110 results on '"Harpaz, D."'
Search Results
2. Conduction Disturbances Complicating Acute Myocardial Infarction
- Author
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Behar, S., Eldar, M., Hod, H., Harpaz, D., Barzilay, J., Backer, B., and Gottlieb, S.
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- 1997
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3. Ventricular aneurysm repair: a new approach.
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Cohen AJ, Rubin O, Hauptman E, Harpaz D, Turkisher V, Schachner A, Cohen, A J, Rubin, O, Hauptman, E, Harpaz, D, Turkisher, V, and Schachner, A
- Published
- 2000
4. Long-Term Thyrotropin-Suppressive Therapy with Levothyroxine Impairs Small and Large Artery Elasticity and Increases Left Ventricular Mass in Patients with Thyroid Carcinoma
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Shargorodsky, M., primary, Serov, S., additional, Gavish, D., additional, Leibovitz, E., additional, Harpaz, D., additional, and Zimlichman, R., additional
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- 2006
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5. Family history of coronary artery disease and prognosis myocardial infarction in the thrombolytic era: Results from the israeli acute myocardial infarction national survey
- Author
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Harpaz, D., primary, Gottlieb, S., additional, Boyko, V., additional, Rozenman, Y., additional, and Behar, S., additional
- Published
- 2000
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6. Gender differences in the use of thrombolysis and invasive coronary procedures after acute myocardial infarction in the ′90s, in Israel
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Gottlieb, S., primary, Boyko, V., additional, Harpaz, D., additional, Hod, H., additional, Mazouz, B., additional, Stern, S., additional, and Behar, S., additional
- Published
- 1998
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7. Long-term (12-year) gender differences in prognosis after acute myocardial infarction in young (<65 years) and elderly (≥65 years) patients
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Gottlieb, S., primary, Benderly, M., additional, Goldbourt, Uri, additional, Harpaz, D., additional, Reicher-Reiss, Henrietta, additional, Stern, S., additional, Kaplinsky, Elieser, additional, and Behar, Solomon, additional
- Published
- 1998
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8. Mortality trends in men and women with acute myocardial infarction in coronary care units in Israel. A comparison between 1981–1983 and 1992–1994.
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Gottlieb, S, Goldbourt, U, Boyko, V, Harpaz, D, Mandelzweig, L, Khoury, Z, Stern, S, and Behar, S
- Abstract
Aims To assess trends in the management and subsequent outcome in men and women in two cohorts of consecutive patients with acute myocardial infarction hospitalized in coronary care units in Israel, in the pre-reperfusion and the reperfusion eras.Methods and Results We compared trends in the in-hospital management, and 30-day and 1-year mortality in men and women in two cohorts of patients hospitalized with acute myocardial infarction in coronary care units in Israel, in the pre-reperfusion and the reperfusion eras. The first cohort of 5839 consecutive patients (4315 men, 74%) was from the Secondary Prevention Reinfarction Israeli Nifedipine Trial (SPRINT) registry of 1981–1983; the second cohort of 1940 patients (1429 males, 74%) derived from two prospective nationwide surveys conducted in all coronary care units in Israel in January/February 1992 and 1994. The demographic and clinical characteristics of patients with acute myocardial infarction in both periods were comparable. Patients in 1992–94 received aspirin, angiotensin-converting enzyme inhibitors, beta-blockers and nitrates more frequently than in 1981–83. Thrombolysis, coronary angiography, angioplasty and bypass grafting were not used in 1981–83, whereas in 1992–94 these procedures were used in 45%, 28%, 11% and 4% of men, respectively, and in 39%, 20%, 9% and 3% of women, respectively. The 30-day age-adjusted mortality declined, in men, from 17·0% in 1981–83 to 10·8% in 1992–94 (multivariate-adjusted odds ratio [OR]=0·69; 95% confidence interval [CI] 0·55 to 0·87), and the cumulative 1-year age-adjusted mortality declined from 24·6% to 16·9% (adjusted hazard ratio [HR]=0·70%; 95% CI 0·60 to 0·81). In women, the decline in mortality rates were of similar magnitude, from 24·0% to 15·1% (OR=0·70; 95% CI 0·52 to 0·94), and from 33·6% to 21·0% (HR=0·67; 95% CI 0·55 to 0·81), respectively. In both sexes, the decline in mortality was more marked in patients reperfused by thrombolysis and/or mechanical revascularization, but was also evident in non-reperfused patients.Conclusions Despite higher mortality in both periods in women compared to men, the prognosis of men and women with acute myocardial infarction improved considerably during the last decade, with a similar decline in 1-year mortality of ≈30%. The implementation in daily practice of new therapeutic modalities proven to be effective in clinical trials after acute myocardial infarction, probably played a major role in this favourable outcome in both sexes. [ABSTRACT FROM PUBLISHER]
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- 2000
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9. Sizing up the benefits of aspirin for women with coronary artery disease
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Harpaz, D., Benderly, M., and Goldbourt, U.
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Drug therapy ,Risk factors ,Health aspects ,Mortality -- Risk factors ,Women patients -- Drug therapy -- Health aspects ,Aspirin -- Health aspects ,Cardiac patients -- Drug therapy - Abstract
Aspirin therapy has proved beneficial in men who have coronary artery disease (CAD), but is the same true for women? Yes, say Harpaz and colleagues, who found that aspirin significantly [...]
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- 1997
10. Effect of Aspirin on Mortality in Women With Symptomatic or Silent Myocardial Ischemia
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Harpaz, D., Benderly, M., Goldbourt, U., Kishon, Y., and Behar, S.
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- 1996
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11. Hemodynamic performance of four mechanical bileaflet prosthetic valves in the mitral position: an echocardiographic study
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Reisner, S. A., Harpaz, D., Skulski, R., Borenstein, D., Milo, S., and Meltzer, R. S.
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- 1998
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12. Dexamethasone-induced perineal irritation
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Harpaz D, Mittelman M, Lewinski Uh, and Baharav E
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business.industry ,General Medicine ,Perineum ,Dexamethasone ,Anesthesia ,Neoplasms ,Irritants ,Medicine ,Antiemetics ,Humans ,Perineal irritation ,business ,medicine.drug - Published
- 1986
13. X-Ray Microanalysis of the Fingernails in Cirrhotic Patients.
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Djaldetti, M., Fishman, P., Harpaz, D., and Lurie, B.
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- 1987
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14. Effects of High Gravity on Cardiac Dimensions in Trained Air Crew
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Harpaz, D., Kriwisky, M., Fineman, R., Haim, A., Lewis, B. S., and Shamiss, A.
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- 1996
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15. Unilateral Pulmonary Edema During Transesophageal Echocardiography
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Stienlauf, S., Witzling, M., Herling, M., and Harpaz, D.
- Abstract
Transesophageal echocardiography is considered to be a relatively safe procedure, the complications of which are well known and include probe-related and procedure-related complications. Congestive heart failure rarely occurs. Unilateral pulmonary edema is relatively uncommon and to the best of our knowledge has never been reported in association with transesophageal echocardiography. Herein we describe an unusual case of unilateral pulmonary edema that developed during the course of transesophageal echocardiography. (J Am Soc Echocardiogr 1998;11:491-3.)
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- 1998
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16. Aspirin lowers mortality in women with coronary artery disease.
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Benderly, M., Harpaz, D., and Goldbourt, U.
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ASPIRIN ,CORONARY heart disease treatment ,CORONARY heart disease risk factors ,DRUG efficacy - Abstract
Recommends that aspirin reduces mortality in women with coronary artery disease (CAD) and should be given a preventive therapy for patients unless contraindications exist. Aspirin's effect on the survival of women with CAD; Analysis on the risk factor of aspirin; Comments from the reader about aspirin.
- Published
- 1997
17. Effects of aspirin treatment on survival in non-insulin-dependent diabetic patients with coronary artery disease. Israeli Bezafibrate Infarction Prevention Study Group.
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Harpaz, David, Gottlieb, Shmuel, Harpaz, D, Gottlieb, S, Graff, E, Boyko, V, Kishon, Y, and Behar, S
- Subjects
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ASPIRIN , *TREATMENT of diabetes , *CORONARY disease , *PEOPLE with diabetes , *DRUG efficacy , *MORTALITY , *CORONARY heart disease complications , *VASODILATORS , *TYPE 2 diabetes complications , *CEREBROVASCULAR disease , *COMPARATIVE studies , *RESEARCH methodology , *MEDICAL cooperation , *RESEARCH , *EVALUATION research , *RELATIVE medical risk , *CONFOUNDING variables , *THERAPEUTICS - Abstract
Purpose: The benefit of aspirin treatment among diabetic patients with chronic coronary artery disease is not well established. The purpose of this study was to assess the effect of aspirin on cardiac and total mortality in a large cohort of diabetic patients with established coronary artery disease and to compare it with the effect of aspirin in nondiabetic counterparts.Patients and Methods: In this observational study among patients screened for participation in the Bezafibrate Infarction Prevention Study, the effects of aspirin treatment in 2,368 non-insulin-dependent diabetic patients with coronary artery disease were compared to those in 8,586 nondiabetic patients. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated with proportional hazards models.Results: Fifty-two percent of diabetic patients and 56% of nondiabetic patients reported aspirin therapy. After 5.1 +/- 1.3 (mean +/- SD) years of follow-up, the absolute benefit per 100 patients treated with aspirin was greater in diabetic patients than in nondiabetic patients (cardiac mortality benefit: 5.0 versus 2.1, and all-cause mortality benefit: 7.8 versus 4.1). Overall cardiac mortality among diabetic patients treated with aspirin was 10.9% versus 15.9% in the nonaspirin group (P < 0.001), and all-cause mortality was 18.4% and 26.2% (P < 0.001). After adjustment for possible confounders, treatment with aspirin was an independent predictor of reduced overall cardiac (HR = 0.8; 95% CI: 0.6-1.0) and all-cause mortality (HR = 0.8; 95% CI: 0.7-0.9) among diabetic patients, similar to those in nondiabetic patients.Conclusion: Treatment with aspirin was associated with a significant reduction in cardiac and total mortality among non-insulin-dependent diabetic patients with coronary artery disease. The absolute benefit of aspirin was greater in diabetic patients than in those without diabetes. [ABSTRACT FROM AUTHOR]- Published
- 1998
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18. Comparison of effectiveness of angiotensin-converting enzyme inhibitors after acute myocardial infarction in diabetic versus nondiabetic patients.
