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Find video protocols related to scientific articles indexed in Pubmed.
How Do We Prevent the Vulnerable Atherosclerotic Plaque From Rupturing? Insights From In Vivo Assessments of Plaque, Vascular Remodeling, and Local Endothelial Shear Stress.
J. Cardiovasc. Pharmacol. Ther.
PUBLISHED: 10-23-2014
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Coronary atherosclerosis progresses both as slow, gradual enlargement of focal plaque and also as a more dynamic process with periodic abrupt changes in plaque geometry, size, and morphology. Systemic vasculoprotective therapies such as statins, angiotensin-converting enzyme inhibitors, and antiplatelet agents are the cornerstone of prevention of plaque rupture and new adverse clinical outcomes, but such systemic therapies are insufficient to prevent the majority of new cardiac events. Invasive imaging methods have been able to identify both the anatomic features of high-risk plaque and the ongoing pathobiological stimuli responsible for progressive plaque inflammation and instability and may provide sufficient information to formulate preventive local mechanical strategies (eg, preemptive percutaneous coronary interventions) to avert cardiac events. Local endothelial shear stress (ESS) triggers vascular phenomena that synergistically exacerbate atherosclerosis toward an unstable phenotype. Specifically, low ESS augments lipid uptake and catabolism, induces plaque inflammation and oxidation, downregulates the production, upregulates the degradation of extracellular matrix, and increases cellular apoptosis ultimately leading to thin-cap fibroatheromas and/or endothelial erosions. Increases in blood thrombogenicity that result from either high or low ESS also contribute to plaque destabilization. An understanding of the actively evolving vascular phenomena, as well as the development of in vivo imaging methodologies to identify the presence and severity of the different processes, may enable early identification of a coronary plaque destined to acquire a high-risk state and allow for highly selective, focal preventive interventions to avert the adverse natural history of that particular plaque. In this review, we focus on the role of ESS in the pathobiologic processes responsible for plaque destabilization, leading either to accelerated plaque growth or to acute coronary events, and emphasize the potential to utilize in vivo risk stratification of individual coronary plaques to optimize prevention strategies to preclude new cardiac events.
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Endothelial Shear Stress and Coronary Plaque Characteristics in Humans: Combined Frequency-Domain Optical Coherence Tomography and Computational Fluid Dynamics Study.
Circ Cardiovasc Imaging
PUBLISHED: 09-04-2014
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Despite the exposure of the entire vasculature to the atherogenic effects of systemic risk factors, atherosclerotic plaques preferentially develop at sites with disturbed flow. This study aimed at exploring in vivo the relationship between local endothelial shear stress (ESS) and coronary plaque characteristics in humans using computational fluid dynamics and frequency-domain optical coherence tomography.
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Anatomically correct three-dimensional coronary artery reconstruction using frequency domain optical coherence tomographic and angiographic data: head-to-head comparison with intravascular ultrasound for endothelial shear stress assessment in humans.
EuroIntervention
PUBLISHED: 07-01-2014
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Aims: To develop a methodology that permits accurate 3-dimensional (3D) reconstruction from FD-OCT and angiographic data enabling reliable evaluation of the ESS distribution, and to compare the FD-OCT-derived models against the established models based on angiography/IVUS. Methods and results: Fifteen patients (17 coronary arteries) who underwent angiography, FD-OCT and IVUS examination during the same procedure were studied. The FD-OCT and IVUS lumen borders were placed onto the 3D luminal centreline derived from angiographic data. Three-dimensional geometry algorithms and anatomical landmarks were used to estimate the orientation of the borders appropriately. ESS was calculated using computational fluid dynamics. In 188 corresponding consecutive 3-mm segments, FD-OCT- and IVUS-derived models were highly correlated for lumen area (r=0.96) and local ESS (r=0.89) measurements. FD-OCT-based 3D reconstructions had a high diagnostic accuracy for detecting regions exposed to proatherogenic low ESS identified on the IVUS-based 3D models, considered as the gold standard (receiver operator characteristic area under the curve: 94.9%). Conclusions: FD-OCT-based 3D coronary reconstruction provides anatomically correct models and permits reliable ESS computation. ESS assessment in combination with the superior definition of plaque characteristics by FD-OCT is expected to provide valuable insights into the effect of the haemodynamic environment on the development and destabilisation of high-risk plaques.
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The Durban World Congress Ethics Round Table Conference Report: I. Differences between withholding and withdrawing life-sustaining treatments.
J Crit Care
PUBLISHED: 06-30-2014
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Withholding life-sustaining treatments (WHLST) and withdrawing life-sustaining treatments (WDLST) occur in most intensive care units (ICUs) around the world to varying degrees.
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Review: current and new generation pneumococcal vaccines.
J. Infect.
PUBLISHED: 05-15-2014
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Pneumococcal polysaccharide vaccines (PPVs) and conjugate vaccines (PCVs), of which PPV23 and PCV13 are the current front runners, have had a significant, beneficial impact on public health. With regard to PPV23, there has been some debate, however, about its protective efficacy against all-cause pneumonia, as opposed to invasive pneumococcal disease, in high-risk cases. PCVs, on the other hand, have been included in many national immunisation programmes for prevention of severe pneumococcal disease in infants and young children, as well as for adults in various high-risk categories. Although innovative and effective, the protective efficacy of PCVs, the composition of which is based on the geographic prevalence and virulence of pneumococcal serotypes, is limited due to colonisation of the nasopharynx with non-vaccine serotypes. This phenomenon of serotype replacement has provided the impetus for development of new generation recombinant protein and whole cell pneumococcal vaccines with the potential to provide serotype-independent protection. In addition to an overview of the successes and limitations of PPVs and PCVs, this review is focused on emerging and pipeline protein-based and whole cell vaccines, preceded by a consideration of conserved pneumococcal virulence factors which are potential vaccine candidates.
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Factors associated with ceftriaxone nonsusceptibility of Streptococcus pneumoniae: analysis of South African national surveillance data, 2003 to 2010.
Antimicrob. Agents Chemother.
