Synthesis and antibacterial activity of new sulfonamide isoxazolo[5,4-b]pyridine derivatives

A series of novel sulfonamide isoxazolo[5,4-b]pyridines were synthesized. The substrates for their synthesis were 3-aminoisoxazolo[5,4-b]pyridine and selected aryl sulfonic chlorides, chlorosulfonic acid and selected amines. Reactions were carried out using the classical and microwave methods. Selected compounds were tested towards antibacterial and antiproliferative activity. The structure of the obtained new derivatives was determined by elemental analysis and acquired IR and 1H NMR spectra. Among the tested compounds: N-isoxazolo[5,4-b]pyridine-3-yl-benzenesulfonamide (2) and N-isoxazolo[5,4-b]pyridine-3-yl-4-methylbenzene-sulfonamide (5) showed antimicrobial activity towards Pseudomonas aeruginosa (ATCC 27853) and Escherichia coli (ATCC 25922) at doses: 125, 250 and 500 μg. Both compounds showed a 50% inhibition of proliferation of breast carcinoma cell line MCF7 at concentrations of 152.56 μg/mL and 160 161.08 Ïg/mL, respectively

Vibration induced by railway traffic-zones of influence on buildings and humans

The article presents selected results of evaluation of the harmfulness of buildings vibrations and influence on humans in buildings caused by railway traffic. The results presented in the paper were part of larger group of in field test which gather, were the basis of creation the zones of influence of railway vibrations. The paper presents the methodology of field test as well as some selected results. The discussion of the results leads to conclusions which are presented, as mentioned above, zones of influence of railway vibrations on building construction as well as on human in the buildings. The proposed zones are different for cargo and passenger trains. The ranges of zones are also different in case of building structure and human perception. All analyzes are compatible with polish codes PN-B-02170:2016 [1] and PN-B-02171:2017 [2] and executed by accredited laboratory with significant participation of the authors. The proposed zones were assumed by manager of the national railway network PKP PLK S.A

Using Unused: Non-Invasive Dynamic FaaS Infrastructure with HPC-Whisk

Modern HPC workload managers and their careful tuning contribute to the high utilization of HPC clusters. However, due to inevitable uncertainty it is impossible to completely avoid node idleness. Although such idle slots are usually too short for any HPC job, they are too long to ignore them. Function-as-a-Service (FaaS) paradigm promisingly fills this gap, and can be a good match, as typical FaaS functions last seconds, not hours. Here we show how to build a FaaS infrastructure on idle nodes in an HPC cluster in such a way that it does not affect the performance of the HPC jobs significantly. We dynamically adapt to a changing set of idle physical machines, by integrating open-source software Slurm and OpenWhisk. We designed and implemented a prototype solution that allowed us to cover up to 90\% of the idle time slots on a 50k-core cluster that runs production workloads

IL16 and IL18 gene polymorphisms in women with gestational diabetes

Objectives: Gestational diabetes mellitus is a carbohydrate intolerance that occurs during pregnancy. Various inflammatory mediators are considered to be risk factors leading to GDM development. Among them are pro-inflammatory cytokines, such as IL16 and IL18. The aim of this study was to examine the association between IL16 and IL18 polymorphisms and GDM. Material and methods: This study included 204 pregnant women with GDM and 207 pregnant women with normal glucose tolerance (NGT). All samples were genotyped in duplicate using allelic discrimination assays with TaqMan® probes. Results: We observed that there was a decreased frequency of IL16 rs4778889 CC genotype carriers among women with GDM (CC vs. CT + TT: OR = 0.14; 95% CI = 0.02–1.15; p = 0.034). However, there was no significant difference in the distri­bution of alleles (C vs. T: OR = 0.81; 95% CI = 0.54–1.21; p = 0.30). There was a decreased frequency of the IL18 rs187238 G allele among GDM women (G vs. C: OR = 0.71; 95% CI = 0.53–0.96; p = 0.027). We also observed a decreased frequency of the IL18 rs1946518 T allele among women with GDM; however, this difference had only borderline statistical significance. We observed an association between IL18 rs187238, rs1946518 and BMI in pregnant women. Conclusions: The results of this study suggest that IL18 rs187238 and rs1946518 polymorphisms may be associated with an increased risk of GDM as well as with BMI in pregnant women

The role of the light source in antimicrobial photodynamic therapy

This work was financially supported by the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant (agreement no. 764837) and NCN Opus grant no. 2019/35/B/ST4/03280. We are also grateful to the Engineering and Physical Sciences Research Council of the UK for financial support from grants EP/R511778/1 and EP/L015110/1.Antimicrobial photodynamic therapy (APDT) is a promising approach to fight the growing problem of antimicrobial resistance that threatens health care, food security and agriculture. APDT uses light to excite a light-activated chemical (photosensitiser), leading to the generation of reactive oxygen species (ROS). Many APDT studies confirm its efficacy in vitro and in vivo against bacteria, fungi, viruses and parasites. However, the development of the field is focused on exploring potential targets and developing new photosensitisers. The role of light, a crucial element for ROS production, has been neglected. What are the main parameters essential for effective photosensitiser activation? Does an optimal light radiant exposure exist? And finally, which light source is best? Many reports have described the promising antibacterial effects of APDT in vitro, however, its application in vivo, especially in clinical settings remains very limited. The restricted availability may partially be due to a lack of standard conditions or protocols, arising from the diversity of selected photosensitising agents (PS), variable testing conditions including light sources used for PS activation and methods of measuring anti-bacterial activity and their effectiveness in treating bacterial infections. We thus sought to systematically review and examine the evidence from existing studies on APDT associated with the light source used. We show how the reduction of pathogens depends on the light source applied, radiant exposure and irradiance of light used, and type of pathogen, and so critically appraise the current state of development of APDT and areas to be addressed in future studies. We anticipate that further standardisation of the experimental conditions will help the field advance, and suggest key optical and biological parameters that should be reported in all APDT studies. More in vivo and clinical studies are needed and are expected to be facilitated by advances in light sources, leading to APDT becoming a sustainable, alternative therapeutic option for bacterial and other microbial infections in the future.Publisher PDFPeer reviewe