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Gottlieb S, Leor J, Shotan A, Harpaz D, Boyko V, Rott D, Mandelzweig L, Behar S, Israel Heart Society Working Group on Intensive Cardiac Care, Gottlieb, Shmuel, Leor, Jonathan, Shotan, Avraham, Harpaz, David, Boyko, Valentina, Rott, David, Mandelzweig, Lori, Behar, Solomon, and Working Group on Intensive Cardiac Care, Israel Heart Society
- Abstract
Mortality and morbidity after acute myocardial infarction (AMI) is higher in diabetic than in nondiabetic patients. Angiotensin-converting enzyme (ACE) inhibitors have been shown to exert a beneficial effect after AMI. We sought to evaluate the association between treatment with ACE inhibitors and 1-year outcome after AMI in diabetic and nondiabetic patients in a national survey. The study population was drawn from a national survey conducted in all coronary care units operating in Israel during a 5-month period in 1996, and included 2,179 patients with AMI: 533 diabetics (24%), 322 of whom received ACE inhibitors (60%) and 211 who did not; and 1,646 nondiabetics, 805 of whom received ACE inhibitors and 841 who did not. In both groups of patients, those treated with ACE inhibitors were older, included more women, more had a history of AMI, anterior wall AMI, or hypertension, and more had worse Killip class on admission. Diabetic patients treated with ACE inhibitors experienced lower 1-year mortality rates than diabetics not treated with ACE inhibitors (16.2% vs 18.8%, respectively; covariate adjusted hazard ratio 0.47, 95% confidence interval 0.30 to 0.74). In nondiabetic patients, however, ACE inhibitor treatment was not associated with a better outcome (10.2% vs 7.3%, respectively; covariate adjusted hazard ratio 0.80; 95% confidence interval 0.56 to 1.15). Thus, treatment with ACE inhibitors after AMI appears to be particularly beneficial in diabetic patients. The beneficial effect observed supports the widespread use of ACE inhibitors in diabetic patients after AMI. [ABSTRACT FROM AUTHOR]
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- 2003
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19. Detection of Cannabinoids in Oral Fluid Specimens as the Preferred Biological Matrix for a Point-of-Care Biosensor Diagnostic Device.
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Trif C, Harpaz D, Eltzov E, Parcharoen Y, Pechyen C, and Marks RS
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- Humans, Point-of-Care Systems, Saliva, Substance Abuse Detection methods, Cannabinoids, Marijuana Smoking, Cannabis
- Abstract
An increasing number of countries have started to decriminalize or legalize the consumption of cannabis for recreational and medical purposes. The active ingredients in cannabis, termed cannabinoids, affect multiple functions in the human body, including coordination, motor skills, memory, response time to external stimuli, and even judgment. Cannabinoids are a unique class of terpeno-phenolic compounds, with 120 molecules discovered so far. There are certain situations when people under the influence of cannabis may be a risk to themselves or the public safety. Over the past two decades, there has been a growing research interest in detecting cannabinoids from various biological matrices. There is a need to develop a rapid, accurate, and reliable method of detecting cannabinoids in oral fluid as it can reveal the recent intake in comparison with urine specimens, which only show a history of consumption. Significant improvements are continuously made in the analytical formats of various technologies, mainly concerning improving their sensitivity, miniaturization, and making them more user-friendly. Additionally, sample collection and pretreatment have been extensively studied, and specific devices for collecting oral fluid specimens have been perfected to allow rapid and effective sample collection. This review presents the recent findings regarding the use of oral fluid specimens as the preferred biological matrix for cannabinoid detection in a point-of-care biosensor diagnostic device. A critical review is presented, discussing the findings from a collection of review and research articles, as well as publicly available data from companies that manufacture oral fluid screening devices. Firstly, the various conventional methods used to detect cannabinoids in biological matrices are presented. Secondly, the detection of cannabinoids using point-of-care biosensors is discussed, emphasizing oral fluid specimens. This review presents the current pressing technological challenges and highlights the gaps where new technological solutions can be implemented.
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- 2024
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20. Characterization and optimization of bioluminescent bacterial cells immobilization process in calcium alginate hydrogel tablets.
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Harpaz D, Zoabi K, and Eltzov E
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- Alginates, Tablets, Hydrogels, Biosensing Techniques methods
- Abstract
Aims: Whole-cell biosensors are increasingly utilized in various applications. These platforms integrate cells with a signal measurement device. One of the main challenges in the development of such platforms is the immobilization matrix that is used to keep the cells stable, which also affects the portability of the device. In this study, a portable and simple immobilization of bioluminescent bacterial cells in calcium alginate hydrogel was examined., Methods and Results: The effects of several physical parameters were investigated (e.g. calcium alginate solution volume, drying, incubation time, mixing procedure, bacterial concentration, and tablet location within the cylinder). An alginate solution volume of 3 ml was preferred as well as the addition of 400 μl solution after the 15 min of compressing step and before the polymerization step. Also, a stirring mixing mode is favored over vortexing due to the creation of better homogenized tablets, as well as a bacterial concentration of 0.15 OD600nm that produced a high light response while maintaining a lower variance. Lastly, the findings showed a significantly higher response [induction factor (IF)] in the tablets using the optimized immobilization protocol (IF = 8.814) than the old one (IF = 1.979)., Conclusions: To conclude, bacterial cells immobilization in calcium alginate tablets provides improved sensitivity and storability., (© The Author(s) 2023. Published by Oxford University Press on behalf of Applied Microbiology International.)
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- 2023
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21. Biocompatibility characterization of vaterite with a bacterial whole-cell biosensor.
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Harpaz D, Barhom H, Veltman B, Ginzburg P, and Eltzov E
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- Calcium Carbonate pharmacology, Calcium Carbonate chemistry, Escherichia coli, Drug Delivery Systems, Nanoparticles, Biosensing Techniques
- Abstract
The growing biomedical challenges impose the continuous development of novel platforms. Ensuring the biocompatibility of drug delivery and implantable biomedical devices is an essential requirement. Calcium carbonate (CaCO3) in the form of vaterite nanoparticles is a promising platform, which has demonstrated distinctive optical and biochemical properties, including high porosity and metastability. In this study, the biocompatibility of differently shaped CaCO
3 vaterite particles (toroids, ellipsoids, and spheroids) are evaluated by bacterial toxicity mode-of-action with a whole-cell biosensor. Different Escherichia coli (E. coli) strains were used in the bioluminescent assay, including cytotoxicity, genotoxicity and quorum-sensing. Firstly, both scanning electron microscopy (SEM) and fluorescence microscopy characterizations were conducted. Bacterial cell death and aggregates were observed only in the highest tested concentration of the vaterite particles, especially in toroids 15-25 µm. After, the bioluminescent bacterial panel was exposed to the vaterite particles, and their bioluminescent signal reflected their toxicity mode-of-action. The vaterite particles resulted in an induction factor (IF > 1) on the bacterial panel, which was higher after exposure to the toroids (1.557 ≤ IF ≤ 2.271) and ellipsoids particles (1.712 ≤ IF ≤ 2.018), as compared to the spheroids particles (1.134 ≤ IF ≤ 1.494), in all the tested bacterial strains. Furthermore, the vaterite particles did not affect the viability of the bacterial cells. The bacterial monitoring demonstrated the biofriendly nature of especially spheroids vaterite nanoparticles., Competing Interests: Declaration of Competing Interest The authors declared no potential conflicts of interest concerning the research, authorship, and/or publication of this article., (Copyright © 2022 Elsevier B.V. All rights reserved.)- Published
- 2023
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22. Portable biosensors for rapid on-site determination of cannabinoids in cannabis, a review.
