoration of circulating volume are critical to the management of trauma shock, and transfusion of blood components is a key intervention. Vital signs may be inadequate to determine the need for transfusion, and resuscitation regimens targeting vital signs may be harmful in the context of uncontrolled bleeding. This article addresses current concepts in haemostatic resuscitation. Recent guidelines on the diagnosis and treatment of coagulopathy in major trauma, and the role of component and adjuvant therapies, are considered. Finally, the potential role of thromboelastography and rotational thromboelastometry are discussed.
Barriers to senior centre implementation of falls prevention programmes
Authors: Zachary Ciara , Casteel Carri , Nocera Maryalice , Runyan Carol W
Published: February 2012

This study examined the prevalence of senior centres providing multi-component falls prevention education and the perceived barriers in implementing this education. A telephone interview was conducted in 2006 with 500 senior centres nationwide. Centre directors were asked about the types of multi-component falls prevention education offered (ie, balance exercise classes, medication management, home safety information) and barriers to offering this education. Seventy percent of senior centres offered balance exercise classes, 68% offered medication management and 53% provided home safety information. Thirty-two percent offered all three components. Lack of staff, time and staff not feeling they had sufficient knowledge to deliver falls prevention education were the leading barriers to providing multi-component education. Senior centres provide components of effective falls prevention education and, while some may not address all components of a multifaceted programme, many have existing resources that may be adapted for translation of evidence-based programmes.
Characteristics of non-fatal abusive head trauma among children in the USA, 2003–2008: application of the CDC operational case definition to national hospital inpatient data
Authors: Parks Sharyn , Sugerman David , Xu Likang , Coronado Victor
Published: February 2012

Objective

An International Classification of Diseases code-based case definition for non-fatal abusive head trauma (AHT) in children <5 years of age was developed in March 2008 by an expert panel convened at the Centers for Disease Control and Prevention (CDC). This study presents an application of the CDC recommended operational case definition of AHT to US hospital inpatient data to characterise the AHT hospitalisation rate for children <5 years of age.

Methods

Nationwide Inpatient Sample (NIS) data from the Healthcare Cost and Utilisation Project from 2003 to 2008 were examined.

Results

Inspection of the NIS data resulted in the identification of an estimated 10 555 non-fatal AHT hospitalisations with 9595 classified as definite/presumptive AHT and 960 classified as probable AHT. The non-fatal AHT rate was highest among children aged <1 year (32.3 per 100 000) with a peak in hospitalisations between 1 and 3 months of age. Non-fatal AHT hospitalisation rates for children <2 years of age were higher for boys (21.9 per 100 000) than girls (15.3 per 100 000). The non-fatal AHT hospitalisation rate showed little variation across seasons.

Conclusions

To reduce the burden of AHT in the USA, a preventable public health problem, concerted prevention efforts targeting populations at risk should be implemented. This report demonstrates a model procedure for using the new CDC definition for public health surveillance and research purposes. Such findings can be used to inform parents and providers about AHT (eg, dangers of shaking, strategies for managing infant crying) as well as to monitor better the impact of prevention strategies over time.
Vessel occlusion using a single long oversized coil in vertebral artery dissection: a technical note
Authors: Grigoryan Mikayel , Cordina Steve M , Khatri Rakesh , Hassan Ameer E , Rodriguez Gustavo J
Published: February 2012

Vertebral artery dissection may lead to stroke. Medical therapy is usually the first line of treatment. The endovascular approach of medically refractory vertebral artery dissection may include numerous techniques, including coil occlusion of the parent vessel. Two cases are presented of medically refractory symptomatic vertebral artery dissections in which vessel coil occlusion was successfully achieved with a single long oversized coil. There were no periprocedural complications and both patients had excellent clinical and angiographic outcome and remained asymptomatic on follow-up. The use of a single long oversized coil in vessel sacrifice has not been described previously. It represents a safe, rapid and cost effective alternative to the current existing techniques for vessel sacrifice.
A B cell explanation for autoimmune disease: the forbidden clone returns
Authors: McQueen Fiona
Published: February 2012

