Haptoglobin genotype is a determinant of survival and cardiac remodeling after myocardial infarction in diabetic mice

<p>Abstract</p> <p>Background</p> <p>We have recently demonstrated in man that a functional allelic polymorphism in the Haptoglobin (Hp) gene plays a major role in determining survival and congestive heart failure after myocardial infarction (MI). We sought to recapitulate the effect of Hp type on outcomes and cardiac remodeling after MI in transgenic mice.</p> <p>Methods</p> <p>The Hp 2 allele exists only in man. Wild type C57Bl/6 mice carry the Hp 1 allele with high homology to the human Hp 1 allele. We genetically engineered a murine Hp 2 allele and targeted its insertion by homologous recombination to the murine Hp locus to create Hp 2 mice. Diabetes Mellitus (DM) was induced with streptozotocin. MI was produced by occlusion of the left anterior descending artery in DM C57Bl/6 mice carrying the Hp 1 or Hp 2 allele. MI size was determined with TTC staining. Left ventricular (LV) function and dimensions were assessed by 2-dimensional echocardiography.</p> <p>Results</p> <p>In the absence of DM, Hp 1-1 and Hp 2-2 mice had similar LV dimensions and LV function. MI size was similar in DM Hp 1-1 and 2-2 mice 24 hours after MI (50.2 ± 2.1%and 46.9 ± 5.5%, respectively, p = 0.6). However, DM Hp 1-1 mice had a significantly lower mortality rate than DM Hp 2-2 mice 30 days after MI (HR 0.41, 95% CI (0.19–0.95), p = 0.037 by log rank). LV chamber dimensions were significantly increased in DM Hp 2-2 mice compared to DM Hp 1-1 mice 30 days after MI (0.196 ± 0.01 cm²vs. 0.163 ± 0.01 cm², respectively; p = 0.029).</p> <p>Conclusion</p> <p>In DM mice the Hp 2-2 genotype is associated with increased mortality and more severe cardiac remodeling 30 days after MI.</p

Correction of HDL Dysfunction in Individuals With Diabetes and the Haptoglobin 2-2 Genotype

OBJECTIVE—Pharmacogenomics is a key component of personalized medicine. The Israel Cardiovascular Events Reduction with Vitamin E Study, a prospective placebo-controlled study, recently demonstrated that vitamin E could dramatically reduce CVD in individuals with diabetes and the haptoglobin (Hp) 2-2 genotype (40% of diabetic individuals). However, because of the large number of clinical trials that failed to demonstrate benefit from vitamin E coupled with the lack of a mechanistic explanation for why vitamin E should be beneficial only in diabetic individuals with the Hp 2-2 genotype, enthusiasm for this pharmacogenomic paradigm has been limited. In this study, we sought to provide such a mechanistic explanation based on the hypothesis that the Hp 2-2 genotype and diabetes interact to promote HDL oxidative modification and dysfunction

BXT-51072 and the Prevention of Myocardial Ischemia-Reperfusion Injury

Abstract: Oxidative stress is responsible for myocardial injury occurring after ischemia and reperfusion (IR) and has been shown to be modulated by the Haptoglobin (Hp) genotype. In this manuscript we demonstrate that the antioxidant BXT -51072, a glutathione peroxidase synthetic mimic, provides protection against IR injury in a Hp genotype dependent fashion

Health care professionals' knowledge of commonly used sedative, analgesic and neuromuscular drugs: A single center (Rambam Health Care Campus), prospective, observational survey.

