transcriptional response of human umbilical vein endothelial cells to low doses of ionizing radiation

We used cDNA microarray hybridization technology to monitor the transcriptional response of Human Umbilical Vein Endothelial (HUVEC) cells to x-rays doses ranging from 2 to 200 cGy. An early time window from irradiation (4h) was selected in order to minimize the effects of the cell cycle blockage eventually induced at high doses of irradiation. Three different gene-clustering algorithms have been used to group the 4134 monitored ORF based on their transcriptional response in function of the irradiation dose. The results show that while few genes exhibit a typical dose-dependent modulation with a variable threshold, most of them have a different modulation pattern, peaking at the two intermediate doses. Strikingly even the lowest dose used (2 cGy) seems to be very effective in transcriptional modulation. These results confirm the physiological relevance of sublethal-dose exposures of endothelial cells and strengthens the hypothesis that alternative dose-specific pathways of radioadaptive response exist in the mammalian cells. 111 genes were found to be modulated at all doses of irradiation. These genes were functionally classified by cellular process or by molecular function. Genes involved in coagulation and peroxidase activity and structural constituent of ribosomes were over-represented among the up-regulated genes as compared with their expected statistical occurrence. Three genes coding for regulatory kinase activities (CDK6; PRCKB1 and TIE) are found down-regulated at all doses of irradiation

Information Flow Analysis for Detecting Non-Determinism in Blockchain

A mandatory feature for blockchain software, such as smart contracts and decentralized applications, is determinism. In fact, non-deterministic behaviors do not allow blockchain nodes to reach one common consensual state or a deterministic response, which causes the blockchain to be forked, stopped, or to deny services. While domain-specific languages are deterministic by design, general purpose languages widely used for the development of smart contracts such as Go, provide many sources of non-determinism. However, not all non-deterministic behaviours are critical. In fact, only those that affect the state or the response of the blockchain can cause problems, as other uses (for example, logging) are only observable by the node that executes the application and not by others. Therefore, some frameworks for blockchains, such as Hyperledger Fabric or Cosmos SDK, do not prohibit the use of non-deterministic constructs but leave the programmer the burden of ensuring that the blockchain application is deterministic. In this paper, we present a flow-based approach to detect non-deterministic vulnerabilities which could compromise the blockchain. The analysis is implemented in GoLiSA, a semantics-based static analyzer for Go applications. Our experimental results show that GoLiSA is able to detect all vulnerabilities related to non-determinism on a significant set of applications, with better results than other open-source analyzers for blockchain software written in Go

Information Flow Analysis for Detecting Non-Determinism in Blockchain (Artifact)

A mandatory feature for blockchain software, such as smart contracts and decentralized applications, is determinism. In fact, non-deterministic behaviors do not allow blockchain nodes to reach one common consensual state or a deterministic response, which causes the blockchain to be forked, stopped, or to deny services. While domain-specific languages are deterministic by design, general-purpose languages widely used for the development of smart contracts such as Go, provide many sources of non-determinism. However, not all non-deterministic behaviours are critical. In fact, only those that affect the state or the response of the blockchain can cause problems, as other uses (for example, logging) are only observable by the node that executes the application and not by others. Therefore, some frameworks for blockchains, such as Hyperledger Fabric or Cosmos SDK, do not prohibit the use of non-deterministic constructs but leave the programmer the burden of ensuring that the blockchain application is deterministic. In this paper, we present a flow-based approach to detect non-deterministic vulnerabilities which could compromise the blockchain. The analysis is implemented in GoLiSA, a semantics-based static analyzer for Go applications. Our experimental results show that GoLiSA is able to detect all vulnerabilities related to non-determinism on a significant set of applications, with better results than other open-source analyzers for blockchain software written in Go

Polydatin beneficial effects in zebrafish larvae undergoing multiple stress types

none8noPolydatin is a polyphenol, whose beneficial properties, including anti-inflammatory and antioxidant activity, have been largely demonstrated. At the same time, copper has an important role in the correct organism homeostasis and alteration of its concentration can induce oxidative stress. In this study, the efficacy of polydatin to counteract the stress induced by CuSO4 exposure or by caudal fin amputation was investigated in zebrafish larvae. The study revealed that polydatin can reduced the stress induced by a 2 h exposure to 10 µM CuSO4 by lowering the levels of il1b and cxcl8b.1 and reducing neutrophils migration in the head and along the lateral line. Similarly, polydatin administration reduced the number of neutrophils in the area of fin cut. In addition, polydatin upregulates the expression of sod1 mRNA and CAT activity, both involved in the antioxidant response. Most of the results obtained in this study support the working hypothesis that polydatin administration can modulate stress response and its action is more effective in mitigating the effects rather than in preventing chemical damages.openPessina A.; Di Vincenzo M.; Maradonna F.; Marchegiani F.; Olivieri F.; Randazzo B.; Gioacchini G.; Carnevali O.Pessina, A.; Di Vincenzo, M.; Maradonna, F.; Marchegiani, F.; Olivieri, F.; Randazzo, B.; Gioacchini, G.; Carnevali, O