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Harpaz D, Bernstein N, Namdar D, and Eltzov E
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- Dronabinol, Cannabis, Cannabinoids, Cannabidiol, Biosensing Techniques
- Abstract
Recent studies highlight the therapeutic virtues of cannabidiol (CBD). Furthermore, due to their molecular enriched profiles, cannabis inflorescences are biologically superior to a single cannabinoid for the treatment of various health conditions. Thus, there is flourishing demand for Cannabis sativa varieties containing high levels of CBD. Additionally, legal regulations around the world restrict the cultivation and consumption of tetrahydrocannabinol (THC)-rich cannabis plants for their psychotropic effects. Therefore, the use of cannabis varieties that are high in CBD is permitted as long as their THC content does not exceed a low threshold of 0.3%-0.5%, depending on the jurisdiction. These chemovars are legally termed 'hemp'. This controlled cannabinoid requirement highlights the need to detect low levels of THC, already in the field. In this review, cannabis profiling and the existing methods used for the detection of cannabinoids are firstly evaluated. Then, selected valuable biosensor technologies are discussed, which suggest portable, rapid, sensitive, reproducible, and reliable methods for on-site identification of cannabinoids levels, mainly THC. Recent cutting-edge techniques of promising potential usage for both cannabis and hemp analysis are identified, as part of the future cultivation and agricultural improvement of this crop., Competing Interests: Declaration of Competing Interest The authors declared no potential conflicts of interest concerning the research, authorship, and/or publication of this article., (Copyright © 2022 Elsevier Inc. All rights reserved.)
- Published
- 2022
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23. Whole-cell bacterial biosensor with the capability to detect red palm weevil, Rhynchophorus ferrugineus, in date palm trees, Phoenix dactylifera: a proof of concept study.
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Harpaz D, Veltman B, Katz D, and Eltzov E
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- Animals, Bacteria, Proof of Concept Study, Sugars, Biosensing Techniques, Phoeniceae, Volatile Organic Compounds, Weevils microbiology
- Abstract
The red palm weevil (RPW), Rhynchophorus ferrugineus, is considered a severe pest of palms. Usually, the early stages of infection are without visible signs. An attractive early sensing approach of non-visible infections is based on volatile organic compounds (VOCs). In this study, a whole-cell bacterial biosensor was used for the identification of RPW in date palm (Phoenix dactylifera). The cells are genetically modified to produce light in the presence of general stresses. The bioluminescent bacterial panel is based on three genetically engineered Escherichia coli strains that are sensitive to cytotoxicity (TV1061), genotoxicity (DPD2794), or quorum-sensing (K802NR). The bioluminescent bacterial panel detects the presence of VOCs and a change in the light signal is then generated, reflecting the health status of the date palm tree. The bioreporter bacteria cells are immobilized in calcium alginate tablets and placed in a sealed jar without direct contact with the tested sample, thereby exposing them only to the VOCs in the surrounding air. The immobilized bacteria cells were exposed to the air near infected by RPW or uninfected sugar canes, date palm tree pieces, and on date palm trees. Commercial plate reader was used for signal measurement. The findings show that quorum-sensing was induced by all the tested samples of infected sugar canes, date palm tree pieces, and date palm trees. While, cytotoxicity was induced only by infected date palm tree pieces, and genotoxicity was induced only by infected date palm trees. The bacterial monitoring results enable the identification of specific signatures that will allow a quick and accurate diagnosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)
- Published
- 2022
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24. Whole-cell bacterial biosensor for volatile detection from Pectobacterium-infected potatoes enables early identification of potato tuber soft rot disease.
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Veltman B, Harpaz D, Melamed S, Tietel Z, Tsror L, and Eltzov E
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- Plant Diseases, Biosensing Techniques, Pectobacterium, Solanum tuberosum, Volatile Organic Compounds
- Abstract
Half of the harvested food is lost due to rots caused by microorganisms. Plants emit various volatile organic compounds (VOCs) into their surrounding environment, and the VOC profiles of healthy crops are altered upon infection. In this study, a whole-cell bacterial biosensor was used for the early identification of potato tuber soft rot disease caused by the pectinolytic bacteria Pectobacterium in potato tubers. The detection is based on monitoring the luminescent responses of the bacteria panel to changes in the VOC profile following inoculation. First, gas chromatography-mass spectrometry (GC-MS) was used to specify the differences between the VOC patterns of the inoculated and non-inoculated potato tubers during early infection. Five VOCs were identified, 1-octanol, phenylethyl alcohol, 2-ethyl hexanol, nonanal, and 1-octen-3-ol. Then, the infection was detected by the bioreporter bacterial panel, firstly measured in a 96-well plate in solution, and then also tested in potato plugs and validated in whole tubers. Examination of the bacterial panel responses showed an extensive cytotoxic effect over the testing period, as seen by the elevated induction factor (IF) values in the bacterial strain TV1061 after exposure to both potato plugs and whole tubers. Moreover, quorum sensing influences were also observed by the elevated IF values in the bacterial strain K802NR. The developed whole-cell biosensor system based on bacterial detection will allow more efficient crop management during postharvest, storage, and transport of crops, to reduce food losses., (Copyright © 2022 Elsevier B.V. All rights reserved.)
- Published
- 2022
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25. Characterization of the selective binding of modified chitosan nanoparticles to Gram-negative bacteria strains.
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Veltman B, Harpaz D, Cohen Y, Poverenov E, and Eltzov E
- Subjects
- Microbial Viability, Anti-Bacterial Agents pharmacology, Chitosan pharmacology, Gram-Negative Bacteria drug effects, Nanoparticles metabolism
- Abstract
Chitosan is a nature-sourced polysaccharide widely used in numerous applications. The antibacterial potential of chitosan has attracted researchers to further develop and utilize this polymer for the formation of biocompatible antibacterial agents for both the food and healthcare industries. The tested hypothesis in this study is that modified N-alkylaminated chitosan nanoparticles (CNPs) have selective binding properties to Gram-negative bacteria strains that result in bacterial aggregation. Various bacterial strains were tested of five Gram-negative bacteria including Erwinia carotovora, Escherichia coli, Pseudomonas aeruginosa, Salmonella, and Serratia marcescens, as well as three Gram-positive bacteria strains including Bacillus licheniformis, Bacillus megaterium, and Bacillus subtilis. The fluorescence microscopy characterization showed that the presence of CNPs caused the aggregation of Escherichia coli bacteria cells, where modified CNPs with a shorter chain length of the substituent caused a higher aggregation effect. Moreover, it was found that the CNPs exhibited a selective binding behavior to Gram-negative as compared to Gram-positive bacteria strains, mainly to Escherichia coli and Salmonella. Also, the scanning electron microscopy characterization showed that CNPs exhibited selective binding to Gram-negative bacteria, which was especially understood when both Gram-negative and Gram-positive bacteria strains were within the same sample. In addition, the bacterial viability assay suggests that CNPs with a lower degree of substitution have a higher inhibitory effect on bacterial growth. CNPs with longer side chains had a less inhibitory effect on the bacterial growth of Gram-negative strains, where a concentration-dependent response pattern was only seen for the cases of Gram-negative strains, and not for the case of Gram-positive strain. To conclude, the further understanding of the selective binding of CNPs to Gram-negative bacteria strains may produce new opportunities for the discovery and characterization of effective antibacterial agents., (Copyright © 2021 Elsevier B.V. All rights reserved.)
- Published
- 2022
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26. Learning the Abstract General Task Structure in a Rapidly Changing Task Content.
- Author
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Pereg M, Harpaz D, Sabah K, Ben-Shachar MS, Amir I, Dreisbach G, and Meiran N
- Abstract
The ability to learn abstract generalized structures of tasks is crucial for humans to adapt to changing environments and novel tasks. In a series of five experiments, we investigated this ability using a Rapid Instructed Task Learning paradigm (RITL) comprising short miniblocks, each involving two novel stimulus-response rules. Each miniblock included (a) instructions for the novel stimulus-response rules, (b) a NEXT phase involving a constant (familiar) intervening task (0-5 trials), (c) execution of the newly instructed rules (2 trials). The results show that including a NEXT phase (and hence, a prospective memory demand) led to relatively more robust abstract learning as indicated by increasingly faster responses with experiment progress. Multilevel modeling suggests that the prospective memory demand was just another aspect of the abstract task structure which has been learned., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2021 The Author(s).)
- Published
- 2021
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27. Blood biomarkers to detect new-onset atrial fibrillation and cardioembolism in ischemic stroke patients.