More than 60 years ago, Burnet first proposed the ‘forbidden clone’ hypothesis postulating that autoimmune disease arises as a result of persistence of self-reactive clones of lymphocytes that should have been deleted via immune tolerance. These autoreactive clones could effect immune-mediated end-organ damage via peripheral self-antigen recognition. Recent evidence that stretches across the boundaries of many medical specialties supports this proposal, implicating a B cell precursor as the culprit. The success of B cell depleting therapy in rheumatoid arthritis, anti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitis, polymyositis, lupus and autoimmune diseases as diverse as multiple sclerosis and idiopathic thrombocytopenic purpura supports this proposal. Clonality of B cells and plasma cells has been described in a number of autoimmune disorders and the presence of autoantibodies, which may arise years before the onset of clinical disease, supports the notion of autoreactivity within the B cell lineage. T cell activation within the end-organ would be predicted by cognate B–T cell interactions and resultant tissue inflammation and destruction could produce diverse clinical manifestations dictated by the original specificity of the autoimmune B cell.
Hyperosmotic and isosmotic shrinkage differentially affect protein phosphorylation and ion transport
Authors: Koltsova Svetlana V. , Akimova Olga A. , Kotelevtsev Sergei V. , Grygorczyk Ryszard , Orlov Sergei N.
Published: February 2012

In the present work, we compared the outcome of hyperosmotic and isosmotic shrinkage on ion transport and protein phosphorylation in C11-MDCK cells resembling intercalated cells from collecting ducts and in vascular smooth muscle cells (VSMC) from the rat aorta. Hyperosmotic shrinkage was triggered by cell exposure to hypertonic medium, whereas isosmotic shrinkage was evoked by cell transfer from an hypoosmotic to an isosmotic environment. Despite a similar cell volume decrease of 40%–50%, the consequences of hyperosmotic and isosmotic shrinkage on cellular functions were sharply different. In C11-MDCK and VSMC, hyperosmotic shrinkage completely inhibited Na+,K+-ATPase and Na+,Picotransport. In contrast, in both types of cells isosmotic shrinkage slightly increased rather than suppressed Na+,K+-ATPase and did not change Na+,Picotransport. In C11-MDCK cells, phosphorylation of JNK1/2 and Erk1/2 mitogen-activated protein kinases was augmented in hyperosmotically shrunken cells by ∼7- and 2-fold, respectively, but was not affected in cells subjected to isosmotic shrinkage. These results demonstrate that the data obtained in cells subjected to hyperosmotic shrinkage cannot be considered as sufficient proof implicating cell volume perturbations in the regulation of cellular functions under isosmotic conditions.
The relationship between antiglycation activity and procyanidin and phenolic content in commercial grape seed products
Authors: Sun Cathy , McIntyre Kristina , Saleem Ammar , Haddad Pierre Selim , Arnason John Thor
Published: February 2012

Eight commercial grape seed products (GSPs) were assessed for their inhibition of the formation of advanced glycation end-products in vitro. All 8 commercial GSPs included in this study were potent inhibitors of advanced glycation end-product formation with IC50values ranging from 2.93 to 20.0 µg/mL. Total procyanidin content ranged from 60% to 73%. HPLC–DAD–ELSD results indicate that (+)-catechin, (–)-epicatechin, procyanidin B1, and procyanidin B2 were predominant and ubiquitously present in all the products under study, while gallic acid and procyanidin B4 were present in relatively minor amounts. The IC50values correlated with total phenolic content, and multiple regression analysis indicated that IC50is a linear function of the concentration of gallic acid and procyanidins B1, B2, and B4. Based on this study, GSPs have the potential to complement conventional diabetes medication toward disease management and prevention.
MASTER ACTIONS FOR LINEARIZED MASSIVE GRAVITY MODELS IN 3D
Authors: ARIAS PIO J. , KHOUDEIR ADEL , STEPHANY J.
Published: February 2012

We present a unified analysis of the self-dual, second order, topologically massive and the recently introduced fourth-order models of massive gravity in 3D. We show that there is a family of first-order actions which interpolate between these different single excitation models. We show how the master actions are related by duality transformation. We construct by the same method the master action which relates the fourth-order new massive model with two excitations and the usual second-order model with Fierz–Pauli mass. We show that the more general model obtained by adding a Chern–Simons term to the new massive model is equivalent off-shell to the second-order spontaneously broken linearized massive gravity.
DEPPDB — DNA ELECTROSTATIC POTENTIAL PROPERTIES DATABASE: ELECTROSTATIC PROPERTIES OF GENOME DNA ELEMENTS
Authors: OSYPOV ALEXANDER A. , KRUTININ GLEB G. , KRUTININA EUGENIA A. , KAMZOLOVA SVETLANA G.
Published: February 2012