Molecular Mechanisms Mediating Antiangiogenic Action of the Urokinase Receptor-Derived Peptide UPARANT in Human Retinal Endothelial Cells

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Intraoperative fetal heart monitoring for non-obstetric surgery: A systematic review

Limited data are available on fetal monitoring during non-obstetric surgery in pregnancy. We performed a systematic review to evaluate the incidence of emergent cesarean delivery performed for non-reassuring fetal heart rate patterns during non-obstetric surgery. Electronic databases were searched from their inception until October 2018 without limit for language. We included studies evaluating at least five cases of intraoperative fetal heart rate monitoring -either with ultrasound or cardiotocography- during non-obstetric surgery in pregnant women at ≥22 weeks of gestation. The primary outcome was the incidence of intraoperative cesarean delivery performed for non-reassuring fetal heart rate monitoring. Non-reassuring fetal heart rate monitoring was defined by attendant personnel, meeting NICHD criteria for category II or III patterns. Data extracted regarded type of study, demographic characteristics, maternal and perinatal outcomes. Statistical analysis was performed for continuous outcomes by calculating mean and standard deviations for appropriate variables. Of 120 studies identified, 4 with 41 cases of intraoperative monitoring met criteria for inclusion and were analyzed. Most (66%) surgeries were indicated for neurological or abdominal maternal issues and were performed under general anesthesia (88%) at a mean gestational age of 28 weeks. Minimal or absent fetal heart variability was noted in most cases and a 10-25 beats per minutes decrease in fetal heart rate baseline was observed in cases with general anesthesia. No intraoperative cesarean deliveries were needed. The incidence of non-reassuring fetal heart rate monitoring was 4.9% (2/41) and were limited to fetal tachycardia during maternal fever. Two (4.9%) cases of non-reassuring fetal heart rate monitoring were noted within the immediate 48 h after surgery, necessitating cesarean delivery. A single case of intrauterine fetal demise occurred four days postoperatively in a woman who had neurosurgery and remained comatose. In conclusion, limited data exist regarding the clinical application of fetal heart rate monitoring at viable gestational ages during non-obstetric surgical procedures. Fetal heart rate monitoring during non-obstetric surgery at ≥22 weeks was not associated with need for intraoperative cesarean delivery, but two (4.9%) cesarean deliveries were performed for non-reassuring fetal heart rate monitoring within 48 h after surgery

N-Glycomic changes in serum proteins in type 2 diabetes mellitus correlate with complications and with metabolic syndrome parameters

Background: Glycosylation, i.e the enzymatic addition of oligosaccharides (or glycans) to proteins and lipids, known as glycosylation, is one of the most common co-/posttranslational modifications of proteins. Many important biological roles of glycoproteins are modulated by N-linked oligosaccharides. As glucose levels can affect the pathways leading to glycosylation of proteins, we investigated whether metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM), pathological conditions characterized by altered glucose levels, are associated with specific modifications in serum N-glycome. Methods: We enrolled in the study 562 patients with Type 2 Diabetes Mellitus (T2DM) (mean age 65.6 +/- 8.2 years) and 599 healthy control subjects (CTRs) (mean age, 58.5 +/- 12.4 years). N-glycome was evaluated in serum glycoproteins. Results: We found significant changes in N-glycan composition in the sera of T2DM patients. In particular, alpha(1,6)-linked arm monogalactosylated, core-fucosylated diantennary N-glycans (NG1(6)A2F) were significantly reduced in T2DM compared with CTR subjects. Importantly, they were equally reduced in diabetic patients with and without complications (P<0.001) compared with CTRs. Macro vascular-complications were found to be related with decreased levels of NG1(6) A2F. In addition, NG1(6) A2F and NG1(3) A2F, identifying, respectively, monogalactosylated N-glycans with alpha(1,6)- and alpha(1,3)-antennary galactosylation, resulted strongly correlated with most MS parameters. The plasmatic levels of these two glycans were lower in T2DM as compared to healthy controls, and even lower in patients with complications and MS, that is the extreme "unhealthy" phenotype (T2DM+ with MS). Conclusions: Imbalance of glycosyltransferases, glycosidases and sugar nucleotide donor levels is able to cause the structural changes evidenced by our findings. Serum N-glycan profiles are thus sensitive to the presence of diabetes and MS. Serum N-glycan levels could therefore provide a non-invasive alternative marker for T2DM and MS