- Author
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Harpaz D, Bajpai R, Ng GJL, Soljak M, Marks RS, Cheung C, Arumugam TV, Quek AML, Tok AIY, and Seet RCS
- Subjects
- Aged, Atrial Fibrillation blood, Atrial Fibrillation complications, Embolism blood, Embolism etiology, Female, Follow-Up Studies, Heart Diseases blood, Heart Diseases etiology, Humans, Ischemic Stroke blood, Ischemic Stroke etiology, Male, Middle Aged, Retrospective Studies, Atrial Fibrillation diagnosis, Biomarkers blood, Embolism diagnosis, Heart Diseases diagnosis, Ischemic Stroke diagnosis
- Abstract
Background: Accumulating data suggest blood biomarkers could inform stroke etiology., Objective: The purpose of this study was to investigate the performance of multiple blood biomarkers in elucidating stroke etiology with a focus on new-onset atrial fibrillation (AF) and cardioembolism., Methods: Between January and December 2017, information on clinical and laboratory parameters and stroke characteristics was prospectively collected from ischemic stroke patients recruited from the National University Hospital, Singapore. Multiple blood biomarkers (N-terminal pro-brain natriuretic peptide [NT-proBNP], d-dimer, S100β, neuron-specific enolase, vitamin D, cortisol, interleukin-6, insulin, uric acid, and albumin) were measured in plasma. These variables were compared with stroke etiology and the risk of new-onset AF and cardioembolism using multivariable regression methods., Results: Of the 515 ischemic stroke patients (mean age 61 years; 71% men), 44 (8.5%) were diagnosed with new-onset AF, and 75 (14.5%) had cardioembolism. The combination of 2 laboratory parameters (total cholesterol ≤169 mg/dL; triglycerides ≤44.5 mg/dL) and 3 biomarkers (NT-proBNP ≥294 pg/mL; S100β ≥64 pg/mL; cortisol ≥471 nmol/l) identified patients with new-onset AF (negative predictive value [NPV] 90%; positive predictive value [PPV] 73%; area under curve [AUC] 85%). The combination of 2 laboratory parameters (total cholesterol ≤169 mg/dL; triglycerides ≤44.5 mg/dL) and 2 biomarkers (NT-proBNP ≥507 pg/mL; S100β ≥65 pg/mL) identified those with cardioembolism (NPV 86%; PPV 78%; AUC 87%). Adding clinical predictors did not improve the performance of these models., Conclusion: Blood biomarkers could identify patients with increased likelihood of cardioembolism and direct the search for occult AF., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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28. Cigarette smoke toxicity modes of action estimated by a bioluminescent bioreporter bacterial panel.
- Author
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Axelrod T, Eltzov E, Lerman M, Harpaz D, and Marks RS
- Subjects
- Bacteria, Humans, Smoking, Nicotiana, Filtration, Smoke
- Abstract
Cigarette smoking is considered to be a risk factor for several chronic diseases and even premature death. However, despite the importance of this detrimental habit, little seems known in terms of the overall toxicity potential of its ingredients in humans. In this study, a panel of genetically modified bioluminescent bioreporter bacteria was used to evaluate its usefulness in estimating the cigarette smoke's complex molecular mixture on a bacterial toxicity-bioreporter panel, both filtered or unfiltered. This work enabled to confirm the usefulness of cigarette filters, with better protection found in higher priced brands despite both having genotoxic and cytotoxic attributes. Quorum sensing interference was also shown, which may explain why cigarette smokers are at greater risk for pulmonary infections. Moreover, the findings of this study support the fact that the filter is a dominating contributor to reducing the harm caused by cigarette smoke. Increased efforts should be conducted to reduce the harmful effects of cigarette smoke, via increasingly effective filters. To conclude, the panel of bioreporter bacteria was found to be useful in the evaluation of the general effect of the toxic mixture found in cigarette smoke and therefore has the potential to be used in cigarette research, helping researchers pinpoint the reduction of toxicity when working with filter improvement., (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Published
- 2021
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29. The effect of cannabis toxicity on a model microbiome bacterium epitomized by a panel of bioluminescent E. coli.
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Harpaz D, Veltman B, Sadeh Y, Marks RS, Bernstein N, and Eltzov E
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- Dronabinol toxicity, Escherichia coli genetics, Humans, Plant Extracts, Cannabis toxicity, Microbiota
- Abstract
The world acceptance of medical cannabis slowly widens. Cannabinoids are known as the main therapeutic active compounds in the cannabis plant, yet their bioactive physiological effects are still unknown. In this study, the mode of action of nine selected cannabinoids was examined using a bioluminescent bacterial panel, as well as the extracts of six different cannabis varieties and cannabinoids standards artificial mixtures. The bacterial panel was composed of genetically modified E. coli bacteria that is commonly found in the gut microbiome, to which a lux operon was added to various stress promoters. The panel was exposed to the cannabinoids in order to identify bacterial defense mechanism, via the aforementioned specific stress types response. This enables the understanding of the toxicity mode of action of cannabinoids. From all the tested cannabinoids, only delta-9-tetrahydrocannabinol (THC) and delta-9-tetrahydrocannabinolic acid A (THCA) produced a genotoxic effect, while the other tested cannabinoids, demonstrated cytotoxic or oxidative damages. Unlike pure cannabinoids, cannabis plant extracts exhibited mostly genotoxicity, with minor cytotoxicity or oxidative stress responses. Moreover, cannabinoids standards artificial mixtures produced a different response patterns compared to their individual effects, which may be due to additional synergistic or antagonistic reactions between the mixed chemicals on the bacterial panel. The results showed that despite the lack of cannabigerol (CBG), cannabidivarin (CBDV), cannabinol (CBN), and cannabichromene (CBC) in the artificial solution mimicking the CN6 cannabis variety, a similar response pattern to the cannabinoids standards mixture was obtained. This work contributes to the understanding of such correlations and may provide a realistic view of cannabinoid effects on the human microbiome., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2021
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30. The Incorporation of Amplified Metal-Enhanced Fluorescence in a CMOS-Based Biosensor Increased the Detection Sensitivity of a DNA Marker of the Pathogenic Fungus Colletotrichum gloeosporioides .
- Author
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Harpaz D, Alkan N, and Eltzov E
- Subjects
- Biosensing Techniques, Colletotrichum genetics, DNA, Fungal analysis, Genetic Markers, Semiconductors
- Abstract
Half of the global agricultural fresh produce is lost, mainly because of rots that are caused by various pathogenic fungi. In this study, a complementary metal-oxide-semiconductor (CMOS)-based biosensor was developed, which integrates specific DNA strands that allow the detection of enoyl-CoA-hydratase/isomerase, which is a quiescent marker of Colletotrichum gloeosporioides fungi. The developed biosensor mechanism is based on the metal-enhanced fluorescence (MEF) phenomenon, which is amplified by depositing silver onto a glass surface. A surface DNA strand is then immobilized on the surface, and in the presence of the target mRNA within the sample, the reporter DNA strand that is linked to horseradish peroxidase (HRP) enzyme will also bind to it. The light signal that is later produced from the HRP enzyme and its substrate is enhanced and detected by the coupled CMOS sensor. Several parameters that affect the silver-deposition procedure were examined, including silver solution temperature and volume, heating mode, and the tank material. Moreover, the effect of blocking treatment (skim milk or bovine serum albumin (BSA)) on the silver-layer stability and nonspecific DNA absorption was tested. Most importantly, the effect of the deposition reaction duration on the silver-layer formation and the MEF amplification was also investigated. In the study findings a preferred silver-deposition reaction duration was identified as 5-8 min, which increased the deposition of silver on the glass surface up to 13-times, and also resulted in the amplification of the MEF phenomenon with a maximum light signal of 50 relative light units (RLU). It was found that MEF can be amplified by a customized silver-deposition procedure that results in increased detection sensitivity. The implementation of the improved conditions increased the biosensor sensitivity to 3.3 nM (4500 RLU) with a higher detected light signal as compared to the initial protocol (400 RLU). Moreover, the light signal was amplified 18.75-, 11.11-, 5.5-, 11.25-, and 3.75-times in the improved protocol for all the tested concentrations of the target DNA strand of 1000, 100, 10, 3.3, and 2 nM, respectively. The developed biosensor system may allow the detection of the pathogenic fungus in postharvest produce and determine its pathogenicity state.
- Published
- 2020
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31. Environmental pollutants induce noninherited antibiotic resistance to polymyxin B in Escherichia coli .
- Author
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Harpaz D, Marks RS, Kushmaro A, and Eltzov E
- Subjects
- Escherichia coli genetics, Escherichia coli metabolism, Escherichia coli Proteins genetics, Escherichia coli Proteins metabolism, Microbial Sensitivity Tests, Anti-Bacterial Agents pharmacology, Drug Resistance, Bacterial, Environmental Pollutants toxicity, Escherichia coli drug effects, Polymyxin B pharmacology
- Abstract
Aim: The mechanisms behind antibiotic resistance by bacteria are important to create alternative molecules. Objective: This study focuses on the impact of environmental pollutants on bacterial resistance to antibiotics. Materials & methods: The effect of various environmental pollutants on noninherited bacterial resistance to antibiotics was examined. Results: The tolerance to the polymyxin-B antibiotic was shown to be conferred to Escherichia coli , by pretreatment with subinhibitory concentrations of environmental toxicants. The cell survival to a sublethal dosage of antibiotics was tested. Exposure to low concentrations of toxic compounds (500 ppb copper, 2% [v/v] ethanol or 0.5 μg/ml trimethoprim) stimulated the bacterial heat shock systems and led to increased tolerance to polymyxin B. Conclusion: Environmental pollutants induce a temporary bacterial noninheritable resistance to antibiotic.
- Published
- 2020
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32. Blood-Based Biomarkers Are Associated with Different Ischemic Stroke Mechanisms and Enable Rapid Classification between Cardioembolic and Atherosclerosis Etiologies.