Electrostatic properties of genome DNA are important to its interactions with different proteins, in particular, related to transcription. DEPPDB — DNA Electrostatic Potential (and other Physical) Properties Database — provides information on the electrostatic and other physical properties of genome DNA combined with its sequence and annotation of biological and structural properties of genomes and their elements. Genomes are organized on taxonomical basis, supporting comparative and evolutionary studies. Currently, DEPPDB contains all completely sequenced bacterial, viral, mitochondrial, and plastids genomes according to the NCBI RefSeq, and some model eukaryotic genomes. Data for promoters, regulation sites, binding proteins, etc., are incorporated from established DBs and literature. The database is complemented by analytical tools. User sequences calculations are available. Case studies discovered electrostatics complementing DNA bending in E.coli plasmid BNT2 promoter functioning, possibly affecting host-environment metabolic switch. Transcription factors binding sites gravitate to high potential regions, confirming the electrostatics universal importance in protein–DNA interactions beyond the classical promoter–RNA polymerase recognition and regulation. Other genome elements, such as terminators, also show electrostatic peculiarities. Most intriguing are gene starts, exhibiting taxonomic correlations. The necessity of the genome electrostatic properties studies is discussed.
Approach and impact of a protocol for selection of service in web service platform
Authors: Mohana Rajni , Dahiya Deepak
Published: February 2012

Business agility is an important challenge while designing an enterprise application. Service oriented architecture is used to combine many outsourced web services to provide value added services to the users with agility. A service registry is maintained to keep track of various web service published by the service providers. The key challenge for the service requester is to pick the best web service among the various functionally equivalent web services in the service registry. This paper describes and analyses various service selection protocols given by the researchers. The approaches are classified into semantic and non-semantic approach. It also proposes a novel technique to look for the best web service based on QoS like reliability, throughput etc. The solution to the problem of selecting the best web service according to the requirements is designed as a fuzzy expert system. This rule based approach of Service registration and lookup is adaptive and responds dynamically to quality of service changes in the web services.
Evolution of software engineers' personality profile
Authors: Varona Daniel , Capretz Luiz Fernando , Piñero Yadenis , Raza Arif
Published: February 2012

The Myers-Briggs Type Indicator (MBTI) has been applied to several studies that explore various dimensions of human factors in software engineering. Accordingly, this work reviews the results of these studies to explore existing trends. In order to attain a greater understanding of human resources in the software industry, we have reviewed sixteen studies that had been performed between 1985 and 2011. This review concludes that the changes in the complexity of software processes and products have created new roles and demanded new skills for software engineers.
The Case Against Pre-Testing For Online Courses
Authors: Quinn Clark
Published: February 2012

Too often, online courses begin with pre-tests. Are pre-tests anything more than learner abuse? Under the best of circumstances, quizzes can be tedious and even anxiety-inducing. Putting tests before your content casts a negative shadow over a course before it has even begun.
Evaluating auditory graphs with blind students in a classroom
Authors: Davison Benjamin K.
Published: February 2012

Graphs are an important part of mathematics education. 30 years of auditory graphs research has led to a better understanding of their potential. However, questions remain about the effectiveness of auditory graphs in a classroom setting. I will be defining success criteria for a system based on graphing problems from an introductory high school math class. These criteria will shape the development and evaluation of an auditory graphs system.
Leveraging crowds and clouds
Authors: Hoehl Jeffery
Published: February 2012

This paper discusses our research project for using an intercommunity approach to combine technical web solutions from many online communities into one tool that can provide simplified web pages to users with cognitive disabilities who find traditional websites difficult to use. We discuss our current progress, future directions, and benefits to the accessibility community as a whole.
Disabled 'R' all
Authors: Nicolau Hugo
Published: February 2012