PUBLISHED: 03-31-2014
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It is important to monitor ?-lactam antimicrobial nonsusceptibility trends for Streptococcus pneumoniae to inform empirical treatment guidelines. In this study, we describe penicillin and ceftriaxone susceptibility trends using national laboratory-based pneumococcal surveillance data from 2003 to 2010. A sentinel enhanced-site patient subset (2009 to 2010) contributed to the risk factor and mortality analyses. We included 9,218 invasive pneumococcal disease (IPD) cases for trend analyses and 2,854 IPD cases for risk factor and mortality analyses. Overall, we detected no significant changes in penicillin (patients <5 years of age, P = 0.50; patients ? 5 years of age, P = 0.05) or ceftriaxone nonsusceptibility rates (patients <5 years of age, P = 0.21; patients ? 5 years of age, P = 0.60). Factors associated with ceftriaxone nonsusceptibility on multivariate analysis were an age of <5 years (<1 year of age: adjusted odds ratio [aOR], 2.87; 95% confidence interval [CI], 1.70 to 4.86; 1 to 4 years of age: aOR, 2.58; 95% CI, 1.53 to 4.35, versus 25 to 44 years of age), province (Gauteng [aOR, 2.46; 95% CI, 1.26 to 4.84], and Northern Cape [aOR, 4.52; 95% CI, 1.95 to 10.52] versus KwaZulu-Natal), ?-lactam use within 24 h preceding admission (aOR, 2.52; 95% CI, 1.41 to 4.53), and 13-valent vaccine serotypes (aOR, 51.64; 95% CI, 7.18 to 371.71). Among patients ? 5 years of age with meningitis who were treated according to current guidelines, HIV-infected patients (aOR, 2.94; 95% CI, 1.32 to 6.54) and patients infected with ceftriaxone-nonsusceptible isolates (aOR, 3.17; 95% CI, 1.27 to 7.89) had increased mortality rates. Among children <5 years of age with meningitis, mortality was increased in HIV-infected patients (aOR, 3.04; 95% CI, 1.40 to 6.56) but not in those with ceftriaxone-nonsusceptible isolates. Penicillin and ceftriaxone nonsusceptibility remained stable over the study period. Ceftriaxone nonsusceptibility was associated with increased mortality among patients ?5 years of age with meningitis. The introduction of a pneumococcal conjugate vaccine may reduce ceftriaxone-nonsusceptible meningitis.
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The Durban World Congress Ethics Round Table Conference Report: II. Withholding or withdrawing of treatment in elderly patients admitted to the intensive care unit.
J Crit Care
PUBLISHED: 02-19-2014
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Life-sustaining treatment (LST) limitation for elderly patients is highly controversial. In that context, it is useful to evaluate the attitudes to LST in the elderly among experienced intensive care unit (ICU) physicians with different backgrounds and cultures.
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Exposure of a 23F serotype strain of Streptococcus pneumoniae to cigarette smoke condensate is associated with selective upregulation of genes encoding the two-component regulatory system 11 (TCS11).
Biomed Res Int
PUBLISHED: 02-07-2014
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Alterations in whole genome expression profiles following exposure of the pneumococcus (strain 172, serotype 23F) to cigarette smoke condensate (160??g/mL) for 15 and 60?min have been determined using the TIGR4 DNA microarray chip. Exposure to CSC resulted in the significant (P<0.014-0.0006) upregulation of the genes encoding the two-component regulatory system 11 (TCS11), consisting of the sensor kinase, hk11, and its cognate response regulator, rr11, in the setting of increased biofilm formation. These effects of cigarette smoke on the pneumococcus may contribute to colonization of the airways by this microbial pathogen.
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The beta-2-adrenoreceptor agonists, formoterol and indacaterol, but not salbutamol, effectively suppress the reactivity of human neutrophils in vitro.
Mediators Inflamm.
PUBLISHED: 01-15-2014
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The clinical relevance of the anti-inflammatory properties of beta-2 agonists remains contentious possibly due to differences in their molecular structures and agonist activities. The current study has compared the effects of 3 different categories of ? 2-agonists, namely, salbutamol (short-acting), formoterol (long-acting) and indacaterol (ultra-long-acting), at concentrations of 1-1000?nM, with human blood neutrophils in vitro. Neutrophils were activated with either N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP, 1?µM) or platelet-activating factor (PAF, 200?nM) in the absence and presence of the ? 2-agonists followed by measurement of the generation of reactive oxygen species and leukotriene B4, release of elastase, and expression of the ? 2-integrin, CR3, using a combination of chemiluminescence, ELISA, colorimetric, and flow cytometric procedures respectively. These were correlated with alterations in the concentrations of intracellular cyclic-AMP and cytosolic Ca(2+). At the concentrations tested, formoterol and indacaterol caused equivalent, significant (P < 0.05 at 1-10?nM) dose-related inhibition of all of the pro-inflammatory activities tested, while salbutamol was much less effective (P < 0.05 at 100?nM and higher). Suppression of neutrophil reactivity was accompanied by elevations in intracellular cAMP and accelerated clearance of Ca(2+) from the cytosol of activated neutrophils. These findings demonstrate that ? 2-agonists vary with respect to their suppressive effects on activated neutrophils.
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Recent advances in our understanding of Streptococcus pneumoniae infection.
F1000Prime Rep
PUBLISHED: 01-01-2014
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A number of significant challenges remain with regard to the diagnosis, treatment, and prevention of infections with Streptococcus pneumoniae (pneumococcus), which remains the most common bacterial cause of community-acquired pneumonia. Although this infection is documented to be extremely common in younger children and in older adults, the burden of pneumonia it causes is considerably underestimated, since the incidence statistics are derived largely from bacteremic infections, because they are easy to document, and yet the greater burden of pneumococcal pneumonias is non-invasive. It has been estimated that for every bacteremic pneumonia that is documented, three non-bacteremic infections occur. Management of these infections is potentially complicated by the increasing resistance of the isolates to the commonly used antibiotics. Furthermore, it is well recognized that despite advances in medical care, the mortality of bacteremic pneumococcal pneumonia has remained largely unchanged over the past 50 years and averages approximately 12%. Much recent research interest in the field of pneumococcal infections has focused on important virulence factors of the organism, on improved diagnostic and prognostication tools, on defining risk factors for death, on optimal treatment strategies involving both antibiotics and adjunctive therapies, and on disease prevention. It is hoped that through these endeavors the outlook of pneumococcal infections will be improved.
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Lack of association of the caspase-12 long allele with community-acquired pneumonia in people of African descent.
PLoS ONE
PUBLISHED: 01-01-2014
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Community-acquired pneumonia (CAP) is a common cause of sepsis. Active full-length caspase-12 (CASP12L), confined to the people of African descent, has been associated with increased susceptibility to and mortality from severe sepsis. The objective of this study was to determine whether CASP12L was a marker for susceptibility and/or severity of CAP. We examined three CAP cohorts and two control populations: 241 adult Memphis African American CAP patients, 443 pediatric African American CAP patients, 90 adult South African CAP patients, 120 Memphis healthy adult African American controls and 405 adult Chicago African American controls. Clinical outcomes including mortality, acute respiratory distress syndrome (ARDS), septic shock or severe sepsis, need for mechanical ventilation, and S. pneumoniae bacteremia. Neither in the three individual CAP cohorts nor in the combined CAP cohorts, was mortality in CASP12L carriers significantly different from that in non-CASP12L carriers. No statistically significant association between genotype and any measures of CAP severity was found in any cohort. We conclude that the functional CASP12L allele is not a marker for susceptibility and/or severity of CAP.