Multidisciplinary studies on a sick-leader syndrome-associated mass stranding of sperm whales (Physeter macrocephalus) along the Adriatic coast of Italy

Mass strandings of sperm whales (Physeter macrocephalus) are rare in the Mediterranean Sea. Nevertheless, in 2014 a pod of 7 specimens stranded alive along the Italian coast of the Central Adriatic Sea: 3 individuals died on the beach after a few hours due to internal damages induced by prolonged recumbency; the remaining 4 whales were refloated after great efforts. All the dead animals were genetically related females; one was pregnant. All the animals were infected by dolphin morbillivirus (DMV) and the pregnant whale was also affected by a severe nephropathy due to a large kidney stone. Other analyses ruled out other possible relevant factors related to weather conditions or human activities. The results of multidisciplinary post-mortem analyses revealed that the 7 sperm whales entered the Adriatic Sea encountering adverse weather conditions and then kept heading northward following the pregnant but sick leader of the pod, thereby reaching the stranding site. DMV infection most likely played a crucial role in impairing the health condition and orientation abilities of the whales. They did not steer back towards deeper waters, but eventually stranded along the Central Adriatic Sea coastline, a real trap for sperm whales

Potential Impact of Microplastics and Additives on the Health Status of Loggerhead Turtles (Caretta caretta) Stranded Along the Central Adriatic Coast

AbstractLoggerhead sea turtle (C. caretta) is the official European bioindicator of marine litter in the Mediterranean Sea. In 2019, 8 sea turtles, out of 28 specimens loggerhead on the Adriatic coast of Molise, were subjected to necropsy. The intestinal contents were collected and the microplastics until 0.45 μm were extracted. Qualitative and quantitative assessments were performed by stereomicroscope observation and spectroscopic analyses (attenuated total reflection-Fourier transform infrared spectroscopy, ATR-FTIR and Raman microspectroscopy, RMS). Moreover, the analytical quantification of polyethylene terephthalate (PET), polycarbonate (PC), para phthalic acid (PTA) and bisphenol A (BPA) in fat and liver tissues was performed by LC-MS/MS. Microparticles ranging from 0.45 μm to 1 mm were found in all turtles, for a total of 623, while plastic litter greater than 1 mm were found only in 4 specimens (ranging from 0.03 to 0.11 g). Nineteen different polymers and 10 pigments, including polyester (100% of animals), high-density polyethylene (50%) and polypropylene (50%) were identified. BPA, PTA and PET were detected in fat and liver tissues of all animals, while PC was found only in 50%. A major prevalence was registered in the abdominal fat tissue, although only PC compounds were significantly higher in abdominal tissue (p < 0.05), except for free PTA with liver tissue being the most contaminated (p < 0.05). Microplastics and additives surely impact the health status of turtles that showed gastrointestinal impairment and an important level of contamination in tissues. Graphical abstrac

Survival after Locoregional Treatments for Hepatocellular Carcinoma: A Cohort Study in Real-World Patients

Evidence of relative effectiveness of local treatments for hepatocellular carcinoma (HCC) is scanty. We investigated, in a retrospective cohort study, whether surgical resection, radiofrequency ablation (RFA), percutaneous ethanol injection (PEI), and transarterial embolization with (TACE) or without (TAE) chemotherapy resulted in different survival in clinical practice. All patients first diagnosed with HCC and treated with any locoregional therapy from 1998 to 2002 in twelve Italian hospitals were eligible. Overall survival (OS) was the unique endpoint. Three main comparisons were planned: RFA versus PEI, surgical resection versus RFA/PEI (combined), TACE/TAE versus RFA/PEI (combined). Propensity score method was used to minimize bias related to non random treatment assignment. Overall 425 subjects were analyzed, with 385 (91%) deaths after a median followup of 7.7 years. OS did not significantly differ between RFA and PEI (HR 1.11, 95% CI 0.79–1.57), between surgery and RFA/PEI (HR 0.95, 95% CI 0.64–1.41) and between TACE/TAE and RFA/PEI (HR 0.88, 95% CI 0.66–1.17). 5-year OS probabilities were 0.14 for RFA, 0.18 for PEI, 0.27 for surgery, and 0.15 for TACE/TAE. No locoregional treatment for HCC was found to be more effective than the comparator. Adequately powered randomized clinical trials are still needed to definitely assess relative effectiveness of locoregional HCC treatment