More and more people interact with mobile devices whilst walking. This new interaction paradigm imposes a novel set of challenges and restrictions to mobile users, denominated Situationally-Induced Impairments and Disabilities. The tremor originated of such contexts results in inaccurate movements and erroneous actions. These difficulties are particularly visible in recent touch interfaces that lack the tactile cues and physical stability provided by their keypad-based counterparts. Nevertheless, these difficulties are not new to the accessibility community, particularly for those studying motor impaired users. In fact, both user populations (situationally and physically impaired) seem to share similar interaction problems. This work aims to thoroughly understand to what extend technology can be transferred between those domains. Unlike the embryonic stage of mobile research, the accessibility community has the accumulated knowledge of more than two decades of research. Building a relationship between these domains will contribute towards a more inclusive and universal design approach, which will benefit and bring closer two distinct research communities.
DysWebxia
Authors: Rello Luz
Published: February 2012

The goal of this research is to make textual content in the Web --especially in Spanish and English-- more accessible to people with dyslexia. The techniques that we will use to make the Web more accessible are Natural Language Processing (NLP) for its content (text) and Web design guidelines for its layout. To find out which solutions tackle better our purpose we will test a diverse set of Web pages examples. The main methodology to evaluate these examples will be eye tracking using regular and dyslexic students. In the case that our findings show that there are strategies that make the Web more accessible for dyslexic users, we plan to develop and application which includes such results, transforming a regular Web site into a dyslexic friendly Web site.
Glucagon-like peptide-2 increases dysplasia in rodent models of colon cancer
Authors: Trivedi Shivangi , Wiber Stuart C. , El-Zimaity Hala M. , Brubaker Patricia L.
Published: February 2012

The intestinal hormone, glucagon-like peptide-2 (GLP-2), enhances intestinal growth and reduces inflammation in rodent models. Hence, a degradation-resistant GLP-2 analog is under investigation for treatment of Crohn's disease. However, GLP-2 increases colonic dysplasia in murine azoxymethane (AOM)-induced colon cancer. Considering the increased colon cancer risk associated with chronic colitis, we have therefore examined the effects of long-acting hGly2GLP-2, as well as of endogenous GLP-2 using the antagonist hGLP-23–33 in two novel models of inflammation-associated colon cancer: rats fed the carcinogen 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and a high-fat diet (HFD) for one or three cycles, and mice with chronic dextran sodium-sulfate (DSS)-induced colitis administered AOM. hGly2GLP-2 treatment of one-cycle PhIP/HFD rats increased the number of colonic aberrant crypt foci by 72 ± 11% ( P < 0.01). Fifty-one weeks after three PhIP/HFD cycles, hGly2GLP-2-treated rats had a 22% incidence of colon cancer, compared with 0% in vehicle-treated rats. AOM-DSS mice treated with vehicle or hGly2GLP-2 had high-grade dysplasia/colon cancer incidences of 56 and 64%, respectively, compared with 46% in hGLP-23–33-treated AOM-DSS animals ( P < 0.05). Unexpectedly, hGLP-23–33 also reduced the colitis damage score by 32.0 ± 8.4% ( P < 0.05). All high-grade dysplastic/cancerous tumors had nuclear localization of β-catenin although β-catenin mRNA transcript and protein levels did not differ between treatment groups. GLP-2 receptor mRNA expression also was not different. However, hGLP-23–33-treated mice had markedly reduced numbers of doublecortin-and-calmodulin-kinase-like-1-positive stem cells, by 73.7 ± 8.6% ( P < 0.05). In conclusion, the results of this study indicate a role for hGly2GLP-2 and endogenous GLP-2 as potential cancer promoters in rodents.
Downregulation of doxorubicin-induced myocardial apoptosis accompanies postnatal heart maturation
Authors: Shi Jianjian , Zhang Lumin , Zhang Yi-Wei , Surma Michelle , Mark Payne R. , Wei Lei
Published: February 2012