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Synergistic effect of local endothelial shear stress and systemic hypercholesterolemia on coronary atherosclerotic plaque progression and composition in pigs.
Int. J. Cardiol.
PUBLISHED: 08-25-2013
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Systemic risk factors and local hemodynamic factors both contribute to coronary atherosclerosis, but their possibly synergistic inter-relationship remains unknown. The purpose of this natural history study was to investigate the combined in-vivo effect of varying levels of systemic hypercholesterolemia and local endothelial shear stress (ESS) on subsequent plaque progression and histological composition.
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The prevalence of smoking and the knowledge of smoking hazards and smoking cessation strategies among HIV- positive patients in Johannesburg, South Africa.
S. Afr. Med. J.
PUBLISHED: 08-20-2013
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Background. While the detrimental effects of smoking among HIV-positive patients have been well documented, there is a paucity of data regarding cigarette smoking prevalence among these patients in South Africa (SA).Objectives. To establish the frequency, demographics, knowledge of harmful effects, and knowledge of smoking cessation strategies among HIV-positive patients in Johannesburg, SA.Methods. We conducted a prospective cross-sectional survey using a structured questionnaire to interview HIV-positive patients attending the HIV Clinic at the Charlotte Maxeke Johannesburg Academic Hospital between 1 July and 31 October 2011.Results. Of 207 HIV-positive patients attending an antiretroviral therapy (ART) roll-out clinic, 31 (15%) were current smokers (23.2% of males and 7.4% of females) and a further 45 (21.7%) were ex-smokers. Most of the current smokers (30/31 patients) indicated their wish to quit smoking, and among the group as a whole, most patients were aware of the general (82.1%) and HIV-related (77.8%) risks of smoking and of methods for quitting smoking. Despite this, however, most (62.3%) were not aware of who they could approach for assistance and advice.Conclusions. Given the relatively high prevalence of current and ex-smokers among HIV-positive patients, there is a need for the introduction of smoking-cessation strategies and assistance at ART roll-out clinics in SA. 
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Thin-capped atheromata with reduced collagen content in pigs develop in coronary arterial regions exposed to persistently low endothelial shear stress.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 05-02-2013
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The mechanisms promoting the focal formation of rupture-prone coronary plaques in vivo remain incompletely understood. This study tested the hypothesis that coronary regions exposed to low endothelial shear stress (ESS) favor subsequent development of collagen-poor, thin-capped plaques.
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A new methodology for accurate 3-dimensional coronary artery reconstruction using routine intravascular ultrasound and angiographic data: implications for widespread assessment of endothelial shear stress in humans.
EuroIntervention
PUBLISHED: 04-24-2013
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Aims: To develop and validate a new methodology that allows accurate 3-dimensional (3-D) coronary artery reconstruction using standard, simple angiographic and intravascular ultrasound (IVUS) data acquired during routine catheterisation enabling reliable assessment of the endothelial shear stress (ESS) distribution. Methods and results: Twenty-two patients (22 arteries: 7 LAD; 7 LCx; 8 RCA) who underwent angiography and IVUS examination were included. The acquired data were used for 3-D reconstruction using a conventional method and a new methodology that utilised the luminal 3-D centreline to place the detected IVUS borders and anatomical landmarks to estimate their orientation. The local ESS distribution was assessed by computational fluid dynamics. In corresponding consecutive 3 mm segments, lumen, plaque and ESS measurements in the 3-D models derived by the centreline approach were highly correlated to those derived from the conventional method (r>0.98 for all). The centreline methodology had a 99.5% diagnostic accuracy for identifying segments exposed to low ESS and provided similar estimations to the conventional method for the association between the change in plaque burden and ESS (centreline method: slope= -1.65%/Pa, p=0.078; conventional method: slope= -1.64%/Pa, p=0.084; p =0.69 for difference between the two methodologies). Conclusions: The centreline methodology provides geometrically correct models and permits reliable ESS computation. The ability to utilise data acquired during routine coronary angiography and IVUS examination will facilitate clinical investigation of the role of local ESS patterns in the natural history of coronary atherosclerosis.
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Cigarette smoking and mechanisms of susceptibility to infections of the respiratory tract and other organ systems.
J. Infect.
PUBLISHED: 04-23-2013
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The predisposition of cigarette smokers for development of oral and respiratory infections caused by microbial pathogens is well recognised, with those infected with the human immunodeficiency virus (HIV) at particularly high risk. Smoking cigarettes has a suppressive effect on the protective functions of airway epithelium, alveolar macrophages, dendritic cells, natural killer (NK) cells and adaptive immune mechanisms, in the setting of chronic systemic activation of neutrophils. Cigarette smoke also has a direct effect on microbial pathogens to promote the likelihood of infective disease, specifically promotion of microbial virulence and antibiotic resistance. In addition to interactions between smoking and HIV infection, a number of specific infections/clinical syndromes have been associated epidemiologically with cigarette smoking, including those of the upper and lower respiratory tract, gastrointestinal tract, central nervous and other organ systems. Smoking cessation benefits patients in many ways, including reduction of the risk of infectious disease.
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Chronic rhinitis in South Africa: update 2013.
S. Afr. Med. J.
PUBLISHED: 04-18-2013
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The term rhinitis implies inflammation of the lining of the nose. Characteristic symptoms are a blocked nose, anterior and posterior rhinorrhea, sneezing and itching. Not all cases of chronic rhinitis have an allergic basis. Chronic non-allergic rhinitis is defined as a condition where ongoing rhinitic symptoms are present for many months (as for persistent allergic rhinitis) but there is no IgE basis. Many common conditions may present as chronic rhinitis, which will need to be investigated and managed on their own merits. Not all cases of chronic rhinitis respond to allergic rhinitis therapy: continued attempts to manage chronic rhinitis as allergic rhinitis may be hampered by pathophysiological conditions where other specific therapy may be required. Chronic rhinitis impacts on patient quality of life, and therefore therapy is important. Managing patients with chronic rhinitis requires attention to patient education in order to achieve the maximal therapeutic benefit of medication. This update is intended to provide clinicians with a sound basis for management of a common condition.
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HIV-associated bacterial pneumonia.
Clin. Chest Med.
PUBLISHED: 04-08-2013
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Community-acquired bacterial pneumonia (CAP) remains one of the most common opportunistic infections in patients who are infected with the human immunodeficiency virus (HIV). The risk of CAP increases as the CD4 cell count decreases. The common bacterial pathogens that cause CAP in HIV-infected persons are similar to those in HIV-uninfected individuals, with the pneumococcus being the most common pathogen. Prevention of CAP remains critical and necessitates a comprehensive approach addressing, among many other factors, cigarette smoking cessation strategies, antiretroviral therapy adherence, and immunization against those infections for which effective vaccinations are available.
