Effects of genistein on insulin pathway-related genes in mouse differentiated myoblast C2C12 cell line: evidence for two independent modes of action

Introduction. Genistein (plant isoflavone) is a well-known anti-cancer drug with estrogenic-like properties. Genistein also regulates sugar and lipid metabolism; thus, it has anti-diabetic properties. The aim of the study was to evaluate in vitro effects of genistein on glucose transport, fatty acids oxidation, activation of PKB, and expression of genes related to insulin pathway in differentiated myoblast C2C12 mouse cell line. Material and methods. Differentiated myoblast C2C12 mouse cell line was used to assess the effects of different genistein concentrations on glucose transport and fatty acids oxidation measured by radioactivity technique, activation of PKB, and expression of selected genes related to insulin signaling pathway (IR-a, IR-b, IRS-1, PKB, GLUT-4, PP2A, SH-PTP2) at the mRNA and protein levels. Cells were incubated with various concentrations of genistein under standard conditions for 0–48 hours.Results. Genistein in low concentrations (0.1–1 μM) significantly increased glucose transport and decreased fatty acids oxidation in C2C12 cells after 48 h of incubation. High concentration of genistein (50 μM) had the opposite effect. Genistein stimulated PKB phosphorylation during the first 5–10 minutes of incubation. There was no significant impact on the protein expression of selected genes (IR-a, IR-b, IRS-1, PKB, GLUT-4, PP2A-Ca, ER-a and ER-b) after 48 h treatment. We observed inverse correlation between genistein concentration and the expression of SH-PTP2 protein. Genistein affected the expression pattern of mRNAs for genes related to the insulin pathway, however, not the expression of the encoded proteins. Conclusions. The results of this study showed that depending on the concentration and time of incubation genistein significantly affects glucose and lipid metabolism and at low concentration modifies expression patternof a few genes in C2C12 cells

Bounded Arithmetic in Free Logic

One of the central open questions in bounded arithmetic is whether Buss' hierarchy of theories of bounded arithmetic collapses or not. In this paper, we reformulate Buss' theories using free logic and conjecture that such theories are easier to handle. To show this, we first prove that Buss' theories prove consistencies of induction-free fragments of our theories whose formulae have bounded complexity. Next, we prove that although our theories are based on an apparently weaker logic, we can interpret theories in Buss' hierarchy by our theories using a simple translation. Finally, we investigate finitistic G\"odel sentences in our systems in the hope of proving that a theory in a lower level of Buss' hierarchy cannot prove consistency of induction-free fragments of our theories whose formulae have higher complexity

Status Update and Interim Results from the Asymptomatic Carotid Surgery Trial-2 (ACST-2)

Objectives: ACST-2 is currently the largest trial ever conducted to compare carotid artery stenting (CAS) with carotid endarterectomy (CEA) in patients with severe asymptomatic carotid stenosis requiring revascularization. Methods: Patients are entered into ACST-2 when revascularization is felt to be clearly indicated, when CEA and CAS are both possible, but where there is substantial uncertainty as to which is most appropriate. Trial surgeons and interventionalists are expected to use their usual techniques and CE-approved devices. We report baseline characteristics and blinded combined interim results for 30-day mortality and major morbidity for 986 patients in the ongoing trial up to September 2012. Results: A total of 986 patients (687 men, 299 women), mean age 68.7 years (SD ± 8.1) were randomized equally to CEA or CAS. Most (96%) had ipsilateral stenosis of 70-99% (median 80%) with contralateral stenoses of 50-99% in 30% and contralateral occlusion in 8%. Patients were on appropriate medical treatment. For 691 patients undergoing intervention with at least 1-month follow-up and Rankin scoring at 6 months for any stroke, the overall serious cardiovascular event rate of periprocedural (within 30 days) disabling stroke, fatal myocardial infarction, and death at 30 days was 1.0%. Conclusions: Early ACST-2 results suggest contemporary carotid intervention for asymptomatic stenosis has a low risk of serious morbidity and mortality, on par with other recent trials. The trial continues to recruit, to monitor periprocedural events and all types of stroke, aiming to randomize up to 5,000 patients to determine any differential outcomes between interventions. Clinical trial: ISRCTN21144362. © 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved

Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

Background: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods: ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings: Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation: Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding: UK Medical Research Council and Health Technology Assessment Programme

Predictors for Outcome After Open and Endovascular Repair of Ruptured Abdominal Aortic Aneurysms.

Objectives. The aims of the present study were to analyze patient- and management-related predictors for outcome after open (OR) and endovascular repair (EVAR) of ruptured abdominal aortic aneurysm (rAAA). Design. Retrospective study. Materials. The in-hospital registry of Malmo University Hospital identified 162 patients operated on due to rAAA between 2000 and 2004. Methods. Patient- and management-related predictors for outcome were analysed. Results. Preoperative CT in 39 out of 62 circulatory unstable patients was not associated with increased mortality (P = 0.60). There was a significant increase in repairs performed by EVAR during the study period (p < 0.001), and in 2004 EVAR exceeded the annual rate of OR. Patients in the EVAR group were older (p = 0.025), whereas patients in the OR group more often suffered from unconsciousness after presentation (p = 0.004). Age, unconsciousness after presentation and haemoglobin were significantly associated with in-hospital mortality when tested in a multivariate logistic regression model (p = 0.002, p = 0.003 and p < 0.001, respectively). The in-hospital mortality for patients undergoing OR and EVAR was 45% (48/106) and 34% (19/56), respectively (p = 0.16). Diagnosis of abdominal compartment syndrome (p = 0.005) and intestinal infarction (p = 0.002) was associated with poor survival. Conclusions. Patient-related factors such as age, loss of consciousness and haemoglobin predicts outcome in a population where both emergency OR and EVAR for the treatment of rAAA is feasible