Doxorubicin is a highly effective chemotherapeutic agent used for treating a wide spectrum of tumors, but its usage is limited because of its dose-dependent cardiotoxicity, especially in pediatric patients. Accumulating evidence indicates that caspase-dependent apoptosis contributes to the cardiotoxicity of doxorubicin. However, less attention has been paid to the effects of age on doxorubicin-induced apoptosis signaling in myocardium. This study focused on investigating differential apoptotic sensitivity between neonatal and adult myocardium, in particular, between neonatal and adult cardiomyocytes in vivo. Our results show that caspase-3 activity in normal mouse hearts decreased by ≥20-fold within the first 3 wk after birth, associated with a rapid downregulation in the expression of key proapoptotic proteins in intrinsic and extrinsic pathways. This rapid downregulation of caspase-3 activity was confirmed by immunostaining for cleaved caspase-3 and terminal deoxynucleotidyl transferase dUTP-mediated nick-end label staining. Doxorubicin treatment induced a dose-dependent increase in caspase-3 activity and apoptosis in neonatal mouse hearts, and both caspase-8 and caspase-9 activations were involved. Using transgenic mice with a nuclear localized LacZ reporter gene to label cardiomyocytes in vivo, we observed a fourfold higher level of doxorubicin-induced cardiomyocyte apoptosis in 1-wk-old mice compared with that in 3-wk-old mice. This study points to a major difference in apoptotic signaling in doxorubicin cardiotoxicity between neonatal and adult mouse hearts and reveals a critical transition from high to low susceptibility to doxorubicin-induced apoptosis during postnatal heart maturation.
Endothelial leptin receptor mutation provides partial resistance to diet-induced obesity
Authors: Pan Weihong , Hsuchou Hung , Cornelissen-Guillaume Germaine G. , Jayaram Bhavvani , Wang Yuping , Tu Hong , Halberg Franz , Wu Xiaojun , Chua Streamson C. , Kastin Abba J.
Published: February 2012

Leptin, a polypeptide hormone produced mainly by adipocytes, has diverse effects in both the brain and peripheral organs, including suppression of feeding. Other than mediating leptin transport across the blood-brain barrier, the role of the endothelial leptin receptor remains unclear. We recently generated a mutant mouse strain lacking endothelial leptin receptor signaling, and showed that there is an increased uptake of leptin by brain parenchyma after its delivery by in situ brain perfusion. Here, we tested the hypothesis that endothelial leptin receptor mutation confers partial resistance to diet-induced obesity. These ELKO mice had similar body weight and percent fat as their wild-type littermates when fed with rodent chow, but blood concentrations of leptin were significantly elevated. In response to a high-fat diet, wild-type mice had a greater gain of body weight and fat than ELKO mice. As shown by metabolic chamber measurement, the ELKO mice had higher oxygen consumption, carbon dioxide production, and heat dissipation, although food intake was similar to that of the wild-type mice and locomotor activity was even reduced. This indicates that the partial resistance to diet-induced obesity was mediated by higher metabolic activity in the ELKO mice. Since neuronal leptin receptor knockout mice show obesity and diabetes, the results suggest that endothelial leptin signaling shows opposite effects from that of neuronal leptin signaling, with a facilitatory role in diet-induced obesity.
Effects of recombinant human keratinocyte growth factor on surfactant, plasma, and liver phospholipid homeostasis in hyperoxic neonatal rats
Authors: Raith Marco , Schaal Katharina , Koslowski Roland , Fehrenbach Heinz , Poets Christian F. , Schleicher Erwin , Bernhard Wolfgang
Published: February 2012

Respiratory distress and bronchopulmonary dysplasia (BPD) are major problems in preterm infants that are often addressed by glucocorticoid treatment and increased oxygen supply, causing catabolic and injurious side effects. Recombinant human keratinocyte growth factor (rhKGF) is noncatabolic and antiapoptotic and increases surfactant pools in immature lungs. Despite its usefulness in injured neonatal lungs, the mechanisms of improved surfactant homeostasis in vivo and systemic effects on lipid homeostasis are unknown. We therefore exposed newborn rats to 85% vs. 21% oxygen and treated them systemically with rhKGF for 48 h before death at 7 days. We determined type II pneumocyte (PN-II) proliferation, surfactant protein (SP) mRNA expression, and the pulmonary metabolism of individual phosphatidylcholine (PC) species using [D9-methyl]choline and tandem mass spectrometry. In addition, we assessed liver and plasma lipid metabolism, addressing PC synthesis de novo, the liver-specific phosphatidylethanolamine methyl transferase (PEMT) pathway, and triglyceride concentrations. rhKGF was found to maintain PN-II proliferation and increased SP-B/C expression and surfactant PC in both normoxic and hyperoxic lungs. We found increased total PC together with decreased [D9-methyl]choline enrichment, suggesting decreased turnover rather than increased secretion and synthesis as the underlying mechanism. In the liver, rhKGF increased PC synthesis, both de novo and via PEMT, underlining the organotypic differences of rhKGF actions on lipid metabolism. rhKGF increased the hepatic secretion of newly synthesized polyunsaturated PC, indicating improved systemic supply with choline and essential fatty acids. We suggest that rhKGF has potential as a therapeutic agent in neonates by improving pulmonary and systemic PC homeostasis.
Effect of exercise training on nitric oxide and superoxide/H2O2signaling pathways in collateral-dependent porcine coronary arterioles
Authors: Xie Wei , Parker Janet L. , Heaps Cristine L.
Published: February 2012

