Therapeutic hypothermia after sudden cardiac arrest

Od niedawna metoda łagodnej hipotermii leczniczej jest uznawana za standardowe postępowanie, zaakceptowane przez amerykańskie i europejskie towarzystwa naukowe (Europejska Rada Resuscytacji, American Heart Association). W Klinice Kardiologii Uniwersytetu Medycznego w Lublinie od 2013 roku istnieje możliwość zastosowania hipotermii — zarówno zewnętrznej, jak i wewnątrznaczyniowej. W klinice rozpoczęto zbieranie własnych doświadczeń i zgłoszono ośrodek do zarejestrowania w Polskim Rejestrze Hipotermii Leczniczej. Z tego wynika zainteresowanie tematem i motywacja do napisania niniejszego opracowania. W 2012 roku, pod patronatem i z inicjatywy Sekcji Intensywnej Terapii i Resuscytacji Polskiego Towarzystwa Kardiologicznego oraz ówczesnego Krajowego Konsultanta ds. Kardiologii Profesora Grzegorza Opolskiego, powstał Polski Rejestr Hipotermii Leczniczej. Powołano również Radę Naukową Projektu. Zostały w nim zaproponowane standardowe procedury postępowania w celu ujednolicenia zasad leczenia chorych metodą hipotermii. W tym artykule omówiono wskazania i przeciwwskazania, możliwe powikłania i aspekty techniczne hipotermii.Mild therapeutic hypothermia has recently been recognized as standard procedure, accepted by American and European scientific societies (European Resuscitation Council, American Heart Association). In the Department of Cardiology at Medical University of Lublin we recently have possibility to use both invasive and non-invasive hypothermia. In the clinic began gathering our own experience and this center has been submitted for registration in Polish Register of Therapeutic Hypothermia, and that was the reason of our interest in the subject and motivation for the present study. The Polish Registry of Therapeutic Hypothermia came into 2012 year under the patronage of Section of Intensive Care and Resuscitation of Polish Cardiac Society and National Cardiac Consultant Professor Grzegorz Opolski. The Project Scientific Council has been created as well. Standard procedures have been proposed in order to standardize procedures used in treating patients with therapeutic hypothermia. The present study discusses indications and contraindications, possible complications and technical aspects of hypothermia

Gaussianity of Cosmic Velocity Fields and Linearity of the Velocity-Gravity Relation

We present a numerical study of the relation between the cosmic peculiar velocity field and the gravitational acceleration field. We show that on mildly non-linear scales (4-10 Mpc Gaussian smoothing), the distribution of the Cartesian coordinates of each of these fields is well approximated by a Gaussian. In particular, their kurtoses and negentropies are small compared to those of the velocity divergence and density fields. We find that at these scales the relation between the velocity and gravity field follows linear theory to good accuracy. Specifically, the systematic errors in velocity-velocity comparisons due to assuming the linear model do not exceed 6% in beta. To correct for them, we test various nonlinear estimators of velocity from density. We show that a slight modification of the alpha-formula proposed by Kudlicki et al. yields an estimator which is essentially unbiased and has a small variance.Comment: 11 pages, 15 figures; matches the version accepted for publication in MNRA

The Optimal Exponent Base for emPAI Is 6.5

Exponentially Modified Protein Abundance Index (emPAI) is an established method of estimating protein abundances from peptide counts in a single LC-MS/MS experiment. EmPAI is defined as 10PAI minus one, where PAI (Protein Abundance Index) denotes the ratio of observed to observable peptides. EmPAI was first proposed by Ishihama et al [1] who found that PAI is approximately proportional to the logarithm of absolute protein concentration. I define emPAI65 = 6.5PAI-1 and show that it performs significantly better than emPAI, while it is equally easy to compute. The higher accuracy of emPAI65 is demonstrated by analyzing three data sets, including the one used in the original study [1]. I conclude that emPAI65 ought to be used instead of the original emPAI for protein quantitation

Reconstructing Cosmic Peculiar Velocities from the Mildly Nonlinear Density Field

