Primary Percutaneous Coronary Intervention in Acute ST-Elevation Myocardial Infarction: The Experience of "Evagelismos" General Hospital of Athens

BACKROUND: Primary percutaneous coronary intervention (PCI) has been shown to be a better reperfusion strategy in patients with ST-elevation myocardial infarction (STEMI) compared with thrombolysis, particularly when applied early. The objective of the present study was to report our experience from treating patients presenting to the emergency room of our hospital with STEMI with primary PCI. PATIENTS AND METHODS: The population of the study included 100 patients who presented to our hospital with STEMI and underwent primary PCI over a 12-month period. Patients’ clinical and angiographic data were retrospectively collected and patients were followed up for 9 months. Technical details of the primary PCI, including stent implantation, and use of drug eluting stents, thrombus aspiration catheter, or platelet glycoprotein IIb/ΙΙΙa inhibitors were recorded and correlated to clinical and angiographic patient data. RESULTS: Of 196 patients who presented o the emergency room with STEMI during the study period, 100 (51%) patients (85 men and 15 women) underwent primary PCI. PCI was successful with TIMI 3 flow of the infarct-related coronary artery in 79 (79%) patients. Six (6%) patients died during hospitalization and another 4 (4.3%) patients died during the 9-month follow up period. Twenty one (22%) patients required rehospitalization for acute coronary syndrome, of whom 17 needed a repeat PCI and 4 patients were submitted to coronary artery bypass grafting. Left ventricular ejection fraction (LVEF) was <50% in 54 (54%) patients. In 52 patients primary PCI was performed in less than 4 hours from onset of symptoms. In his cohort, 19 patients were thrombolyzed before arriving to the catheterization laboratory. Antithrombotic therapy with platelet glycoprotein IIb/IIIa inhibitors was used in 48 (48%) patients. Univariate analysis showed that the odds of achieving TIMI 3 flow were higher after using IIb/ΙΙΙa inhibitors (odds ratio-OR 6.4) or if the LVEF ≥50% (vs LVEF < 50%) at the beginning of the PCI (OR 6.4). If the time from the onset of symptoms to PCI was >4 hours, the odds of achieving TIMI 3 flow were reduced by 23.4% compared to time from symptoms to PCI <4 hours. The presence of TIMI 3 flow of the infarct-related artery reduced the odds of death by 10.2% compared to the absence of TIMI 3 flow of the infarct-related coronary artery. CONCLUSION: Our results are in keeping with those published by other groups performing primary PCI. We demonstrated the importance of time interval from onset of symptoms until PCI is started. We found that the use of GP IIb/IIIa inhibitors was beneficial and emphasized the predictive value of LVEF >50% and the importance of achieving TIMI 3 flow in the IRA at the end of the procedure

Symbolic Value-Flow Static Analysis: Deep, Precise, Complete Modeling of Ethereum Smart Contracts

We present a static analysis approach that combines concrete values and symbolic expressions. This symbolic value-flow (”symvalic”) analysis models program behavior with high precision, e.g., full path sensitivity. To achieve deep modeling of program semantics, the analysis relies on a symbiotic relationship between a traditional static analysis fixpoint computation and a symbolic solver: the solver does not merely receive a complex “path condition” to solve, but is instead invoked repeatedly (often tens or hundreds of thousands of times), in close cooperation with the flow computation of the analysis. The result of the symvalic analysis architecture is a static modeling of program behavior that is much more complete than symbolic execution, much more precise than conventional static analysis, and domain-agnostic: no special-purpose definition of anti-patterns is necessary in order to compute violations of safety conditions with high precision. We apply the analysis to the domain of Ethereum smart contracts. This domain represents a fundamental challenge for program analysis approaches: despite numerous publications, research work has not been effective at uncovering vulnerabilities of high real-world value. In systematic comparison of symvalic analysis with past tools, we find significantly increased completeness (shown as 83-96% statement coverage and more true error reports) combined with much higher precision, as measured by rate of true positive reports. In terms of real-world impact, since the beginning of 2021, the analysis has resulted in the discovery and disclosure of several critical vulnerabilities, over funds in the many millions of dollars. Six separate bug bounties totaling over $350K have been awarded for these disclosures

Aldehyde Dehydrogenase 1B1 Is Implicated in DNA Damage Response in Human Colorectal Adenocarcinoma