Endothelial nitric oxide (NO) synthase (NOS) has been shown to contribute to enhanced vascular function after exercise training. Recent studies have revealed that relatively low concentrations of reactive oxygen species can contribute to endothelium-dependent vasodilation under physiological conditions. We tested the hypothesis that exercise training enhances endothelial function via endothelium-derived vasodilators, NO and superoxide/H2O2, in the underlying setting of chronic coronary artery occlusion. An ameroid constrictor was placed around the proximal left circumflex coronary artery to induce gradual occlusion in Yucatan miniature swine. At 8 wk postoperatively, pigs were randomly assigned to sedentary (pen-confined) or exercise-training (treadmill-run: 5 days/wk for 14 wk) regimens. Exercise training significantly enhanced concentration-dependent, bradykinin-mediated dilation in cannulated collateral-dependent arterioles (∼130 μm diameter) compared with sedentary pigs. NOS inhibition reversed training-enhanced dilation at low bradykinin concentrations in collateral-dependent arterioles, although increased dilation persisted at higher bradykinin concentrations. Total and phosphorylated (Ser1179) endothelial NOS protein levels were significantly increased in arterioles from collateral-dependent compared with the nonoccluded region, independent of exercise. The H2O2scavenger polyethylene glycol-catalase abolished the training-enhanced bradykinin-mediated dilation in collateral-dependent arterioles; similar results were observed with the SOD inhibitor diethyldithiocarbamate. Fluorescence measures of bradykinin-stimulated H2O2levels were significantly increased by exercise training, independent of occlusion. The NADPH inhibitor apocynin significantly attenuated bradykinin-mediated dilation in arterioles of exercise-trained, but not sedentary, pigs and was associated with significantly increased protein levels of the NADPH subunit p67phox. These data provide evidence that, in addition to NO, the superoxide/H2O2signaling pathway significantly contributes to exercise training-enhanced endothelium-mediated dilation in collateral-dependent coronary arterioles.
Microparticle production, neutrophil activation, and intravascular bubbles following open-water SCUBA diving
Authors: Thom Stephen R. , Milovanova Tatyana N. , Bogush Marina , Bhopale Veena M. , Yang Ming , Bushmann Kim , Pollock Neal W. , Ljubkovic Marko , Denoble Petar , Dujic Zeljko
Published: February 2012

The goal of this study was to evaluate annexin V-positive microparticles (MPs) and neutrophil activation in humans following decompression from open-water SCUBA diving with the hypothesis that changes are related to intravascular bubble formation. Sixteen male volunteer divers followed a uniform profile of four daily SCUBA dives to 18 m of sea water for 47 min. Blood was obtained prior to and at 80 min following the first and fourth dives to evaluate the impact of repetitive diving, and intravascular bubbles were quantified by trans-thoracic echocardiography carried out at 20-min intervals for 2 h after each dive. MPs increased by 3.4-fold after each dive, neutrophil activation occurred as assessed by surface expression of myeloperoxidase and the CD18 component of β2-integrins, and there was an increased presence of the platelet-derived CD41 protein on the neutrophil surface indicating interactions with platelet membranes. Intravascular bubbles were detected in all divers. Surprisingly, significant inverse correlations were found among postdiving bubble scores and MPs, most consistently at 80 min or more after the dive on the fourth day. There were significant positive correlations between MPs and platelet-neutrophil interactions after the first dive and between platelet-neutrophil interactions and neutrophil activation documented as an elevation in β2-integrin expression after the fourth dive. We conclude that MPs- and neutrophil-related events in humans are consistent with findings in an animal decompression model. Whether there are causal relationships among bubbles, MPs, platelet-neutrophil interactions, and neutrophil activation remains obscure and requires additional study.
Mechanism of the lung-deflating action of the canine diaphragm at extreme lung inflation
Authors: Leduc Dimitri , Cappello Matteo , Gevenois Pierre Alain , De Troyer André
Published: February 2012