- Author
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Harpaz D, Seet RCS, Marks RS, and Tok AIY
- Abstract
Stroke is a top leading cause of death, which occurs due to interference in the blood flow of the brain. Ischemic stroke (blockage) accounts for most cases (87%) and is further subtyped into cardioembolic, atherosclerosis, lacunar, other causes, and cryptogenic strokes. The main value of subtyping ischemic stroke patients is for a better therapeutic decision-making process. The current classification methods are complex and time-consuming (hours to days). Specific blood-based biomarker measurements have promising potential to improve ischemic stroke mechanism classification. Over the past decades, the hypothesis that different blood-based biomarkers are associated with different ischemic stroke mechanisms is increasingly investigated. This review presents the recent studies that investigated blood-based biomarker characteristics differentiation between ischemic stroke mechanisms. Different blood-based biomarkers are specifically discussed (b-type natriuretic peptide, d-dimer, c-reactive protein, tumor necrosis factor-α, interleukin-6, interleukin-1β, neutrophil-lymphocyte ratio, total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein and apolipoprotein A), as well as the different cut-off values that may be useful in specific classifications for cardioembolic and atherosclerosis etiologies. Lastly, the structure of a point-of-care biosensor device is presented, as a measuring tool on-site. The information presented in this review will hopefully contribute to the major efforts to improve the care for stroke patients.
- Published
- 2020
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33. Smartphone-Based Whole-Cell Biosensor Platform Utilizing an Immobilization Approach on a Filter Membrane Disk for the Monitoring of Water Toxicants.
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Ma J, Harpaz D, Liu Y, and Eltzov E
- Subjects
- Bacteria, Hydrogen Peroxide, Luminescent Measurements, Water analysis, Biosensing Techniques, Cells, Immobilized microbiology, Environmental Monitoring instrumentation, Smartphone, Water Pollutants analysis
- Abstract
Bioluminescent bacteria whole-cell biosensors (WCBs) have been widely used in a range of sensing applications in environmental monitoring and medical diagnostics. However, most of them use planktonic bacteria cells that require complicated signal measurement processes and therefore limit the portability of the biosensor device. In this study, a simple and low-cost immobilization method was examined. The bioluminescent bioreporter bacteria was absorbed on a filter membrane disk. Further optimization of the immobilization process was conducted by comparing different surface materials (polyester and parafilm) or by adding glucose and ampicillin. The filter membrane disks with immobilized bacteria cells were stored at -20 °C for three weeks without a compromise in the stability of its biosensing functionality for water toxicants monitoring. Also, the bacterial immobilized disks were integrated with smartphones-based signal detection. Then, they were exposed to water samples with ethanol, chloroform, and H
2 O2 , as common toxicants. The sensitivity of the smartphone-based WCB for the detection of ethanol, chloroform, and H2 O2 was 1% ( v / v ), 0.02% ( v / v ), and 0.0006% ( v / v ), respectively. To conclude, this bacterial immobilization approach demonstrated higher sensitivity, portability, and improved storability than the planktonic counterpart. The developed smartphone-based WCB establishes a model for future applications in the detection of environmental water toxicants.- Published
- 2020
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34. B-Type Natriuretic Peptide as a Significant Brain Biomarker for Stroke Triaging Using a Bedside Point-of-Care Monitoring Biosensor.
- Author
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Harpaz D, Seet RCS, Marks RS, and Tok AIY
- Subjects
- Aged, Biomarkers, Female, Humans, Male, Peptide Fragments, Stroke, Tissue Plasminogen Activator, Biosensing Techniques, Brain metabolism, Monitoring, Physiologic, Natriuretic Peptide, Brain metabolism, Point-of-Care Systems
- Abstract
Stroke is a widespread condition that causes 7 million deaths globally. Survivors suffer from a range of disabilities that affect their everyday life. It is a complex condition and there is a need to monitor the different signals that are associated with it. Stroke patients need to be rapidly diagnosed in the emergency department in order to allow the admission of the time-limited treatment of tissue plasminogen activator (tPA). Stroke diagnostics show the use of sophisticated technologies; however, they still contain limitations. The hidden information and technological advancements behind the utilization of biomarkers for stroke triaging are significant. Stroke biomarkers can revolutionize the way stroke patients are diagnosed, monitored, and how they recover. Different biomarkers indicate different cascades and exhibit unique expression patterns which are connected to certain pathologies in the human body. Over the past decades, B-type natriuretic peptide (BNP) and its derivative N-terminal fragment (NT-proBNP) have been increasingly investigated and highlighted as significant cardiovascular biomarkers. This work reviews the recent studies that have reported on the usefulness of BNP and NT-proBNP for stroke triaging. Their classification association is also presented, with increased mortality in stroke, correlation with cardioembolic stroke, and an indication of a second stroke recurrence. Moreover, recent scientific efforts conducted for the technological advancement of a bedside point-of-care (POC) device for BNP and NT-proBNP measurements are discussed. The conclusions presented in this review may hopefully assist in the major efforts that are currently being conducted in order to improve the care of stroke patients.
- Published
- 2020
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35. Functionalized silicon dioxide self-referenced plasmonic chip as point-of-care biosensor for stroke biomarkers NT-proBNP and S100β.
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Harpaz D, Koh B, Seet RCS, Abdulhalim I, and Tok AIY
- Subjects
- Animals, Antibodies, Immobilized immunology, Biomarkers blood, Humans, Natriuretic Peptide, Brain immunology, Peptide Fragments immunology, Point-of-Care Testing, Propylamines chemistry, S100 Calcium Binding Protein beta Subunit immunology, Silanes chemistry, Surface Plasmon Resonance methods, Swine, Natriuretic Peptide, Brain blood, Peptide Fragments blood, S100 Calcium Binding Protein beta Subunit blood, Silicon Dioxide chemistry, Stroke blood, Surface Plasmon Resonance instrumentation
- Abstract
Surface plasmon resonance (SPR) biosensors are often used in the detection of solid, liquid or gaseous samples in diagnostics, pharmaceutics and military defense. Plasmon waveguide resonance (PWR) mode is obtained when a dielectric waveguide layer is added to the metal film. In this study, a self-referenced PWR (SRPWR) silicon dioxide (SiO
2 ) chip was examined. The self-referenced measurement is important to compensate for temperature fluctuations, other instabilities and allows RI signal measurement without an additional reference sample, thus minimising the sample volume needed. The chip was fabricated with a multi-layer of metals and dielectrics, consisting of a 420 nm SiO2 layer, a 40 nm Ag layer and another 480 nm SiO2 layer. This chip was shown to give one internal plasmon excited on the bottom interface SiO2 /Ag, which is used as self-reference in the detection. The top layer acts as a waveguide layer and can be designed to give modes with ultrahigh penetration depth. A direct assay was developed, where the recognition molecule (specific antibody) was immobilized onto the SiO2 plasmonic chip surface, via a covalent coupling protocol based on 3-aminopropyltriethoxysilane (APTES) and glutaraldehyde. The SRPWR biosensor was developed for the sensing of two chosen stroke biomarkers: NT-proBNP and S100β, which are sensitive and specific for stroke diagnostics. For both biomarkers, a linear decreasing pattern in the RI signal was recognized with the increasing biomarkers concentrations. Biomarkers detection was conducted in deionized water and validation was done in spiked porcine plasma. The SiO2 based plasmonic chip demonstrates a limit-of-detection of less than 1 ng/mL that is clinically relevant for both stroke biomarkers., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2020 Elsevier B.V. All rights reserved.)- Published
- 2020
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36. Enhanced Colorimetric Signal for Accurate Signal Detection in Paper-Based Biosensors.
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Harpaz D, Eltzov E, Ng TSE, Marks RS, and Tok AIY
- Abstract
A bstract: Paper-based colorimetric biosensors combine the use of paper with colorimetric signal detection. However, they usually demonstrate lower sensitivities because a signal amplification procedure has not been used. Stopping the reaction of colorimetric signal generation is often used in lab-based assays in order to amplify and stabilize the colorimetric signal for detection. In this study, the generation of a stopped colorimetric signal was examined for accurate and enhanced signal detection in paper-based biosensors. The colorimetric reaction in biosensors is usually based on the interaction between the enzyme horseradish peroxidase (HRP) and a selected chromogenic substrate. The two most commonly used HRP substrates, 3, 3', 5, 5'-tetramethylbenzidine (TMB) and 2'-azinobis (3-ethylbenzothiazoline-6-sulfonic-acid) (ABTS), were compared in terms of their ability to generate a stopped colorimetric signal on membrane. The stopped colorimetric signal was visible for TMB but not for ABTS. Moreover, the generation of stopped colorimetric signal was dependent on the presence of polyvinylidene-difluoride (PVDF) membrane as the separation layer. With PVDF the colorimetric signal (color intensity) was higher (TMB: 126 ± 6 and ABTS: 121 ± 9) in comparison to without PVDF (TMB: 110 ± 2 and ABTS: 102 ± 4). The TMB stopped colorimetric signal demonstrated a more stable signal detection with lower standard deviation values. To conclude, a stopped colorimetric signal can be generated in paper-based biosensors for enhanced and accurate signal detection., Competing Interests: The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
- Published
- 2020
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37. Point-of-Care Surface Plasmon Resonance Biosensor for Stroke Biomarkers NT-proBNP and S100β Using a Functionalized Gold Chip with Specific Antibody.
