The Architecture of Coupon-Based, Semi-off-Line, Anonymous Micropayment System for Internet of Things

Part 6: Computational Systems ApplicationsInternational audienceIn the Internet of Things a lot of business opportunities may be identified. The devices in IoT may create ad-hoc temporary networks to provide services or share some resources. Such services are characterized by a great economical potential, especially while provided at mass-scale and for incidental users. However, the development of paid services or resources in IoT is hampered by relatively big transaction costs of payment operations. To deal with this problem, we propose a novel architecture of coupon based, semi off line, anonymous micropayment system to enable transactions in the scope of Internet of Things. User anonymity and security is assured by the usage of standard cryptographic techniques together with novel architectural design of the payment processes. Utilization of a hash function allows generating and verifying electronic coins in computationally efficient way, so as to be executed even in hardware- and software-restricted environment such as Internet of Things

Clinical utility of adjunctive retigabine in partial onset seizures in adults

In ~30% of epileptic patients, full seizure control is not possible, which is why the search for novel antiepileptic drugs continues. Retigabine exhibits a mechanism of action that is not shared by the available antiepileptic drugs. This antiepileptic enhances potassium currents via Kv7.2–7.3 channels, which very likely results from destabilization of a closed conformation or stabilization of the open conformation of the channels. Generally, the pharmacokinetics of retigabine are linear and the drug undergoes glucuronidation and acetylation. Results from clinical trials indicate that, in the form of an add-on therapy, retigabine proves an effective drug in refractory epileptic patients. The major adverse effects of the add-on treatment are dizziness, somnolence, and fatigue. This epileptic drug is also considered for other conditions – neuropathic pain, affective disorders, stroke, or even Alzheimer’s disease

Isobolographic analysis demonstrates the additive and synergistic effects of gemcitabine combined with fucoidan in uterine sarcomas and carcinosarcoma cells

Background: Uterine sarcomas and carcinosarcoma are associated with unfavorable prognosis. The regimens that are used in chemotherapy are associated with high incidence of side effects and usually do not significantly increase patients’ survival rates. In this study we investigated the activity and interactions between gemcitabine and fucoidan, the natural compound known for its anti-tumor properties, in human sarcomas and carcinosarcoma cell models. Methods: SK-UT-1, SK-UT1-B (carcinosarcoma), MES-SA (leiomyosarcoma), and ESS-1 (endometrial stromal sarcoma) cell lines were used for the experiments. Cells were incubated in the presence of gemcitabine, fucoidan, and mixtures, after the incubation the MTT tests were performed. In order to assess the interactions between tested compounds isobolographic analysis was performed. Additional assessments of apoptosis and cell cycle were done. Results: Additive effect of combined treatment with gemcitabine and fucoidan was observed in ESS-1 and SK-UT-1 cell line. Although the supra-additive (synergistic) effect noticed in SK-UT-1B cell line. It was not possible to determine the interactions of fucoidan and gemcitabine in MES-SA cell line due to insuffcient response to treatment. Addition of fucoidan to gemcitabine enhances its proapoptotic activity, what was observed especially in ESS-1 and SK-UT-1B cell lines. The arrest of cell cycle induced by mixture of gemcitabine and fucoidan, superior comparing gemcitabine alone was observed in SK-UT-1B. Conclusions: Obtained data showed that a combination of fucoidan and gemcitabine in uterine endometrial stromal sarcoma and carcinosarcoma cell lines has additive or even synergistic effect in decreasing cell viability. Furthermore, this drug combination induces apoptosis and arrest of cell cycle. The resistance of uterine leiomyosarcoma cell line, justifies searching for other drugs combinations to improve therapy effcacyThe research was founded by Medical University of Lublin (grants No. DS 120, DS 121 and MNmd129)

Occupational exposure to biological agents in Polish paramedics: a narrative review

INTRODUCTION: Research into occupational exposure to biological pathogens during medical personnel workis to a small degree concerned with paramedics. Coming in contact with biological pathogens, like HIV, HCVand HBV viruses, tubercle bacilli, or recently the SARS-CoV-2 virus in the workplace is a contamination risk.This study aims to analyze the occupational exposure of paramedics to biological pathogens at work, thepossibilities of paramedics developing contagious diseases as occupational illnesses, and the prophylaxisthis involves.MATERIAL AND METHODS: The publication was prepared on the basis of a literature review of works availablein the PubMed, SCOPUS, and Google Scholar databases, and on websites of institutions functioning in thearea of public health.BRIEF DESCRIPTION OF THE STATE OF KNOWLEDGE: In Poland, in 2020, there were 1 255 625 cases of SARSCoV-2 registered, 3020 of which are cases found in paramedics, and 12 524 cases of Lyme borreliosis,990 HBV cases, 942 HCV cases, 934 HIV cases. In 2020, there were 1861 occupational diseases, 504 of whichwere contagious or parasitic. Approximately 37 000 needlesticks are estimated to happen every year in medicalfacilities. 40% to 80% of the people who got injuries or cut in the workplace did not report the incident.CONCLUSIONS: There is a need to implement prophylactic and preventative measures to prevent occupationalneedlestick injuries and blood-borne infections amongst paramedics. Paramedics show insufficientknowledge of their ability to apply for an occupational disease diagnosis caused by exposure to biologicalpathogens present in the work environment

Preclinical evaluation of 1,2,4-triazole-based compounds targeting voltage-gated sodium channels (VGSCs) as promising anticonvulsant drug candidates

