Low thrombin generation predicts poor prognosis in ischemic stroke patients after thrombolysis.

Thrombolysis by intravenous recombinant tissue plasminogen activator (rt-PA) is an effective therapy in acute ischemic stroke (AIS). Thrombin generation test (TGT) is a global hemostasis test providing information about the speed and amount of generated thrombin in plasma. Here we aimed to find out whether results of this test before the initiation of thrombolysis might predict outcomes. Study population included 120 consecutive AIS patients, all within 4.5 hours of their symptom onset, who underwent thrombolysis by rt-PA. Blood samples were collected from all patients upon admission and TGT was performed using platelet poor plasma. Clinical data of patients including the NIHSS were registered at admission, day 1 and 7 after therapy. The ASPECT score was assessed using CT images taken before and 24 hours after thrombolysis. Long-term functional outcome was defined 3 months after the event by the modified Rankin Scale. Endogenous Thrombin Potential (ETP) and Peak Thrombin were significantly lower in patients with cardioembolic IS. Symptomatic intracranial hemorrhage (SICH) was found in 6 patients and was significantly associated with low ETP and Peak Thrombin levels. A multiple logistic regression model revealed that an ETP result in the lower quartile is an independent predictor of mortality within the first two weeks (OR: 6.03; 95%CI: 1.2-30.16, p<0.05) and three months after the event (OR: 5.28; 95%CI: 1.27-21.86, p<0.05). Low levels of ETP and Peak Thrombin parameters increase the risk of therapy associated SICH. A low ETP result is an independent predictor of short- and long-term mortality following thrombolysis

Kepler photometry of RRc stars: peculiar double-mode pulsations and period doubling

We present the analysis of four first overtone RR Lyrae stars observed with the Kepler space telescope, based on data obtained over nearly 2.5 yr. All four stars are found to be multiperiodic. The strongest secondary mode with frequency f2 has an amplitude of a few mmag, 20–45 times lower than the main radial mode with frequency f1. The two oscillations have a period ratio of P2/P1 = 0.612–0.632 that cannot be reproduced by any two radial modes. Thus, the secondary mode is non-radial. Modes yielding similar period ratios have also recently been discovered in other variables of the RRc and RRd types. These objects form a homogenous group and constitute a new class of multimode RR Lyrae pulsators, analogous to a similar class of multimode classical Cepheids in the Magellanic Clouds. Because a secondary mode with P2/P1 ∼ 0.61 is found in almost every RRc and RRd star observed from space, this form of multiperiodicity must be common. In all four Kepler RRc stars studied, we find subharmonics of f2 at ∼1/2f2 and at ∼3/2f2. This is a signature of period doubling of the secondary oscillation, and is the first detection of period doubling in RRc stars. The amplitudes and phases of f2 and its subharmonics are variable on a time-scale of 10–200 d. The dominant radial mode also shows variations on the same time-scale, but with much smaller amplitude. In three Kepler RRc stars we detect additional periodicities, with amplitudes below 1 mmag, that must correspond to non-radial g-modes. Such modes never before have been observed in RR Lyrae variables

CONSCIOUS curriculum projects

Rychlickova, J., Batuca, J. R., Nagy, V., Shiely, F., Cechova, Z., Nebeska, K., Souckova, L., Mouly, S., Kovács, G. L., Németh, A., Oliveira, T., Painho, M., Maia, S., & Monteiro, E. C. (2023). Building key competencies clinical trialists of the future: CONSCIOUS curriculum projects. Poster session presented at ORPHEUS2023, "Putting the i’s and o’s in Doctoral Training; International, Intersectoral, Interdisciplinary, and Open Science", Leuven, Belgium. --- This work was supported by the Erasmus+ Programme of the Europe Union (2018-1-HU01-KA203-047811 and 2021-1-CZ01-KA220-HED-000023177).Investigator-initiated clinical trials (IIT) are a broadly interprofessional field that is becoming increasingly relevant to biomedical postgraduate students, especially to validate their research question in clinical practice. Indeed, IIT represent a way to develop individualized treatment and obtain objective evidence to answer questions of day-to-day practice. On the other hand, IIT place greater demands on investigators as they extend their position to include the coordination and management role of the sponsor. At the same time, little formal training in clinical trials is available across European countries in both undergraduate and postgraduate education, and the understanding of biomedical graduates in clinical research organization may not be optimal. A consortium of six European universities was established to fill this gap by preparing a highly practice-based and -oriented curriculum within two consequent projects – CONSCIOUS and CONSCIOUS II. Especially the CONSCIOUS II is focused on postgraduate students and provides them with e-learning lessons of practical guidance on how to design a research question and a clinical trial, the regulatory requirements that need to be met, how to conduct the trial, what activities can be delegated, and how to analyze the results. The second part targets transdisciplinary skills such as leadership, publishing, and teaching. The CONSCIOUS II pedagogical approach moves on to contextualized, case-based exercises allowing to test the acquired skills in simulated situations. Both CONSCIOUS projects thus offer a comprehensive, free-of-charge curriculum for biomedical students but will also open a pilot course with international participation as a further extension of this curriculum.publishersversionpublishersversionpublishe