- Author
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Harpaz D, Koh B, Marks RS, Seet RCS, Abdulhalim I, and Tok AIY
- Subjects
- Antibodies chemistry, Antibodies immunology, Biomarkers chemistry, Gold chemistry, Humans, Natriuretic Peptide, Brain chemistry, Peptide Fragments chemistry, Point-of-Care Systems, S100 Calcium Binding Protein beta Subunit chemistry, Surface Plasmon Resonance, Biosensing Techniques, Natriuretic Peptide, Brain isolation & purification, Peptide Fragments isolation & purification, S100 Calcium Binding Protein beta Subunit isolation & purification, Stroke diagnosis
- Abstract
Surface-plasmon-resonance (SPR) is a quantum-electromagnetic phenomenon arising from the interaction of light with free electrons at a metal-dielectric interface. At a specific angle/wavelength of light, the photon's energy is transferred to excite the oscillation of the free electrons on the surface. A change in the refractive-index (RI) may occur, which is influenced by the analyte concentration in the medium in close contact with the metal surface. SPR has been widely used for the detection of gaseous, liquid, or solid samples. In this study, a functionalized specific SPR chip was designed and used in a novel point-of-care SPR module (PhotonicSys SPR H5) for the detection of the stroke biomarkers NT-proBNP and S100β. These biomarkers have proven to be good for stroke diagnosis, with sensitivity and specificity of >85%. Specific detection was done by binding a biomolecular-recognizing antibody onto the Au SPR-chip. Detection was tested in water and plasma samples. NT-proBNP and S100β were detected in a range of concentrations for stroke, from 0.1 ng/mL to 10 ng/mL. The RI of the blank plasma samples was 1.362412, and the lowest concentration tested for both biomarkers showed a prominent shift in the RI signal (0.25 ng/mL NT-proBNP (1.364215) and S100β (1.364024)). The sensor demonstrated a clinically relevant limit-of-detection of less than ng/mL.
- Published
- 2019
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38. Dissolvable Polyvinyl-Alcohol Film, a Time-Barrier to Modulate Sample Flow in a 3D-Printed Holder for Capillary Flow Paper Diagnostics.
- Author
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Harpaz D, Axelrod T, Yitian AL, Eltzov E, Marks RS, and Tok AIY
- Abstract
Integrating a dissolvable membrane into a sensor allows the control of sample flow, location and duration in critical areas. These time-barrier films stop the flow of samples until the membrane has dissolved, thus, for example, allowing increased exposure time between immunoreagents for the formation of greater numbers of immuno-complexes, ensuring higher sensitivity, reactivity, and helping to reduce false-positive signals. In this study, dissolvable polyvinyl alcohol (PVA) films are used in a 3D-printed sensor holder, which enables film integration without the use of glue. PVA is a synthetic hydrophilic linear polymer, its solubility is dependent on its molecular weight and degree of hydrolysis. Three types of PVAs films were tested herein: (1) PVA 1-Mw: 30⁻70 K, 87⁻90% hydrolyzed; (2) PVA 2-Mw: 31⁻50 K, 98⁻99% hydrolyzed and (3) PVA 3-Mw: 89⁻98 K, >99% hydrolyzed. The films were exposed to water in (1) the novel 3D-printed holder and (2) directly immersed into a water droplet. After comparing the time taken to dissolve PVA 1⁻3 films, PVA 1 films of 5⁻20% (w/v) are found to be most suitable as time barrier films, due to their optimal dissolution times and physical properties for integration into the customized 3D-printed holder.
- Published
- 2019
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39. Measuring Artificial Sweeteners Toxicity Using a Bioluminescent Bacterial Panel.
- Author
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Harpaz D, Yeo LP, Cecchini F, Koon THP, Kushmaro A, Tok AIY, Marks RS, and Eltzov E
- Subjects
- Aspartame chemistry, Bacteria chemistry, Bacteria genetics, Drinking Water chemistry, Escherichia coli genetics, Groundwater chemistry, Saccharin adverse effects, Saccharin chemistry, Sweetening Agents chemistry, Aspartame adverse effects, Bacteria drug effects, Luminescent Measurements, Sweetening Agents adverse effects
- Abstract
Artificial sweeteners have become increasingly controversial due to their questionable influence on consumers' health. They are introduced in most foods and many consume this added ingredient without their knowledge. Currently, there is still no consensus regarding the health consequences of artificial sweeteners intake as they have not been fully investigated. Consumption of artificial sweeteners has been linked with adverse effects such as cancer, weight gain, metabolic disorders, type-2 diabetes and alteration of gut microbiota activity. Moreover, artificial sweeteners have been identified as emerging environmental pollutants, and can be found in receiving waters, i.e., surface waters, groundwater aquifers and drinking waters. In this study, the relative toxicity of six FDA-approved artificial sweeteners (aspartame, sucralose, saccharine, neotame, advantame and acesulfame potassium-k (ace-k)) and that of ten sport supplements containing these artificial sweeteners, were tested using genetically modified bioluminescent bacteria from E. coli . The bioluminescent bacteria, which luminesce when they detect toxicants, act as a sensing model representative of the complex microbial system. Both induced luminescent signals and bacterial growth were measured. Toxic effects were found when the bacteria were exposed to certain concentrations of the artificial sweeteners. In the bioluminescence activity assay, two toxicity response patterns were observed, namely, the induction and inhibition of the bioluminescent signal. An inhibition response pattern may be observed in the response of sucralose in all the tested strains: TV1061 (MLIC = 1 mg/mL), DPD2544 (MLIC = 50 mg/mL) and DPD2794 (MLIC = 100 mg/mL). It is also observed in neotame in the DPD2544 (MLIC = 2 mg/mL) strain. On the other hand, the induction response pattern may be observed in its response in saccharin in TV1061 (MLIndC = 5 mg/mL) and DPD2794 (MLIndC = 5 mg/mL) strains, aspartame in DPD2794 (MLIndC = 4 mg/mL) strain, and ace-k in DPD2794 (MLIndC = 10 mg/mL) strain. The results of this study may help in understanding the relative toxicity of artificial sweeteners on E. coli , a sensing model representative of the gut bacteria. Furthermore, the tested bioluminescent bacterial panel can potentially be used for detecting artificial sweeteners in the environment, using a specific mode-of-action pattern.
- Published
- 2018
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40. Point-of-Care-Testing in Acute Stroke Management: An Unmet Need Ripe for Technological Harvest.
- Author
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Harpaz D, Eltzov E, Seet RCS, Marks RS, and Tok AIY
- Subjects
- Biomarkers blood, Humans, Molecular Diagnostic Techniques instrumentation, Molecular Diagnostic Techniques methods, Point-of-Care Testing, Stroke blood
- Abstract
Stroke, the second highest leading cause of death, is caused by an abrupt interruption of blood to the brain. Supply of blood needs to be promptly restored to salvage brain tissues from irreversible neuronal death. Existing assessment of stroke patients is based largely on detailed clinical evaluation that is complemented by neuroimaging methods. However, emerging data point to the potential use of blood-derived biomarkers in aiding clinical decision-making especially in the diagnosis of ischemic stroke, triaging patients for acute reperfusion therapies, and in informing stroke mechanisms and prognosis. The demand for newer techniques to deliver individualized information on-site for incorporation into a time-sensitive work-flow has become greater. In this review, we examine the roles of a portable and easy to use point-of-care-test (POCT) in shortening the time-to-treatment, classifying stroke subtypes and improving patient's outcome. We first examine the conventional stroke management workflow, then highlight situations where a bedside biomarker assessment might aid clinical decision-making. A novel stroke POCT approach is presented, which combines the use of quantitative and multiplex POCT platforms for the detection of specific stroke biomarkers, as well as data-mining tools to drive analytical processes. Further work is needed in the development of POCTs to fulfill an unmet need in acute stroke management., Competing Interests: The authors declare no conflict of interest
- Published
- 2017
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41. Adiponectin as an independent predictor of left ventricular hypertrophy in nondiabetic patients with hypertension.
- Author
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Peer M, Mashavi M, Matas Z, Harpaz D, and Shargorodsky M
- Subjects
- Aged, Aldosterone blood, Biomarkers blood, Female, Hemodynamics, Humans, Hypertension blood, Hypertension diagnosis, Hypertension physiopathology, Hypertrophy, Left Ventricular blood, Hypertrophy, Left Ventricular diagnosis, Hypertrophy, Left Ventricular physiopathology, Linear Models, Male, Middle Aged, Multivariate Analysis, Predictive Value of Tests, Pulse Wave Analysis, Renin blood, Risk Factors, Adiponectin blood, Hypertension complications, Hypertrophy, Left Ventricular etiology
- Abstract
We evaluated novel and traditional biomarkers as well as hemodynamic parameters associated with the development of left ventricular hypertrophy (LVH) in nondiabetic patients with hypertension. Nondiabetic patients with hypertension (n = 86) were evaluated for lipids, glucose, insulin, homeostasis model assessment-insulin resistance (HOMA-IR), adiponectin, aldosterone, renin, matrix metalloproteinase 2, and endothelin. Arterial elasticity was evaluated using pulse wave contour. The LVH parameters were assessed echographically. Adiponectin was significantly and inversely associated with left ventricular mass (LVM; P = .032). The aldosterone-renin ratio (ARR) was significantly, positively associated with LVM (P = .031). Fasting insulin as well as HOMA-IR was significantly, positively associated with LVM (P = .036 and P = .025, respectively). In multiple linear regression analysis, adiponectin and ARR remained a significant predictor of LVM. The present study found that adiponectin and ARR are important independent determinants of LVH in nondiabetic patients with hypertension., (© The Author(s) 2014.)