When lung volume in animals is passively increased beyond total lung capacity (TLC; transrespiratory pressure = +30 cmH2O), stimulation of the phrenic nerves causes a rise, rather than a fall, in pleural pressure. It has been suggested that this was the result of inward displacement of the lower ribs, but the mechanism is uncertain. In the present study, radiopaque markers were attached to muscle bundles in the midcostal region of the diaphragm and to the tenth rib pair in five dogs, and computed tomography was used to measure the displacement, length, and configuration of the muscle and the displacement of the lower ribs during relaxation at seven different lung volumes up to +60 cmH2O transrespiratory pressure and during phrenic nerve stimulation at the same lung volumes. The data showed that 1) during phrenic nerve stimulation at 60 cmH2O, airway opening pressure increased by 1.5 ± 0.7 cmH2O; 2) the dome of the diaphragm and the lower ribs were essentially stationary during such stimulation, but the muscle fibers still shortened significantly; 3) with passive inflation beyond TLC, an area with a cranial concavity appeared at the periphery of the costal portion of the diaphragm, forming a groove along the ventral third of the rib cage; and 4) this area decreased markedly in size or disappeared during phrenic stimulation. It is concluded that the lung-deflating action of the isolated diaphragm beyond TLC is primarily related to the invaginations in the muscle caused by the acute margins of the lower lung lobes. These findings also suggest that the inspiratory inward displacement of the lower ribs commonly observed in patients with emphysema (Hoover's sign) requires not only a marked hyperinflation but also a large fall in pleural pressure.
Influence of housing conditions from weaning to adulthood on the ventilatory, thermoregulatory, and endocrine responses to hypoxia of adult female rats
Authors: Fournier Sébastien , Kinkead Richard , Joseph Vincent
Published: February 2012

Housing conditions affect animal physiology. We previously showed that the hypoxic ventilatory and thermoregulatory responses to hypoxia of adult male rats housed in triads during the juvenile period (postnatal day 21 to adulthood) were significantly reduced compared with animals housed in pairs. Because sex hormones influence development and responsiveness to environmental stressors, this study investigated the impact of housing on the respiratory and thermoregulatory physiology of female rats. Since neonatal stress attenuates the hypoxic ventilatory response (HVR) of female rats at adulthood, experiments were performed both on “control” (undisturbed) animals and rats subjected to neonatal maternal separation (NMS; 3 h/day, postnatal days 3–12). At adulthood, ventilatory activity was measured by whole body plethysmography under normoxic and hypoxic conditions [fraction of inspired oxygen (FiO2) = 0.12; 20 min]. The ventilatory and body temperature responses to hypoxia of female rats raised in triads were reduced compared with rats housed in pairs. Housing female rats in triads did not affect basal or hypoxic plasma corticosterone levels but did increase levels of estradiol significantly. We conclude that modest changes in housing conditions (pairs vs. triads) from weaning to adulthood does influence basic homeostatic functions such as temperature and respiratory regulation. Triad housing can reverse the manifestations of respiratory instability at adulthood induced by stressful neonatal treatments. This should raise awareness of the benefits of increasing social interactions in clinical settings but also caution researchers of the potential impact of such subtle changes on experimental protocols and interpretation of results.
Vascular Dysfunction as Target Organ Damage in Animal Models of Hypertension
Authors: Neves Mario Fritsch , Kasal Daniel Arthur B. , Cunha Ana Rosa , Medeiros Fernanda
Published: February 2012