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Pneumococcal disease in the Arabian Gulf: recognizing the challenge and moving toward a solution.
J Infect Public Health
PUBLISHED: 03-04-2013
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Pneumococcal disease has substantial incidence, morbidity and mortality in older adults. Decreased birth rates and longer lifespans indicate that the global population is aging, although rates of aging differ between countries [1]. In 2010, the proportion of the population aged >60 years in the general Arab Region was 7%, and this proportion is expected to rise to 19% by 2050 for the region as a whole [2]; the United Nations estimates for the individual countries of the Arabian Gulf by 2050 are 25.7%, 24.9%, 20.7%, 26.7% and 10.5% in the Kuwait, Bahrain, Qatar, United Arab Emirates (UAE) and Oman, respectively, which are comparable to the 26.9% predicted for the USA and lower than that predicted in European countries, in which the 2050 estimates are 32.7%, 34.0% and 38.1% for France, the UK and Germany, respectively [1]. Globally and in the Gulf Region, pneumococcal disease is an increasingly important public health burden in the elderly. The burden of pneumococcal disease can be reduced by effective vaccination programs, but the recommendations on pneumococcal vaccination in adults vary widely. The major barriers to vaccine implementation among healthcare professionals are an incomplete awareness of pneumococcal disease and the vaccination options in adults. The Gulf Advocate Group calls for healthcare providers in the countries of the Arabian Gulf (Kuwait, Bahrain, Qatar, United Arab Emirates and Oman) to support awareness and education programs about adult pneumococcal disease, particularly in high-risk groups such as those >65 years of age, those with type 2 diabetes mellitus, hematological malignancy, organ and bone marrow transplantation or chronic kidney or lung diseases and pilgrims undertaking the Hajj to improve pneumococcal disease surveillance and optimize and disseminate recommendations for adult vaccination. The Gulf Advocate Group recommends following the U.S. Centers for Disease Control and Prevention (CDC) guidelines for pneumococcal vaccination [3,4].
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Using student opinion and design inputs to develop an informed university foodservice menu.
Appetite
PUBLISHED: 01-17-2013
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The potential for Universities and Colleges to be settings that promote health and wellbeing has become the subject for debate where the role of foodservice has been acknowledged as influential. The aim of this research was to evaluate an effective design to promote healthy selections from university foodservice menus. The research was designed around a grounded theory approach utilizing semiological prompts based on different existing nutrition labeling schemes. A total of 39 students (17 male, 22 female) participated in seven focus groups at Montclair State University, US. The participants of this study clearly called for nutrition labeling on college menus and a prototype design had been agreed. The students also itemized five nutrients they wanted listed in a Traffic Light system of colors and then quantified on the menu: calories, sodium, sugar, fat and carbohydrates, plus beneficial ingredients or nutrients for display in menu icons. The nutrients and display order varies somewhat from industry and government standards, though the student recommendations are suggestive of common understandings of published nutrient guidelines. Students have a stake in how menu information is presented on campus and their opinions could positively impact the general selection of healthy foods.
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Relation of distribution of coronary blood flow volume to coronary artery dominance.
Am. J. Cardiol.
PUBLISHED: 01-17-2013
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Coronary artery dominance influences the amount and anatomic location of myocardium that is perfused by the left or right coronary circulation. However, it is unknown whether coronary artery dominance also influences the distribution of coronary blood flow volume. The aim of this study was to evaluate volumetric coronary blood flow in 1,322 vessels from 496 patients in the Prediction of Progression of Coronary Artery Disease and Clinical Outcomes Using Vascular Profiling of Endothelial Shear Stress and Arterial Wall Morphology (PREDICTION) study. Patients were divided into 2 groups (right-dominant and left-dominant or balanced circulation). Coronary blood flow volume was calculated by coronary segment volume measurement using angiography and intravascular ultrasound and the contrast transit time through the segment. Coronary blood flow in the left circumflex coronary artery was significantly higher in left-dominant or balanced circulation than in right-dominant circulation (113 ± 43 vs 72 ± 37 ml/min, p <0.001), whereas flow in the right coronary artery was significantly lower in left-dominant or balanced circulation than in right-dominant circulation (56 ± 40 vs 113 ± 49 ml/min, p = 0.003). There was no significant difference in the left anterior descending coronary artery. In conclusion, coronary artery dominance has an impact on coronary blood flow volume in the left circumflex and right coronary arteries but not in the left anterior descending coronary artery. These findings suggest that the extent of myocardial perfusion area is associated with coronary blood flow volume.
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A reliable and effective method of DNA isolation from old human blood paper cards.
Springerplus
PUBLISHED: 01-01-2013
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Blood paper cards provide an effective DNA storage method. In this study, we used three DNA dissolving reagents (Tris-EDTA [TE] buffer, Tris-HCl buffer, and water) and one common commercially available kit (DN131 from MRC Inc) to elute DNA from 105 human blood paper cards collected up to 10 years ago. These DNA samples were used as templates for amplification of a single nucleotide polymorphism (SNP, C125T) region of human caspase-12 by PCR and a specific Taqman genotyping assay using the same amount of DNA. We show that DNA isolated by Tris-HCl buffer has higher yield and quality in comparison to DN131 solution. PCR success rate to amplify caspase-12 C125T SNP using Tris-HCl is comparable to the method using DN131 (89.5% vs 87.6%). The Taqman genotyping success rate using Tris-HCl is higher than using DN131 (81.9% vs 70.5%). Using TE or water, PCR success rates are lower than using DN131 (73.3% [TE]; 72.4% [H2O]), but Taqman genotyping success rates are comparable to the method using DN131 (70.5% [TE]; 79.1% [H2O]). We concluded that using Tris-HCl is a reliable and effective method to elute DNA from old human blood paper cards. The crude DNA isolated by Tris-HCl can be used to study genetic polymorphisms in human populations.
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Can the anti-inflammatory activities of ?2-agonists be harnessed in the clinical setting?
Drug Des Devel Ther
PUBLISHED: 01-01-2013
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Beta2-adrenoreceptor agonists (?2-agonists) are primarily bronchodilators, targeting airway smooth muscle and providing critical symptomatic relief in conditions such as bronchial asthma and chronic obstructive pulmonary disease. These agents also possess broad-spectrum, secondary, anti-inflammatory properties. These are mediated largely, though not exclusively, via interactions with adenylyl cyclase-coupled ?2-adrenoreceptors on a range of immune and inflammatory cells involved in the immunopathogenesis of acute and chronic inflammatory disorders of the airways. The clinical relevance of the anti-inflammatory actions of ?2-agonists, although often effective in the experimental setting, remains contentious. The primary objectives of the current review are: firstly, to assess the mechanisms, both molecular and cell-associated, that may limit the anti-inflammatory efficacy of ?2-agonists; secondly, to evaluate pharmacological strategies, several of which are recent and innovative, that may overcome these limitations. These are preceded by a consideration of the various types of ?2-agonists, their clinical applications, and spectrum of anti-inflammatory activities, particularly those involving adenosine 3,5-cyclic adenosine monophosphate-activated protein kinase-mediated clearance of cytosolic calcium, and altered gene expression in immune and inflammatory cells.