Direct observation of the thermal demagnetization of magnetic vortex structures in non-ideal magnetite recorders

The thermal demagnetization of pseudo-single-domain (PSD) magnetite (Fe3O4) particles, which govern the magnetic signal in many igneous rocks, is examined using off-axis electron holography. Visualization of a vortex structure held by an individual Fe3O4 particle (~ 250 nm in diameter) during in situ heating is achieved through the construction and examination of magnetic-induction maps. Step-wise demagnetization of the remanence-induced Fe3O4 particle upon heating to above the Curie temperature, performed in a similar fashion to bulk thermal demagnetization measurements, revealed its vortex state remains stable under heating close to its unblocking temperature, and is recovered upon cooling with the same or reversed vorticity. Hence, the PSD Fe3O4 particle exhibits thermomagnetic behavior comparable to a single-domain carrier, and thus vortex-states are considered reliable magnetic recorders for paleomagnetic investigations

Association of Impulsivity and Polymorphic MicroRNA-641 Target Sites in the SNAP-25 Gene.

Impulsivity is a personality trait of high impact and is connected with several types of maladaptive behavior and psychiatric diseases, such as attention deficit hyperactivity disorder, alcohol and drug abuse, as well as pathological gambling and mood disorders. Polymorphic variants of the SNAP-25 gene emerged as putative genetic components of impulsivity, as SNAP-25 protein plays an important role in the central nervous system, and its SNPs are associated with several psychiatric disorders. In this study we aimed to investigate if polymorphisms in the regulatory regions of the SNAP-25 gene are in association with normal variability of impulsivity. Genotypes and haplotypes of two polymorphisms in the promoter (rs6077690 and rs6039769) and two SNPs in the 3' UTR (rs3746544 and rs1051312) of the SNAP-25 gene were determined in a healthy Hungarian population (N = 901) using PCR-RFLP or real-time PCR in combination with sequence specific probes. Significant association was found between the T-T 3' UTR haplotype and impulsivity, whereas no association could be detected with genotypes or haplotypes of the promoter loci. According to sequence alignment, the polymorphisms in the 3' UTR of the gene alter the binding site of microRNA-641, which was analyzed by luciferase reporter system. It was observed that haplotypes altering one or two nucleotides in the binding site of the seed region of microRNA-641 significantly increased the amount of generated protein in vitro. These findings support the role of polymorphic SNAP-25 variants both at psychogenetic and molecular biological levels

Evaluation of Intereye Corneal Asymmetry in Patients with Keratoconus. A Scheimpflug Imaging Study

Purpose: To assess the correlation between keratoconus severity and intereye asymmetry of pachymetric data and posterior elevation values and to evaluate their combined accuracy in discriminating normal corneas from those with keratoconus. Methods: This study included 97 patients: 65 subjects with bilateral normal corneas (NC) and 32 with keratoconus (KC). Central corneal thickness (CCT), thinnest corneal thickness (ThCT) and posterior elevation (PE) at the thinnest point of the cornea were measured in both eyes using Scheimpflug imaging. Intereye asymmetry and its correlation with keratoconus severity were calculated for each variable. The area under the receiver operating characteristic curve (AUROC) was used to compare predictive accuracy of different variables for keratoconus. Results: In normal eyes, intereye differences were significantly lower compared with the keratoconus eyes (p<0.001, for CCT, ThCT and PE). There was a significant exponential correlation between disease severity and intereye asymmetry of steep keratometry (r(2) = 0.55, p<0.001), CCT (r(2) = 0.39, p<0.001), ThCT (r(2) = 0.48, p<0.001) and PE (r(2) = 0.64, p<0.001). After adjustment for keratoconus severity, asymmetry in thinnest pachymetry proved to be the best parameter to characterize intereye corneal asymmetry in keratoconus. This variable had high accuracy and significantly better discriminating ability (AUROC: 0.99) for KC than posterior elevation (AUROC: 0.96), ThCT (AUROC: 0.94) or CCT (AUROC: 0.92) alone. Conclusions: There is an increased intereye asymmetry in keratometry, pachymetry and posterior corneal elevation values in keratoconic patients compared to subjects with normal corneas. Keratoconus patients with more severe disease are also more asymmetric in their disease status which should be taken into account during clinical care