Endothelial dysfunction is one of the main characteristics of chronic hypertension and it is characterized by impaired nitric oxide (NO) bioactivity determined by increased levels of reactive oxygen species. Endothelial function is usually evaluated by measuring the vasodilation induced by the local NO production stimulated by external mechanical or pharmacological agent. These vascular reactivity tests may be carried out in different models of experimental hypertension such as NO-deficient rats, spontaneously hypertensive rats, salt-sensitive rats, and many others. Wire myograph and pressurized myograph are the principal methods used for vascular studies. Usually, increasing concentrations of the vasodilator acetylcholine are added in cumulative manner to perform endothelium-dependent concentration-response curves. Analysis of vascular mechanics is relevant to identify arterial stiffness. Both endothelial dysfunction and vascular stiffness have been shown to be associated with increased cardiovascular risk.
Are Selective Serotonin Reuptake Inhibitors a Secondary Cause of Low Bone Density?
Authors: Chau Kim , Atkinson Stephanie A. , Taylor Valerie H.
Published: February 2012

Background.Osteoporosis is a chronic disease that can significantly impact numerous aspects of health and wellness. The individual consequences of osteoporosis can be devastating, often resulting in substantial loss of independence and sometimes death. One of the few illnesses with greater disease burden than low bone mineral density (BMD) is major depressive disorder (MDD). Both depression and antidepressant use have been identified as secondary causes of osteoporosis. The objective of this paper is to review and summarize the current findings on the relationship between antidepressant use and BMD.Methods.Relevant sources were identified from the Pubmed and MEDLINE databases, citing articles from the first relevant publication to September 1st, 2010.Results.2001 articles initially met the search criteria, and 35 studies were thoroughly reviewed for evidence of an association between SSRI use and BMD, and 8 clinical studies were detailed and summarized in this paper.Conclusions.Current findings suggest a link between mental illness and osteoporosis that is of clinical relevance. Additional longitudinal studies and further research on possible mechanisms surrounding the association between SSRI use on bone metabolism need to be conducted. Treatment algorithms need to recognize this association to ensure that vulnerable populations are screened.
Soft Collinear Degeneracies in an Asymptotically Free Theory
Authors: Lavelle Martin , McMullan David , Steele Tom
Published: February 2012

In asymptotically free theories with collinear divergences it is sometimes claimed that these divergences are cancelled if one sums over initial and final state degenerate cross-sections and uses an off-shell renormalisation scheme. We show for scalarϕ3theory in six dimensions that there are further classes of soft collinear divergences and that they are not cancelled. Furthermore, they yield a nonconvergent series of terms at a fixed order of perturbation theory. Similar effects in gauge theories are also summarised.
Numerical and Experimental Investigation of Combustion and Knock in a Dual Fuel Gas/Diesel Compression Ignition Engine
Authors: Gharehghani A. , Mirsalim S. M. , Jazayeri S. A.
Published: February 2012

Conventional compression ignition engines can easily be converted to a dual fuel mode of operation using natural gas as main fuel and diesel oil injection as pilot to initiate the combustion. At the same time, it is possible to increase the output power by increasing the diesel oil percentage. A detailed performance and combustion characteristic analysis of a heavy duty diesel engine has been studied in dual fuel mode of operation where natural gas is used as the main fuel and diesel oil as pilot. The influence of intake pressure and temperature on knock occurrence and the effects of initial swirl ratio on heat release rate, temperature-pressure and emission levels have been investigated in this study. It is shown that an increase in the initial swirl ratio lengthens the delay period for auto-ignition and extends the combustion period while it reduces NOx. There is an optimum value of the initial swirl ratio for a certain mixture intake temperature and pressure conditions that can achieve high thermal efficiency and low NOxemissions while decreases the tendency to knock. Simultaneous increase of intake pressure and initial swirl ratio could be the solution to power loss and knock in dual fuel engine.
Iliac Vein Compression Syndrome in an Active and Healthy Young Female
Authors: Cerquozzi Sonia , Pineo Graham F. , Wong Jason K. , Valentine Karen A.
Published: February 2012

Iliac vein compression syndrome is a condition involving external compression of the left common iliac vein by the right iliac artery, which was first described in the 1850s. It predominates in females typically between the third and fourth decade of life and has been associated with thrombophilias. Importantly, the syndrome is amenable to endovascular treatment. Here, we describe a case of a young athletic female with an incidental finding of a left iliac vein thrombosis while taking oral contraceptives, who was identified as having iliac vein compression syndrome on follow-up MR venography with positive testing for Factor V Leiden mutation.