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Evaluation of artery visualizations for heart disease diagnosis.
IEEE Trans Vis Comput Graph
PUBLISHED: 10-29-2011
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Heart disease is the number one killer in the United States, and finding indicators of the disease at an early stage is critical for treatment and prevention. In this paper we evaluate visualization techniques that enable the diagnosis of coronary artery disease. A key physical quantity of medical interest is endothelial shear stress (ESS). Low ESS has been associated with sites of lesion formation and rapid progression of disease in the coronary arteries. Having effective visualizations of a patients ESS data is vital for the quick and thorough non-invasive evaluation by a cardiologist. We present a task taxonomy for hemodynamics based on a formative user study with domain experts. Based on the results of this study we developed HemoVis, an interactive visualization application for heart disease diagnosis that uses a novel 2D tree diagram representation of coronary artery trees. We present the results of a formal quantitative user study with domain experts that evaluates the effect of 2D versus 3D artery representations and of color maps on identifying regions of low ESS. We show statistically significant results demonstrating that our 2D visualizations are more accurate and efficient than 3D representations, and that a perceptually appropriate color map leads to fewer diagnostic mistakes than a rainbow color map.
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Calcium-dependent potentiation of the pro-inflammatory functions of human neutrophils by tigecycline in vitro.
J. Antimicrob. Chemother.
PUBLISHED: 10-18-2011
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Tigecycline is the prototype of the recently introduced, intravenously administered glycylcycline class of antibiotics, developed in response to the increasing problem of antibiotic resistance in Gram-positive bacteria, especially Staphylococcus aureus, as well as Gram-negative bacteria and anaerobes. However, relatively little is known about the immunomodulatory potential of tigecycline, specifically its interactions with human neutrophils. In the current study we investigated the effects of tigecycline at therapeutically relevant concentrations and greater (0.625-10 mg/L) on alterations in cytosolic Ca(2+) concentrations, generation of antimicrobial reactive oxygen species (ROS) and release of granule proteases [elastase, matrix metalloproteinase-8 (MMP-8) and matrix metalloproteinase-9 (MMP-9)] by human blood neutrophils activated with the chemoattractant N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP; 1 ?M).
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Factors influencing the food choices and eating habits of restaurant chefs in northern New Jersey: a pilot study.
Ecol Food Nutr
PUBLISHED: 09-06-2011
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This study was conducted to understand the factors influencing the food habits of restaurant chefs in northern New Jersey. Data was collected from participants (N = 12) using dietary recalls, and semi-structured interviews based on the socio-ecological model. Dietary recall analysis revealed multiple nutritional intake hazards including skipping meals, and substitution of foods rich in fats and sugar for fruits and vegetables, and increased consumption of alcohol. Qualitative data analysis revealed that their food habits were influenced by a repertoire of individual, organizational, and interpersonal factors. The relevance of these findings to nutrition intervention programs for this population is discussed.
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Bronchiectasis: new approaches to diagnosis and management.
Clin. Chest Med.
PUBLISHED: 08-27-2011
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Non-cystic fibrosis (CF) bronchiectasis is a common, potentially serious, condition. Further investigations should be performed in an attempt to identify the underlying cause because it may lead to a change in therapy and have significant prognostic implications. MRI is being investigated as a radiation free alternative to high-resolution CT scan of the chest. Many of the treatment recommendations for non-CF bronchiectasis have not been studied in randomized controlled trials but have been extrapolated from the management recommendations for CF. Studies are beginning to inform decisions regarding the management of non-CF bronchiectasis, and an understanding of the best treatment options is beginning to emerge.
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The effect of statins on high-risk atherosclerotic plaque associated with low endothelial shear stress.
Curr. Opin. Lipidol.
PUBLISHED: 08-16-2011
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Low endothelial shear stress (ESS) plays an important role in the progression and severity of atherosclerotic lesions. As 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) appear to stabilize plaque, it would be valuable to understand how statins affect the nature of lesions in the proatherogenic and proinflammatory environment of low ESS and the effect of statins on that atherosclerotic process. The purpose of this review is to summarize the relationship among low ESS, high-risk plaque and statins.
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Increased risk of death in human immunodeficiency virus-infected children with pneumococcal meningitis in South Africa, 2003-2005.
Pediatr. Infect. Dis. J.
PUBLISHED: 07-30-2011
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Pneumococcal disease is a major global cause of morbidity and mortality. This study evaluated risk factors for mortality in children with pneumococcal meningitis and other invasive pneumococcal diseases (IPD).
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An exploratory investigation of the risk of pathogenic contamination at selected New Jersey skilled nursing and assisted living residences.
Perspect Public Health
PUBLISHED: 04-06-2011
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Elderly populations are vulnerable and generally have the highest incidence of morbidity related to foodborne illnesses and this problem may be aggravated in institutional or communal eating settings. The objective of this investigation was to examine the potential risk of food contamination in selected skilled nursing and assisted-living residences using bacteria indicator tests for Listeria spp., Salmonella spp. and E. coli. Of the 45 samples tested for Listeria, three (6.67 %) were found to be contaminated; Salmonella or E. coli contamination was not found in any of the samples. Reported incidents of foodborne illnesses are increasing in institutional settings, therefore there is an urgent need to collect information on practices that can prevent bacterial contamination of food served in elderly residences.
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CURB-65, PSI, and APACHE II to assess mortality risk in patients with severe sepsis and community acquired pneumonia in PROWESS.
J Intensive Care Med
PUBLISHED: 02-23-2011
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Patients with community-acquired pneumonia (CAP) comprised 35.6% of the overall phase 3 Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study and 33.1% of the placebo arm. We investigated the use of CURB-65, the Pneumonia Severity Index (PSI), and Acute Physiology and Chronic Health Evaluation II (APACHE II) prediction scores to identify the CAP population from the PROWESS placebo arm at the greatest mortality risk.
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Bacteraemic pneumococcal pneumonia: current therapeutic options.