We present a numerical study of the cosmic density vs. velocity divergence relation (DVDR) in the mildly non-linear regime. We approximate the dark matter as a non-relativistic pressureless fluid, and solve its equations of motion on a grid fixed in comoving coordinates. Unlike N-body schemes, this method yields directly the volume-averaged velocity field. The results of our simulations are compared with the predictions of the third-order perturbation theory (3PT) for the DVDR. We investigate both the mean `forward' relation (density in terms of velocity divergence) and the mean `inverse' relation (velocity divergence in terms of density), with emphasis on the latter. On scales larger than about 20 megaparsecs, our code recovers the predictions of 3PT remarkably well, significantly better than recent N-body simulations. On scales of a few megaparsecs, the DVDR predicted by 3PT differs slightly from the simulated one. In particular, approximating the inverse DVDR by a third-order polynomial turns out to be a poor fit. We propose a simple analytical description of the inverse relation, which works well for mildly non-linear scales.Comment: 9 pages, 7 figures (9 ps files), mn.st

Comparison of Pattern Detection Methods in Microarray Time Series of the Segmentation Clock

While genome-wide gene expression data are generated at an increasing rate, the repertoire of approaches for pattern discovery in these data is still limited. Identifying subtle patterns of interest in large amounts of data (tens of thousands of profiles) associated with a certain level of noise remains a challenge. A microarray time series was recently generated to study the transcriptional program of the mouse segmentation clock, a biological oscillator associated with the periodic formation of the segments of the body axis. A method related to Fourier analysis, the Lomb-Scargle periodogram, was used to detect periodic profiles in the dataset, leading to the identification of a novel set of cyclic genes associated with the segmentation clock. Here, we applied to the same microarray time series dataset four distinct mathematical methods to identify significant patterns in gene expression profiles. These methods are called: Phase consistency, Address reduction, Cyclohedron test and Stable persistence, and are based on different conceptual frameworks that are either hypothesis- or data-driven. Some of the methods, unlike Fourier transforms, are not dependent on the assumption of periodicity of the pattern of interest. Remarkably, these methods identified blindly the expression profiles of known cyclic genes as the most significant patterns in the dataset. Many candidate genes predicted by more than one approach appeared to be true positive cyclic genes and will be of particular interest for future research. In addition, these methods predicted novel candidate cyclic genes that were consistent with previous biological knowledge and experimental validation in mouse embryos. Our results demonstrate the utility of these novel pattern detection strategies, notably for detection of periodic profiles, and suggest that combining several distinct mathematical approaches to analyze microarray datasets is a valuable strategy for identifying genes that exhibit novel, interesting transcriptional patterns

