• Hall Ditlevsen posted an update 5 hours, 39 minutes ago

    A series of new α-sulfamidophosphonate/sulfonamidophosphonate (4a-n) and cyclosulfamidophosphonate (5a-d) derivatives containing the quinoline or quinolone moiety was designed and synthesized via Kabachnik-Fields reaction in the presence of ionic liquid under ultrasound irradiation. This efficient methodology provides new 1,2,5-thiadiazolidine-1,1-dioxide derivatives 5a-d in one step and optimal conditions. The molecular structures of the novel compounds 4a-n and 5a-d were confirmed using various spectroscopic methods. All these compounds were evaluated for their in vitro antibacterial activity against Gram-negative (Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853) and Gram-positive (Staphylococcus aureus ATCC 27923) bacteria, in addition to three clinical strains (E. coli 1, P. aeruginosa 1, and S. aureus 1). Most of the tested compounds showed more potent inhibitory activities against both Gram-positive and -negative bacteria compared with the sulfamethoxazole reference. The following compounds, 4n, 4f, 4g, 4m, 4l, 4d, and 4e, are the most active sulfamidophosphonate derivatives. Furthermore, these molecules gave interesting zones of inhibition varying between 28 and 49 mm, against all tested bacterial strains, with a low minimum inhibitory concentration (MIC) value ranging from 0.125 to 8 μg/ml. All the synthesized derivatives were also evaluated for their in vitro antifungal activity against Fusarium oxyporum f. Wnt inhibitor sp. lycopersici and Alternaria sp. The results revealed that all the synthesized compounds exhibited excellent antifungal inhibition and the compounds 4f, 4g, 4m, and 4i were the most potent derivatives with MIC values ranging from 0.25 to 1 µg/ml against the two tested fungal strains. The strongest inhibition of bacteria and fungi strains was detected by the effect of quinolone and sulfamide moieties.Magnetic resonance imaging (MRI) has become a commonly used non-ionizing radiation dependent imaging modality which has an excellent spatial resolution with the capability to provide physiological information. Cardiac implantable electronic devices (CIEDs) are used in modern cardiology with a frequency of 150 over 75 years of age and nearly one in three people in this population required MRI during their lifetime. Changes in the CIED structure, electronics, and algorithms paired with changes in the protocol design of MRI have created a relatively safe environment for performing MRI in patients with CIED. Despite their documentation in literature and a guideline document from a professional society, significant skepticism exists in doing MRI in patients with CIEDs. We intend to give an overview of interactions between MRI and CIEDs, including the evidence available in this regard and conclude with the suggestion of a protocol for safely carrying out an MRI in patients with CIEDs.Multiple myeloma (MM) is a heterogeneous bone marrow cancer characterized by proliferation of malignant plasma cells in the bone marrow. One of its major symptoms are hypercalcaemia and bone lesions, which may result in pathologic bone fractures. Receptor activator for nuclear factor κB (RANK) and its ligand, RANKL, are part of an activation pathway for osteoclasts and are thus responsible for bone resorption. Furthermore, RANKL expression is increased in multiple myeloma. In the present study, we investigated the role of single nucleotide polymorphisms (SNPs) in the genes coding for RANK (rs1805034, rs8086340), RANKL (rs7325635, rs7988338), and TACI (rs34562254), a receptor for osteoclast-derived pro-survival factors. The study involved 222 patients and 222 healthy individuals, and the analysis included disease susceptibility, survival, bone lesions, calcium levels, and vascular endothelial growth factor levels. Patients with allele RANK rs1805034 C had higher survival (p = .003). This relationship was especially evident in women (p = .006). Furthermore, allele rs1805034 C was associated with slightly lower median age at diagnosis (64.0 vs. 65.5, p = .008). Allele RANKL rs7325635 A correlated with lower progression-free survival (p = .027), and with lack of early progression (p = .023). Additionally, women with allele rs7325635 G were found to have higher calcium blood concentration (p = .040). Allele TACI rs34562254 A was more common in MM patients in more advanced stages (II and III stage International Staging System) at diagnosis (p = .017), and the SNP showed a slight trend towards association in a multivariate analysis (p = .084). Taken together, our results suggest that RANK rs1805034 and RANKL rs7325635 may have a role in MM development and progression.New imidazolinone-based benzenesulfonamides 3a-e and 4a-e were synthesized in three steps and their chemical structures were confirmed by 1 H NMR (nuclear magnetic resonance), 13 C NMR, and high-resolution mass spectrometry. The benzenesulfonamides used were sulfacetamide (3a, 4a), sulfaguanidine (3b, 4b), sulfanilamide (3c, 4c), sulfadiazine (3d, 4d), sulfamerazine (3e), and sulfathiazole (4e). The compounds were evaluated against carbonic anhydrase (CA) and acetylcholinesterase (AChE) enzymes to obtain possible drug candidate/s. The lead compounds of the series were 3a and 4a against human CA (hCA) I, whereas 3d and 4a were leads against hCA II in terms of Ki values. Series 4 includes more effective CAs inhibitors than series 3 (except 3d). Series 4 compounds having a nitro group (except 4d) were 3.3-4.8 times more selective inhibitors than their corresponding analogues 3a-d in series 3, in which hydrogen was located in place of the nitro group, by considering Ki values against hCA II. Compounds 3c and 4c, where the sulfanilamide moiety is available, were the leads in terms of AChE inhibition with the lowest Ki values. The use of secondary sulfonamides was a more effective modification on CA inhibition, whereas the primary sulfonamide was the effective substitution in terms of AChE inhibitory potency.Neurophysiological investigation of neural processes are hindered by the presence of large artifacts associated with eye movement. Although blind source separation (BSS)-based hybrid algorithms are useful for separating, identifying, and removing these artifacts from EEG, it remains unexamined to what extent neural signals can remain mixed with these artifact components, potentially resulting in unintended removal of critical neural signals. Here, we present a novel validation approach to quantitatively evaluate to what extent horizontal and vertical saccadic eye movement-related artifact components (H and V Comps) are indeed ocular in origin. To automate the identification of the H and V Comps recovered by the second-order blind identification (SOBI), we introduced a novel Discriminant ANd Similarity (DANS)-based method. Through source localization, we showed that over 95% of variance in the SOBI-DANS identified H and V Comps’ scalp projections were ocular in origin. Through the analysis of saccade-related potentials (SRPs), we found that the H and V Comps’ SRP amplitudes were finely modulated by eye movement direction and distance jointly.