Epilepsy is a chronic neurological disorder affecting nearly 65–70 million people worldwide. Despite the observed advances in the development of new antiepileptic drugs (AEDs), still about 30-40% of patients cannot achieve a satisfactory seizure control. In our current research, we aimed at using the combined results of radioligand binding experiments, PAMPA-BBB assay and animal experimentations in order to design a group of compounds that exhibit broad spectrum of anticonvulsant activity. The synthesized 4-alkyl-5-substituted-1,2,4-triazole-3-thione derivatives were primarily screened in the maximal electroshock-induced seizure (MES) test in mice. Next, the most promising compounds (17, 22) were investigated in 6 Hz (32 mA) psychomotor seizure model. Protective effect of compound 22 was almost similar to that of levetiracetam. Moreover, these compounds did not induce genotoxic and hemolytic changes in human cells as well as they were characterized by low cellular toxicity. Taking into account the structural requirements for good anticonvulsant activity of 4-alkyl-5-aryl-1,2,4-triazole-3-thiones, it is visible that small electron-withdrawing substituents attached to phenyl ring have beneficial effects both on affinity towards VGSCs and protective activity in the animal models of epilepsy

Sensitization of MCF7 Cells with High Notch1 Activity by Cisplatin and Histone Deacetylase Inhibitors Applied Together

Histone deacetylase inhibitors (HDIs) are promising anti-cancer agents that inhibit proliferation of many types of cancer cells including breast carcinoma (BC) cells. In the present study, we investigated the influence of the Notch1 activity level on the pharmacological interaction between cisplatin (CDDP) and two HDIs, valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA, vorinostat), in luminal-like BC cells. The type of drug-drug interaction between CDDP and HDIs was determined by isobolographic analysis. MCF7 cells were genetically modified to express differential levels of Notch1 activity. The cytotoxic effect of SAHA or VPA was higher on cells with decreased Notch1 activity and lower for cells with increased Notch1 activity than native BC cells. The isobolographic analysis demonstrated that combinations of CDDP with SAHA or VPA at a fixed ratio of 1:1 exerted additive or additive with tendency toward synergism interactions. Therefore, treatment of CDDP with HDIs could be used to optimize a combined therapy based on CDDP against Notch1-altered luminal BC. In conclusion, the combined therapy of HDIs and CDDP may be a promising therapeutic tool in the treatment of luminal-type BC with altered Notch1 activity

N-Benzyl-(2,5-dioxopyrrolidin-1-yl)propanamide (AS-1) with hybrid structure as a candidate for a broad-spectrum antiepileptic drug

In our recent studies, we identified compound N-benzyl-2-(2,5-dioxopyrrolidin-1-yl)propanamide (AS-1) as a broad-spectrum hybrid anticonvulsant which showed potent protection across the most important animal acute seizure models such as the maximal electroshock (MES) test, the subcutaneous pentylenetetrazole (s.c. PTZ) test, and the 6-Hz (32 mA) test in mice. Therefore, AS-1 may be recognized as a candidate for new anticonvulsant effective in different types of human epilepsy with a favorable safety margin profile determined in the rotarod test in mice. In the aim of further pharmacological evaluation of AS-1, in the current study, we examined its activity in the 6-Hz (44 mA) test, which is known as the model of drug-resistant epilepsy. Furthermore, we determined also the antiseizure activity in the kindling model of epilepsy induced by repeated injection of pentylenetetrazole (PTZ) in mice. As a result, AS-1 revealed relatively potent protection in the 6-Hz (44 mA) test, as well as delayed the progression of kindling induced by repeated injection of PTZ in mice at doses of 15 mg/kg, 30 mg/kg, and 60 mg/kg. Importantly, the isobolographic analysis showed that a combination of AS-1 and valproic acid (VPA) at the fixed ratio of 1:1 displayed a supra-additive (synergistic) interaction against PTZinduced seizures inmice. Thus, AS-1may be potentially used in an add-on therapy with VPA. Moreover, incubation of zebrafish larvae with AS-1 substantially decreased the number, cumulative but not the mean duration of epileptiform-like events in electroencephalographic assay. Finally, the in vitro ADME-Tox studies revealed that AS-1 is characterized by a very good permeability in the parallel artificial membrane permeability assay test, excellent metabolic stability on human liver microsomes (HLMs), no significant influence on CYP3A4/CYP2D6 activity, and moderate inhibition of CYP2C9 in a concentration of 10 $\mu$M, as well as no hepatotoxic properties in HepG2 cells (concentration of 10 $\mu$M)

Virtual Web Services

In this paper we propose an application of software agents to provide Virtual Web Services. A Virtual Web Service is a linked collection of several real and/or virtual Web Services, and public and private agents, accessed by the user in the same way as a single real Web Service. A Virtual Web Service allows unrestricted comparison, information merging, pipelining, etc., of data coming from different sources and in different forms. Detailed architecture and functionality of a single Virtual Web Service is user-dependent, and information gathered from existing Web Services may be used in an individual manner. The main goal of the proposal is twofold. First, virtual services allow unrestricted personalization of any Web Service by user-defined software executed at both the server- and the clientside. Second, virtual services provide efficient server-side monitoring and alerting once “vital” information provided by a real service is changed, and this change is of any interest to particular user. In addition, the service users are able to define their own, non-standard interfaces to existing services without a direct interaction with the service provider (information owner). This feature allows for user-specific versioning of services and continuous improvement of the service from the user point of view. By shifting the personalization aspects to the users, we reduce overall maintenance costs (from the service owner point of view) and improve system flexibility and fast adaptation to dynamic changes in the environment and evolving user requirements