Drugs
PUBLISHED: 02-01-2011
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Streptococcus pneumoniae is the major bacterial cause of pneumonia, meningitis and otitis media, and continues to be associated with significant morbidity and mortality in individuals both in the developed and developing world. Management of these infections is potentially complicated by the emergence of resistance of this pathogen to many of the commonly used first-line antimicrobial agents. A number of significant risk factors exist that predispose to the occurrence of pneumococcal pneumonia, including lifestyle factors, such as exposure to cigarette smoke, as well as underlying medical conditions, such as HIV infection. Several of these predisposing factors also enhance the risk of bacteraemia. The initial step in the pathogenesis of pneumococcal infections is the occurrence of nasopharyngeal colonization, which may be followed by invasive disease. The pneumococcus has a myriad of virulence factors that contribute to these processes, including a polysaccharide capsule, various cell surface structures, toxins and adhesins, and the microorganism is also an effective producer of biofilm. Antibacterial resistance is emerging in this microorganism and affects all the various classes of drugs, including the ?-lactams, the macrolides and the fluoroquinolones. Even multidrug resistance is occurring. Pharmacokinetic/pharmacodynamic parameters allow us to understand the relationship between the presence of antibacterial resistance in the pneumococcus and the outcome of pneumococcal infections treated with the different antibacterial classes. Furthermore, these parameters also allow us to predict which antibacterials are most likely to be effective in the management of pneumococcal infections and the correct dosages to use. Most guidelines for the management of community-acquired pneumonia recommend the use of either a ?-lactam/macrolide combination or fluoroquinolone monotherapy for the empirical therapy of more severe hospitalized cases with pneumonia, including the subset of cases with pneumococcal bacteraemia. There are a number of adjunctive therapies that have been studied for use in combination with standard antibacterial therapy, in an attempt to decrease the high mortality, of which macrolides in particular, corticosteroids and cyclic adenosine monophosphate-elevating agents appear potentially most useful.
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Augmented expression and activity of extracellular matrix-degrading enzymes in regions of low endothelial shear stress colocalize with coronary atheromata with thin fibrous caps in pigs.
Circulation
PUBLISHED: 01-31-2011
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Background- The molecular mechanisms that determine the localized formation of thin-capped atheromata in the coronary arteries remain unknown. This study tested the hypothesis that low endothelial shear stress augments the expression of matrix-degrading proteases and thereby promotes the formation of thin-capped atheromata. Methods and Results- Intravascular ultrasound-based, geometrically correct 3-dimensional reconstruction of the coronary arteries of 12 swine was performed in vivo 23 weeks after initiation of diabetes mellitus and a hyperlipidemic diet. Local endothelial shear stress was calculated in plaque-free subsegments of interest (n=142) with computational fluid dynamics. At week 30, the coronary arteries (n=31) were harvested and the same subsegments were identified. The messenger RNA and protein expression and elastolytic activity of selected elastases and their endogenous inhibitors were assessed. Subsegments with low preceding endothelial shear stress at week 23 showed reduced endothelial coverage, enhanced lipid accumulation, and intense infiltration of activated inflammatory cells at week 30. These lesions showed increased expression of messenger RNAs encoding matrix metalloproteinase-2, -9, and -12, and cathepsins K and S relative to their endogenous inhibitors and increased elastolytic activity. Expression of these enzymes correlated positively with the severity of internal elastic lamina fragmentation. Thin-capped atheromata developed in regions with lower preceding endothelial shear stress and had reduced endothelial coverage, intense lipid and inflammatory cell accumulation, enhanced messenger RNA expression and elastolytic activity of MMPs and cathepsins, and severe internal elastic lamina fragmentation. Conclusions- Low endothelial shear stress induces endothelial discontinuity and accumulation of activated inflammatory cells, thereby augmenting the expression and activity of elastases in the intima and shifting the balance with their inhibitors toward matrix breakdown. Our results provide new insight into the mechanisms of regional formation of plaques with thin fibrous caps.
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Montelukast: more than a cysteinyl leukotriene receptor antagonist?
ScientificWorldJournal
PUBLISHED: 12-21-2010
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The prototype cysteinyl leukotriene receptor antagonist, montelukast, is generally considered to have a niche application in the therapy of exercise- and aspirin-induced asthma. It is also used as add-on therapy in patients whose asthma is poorly controlled with inhaled corticosteroid monotherapy, or with the combination of a long-acting beta(2)-agonist and an inhaled corticosteroid. Recently, however, montelukast has been reported to possess secondary anti-inflammatory properties, apparently unrelated to conventional antagonism of cysteinyl leukotriene receptors. These novel activities enable montelukast to target eosinophils, monocytes, and, in particular, the corticosteroid-insensitive neutrophil, suggesting that this agent may have a broader spectrum of anti-inflammatory activities than originally thought. If so, montelukast is potentially useful in the chemotherapy of intermittent asthma, chronic obstructive pulmonary disease, cystic fibrosis, and viral bronchiolitis, which, to a large extent, involve airway epithelial cell/neutrophil interactions. The primary objective of this mini-review is to present evidence for the cysteinyl leukotriene-independent mechanisms of action of montelukast and their potential clinical relevance.
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In-vivo assessment of the natural history of coronary atherosclerosis: vascular remodeling and endothelial shear stress determine the complexity of atherosclerotic disease progression.
Curr. Opin. Cardiol.
PUBLISHED: 09-15-2010
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Atherosclerotic disease progression is determined by localized plaque growth, which is induced by systemic and local hemodynamic factors, and the nature of the wall remodeling response. The purpose of this review is to summarize the processes underlying the heterogeneity of coronary atherosclerosis progression in relation to the local hemodynamic and arterial remodeling environment.
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Natural history of experimental coronary atherosclerosis and vascular remodeling in relation to endothelial shear stress: a serial, in vivo intravascular ultrasound study.
Circulation
PUBLISHED: 05-03-2010
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The natural history of heterogeneous atherosclerotic plaques and the role of local hemodynamic factors throughout their development are unknown. We performed a serial study to assess the role of endothelial shear stress (ESS) and vascular remodeling in the natural history of coronary atherosclerosis.
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Regulation of heparanase expression in coronary artery disease in diabetic, hyperlipidemic swine.
Atherosclerosis
PUBLISHED: 01-14-2010
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Enzymatic degradation of the extracellular matrix is known to be powerful regulator of atherosclerosis. However, little is known about the enzymatic regulation of heparan sulfate proteoglycans (HSPGs) during the formation and progression of atherosclerotic plaques.
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The role of low endothelial shear stress in the conversion of atherosclerotic lesions from stable to unstable plaque.
Curr. Opin. Cardiol.
PUBLISHED: 10-08-2009
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Local hemodynamic factors are major determinants of the natural history of individual atherosclerotic plaque progression in coronary arteries. The purpose of this review is to summarize the role of low endothelial shear stress (ESS) in the transition of early, stable plaques to high-risk atherosclerotic lesions.
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New advances in cardiac computed tomography.
Curr. Opin. Cardiol.