- Published
- 2015
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42. Cardiac indexes in young subjects with and without bicuspid aortic valve.
- Author
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Grossman A, Prokupetz A, Shiber-Ofer S, and Harpaz D
- Subjects
- Adolescent, Adult, Aerospace Medicine, Aorta diagnostic imaging, Aortic Valve physiopathology, Aortic Valve Insufficiency complications, Bicuspid Aortic Valve Disease, Blood Pressure, Case-Control Studies, Echocardiography, Heart Valve Diseases complications, Humans, Israel, Stroke Volume, Young Adult, Aorta anatomy & histology, Aortic Valve abnormalities, Aortic Valve Insufficiency physiopathology, Heart anatomy & histology, Heart Valve Diseases physiopathology, Military Personnel
- Abstract
Objectives: Bicuspid aortic valve (BAV) is a common congenital anomaly. The aeromedical implications of this condition are unclear. This study attempts to evaluate a possible association between BAV with or without aortic regurgitation (AR) and cardiac and aortic morphology in young healthy subjects., Methods: Air force academy applicants undergo routine echocardiography as part of the screening process. All echocardiographic examinations performed in the years 2004-2011 were evaluated. Applicants in whom BAV was identified were divided into those with and without aortic regurgitation. Both groups were compared with an age-matched group of applicants in whom echocardiography was interpreted as normal. All M-mode parameters were compared between the three groups., Results: There were 7042 echocardiographic examinations performed in the years 2004-2010 and 95 applicants (1.35%) were diagnosed with BAV. Of these, 34 applicants had AR (36%) and 61 had no AR. When compared with normal subjects, systolic blood pressure was higher in applicants with BAV (127 mmHg vs. 123 mmHg, P = 0.01). Aortic root diameter, left atrial diameter, left ventricular end systolic volume, interventricular septum thickness and posterior wall thickness were all increased in applicants with BAV compared with applicants without BAV. In those with BAV, no statistically significant differences in M-mode characteristics were noted between applicants with and without aortic regurgitation., Conclusions: BAV in young healthy subjects may influence cardiac morphology irrespective of the presence of aortic regurgitation. Aeromedical disposition for patients with BAV should be based on the presence of the condition and not on the presence of AR, considering the AR is of a mild or minimal degree.
- Published
- 2014
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43. Echocardiographic evaluation and follow-up of cardiac and aortic indexes in aviators exposed to acceleration forces.
- Author
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Assa A, Prokupetz A, Wand O, Harpaz D, and Grossman A
- Subjects
- Adult, Aerospace Medicine, Aorta, Thoracic physiopathology, Cardiovascular Diseases epidemiology, Cardiovascular Diseases physiopathology, Follow-Up Studies, Humans, Incidence, Israel epidemiology, Male, Prognosis, Risk Factors, Time Factors, Young Adult, Aorta, Thoracic diagnostic imaging, Aviation, Cardiovascular Diseases diagnostic imaging, Echocardiography methods, Heart Septum diagnostic imaging, Myocardial Contraction physiology, Ventricular Function, Left physiology
- Abstract
Background: Military jet fighter pilots are routinely exposed to acceleration (+Gz) forces. This recurrent exposure may influence various cardiac parameters. A few previous studies have evaluated the impact of exposure to acceleration forces on cardiac morphology and function, but these studies were mostly based on small cohorts, and subjects did not undergo baseline echocardiographic examinations before +Gz exposure., Methods: Ninety-six jet fighter pilots with high +Gz exposure underwent echocardiographic evaluation before and 7 to 12 years after repeated +Gz exposure. Echocardiographic parameters were recorded using M-mode echocardiography and included left ventricular diameter at end-systole and end-diastole, interventricular septal thickness, thickness of the posterior wall, aortic root diameter and aortic valve opening, diameter of the left atrium, and left ventricular mass. Medical records of the subjects identified were evaluated for the development of adverse events., Results: The average age at the time of the initial echocardiographic examination was 19.2 years. All subjects were healthy, without cardiovascular risk factors, and had no prior exposure to acceleration forces. The average flying period on jet planes at the time of follow-up examination was 1,812 hours. The mean follow-up period was 9.13 years. All parameters evaluated by M-mode echocardiography were not significantly changed from the baseline examination. No adverse events occurred during the follow-up period., Conclusions: Exposure to acceleration forces has no significant impact on cardiac and aortic morphology., (Copyright © 2011 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)
- Published
- 2011
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44. Acceleration forces and cardiac and aortic indexes in jet fighter pilots.
- Author
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Grossman A, Wand O, Harpaz D, Prokupetz A, and Assa A
- Subjects
- Adult, Aerospace Medicine, Aircraft classification, Echocardiography, Heart anatomy & histology, Humans, Israel, Male, Middle Aged, Prospective Studies, Young Adult, Acceleration, Heart physiology, Military Personnel
- Abstract
Background: Military jet fighter pilots are exposed to acceleration (+G(z)) forces which possibly influence various cardiac parameters. Several previous studies have evaluated the impact of exposure to acceleration forces on cardiac morphology and function, but these studies were not prospective and were either based on small samples or compared jet fighter pilots with pilots of low-performance aircraft. The purpose of this study was to evaluate the effect of acceleration forces on cardiac morphologic changes in jet fighter pilots., Methods: Routine echocardiography has been performed for jet fighter pilots since 2003. Medical records of all military jet fighter pilots who underwent echocardiography following 2003 were retrospectively evaluated. Of those, all jet fighter pilots who underwent an additional echocardiography prior to 2003 were identified. Echocardiographic parameters were recorded using M-mode and included left ventricular diameter at end systole and end diastole, interventricular septum thickness, thickness of the posterior wall, aortic root diameter and aortic valve opening, diameter of the left atrium, and left ventricular mass. Medical records of the subjects were evaluated for development of adverse events., Results: There were 72 subjects who underwent 2 echocardiographic examinations with a mean follow-up period of 8.92 yr. Subjects were 18-50 yr old at the time of the initial echocardiographic examination. All parameters evaluated by M-mode were not significantly changed from the baseline examination. No adverse events occurred during the follow-up period., Discussion: Findings of this study suggest that exposure to acceleration forces is not associated with cardiac and aortic morphologic changes.
- Published
- 2011
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45. Age differences in the adherence to treatment guidelines and outcome in patients with ST-elevation myocardial infarction.
- Author
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Gottlieb S, Behar S, Schwartz R, Harpaz D, Shotan A, Zahger D, Hod H, Tzivoni D, and Moriel M
- Subjects
- Adrenergic beta-Antagonists therapeutic use, Age Factors, Aged, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Aspirin therapeutic use, Chi-Square Distribution, Female, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Israel, Kaplan-Meier Estimate, Male, Middle Aged, Myocardial Infarction drug therapy, Myocardial Infarction mortality, Myocardial Infarction surgery, Myocardial Reperfusion statistics & numerical data, Odds Ratio, Prospective Studies, Statistics, Nonparametric, Treatment Outcome, Guideline Adherence statistics & numerical data, Myocardial Infarction therapy
- Abstract
The aim of this study was to assess age differences in the utilization of class-I treatment guidelines and its effect on mortality in patients with ST-elevation myocardial infarction (STEMI). The study included 1026 consecutive patients from the prospective nationwide Acute Coronary Syndrome Israeli Survey (ACSIS). Primary reperfusion was used less often among elderly (age>75 years) patients than among those aged 65-74 and <65 years (46%, 63%, 64%, respectively, p (for trend)=0.004). Class-I evidence-based medications (EBM) at discharge (aspirin, β-blockers, angiotensin converting-enzyme inhibitors=ACEI, angiotensin receptor-blockers=ARBs and statins) were less frequently prescribed to elderly compared to younger age-subgroup (44%, 61%, 57%, respectively; adjusted odds ratio (OR)=0.62; 0.40-0.97 for age ≥ 75 vs. age<65 years). Early and 1-year mortality rates were 3-5-fold higher among the elderly compared to patients <65 years. In the entire cohort use of primary reperfusion was associated with lower 1-year mortality (OR=0.69; 0.47-1.01), as was the use of EBM (OR=0.26; 0.17-0.41). These effects were similar across all age-subgroups but with a greater impact among the elderly, as the number of patients needed to treat (NNT) was significantly lower with advancing age. Better adherence to treatment guidelines may improve the prognosis of elderly patients with STEMI., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF
46. Effects of repeated exposure to acceleration forces (+Gz) and anti-G manoeuvres on cardiac dimensions and performance.