The impact of multiple sclerosis relapse treatment on migration of effector T cells – Preliminary study

Migration of inflammatory cells from the blood to the central nervous system (CNS) is crucial for development of multiple sclerosis (MS). Inhibition of this process would allow to control disease activity. The first step confirming this approach would be the analysis of the impact of effective MS relapse therapy on migration of effector T cells. The aim of the study was to analyze the influence of methylprednisolone (MP) on the migratory activity of effector CD4+ T cells from MS patients. Moreover, to study the potential mechanism of this process we studied expression of chemokine receptors on migrating cells. Material and methods Peripheral blood samples were obtained from relapsing-remitting MS (RR-MS) patients during relapse (n=23) and from control group (n=23). After isolation CD4+ T cells were incubated with various concentrations of MP. Then they were stimulated in chemotaxis assay with chemokines CCL3 or CXCL10 or were used to CCR1 and CXCR3 expression analysis. Results CXCL10- and CCL3-stimulated migration of CD4+ T cells was significantly increased in MS. MP was able to reduce in vitro migration of effector T cells induced by CXCL10, but not by CCL3. Inhibition by MP was dose-dependent. Expression of analyzed chemokine receptors was unaltered after MP incubation. Conclusions MP reduced CD4+ T cells migration induced by CXCL10 without affecting CXCR3 expression. These observations demonstrate one of the potential mechanisms of MP action in MS, distinct from inducing cell apoptosis, and suggests the new targets for development of more effective MS treatments

Treatment of antibiotic-resistant bacteria colonizing diabetic foot ulcers by OLED induced antimicrobial photodynamic therapy

KM, KJP and IDWS were supported by the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant (Agreement N°764837) and NCN Opus Grant No. 2019/35/B/ST4/03280.We evaluate the efficacy of antimicrobial Photodynamic Therapy (APDT) for inactivating a variety of antibiotic-resistant clinical strains from diabetic foot ulcers. Here we are focused on APDT based on organic light-emitting diodes (OLED). The wound swabs from ten patients diagnosed with diabetic foot ulcers were collected and 32 clinical strains comprising 22 bacterial species were obtained. The isolated strains were identified with the use of mass spectrometry coupled with a protein profile database and tested for antibiotic susceptibility. 74% of isolated bacterial strains exhibited adaptive antibiotic resistance to at least one antibiotic. All strains were subjected to the APDT procedure using an OLED as a light source and 16 µM methylene blue as a photosensitizer. APDT using the OLED led to a large reduction in all cases. For pathogenic bacteria, the reduction ranged from 1.1-log to > 8 log (Klebsiella aerogenes, Enterobacter cloaca, Staphylococcus hominis) even for high antibiotic resistance (MRSA 5-log reduction). Opportunistic bacteria showed a range from 0.4-log reduction for Citrobacter koseri to > 8 log reduction for Kocuria rhizophila. These results show that OLED-driven APDT is effective against pathogens and opportunistic bacteria regardless of drug resistance.Publisher PDFPeer reviewe

Clinical outcomes in patients undergoing complex, high-risk percutaneous coronary intervention and haemodynamic support with intra-aortic balloon versus Impella pump: Real-life single-centre preliminary results

Background: Patients and mechanical circulatory support assortment, as well as peri-procedural and post-procedural clinical outcomes in complex, high-risk percutaneous coronary interventions (PCIs), underpinned by percutaneous left ventricle assist devices (pLVAD), are a disputable debate. Aim: The aim of the study was to seek differences between patients qualified for complex, high-risk PCIs with an intra-aortic balloon pump (IABP) or Impella pump support, and to compare peri- and post-procedural clinical outcomes. Methods: The presented analysis is a single-centre study, which comprised consecutive patients undergoing complex, high-risk PCIs performed with the pLVAD, either IABP or Impella. Patients included in the current analysis were recruited between January 2018 and December 2021. There were 28 (56%) patients in the Impella group and 22 (44%) in the IABP group. The primary endpoints comprised overall mortality and major adverse cardiovascular events (MACE). These included all-cause mortality, myocardial infarction, revascularisation and cerebrovascular events. Results: Patients from the IABP group were significantly older, had higher left ventricular ejection fraction and less frequent history of PCI, while the in-hospital risk of death assessed by Euroscore II remained similar in the Impella and IABP groups median (interquartile range [IQR]) (2.8  [2–3.8] vs. 2.5 [1.8–5.2], P = 0.73). Patients undergoing complex, high-risk PCIs with pLVAD support presented similar results during the follow-up, assessed by log-rank estimates in terms of MACE (p = 0.41) and mortality rate (p = 0.65).  Conclusions: The use of pLVAD devices in patients undergoing complex, high-risk PCIs, with reduced left ventricular ejection fraction, is a promising treatment option for patients disqualified for surgery cardiac surgeons