Aldehyde dehydrogenase 1B1 (ALDH1B1) has been correlated with colorectal tumorigenesis and is considered a potential biomarker for colon cancer. Its expression has been associated with attenuation of the cell cycle in the G2/M phase and resistance to DNA damaging agents. The present study examines the role of ALDH1B1 in DNA damage response (DDR) in human colorectal adenocarcinoma. To this end, we utilized an isogenic HT29 cell line pair differing in the expression of ALDH1B1. The overexpression of ALDH1B1 was related to the translational upregulation of the total and phosphorylated (at ser15) p53. Comet and apoptosis assays revealed that the expression of ALDH1B1 protected HT29 cells from etoposide-induced DNA damage as well as apoptosis, and its overexpression led to increased constitutive phosphorylation of H2AX (at ser139). Furthermore, the expression profile of a variety of DNA damage signaling (DDS)-related genes was investigated by utilizing the RT2 profiler™ PCR array. Our results demonstrated that ALDH1B1 triggered a transcriptional activation of several DNA repair-related genes (MRE11A, PMS1, RAD18 and UNG). Finally, Spearman’s rank correlation coefficient analysis in 531 publicly available colorectal adenocarcinoma clinical samples indicated the statistically significant positive correlation between ALDH1B1 and DDR and repair genes or proteins, such as APEX1, FEN1, MPG, UNG, XRCC1, DDB1, XPC, CIB1, MRE11, PRKDC, RAD50, RAD21, TP53BP1, XRCC6 and H2AX. Collectively, our results suggest that ALDH1B1 may play an essential role in the DDR and DNA repair processes. Further studies on ALDH1B1 will elucidate its precise role in DDR

Dream Recall/Affect and Cortisol: An Exploratory Study

The effect of cortisol on dreams has been scarcely studied. The aim of this exploratory study was to assess the possible effect of cortisol levels on dream recall/affect, considering, in female subjects, their menstrual cycle phase. Fifteen men and fifteen women were recruited. Saliva samples were used for the detection of cortisol levels. Participants were instructed to provide four saliva samples, during three consecutive days. After awakening, on the second and third day, they were asked whether they could recall the previous night’s dreams and whether these were pleasant or unpleasant. Female subjects followed this procedure twice: firstly, during the luteal phase and, secondly, during the follicular phase of the menstrual cycle. Subjects with higher evening or higher morning cortisol levels tended to show increased dream recall; a non-statistically significant association between morning cortisol levels and positive dream affect was also found. This association acquired statistical significance for salivary morning cortisol levels exceeding the upper normal level of 19.1 nmol/L (OR: 4.444, 95% CI: 1.108–17.830, p-value: 0.039). No connection between menstrual cycle stages and dream recall/affect was detected. In conclusion, cortisol may be a crucial neuromodulator, affecting dream recall and content. Therefore, its effects on sleep and dreams should be further studied

No meaningful drug interactions with doravirine, lamivudine and tenofovir disoproxil fumarate co-administration.

BACKGROUND: Doravirine (DOR) is a novel non-nucleoside reverse transcriptase inhibitor available as a single tablet and a three-drug combination with lamivudine (3TC) and tenofovir disoproxil fumarate (TDF) to treat HIV-1 infection. These analyses assessed pharmacokinetic (PK) interactions with co-administration. METHODS: Two trials were conducted. Study 1: two-period, fixed-sequence; 8 healthy participants; Period 1, DOR 100 mg followed by ≥7-day washout; Period 2, TDF 300 mg once daily for 18 days, co-administration of DOR 100 mg on day 14. Study 2: three-period, crossover, 15 healthy participants; Treatment A, DOR 100 mg; Treatment B, 3TC 300 mg + TDF 300 mg; Treatment C, DOR 100 mg + 3TC 300 mg + TDF 300 mg; ≥7-day washout between periods. RESULTS: Study 1: geometric mean ratios (GMRs) (90% confidence interval [CI]) of DOR AUC0–∞ and C24h (DOR + TDF / DOR) were 0.95 (0.80, 1.12) and 0.94 (0.78, 1.12), respectively. Study 2: GMRs (90% CI) of DOR AUC0–∞ and C24h (DOR + 3TC + TDF / DOR) were 0.96 (0.87, 1.06) and 0.94 (0.83, 1.06), respectively. GMRs (90% CI) of 3TC and tenofovir AUC0–∞ (DOR + 3TC + TDF / 3TC + TDF) were 0.94 (0.88, 1.00) and 1.11 (0.97, 1.28), respectively. Study drugs were generally well tolerated. CONCLUSIONS: Multiple doses of TDF did not have a clinically meaningful effect on DOR PK. The PK of DOR were similar when administered alone or in combination with 3TC and TDF. DOR had no meaningful effect on the PK of 3TC and tenofovir

P146 The Predictive Role of Arterial Stiffness in the Development of Acute Kidney Injury in Patients Undergoing Surgical Aortic Valve Replacement