PUBLISHED: 09-16-2009
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Applications of computed tomography (CT) for cardiac imaging have evolved rapidly with the introduction of new hardware. These advances require a technology update, particularly as the new scanners have novel, unique features. This review focuses on post-64 generation CT scanner capabilities and novel clinical research applications enabled by these technologies.
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Attenuation of inflammation and expansive remodeling by Valsartan alone or in combination with Simvastatin in high-risk coronary atherosclerotic plaques.
Atherosclerosis
PUBLISHED: 08-26-2009
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We investigated the role of Valsartan (V) alone or in combination with Simvastatin (S) on coronary atherosclerosis and vascular remodeling, and tested the hypothesis that V or V/S attenuate the pro-inflammatory effect of low endothelial shear stress (ESS).
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Montelukast inhibits neutrophil pro-inflammatory activity by a cyclic AMP-dependent mechanism.
Br. J. Pharmacol.
PUBLISHED: 05-19-2009
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The objective of this study was to characterize the effects of the cysteinyl leukotriene receptor antagonist, montelukast (0.1-2 micromol x L(-1)), on Ca(2+)-dependent pro-inflammatory activities, cytosolic Ca(2+) fluxes and intracellular cAMP in isolated human neutrophils activated with the chemoattractants, N-formyl-L-methionyl-L-leucyl-L-phenylalanine (1 micromol x L(-1)) and platelet-activating factor (200 nmol x L(-1)).
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Therapy for pneumococcal bacteremia: monotherapy or combination therapy?
Curr. Opin. Infect. Dis.
PUBLISHED: 03-12-2009
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The issue of whether the outcome of bacteremic pneumococcal infections is improved with the use of combination antibiotic therapy versus monotherapy is still not resolved. This review highlights recent studies that have addressed this issue.
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New insights into pneumococcal disease.
Respirology
PUBLISHED: 03-11-2009
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Streptococcus pneumoniae (pneumococcus) remains a common cause of disease and death throughout the world. Despite considerable research into various aspects of this infection, there still remain a number of unresolved issues, as well as considerable ongoing controversies, particularly with regard to its optimal management. Among the risk factors for pneumococcal pneumonia, cigarette smoking has been shown to play a major role, more recently among HIV-infected individuals. Considerable recent research has focused on determining the role of the various protein virulence factors in disease pathogenesis. Among the ongoing controversies has been an appreciation of the true impact of antimicrobial resistance on the outcome of pneumococcal infections, as well an understanding of the role of combination antibiotic therapy in the more severely ill hospitalized cases. An important advance in the prevention of pneumococcal infections has been the introduction of the pneumococcal protein conjugate vaccine.
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Clinical outcomes of HIV-infected patients hospitalized with bacterial community-acquired pneumonia.
Int. J. Infect. Dis.
PUBLISHED: 02-10-2009
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There are limited and conflicting data on clinical outcomes of community-acquired pneumonia (CAP) among HIV-infected patients.
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Systems for the management of respiratory disease in primary care--an international series: South Africa.
Prim Care Respir J
PUBLISHED: 01-29-2009
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Progress to democracy in South Africa in 1994 was followed by the adoption of a primary health care approach with free access for all. State health facilities serve 80% of the population, and a private sector comprising general practitioners, specialists and private hospitals, serves the remainder. NATIONAL POLICIES AND MODELS: There are national prescribing guidelines for common diseases, and these specify the medicines on the Essential Drugs List that are available at primary care facilities for respiratory diseases including asthma, COPD, pneumonia and tuberculosis.
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Emergence of OXA-48 and OXA-181 carbapenemases among Enterobacteriaceae in South Africa and evidence of in vivo selection of colistin resistance as a consequence of selective decontamination of the gastrointestinal tract.
J. Clin. Microbiol.
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This study reports on the emergence of OXA-48-like carbapenemases among isolates of Enterobacteriaceae in South Africa. In addition, the emergence during therapy of a colistin-resistant OXA-181-producing Klebsiella pneumoniae isolate was documented following selective digestive tract decontamination with oral colistin, which is therefore strongly discouraged.
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Causes of death on antiretroviral therapy: a post-mortem study from South Africa.
PLoS ONE
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Mortality in the first months of antiretroviral therapy (ART) is a significant clinical problem in sub-Saharan Africa. To date, no post-mortem study has investigated the causes of mortality in these patients.
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Pathogen- and host-directed anti-inflammatory activities of macrolide antibiotics.
Mediators Inflamm.
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Macrolide antibiotics possess several, beneficial, secondary properties which complement their primary antimicrobial activity. In addition to high levels of tissue penetration, which may counteract seemingly macrolide-resistant bacterial pathogens, these agents also possess anti-inflammatory properties, unrelated to their primary antimicrobial activity. Macrolides target cells of both the innate and adaptive immune systems, as well as structural cells, and are beneficial in controlling harmful inflammatory responses during acute and chronic bacterial infection. These secondary anti-inflammatory activities of macrolides appear to be particularly effective in attenuating neutrophil-mediated inflammation. This, in turn, may contribute to the usefulness of these agents in the treatment of acute and chronic inflammatory disorders of both microbial and nonmicrobial origin, predominantly of the airways. This paper is focused on the various mechanisms of macrolide-mediated anti-inflammatory activity which target both microbial pathogens and the cells of the innate and adaptive immune systems, with emphasis on their clinical relevance.
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Shear-activated nanotherapeutics for drug targeting to obstructed blood vessels.
Science
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Obstruction of critical blood vessels due to thrombosis or embolism is a leading cause of death worldwide. Here, we describe a biomimetic strategy that uses high shear stress caused by vascular narrowing as a targeting mechanism--in the same way platelets do--to deliver drugs to obstructed blood vessels. Microscale aggregates of nanoparticles were fabricated to break up into nanoscale components when exposed to abnormally high fluid shear stress. When coated with tissue plasminogen activator and administered intravenously in mice, these shear-activated nanotherapeutics induce rapid clot dissolution in a mesenteric injury model, restore normal flow dynamics, and increase survival in an otherwise fatal mouse pulmonary embolism model. This biophysical strategy for drug targeting, which lowers required doses and minimizes side effects while maximizing drug efficacy, offers a potential new approach for treatment of life-threatening diseases that result from acute vascular occlusion.
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Endothelial shear stress in the evolution of coronary atherosclerotic plaque and vascular remodelling: current understanding and remaining questions.
Cardiovasc. Res.