Double thrombolysis in early pregnancy can be safe

W niniejszej pracy przedstawiono przypadek kobiety w ciąży ze zdiagnozowaną masywną zatorowością płucną, która przeszła pomyślnie podwójną trombolizę. Pacjentka w wieku 23 lat w 7. tygodniu trzeciej ciąży została przyjęta na Oddział Intensywnej Opieki Kardiologicznej 2 h po nagłym pojawieniu się bólu w klatce piersiowej i duszności. W wykonanym w trybie pilnym badaniu elektrokardiograficznym stwierdzono tachykardię zatokową z typowym zespołem S1Q3T3 i rsr’ w odprowadzeniu V1. W przezklatkowym badanie echokardiograficznym przeprowadzonym przy przyjęciu wykazano przeciążenie prawej komory. W tomografii komputerowej klatki piersiowej z opcją naczyniową (angio-TK) wykonanej w trybie nagłym uwidoczniono rozległą skrzeplinę w obu tętnicach płucnych, ograniczającą przepływ krwi. Początkowo stosowano heparynę niefrakcjonowaną we wlewie, pod kontrolą czasu częściowej tromboplastyny po aktywacji. Mimo leczenia stan pacjentki pogarszał się, dlatego też zdecydowano o podaniu pełnej dawki alteplazy (10 mg bolus, następnie 90 mg przez kolejne 2 h). Uzyskano istotną poprawę stanu klinicznego chorej. Badanie ultrasonograficzne naczyń miednicy i kończyn dolnych wykazało wrzecionowatego kształtu skrzeplinę w rozwidleniu prawej żyły biodrowej wspólnej i zewnętrznej żyły biodrowej. W 10. dniu hospitalizacji, podczas uruchamiania, wystąpiły u pacjentki objawy wstrząsu. Chora wymagała intubacji dotchawiczej, wentylacji mechanicznej i stosowania wlewu amin katecholowych. Drugi raz zastosowano pełną dawkę alteplazy. Nie zaobserwowano dalszych komplikacji podczas ciąży. Pacjentka urodziła w 38. tygodniu siłami natury zdrowego syna ważącego 3580 g (10 punktów w skali Apgar). Po porodzie zamieniono heparynę drobnocząsteczkową na warfarynę (pod kontrolą INR). Wykazano, że podwójna tromboliza u kobiety we wczesnym okresie ciąży może być bezpieczna zarówno dla matki, jak i dziecka, ale konieczne jest przeprowadzenie badań obejmującym większą grupę chorych.We describe the case of pregnant patient with diagnosed massive pulmonary embolism, who underwent successful double thrombolysis. A 23-year-old woman in the 7th week of her 3rd pregnancy was admitted to the Intensive Cardiac Care Unit 2 h after sudden onset of chest pain and dyspnoea. An immediate electrocardiography showed sinus tachycardia with typical S1Q3T3 pattern and rsr’ complex in lead V1. Transthoracic echocardiography on admission revealed right ventricular strain. We performed emergent computed tomography angiography of the chest, which showed significant thrombus in both pulmonary arteries, resulting in restricted blood flow. The patient was treated with unfractionated heparin infusion, monitored by activated partial thromboplastin time. Because of her deteriorating condition, we administered alteplase (10 mg bolus, then 90 mg over the next 2 h). Ultrasonography examination of her pelvis and lower extremities revealed spindle-shaped thrombus of the right common iliac and external iliac veins. On her 10th day of hospitalisation, during the patient’s mobilisation, she presented with symptoms of shock. She needed endotracheal intubation, mechanical ventilation and vasoconstrictor support. We treated her with a second round of full dose alteplase. No complications further developed for the mother or foetus in the subsequent days. She gave birth to a healthy son weighing 3580 g with Apgar score of 10 points in her 38th week of pregnancy by natural delivery. After delivery we switched low molecular weight heparin to warfarin according to her international normalised ratio. In conclusion, double thrombolysis in early pregnancy proved to be safe for both the mother and child, but additional studies need to be performed

Comprehensive Structural and Substrate Specificity Classification of the Saccharomyces cerevisiae Methyltransferome

Methylation is one of the most common chemical modifications of biologically active molecules and it occurs in all life forms. Its functional role is very diverse and involves many essential cellular processes, such as signal transduction, transcriptional control, biosynthesis, and metabolism. Here, we provide further insight into the enzymatic methylation in S. cerevisiae by conducting a comprehensive structural and functional survey of all the methyltransferases encoded in its genome. Using distant homology detection and fold recognition, we found that the S. cerevisiae methyltransferome comprises 86 MTases (53 well-known and 33 putative with unknown substrate specificity). Structural classification of their catalytic domains shows that these enzymes may adopt nine different folds, the most common being the Rossmann-like. We also analyzed the domain architecture of these proteins and identified several new domain contexts. Interestingly, we found that the majority of MTase genes are periodically expressed during yeast metabolic cycle. This finding, together with calculated isoelectric point, fold assignment and cellular localization, was used to develop a novel approach for predicting substrate specificity. Using this approach, we predicted the general substrates for 24 of 33 putative MTases and confirmed these predictions experimentally in both cases tested. Finally, we show that, in S. cerevisiae, methylation is carried out by 34 RNA MTases, 32 protein MTases, eight small molecule MTases, three lipid MTases, and nine MTases with still unknown substrate specificity