Abstract Purpose/Background/Objectives Acute kidney injury (AKI) is a serious postoperative complication. Increased arterial stiffness has been shown to be an independent risk factor for cardiovascular events. Our aim was to investigate whether arterial stiffness is a predictor of AKI in patients following surgical aortic valve replacement (SAVR). Methods Eighty-four patients (mean age 72 ± 8 years, 34 females) with moderate to severe aortic stenosis undergoing SAVR were included. As indicators of arterial stiffness aortic hemodynamics, carotid-femoral pulse wave velocity (cfPWV) and brachial-ankle pulse wave velocity (baPWV) were assessed prior to surgery. Renal dysfunction was defined when eGFR was below 60 ml/min (n = 28, 33%). AKI was defined using KDIQO criteria. Results Twelve patients (14%) developed AKI. There was no significant difference in aortic hemodynamics and cfPWV between the two groups. baPWV significantly correlated with AKI (r = 0.313, p = 0.004). In logistic regression analysis, increase of baPWV per 1 Standard Deviation (Odds Ratio [OR] = 2.76, 95% Confidence intervals [CI]: 1.25–6.11, p = 0.012) and presence of renal dysfunction (OR = 14.93, 95% CI: 2.55–87.32, p = 0.003) were associated with higher risk for AKI even after adjustment for age, gender, systolic blood pressure and diabetes. baPWV was a stronger predictor of AKI than baseline creatinine (Area under the curve [AUC] 0.68, 95% CI: 0.52–0.84, p = 0.05 vs AUC 0.61, 95% CI: 0.46–0.77, p = 0.21; p < 0.05). Conclusion baPWV could be considered as a useful predictive biomarker for AKI after SAVR, especially in patients with renal dysfunction prior to surgery

Cobalt stimulates HIF-1-dependent but inhibits HIF-2-dependent gene expression in liver cancer cells

Hypoxia-inducible factors (HIFs) are transcriptional regulators that mediate the cellular response to low oxygen. Although HIF-1 is usually considered as the principal mediator of hypoxic adaptation, several tissues and different cell types express both HIF-1 and HIF-2 isoforms under hypoxia or when treated with hypoxia mimetic chemicals such as cobalt. However, the similarities or differences between HIFI and HIF-2, in terms of their tissue- and inducer-specific activation and function, are not adequately characterized. To address this issue, we investigated the effects of true hypoxia and hypoxia mimetics on HIF-1 and HIF-2 induction and specific gene transcriptional activity in two hepatic cancer cell lines, Huh7 and HepG2. Both hypoxia and cobalt caused rapid induction of both HIF-l alpha and HIF-2 alpha proteins. Hypoxia induced erythropoietin (EPO) expression and secretion in a HIF-2-dependent way. Surprisingly, however, EPO expression was not induced when cells were treated with cobalt. In agreement, both HIFI - and HIF-2-dependent promoters (of PGK and SOD2 genes, respectively) were activated by hypoxia while cobalt only activated the HIF-1-dependent PGK promoter. Unlike cobalt, other hypoxia mimetics such as DFO and DMOG activated both types of promoters. Furthermore, cobalt impaired the hypoxic stimulation of HIF-2, but not HIF-1, activity and cobalt-induced HIF-2a interacted poorly with USF-2, a HIF-2-specific co-activator. These data show that, despite similar induction of HIF-la and HIF-2a protein expression, HIF-1 and HIF-2 specific gene activating functions respond differently to different stimuli and suggest the operation of oxygen-independent and gene- or tissue-specific regulatory mechanisms involving additional transcription factors or co-activators. (C) 2013 Elsevier Ltd. All rights reserved

Primary Percutaneous Coronary Intervention in Acute ST-Elevation Myocardial Infarction: The Experience of "Evagelismos" General Hospital of Athens

We report our experience from treating a large number of patients who presented to the Emergency Department of our Hospital with ST-elevation acute myocardial infarction (AMI) with primary percutaneous coronary intervention (PCI). Of the 196 patients who presented with ST elevation AMI over a period of 12 months, 100 (51%) patients underwent primary PCI. Clinical and angiographic data were collected and patients were followed up for 9 months. Technical details of the primary PCI, including use of balloon, use of thrombus aspiration catheter, stent implantation, use of drug eluting stents, and use of GP IIb/IIIa inhibitors were recorded and correlated to clinical and angiographic patient data. Our results are in keeping with those published by other groups performing primary PCI. We demonstrated the importance of time interval from onset of symptoms until PCI is started. We found that the use of GP IIb/IIIa inhibitors was beneficial and emphasized the predictive value of left ventricular ejection fraction &gt;50% and the importance of achieving TIMI 3 flow in the AMI related artery at the end of the procedure