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The heterogeneity of plaque formation, the vascular remodelling response to plaque formation, and the consequent phenotype of plaque instability attest to the extraordinarily complex pathobiology of plaque development and progression, culminating in different clinical coronary syndromes. Atherosclerotic plaques predominantly form in regions of low endothelial shear stress (ESS), whereas regions of moderate/physiological and high ESS are generally protected. Low ESS-induced compensatory expansive remodelling plays an important role in preserving lumen dimensions during plaque progression, but when the expansive remodelling becomes excessive promotes continued influx of lipids into the vessel wall, vulnerable plaque formation and potential precipitation of an acute coronary syndrome. Advanced plaques which start to encroach into the lumen experience high ESS at their most stenotic region, which appears to promote plaque destabilization. This review describes the role of ESS from early atherogenesis to early plaque formation, plaque progression to advanced high-risk stenotic or non-stenotic plaque, and plaque destabilization. The critical implication of the vascular remodelling response to plaque growth is also discussed. Current developments in technology to characterize local ESS and vascular remodelling in vivo may provide a rationale for innovative diagnostic and therapeutic strategies for coronary patients that aim to prevent clinical coronary syndromes.
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The spread of carbapenem-resistant Enterobacteriaceae in South Africa: risk factors for acquisition and prevention.
S. Afr. Med. J.
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New, effective antibiotics are only likely to become available in 15 - 20 years. To prevent deaths from untreatable Gram-negative infections in South Africa, the rights of any doctor, whether in general or in hospital practice, to indiscriminately prescribe whatever antibiotic they wish, and in whatever fashion, must be challenged. Furthermore, although prevention of the emergence and subsequent spread of carbapenem-resistant Enterobacteriaceae (CRE) has focused on acute and chronic care facilities and inter alia on antibiotic exposure in these institutions, CRE may soon become an issue within entire communities, highlighting a role for public health authorities in CRE prevention efforts.
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Effects of cigarette smoke condensate on pneumococcal biofilm formation and pneumolysin.
Eur. Respir. J.
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Although the well-recognised predisposition of cigarette smokers to the development of severe pneumococcal disease may be attributable to impairment of local host defences, less is known about the direct effects of smoke exposure on airway pathogens, or their virulence factors. In the current study, we have investigated the effects of cigarette smoke condensate (CSC) on biofilm formation by Streptococcus pneumoniae, and on the pore-forming activity of its major toxin, pneumolysin. Biofilm formation following exposure of the pneumococcus to CSC (20-160 ?g·mL(-1)) was measured using a crystal violet-based spectrophotometric procedure, while the pore-forming activity of recombinant pneumolysin was determined by a fura-2/acetoxymethyl ester-based spectrofluorimetric procedure to monitor the uptake of extracellular Ca(2+) by isolated human neutrophils. Exposure of the pneumococcus or pneumolysin to CSC resulted in significant dose-related augmentation of biofilm formation (p?0.05 at 80 and 160 ?g·mL(-1)) and substantial attenuation of the pore-forming interactions of pneumolysin, respectively. Augmentation of biofilm formation and inactivation of pneumolysin as a consequence of smoking are likely to favour microbial colonisation and persistence, both being essential precursors of pneumococcal disease.
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Prediction of progression of coronary artery disease and clinical outcomes using vascular profiling of endothelial shear stress and arterial plaque characteristics: the PREDICTION Study.
Circulation
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Atherosclerotic plaques progress in a highly individual manner. The purposes of the Prediction of Progression of Coronary Artery Disease and Clinical Outcome Using Vascular Profiling of Shear Stress and Wall Morphology (PREDICTION) Study were to determine the role of local hemodynamic and vascular characteristics in coronary plaque progression and to relate plaque changes to clinical events.
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Antibiotic resistance of pathogens causing community-acquired pneumonia.
Semin Respir Crit Care Med
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Community-acquired pneumonia remains an important cause of disease and death in both developed and developing countries and therefore continues to have a major medical impact. The mortality remains high despite the ready availability of potent antimicrobial agents to which the organisms are susceptible. However, management of these infections is potentially complicated by the emerging resistance of many of the common pathogens to the different classes of antibiotics that are usually prescribed. Furthermore, it is also being recognized that antibiotic resistance or treatment failures may occur not only through traditional microbial antibiotic resistance mechanisms but also through less well defined mechanisms, particularly those developed by the microbes in relation to their quorum sensing/biofilm machinery. Much recent research in this field has been focused on evaluating the clinical impact of antibiotic resistance on optimal antibiotic treatment and antimicrobial choices, as well as alternative strategies to deal with antibiotic resistance and treatment failures.
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The use of antiinflammatory therapy and macrolides in bronchiectasis.
Clin. Chest Med.
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Airway inflammation is a major component of disease pathogenesis in bronchiectasis, suggesting that antiinflammatory therapies could be of benefit in treatment. This article addresses the use of anti-inflammatory/immunomodulatory therapies in the management of patients with bronchiectasis and individually discusses the use of corticosteroids, macrolides, and other potential anti-inflammatory agents.
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Primary care physician perceptions on the diagnosis and management of chronic obstructive pulmonary disease in diverse regions of the world.
Int J Chron Obstruct Pulmon Dis
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Chronic obstructive pulmonary disease (COPD) is a multicomponent disorder that leads to substantial disability, impaired quality of life, and increased mortality. Although the majority of COPD patients are first diagnosed and treated in primary care practices, there is comparatively little information on the management of COPD patients in primary care. A web-based pilot survey was conducted to evaluate the primary care physicians, or general practitioners (GPs), knowledge, understanding, and management of COPD in twelve territories across the Asia-Pacific region, Africa, eastern Europe, and Latin America, using a 10-minute questionnaire comprising 20 questions and translated into the native language of each participating territory. The questionnaire was administered to a total of 600 GPs (50 from each territory) involved in the management of COPD patients and all data were collated and analyzed by an independent health care research consultant. This survey demonstrated that the GPs understanding of COPD was variable across the territories, with large numbers of GPs having very limited knowledge of COPD and its management. A consistent finding across all territories was the underutilization of spirometry (median 26%; range 10%-48%) and reliance on X-rays (median 14%; range 5%-22%) for COPD diagnosis, whereas overuse of blood tests (unspecified) was particularly high in Russia and South Africa. Similarly, there was considerable underrecognition of the importance of exacerbation history as an important factor of COPD and its initial management in most territories (median 4%; range 0%-22%). Management of COPD was well below guideline-recommended levels in most of the regions investigated. The findings of this survey suggest there is a need for more ongoing education and information, specifically directed towards GPs outside of Europe and North America, and that global COPD guidelines appear to have limited reach and application in most of the areas studied.
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Antimicrobial susceptibility of gram-negative pathogens isolated from patients with complicated intra-abdominal infections in South African hospitals (SMART Study 2004-2009): impact of the new carbapenem breakpoints.
Surg Infect (Larchmt)
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The Study for Monitoring Antimicrobial Resistance Trends (SMART) follows trends in resistance among aerobic and facultative anaerobic gram-negative bacilli (GNB) isolated from complicated intra-abdominal infections (cIAIs) in patients around the world.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.