- Author
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Carter D, Prokupetz A, Harpaz D, and Barenboim E
- Abstract
Exposure to acceleration forces (+Gz) and anti-G protective manoeuvres causes changes in cardiac preload and afterload. These changes can result in cardiac hypertrophy or enlargement. Previous studies regarding the effect of acceleration in high-G aviators (HGAs) are few and inconclusive. An echocardiographic study was initiated to determine whether there are structural or functional cardiac differences between HGAs and low-G aviators (LGAs).The present study was a cross-sectional study in which echocardiographic parameters in HGAs were compared with those in LGAs. Both retrospective and prospective data were collected. Fifty aviators were included in each group. The aviators who participated in the present study were randomly chosen from a cohort with similar demographic characteristics and flying hours. No major differences were found in cardiac dimensions and function between HGAs and LGAs. The authors speculate that the reason why no major differences were found was due to the short period of total exposure to very high +Gz forces and anti-G measures.
- Published
- 2010
47. Left ventricular ejection fraction assessment by Tl-201 gated SPECT: a comparison with echocardiography.
- Author
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Harpaz D, Asman A, Kuperstein R, Boaz M, and Chouraqui P
- Subjects
- Echocardiography, Female, Humans, Male, Middle Aged, Retrospective Studies, Risk Factors, Statistics as Topic, Cardiac-Gated Single-Photon Emission Computer-Assisted Tomography instrumentation, Myocardial Perfusion Imaging instrumentation, Stroke Volume, Ultrasonography, Doppler, Ventricular Dysfunction, Left diagnostic imaging, Ventricular Function, Left
- Abstract
Background: Few studies including only a limited number of patients have compared left ventricular ejection fraction (LVEF) assessed by 2-dimensional echocardiography (2-DE) and electrocardiography-gated Tl-201 single-photon emission computed tomography (SPECT)., Hypothesis: LVEF assessment by Tl-201 gated spect is comparable with LVEF assessed by 2-DE in two different echocardiographic laboratories., Material and Methods: Patients (n = 402) underwent Tl-201 gated SPECT in the same laboratory and 2-DE in 2 different laboratories. Patients were divided into 2 groups according to the study laboratory: group 1, at the tertiary hospital and group 2, at a community laboratory., Results: LVEF evaluations were similar (mean LVEF: 50.73% +/- 11.67% by 2-DE vs 50.11% +/- 11.41% by SPECT in group 1 and 57.27% +/- 7.44% by 2-DE vs 57.41% +/- 8.37% by SPECT in group 2). All LVEF measurements were highly correlated (r = 0.7, P<.001). Baseline characteristics differed between the groups, with a higher prevalence of past myocardial infarction in the in-hospital vs the community echo group (46.7% vs 22.2%, P<.01), resulting in a higher LVEF in the latter, both by 2-DE (mean 50.7% +/- 11.7% vs 57.3% +/- 7.4%, P<.01) and SPECT (50.1% +/- 11.4% vs 57.4% +/- 8.4%, P<.01)., Conclusions: The Tl-201 gated SPECT is a reliable clinical tool for LVEF assessment, with good correlation when compared to 2-DE. It may be routinely used as an alternative for patients with poor acoustic visualization and should be performed systematically in patients undergoing myocardial perfusion imaging with Tl-201., (Copyright (c) 2009 Wiley Periodicals, Inc.)
- Published
- 2010
- Full Text
- View/download PDF
48. Physical examination and ECG screening in relation to echocardiography findings in young healthy adults.
- Author
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Landau DA, Grossman A, Sherer Y, Harpaz D, Azaria B, Carter D, Barenboim E, and Goldstein L
- Subjects
- Adolescent, Adult, Chi-Square Distribution, Echocardiography, Electrocardiography, Female, Heart Defects, Congenital diagnostic imaging, Humans, Israel, Male, Military Personnel, Physical Examination, Retrospective Studies, Heart Defects, Congenital diagnosis
- Abstract
Background and Aims: Cardiovascular screening in young adults is an important tool in many occupational settings. Our aim was to test whether screening physical examination and ECG influence the rate of abnormal echocardiogarphic findings in young healthy subjects., Methods: Consecutive echocardiography results of 18- to 20-year-old flight candidates were analyzed retrospectively. Echocardiographies were performed as part of a screening protocol, which includes ECG, physical examination and referral for echocardiography for any positive finding. A second stage includes universal echocardiography for all candidates., Results: 1,066 subjects were evaluated; 489 subjects underwent echocardiography following referral because of abnormal auscultatory or ECG findings. Findings (mostly mild valvular insufficiencies) were demonstrated in 12.7%, with only 0.6% of subjects disqualified. In subjects who underwent universal echocardiography (n = 577), findings (mostly mild valvular insufficiencies) were detected in 18%, with only 0.5% of subjects disqualified., Conclusions: The rate of significant echocardiography findings is extremely low in this young and healthy population. The presence of abnormal findings on either physical examination or ECG screening was not demonstrated to alter the rate of abnormal echocardiographic findings. We suggest that the low yield of screening should be weighed against the cost of an unidentified congenital cardiac lesion in the specific setting., (Copyright 2007 S. Karger AG, Basel.)
- Published
- 2008
- Full Text
- View/download PDF
49. Coronary angiography in the elderly with acute myocardial infarction.
- Author
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Harpaz D, Rozenman Y, Behar S, Boyko V, Mandelzweig L, and Gottlieb S
- Subjects
- Aged, Aged, 80 and over, Cohort Studies, Female, Hospitalization, Humans, Likelihood Functions, Male, Myocardial Infarction mortality, Myocardial Infarction physiopathology, Myocardial Infarction therapy, Prognosis, Radionuclide Imaging, Coronary Angiography, Myocardial Infarction diagnostic imaging
- Abstract
Background: Despite the high mortality rate in elderly patients with acute myocardial infarction (AMI), the value of coronary angiography (CA) in the elderly has been questioned due to a less favorable outcome. The aim of the study was to determine the prognostic significance of CA on mortality of elderly patients AMI in "real world" practice., Methods: The study cohort comprised 1009 elderly (age > or = 75 years) patients with AMI who were derived from three prospective national surveys between 1996 and 2000 in all 25 CCUs operating in Israel. Baseline characteristics, hospital course, management and outcome of 274 (27%) elderly patients who underwent CA during the index hospitalization were compared with 735 (73%) counterpart patients who did not., Results: Patients who underwent CA were on average 2.2 years younger, and were more often with hyperlipidemia (p<0.0001 for each) and with a history of previous percutaneous coronary intervention (p<0.03) than the control group. They had a more favorable clinical presentation: a higher systolic blood pressure (p<0.04), a better Killip class (p<0.03) and an increased frequency of non-Q wave MI (p<0.03). They developed more often recurrent MI (p=0.002) and re-ischemia (p<0.0001). Variables associated with CA use during the index hospitalization were re-infarction, re-ischemia, the year of the index AMI and the availability of an on-site a catheterization laboratory in the hospital, while a higher age and fibrinolytic therapy decreased the likelihood of CA use. Of the patients who underwent CA, 67% underwent coronary revascularization (either PCI and/or CABG). Crude and adjusted mortality rates at 1 year were significantly lower in patients who underwent CA, as compared to counterparts who did not: 21% vs. 37.3%, respectively (p<0.0001), hazard ratio=0.52 (95% confidence interval 0.38-0.71). The benefit of CA was noted in a wide range of subgroups analyzed., Conclusions: In "real world" practice, elderly patients with AMI who undergo CA during hospitalization have a better prognosis at 1 year. Age alone should not be a deterrent to performing CA in elderly patients with AMI. Further large randomized trials are needed to confirm that an invasive approach is beneficial in high-risk elderly patients with AMI., Condensed Abstract: To determine the prognostic significance of coronary angiography (CA) during the course of acute myocardial infarction (AMI) in "real world" practice on mortality of elderly patients, 1009 such patients were studied. Re-infarction, re-ischemia, the year of the index AMI and the availability of an on-site a Cath. Lab. were variables which increased the likelihood of undergoing CA, while a higher age and fibrinolytic therapy decreased this likelihood. The crude and covariate adjusted mortality rates at 1 year were significantly lower in patients who underwent CA in comparison to counterparts who did not: 21% vs. 37.3%, respectively (p<0.0001), hazard ratio 0.52 (95% confidence interval 0.38-0.71). The benefit of CA was noted across a wide range of subgroups analyzed.
- Published
- 2007
- Full Text
- View/download PDF
50. Quadrivalvular heart disease: transition from congenital pulmonary stenosis to rheumatic disease.
- Author
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Katz MG, Schachner A, Harpaz D, Kravtsov V, Rozenman Y, and Sasson L
- Subjects
- Adult, Catheterization, Chronic Disease, Disease Progression, Heart Valve Diseases pathology, Humans, Male, Pulmonary Valve Stenosis congenital, Pulmonary Valve Stenosis pathology, Pulmonary Valve Stenosis therapy, Recurrence, Heart Valve Diseases surgery, Rheumatic Heart Disease complications
- Abstract
The case is reported of a 36-year-old male patient suffering from congenital pulmonary stenosis who previously had undergone pulmonary balloon valvuloplasty. During the past nine years, he had experienced recurrent attacks of rheumatic fever that gradually damaged all four heart valves. The patient underwent aortic, mitral and pulmonary valve replacement with tricuspid valve annuloplasty and pulmonary artery reconstruction. Histologically, all heart valves--including the pulmonary--had similar changes that corresponded to chronic rheumatic disease.
- Published
- 2007
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