BACKGROUND:Pain management and sedation are important aspects in the treatment of hospitalized patients, especially those mechanically ventilated. In many hospitals, such patients are treated not only in intensive care units, but also in other wards. In the nineteen eighties, numerous studies demonstrated a wide array of misconceptions and inadequate knowledge related to commonly used sedative, analgesics and muscle relaxants which may prevent appropriate treatment. Since these publications, multiple studies have shown that appropriate sedation and analgesia are associated with improved clinical outcomes, educational programs were developed and guidelines published. Whether the personnel's knowledge kept up with these changes is unknown. The aim of this study was to determine the current rate of misconceptions and knowledge gaps regarding commonly used sedative, analgesic and neuromuscular drugs. METHODS:In this prospective, observational, cross-sectional survey, a questionnaire was e-mailed to physicians and nurses routinely treating mechanically ventilated patients in Rambam Health Care Campus (Haifa, Israel). RESULTS:355 questionnaires were returned. 82.54% knew that midazolam has no analgesic effect. 71-72% were familiar with the sedative effect of opiates. 27% believed that propofol has analgesic properties and 30.52% thought that rocuronium has a sedative effect. CONCLUSION:Our findings demonstrate that although a lot has been done during the last decades in order to improve the treatment of critically ill patients, the rate of misconceptions regarding pharmacological characteristics of commonly used drugs is unacceptably high. We call for performance of similar surveys in other institutes and for immediate action to improve patients' care

Descriptive characteristics of continuous oximetry measurement in moderate to severe covid-19 patients

Abstract Non-invasive oxygen saturation (SpO2) is a central vital sign used to shape the management of COVID-19 patients. Yet, there have been no report quantitatively describing SpO2 dynamics and patterns in COVID-19 patients using continuous SpO2 recordings. We performed a retrospective observational analysis of the clinical information and 27 K hours of continuous SpO2 high-resolution (1 Hz) recordings of 367 critical and non-critical COVID-19 patients hospitalised at the Rambam Health Care Campus, Haifa, Israel. An absolute SpO2 threshold of 93% most efficiently discriminated between critical and non-critical patients, regardless of oxygen support. Oximetry-derived digital biomarker (OBMs) computed per 1 h monitoring window showed significant differences between groups, notably the cumulative time below 93% SpO2 (CT93). Patients with CT93 above 60% during the first hour of monitoring, were more likely to require oxygen support. Mechanical ventilation exhibited a strong effect on SpO2 dynamics by significantly reducing the frequency and depth of desaturations. OBMs related to periodicity and hypoxic burden were markedly affected, up to several hours before the initiation of the mechanical ventilation. In summary, OBMs, traditionally used in the field of sleep medicine research, are informative for continuous assessment of disease severity and response to respiratory support of hospitalised COVID-19 patients. In conclusion, OBMs may improve risk stratification and therapy management of critical care patients with respiratory impairment

Fermi/gamma-ray burst monitor observations of SGR J0501+4516 bursts

‘In these times, during the rise in the popularity of institutional repositories, the Society does not forbid authors from depositing their work in such repositories. However, the AAS regards the deposit of scholarly work in such repositories to be a decision of the individual scholar, as long as the individual's actions respect the diligence of the journals and their reviewers.’ Original article can be found at : http://iopscience.iop.org/ Copyright American Astronomical SocietyWe present our temporal and spectral analyses of 29 bursts from SGR J0501+4516, detected with the gamma-ray burst monitor on board the Fermi Gamma-ray Space Telescope during 13 days of the source's activation in 2008 (August 22-September 3). We find that the T-90 durations of the bursts can be fit with a log-normal distribution with a mean value of similar to 123 ms. We also estimate for the first time event durations of soft gamma repeater (SGR) bursts in photon space (i.e., using their deconvolved spectra) and find that these are very similar to the T-90 values estimated in count space (following a log-normal distribution with a mean value of similar to 124 ms). We fit the time-integrated spectra for each burst and the time-resolved spectra of the five brightest bursts with several models. We find that a single power law with an exponential cutoff model fits all 29 bursts well, while 18 of the events can also be fit with two blackbody functions. We expand on the physical interpretation of these two models and we compare their parameters and discuss their evolution. We show that the time-integrated and time-resolved spectra reveal that E-peak decreases with energy flux (and fluence) to a minimum of similar to 30 keV at F = 8.7 x 10(-6) erg cm(-2) s(-1), increasing steadily afterward. Two more sources exhibit a similar trend: SGRs J1550-5418 and 1806-20. The isotropic luminosity, L-iso, corresponding to these flux values is roughly similar for all sources (0.4-1.5 x 10(40) erg s(-1)).Peer reviewedFinal Accepted Versio