Application of SAR data for the monitoring of ground deformations caused by mining activities in the area of the upper Silesian Coal Basin : the results of DORIS project (EC-FP7)

W artykule zaprezentowano wykorzystanie metod interferometrii satelitarnej (PSInSAR i DInSAR) dla obserwacji deformacji powierzchni terenu na obszarze Górnośląskiego Zagłębia Węglowego (GZW). Prezentowane wyniki zostały pozyskane w trakcie realizacji projektu DORIS (ECFP 7, Grant Agreement n. 242212, www.doris-project.eu). Większość satelitarnych danych interferometrycznych przetworzono w wyspecjalizowanej firmie Tele – Rilevamento Europa – T. R. E, we Włoszech. Dane te pochodziły z różnych satelitów, takich jak: ERS 1 i 2, ENVISAT, ALOS- PALSAR oraz TerraSAR-X i objęły trzy pasma zakresu widma mikrofal (SAR): L, C oraz X. Archiwalne dane pasma C z satelitów Europejskiej Agencji Kosmicznej objęły obserwację przemieszczeń powierzchni terenu w okresie od 1992 do 2010, w dwóch oddzielnych pakietach danych z przedziałów czasowych 1992÷2000 oraz 2003÷2010. Jako obszary testowe dla obserwacji przemieszczeń na terenach zamkniętych kopalń wybrano Kopalnie Węgla Kamiennego „Sosnowiec” i „Saturn”, które zakończyły działalność w 1995 i 1997 r. Pomimo bieżącego wypompowywania wód z zamkniętych kopalni ich poziom podniósł się o kilkadziesiąt metrów. W związku z powyższym, wskutek zmian ciśnienia piezometrycznego i jego oddziaływania na górotwór zaobserwowano podnoszenie powierzchni terenu. Analiza danych z pasm L i X pozwoliła z kolei na śledzenie w ciągu kilku miesięcy przebiegu zmian podziemnego frontu robót, który odzwierciedlał się na powierzchni terenu, na przetworzonych zobrazowaniach radarowych. Analizę taką przeprowadzono w rejonie KWK „Halemba-Wirek”. Najbardziej efektywne w tym zakresie okazały się wysoko rozdzielcze dane TerraSAR-X, przetwarzane przy pomocy algorytmu SqueeSAR. Serie czasowe PS pasma X pomogły zidentyfikować bardzo niewielkie przemieszczenia, natomiast uzupełniające dane na temat większych przemieszczeń (w zakresie kilkudziesięciu centymetrów) można było uzyskać dzięki analizie prążków interferometrycznych. Uzyskane rezultaty dowiodły, że przemieszczenia powierzchni terenu w rejonie zamkniętych kopalń zachodzą bardzo długo i znacznie przekraczają okres 5 lat, który oficjalnie uznawany jest za granicę bezpieczeństwa i dopuszczają dowolne zagospodarowanie tych obszarów.The application of satellite interferometric methods (PSInSAR and DInSAR) for observations of ground deformations in the Upper Silesian Coal Basin (Southern Poland) is the subject of this paper. The presented results were obtained during implementation of the DORIS project (EC FP7, Grant Agreement n. 242212, www.doris-project.eu). Several InSAR datasets were analysed in this area. Most of them were processed by Tele-Rilevamento Europe - T.R.E. s.r.l. Italy. The sets of data came from different SAR satellites: ERS 1 and 2, ENVISAT, ALOS- PALSAR and TerraSAR-X and cover three different SAR bands (L, C and X). Archival data from C-band European Space Agency satellites ERS and ENVISAT, allowed to obtain information on ground movement from 1992 to 2010 in two separate datasets (1992-2000 and 2003-2010). As an example of ground motion upon inactive mining areas, two coal mines were selected: Sosnowiec and Saturn where exploitation of coal mine stopped in 1995 and 1997, respectively. Despite of well pumping after the closure of the mines, underground waters returned to the natural horizon, raising up several dozen meters; the high permeability of hydrogeological subregion and an insufficient water withdrawal from the abandoned mines. The analysis of interferometric L and X-band data in the Upper Silesia has enabled observation and monitoring of the underground mining front in a period of several months. It was indicated at the example from Halemba-Wirek coal mine. The analysis of the TerraSAR X dataset, processed by SqueeSAR algorithms proved to be the most effective for this purpose. X-band PSI time series can help to identify small, seemingly, negligible movements and are successfully supplemented by fringes when a displacement becomes significant. The obtained results on ground deformation proved that ground motion above the abandoned mines continues long after their closure. Therefore, the existing regulations stating that abandoned mines are considered as fully safe, in five years after mine closure, should be changed. Moreover, it should be emphasized that constructions in these area should be avoided as potential risk exists