Expanding the scope of prenylated 1,2,3-triazoles as new antiparasitic drug candidates

We have previously shown that prenyl and aliphatic triazoles are interesting motifs to prepare new chemical entities for antiparasitic and antituberculosis drug development. In this opportunity a new series of prenyl-1,2,3-triazoles were prepared from isoprenyl azides and different alkynes looking for new antimalarial drug candidates. The compounds were prepared by copper(I) catalyzed dipolar cycloaddition of the isoprenyl azide equilibrium mixture providing exclusively 1,4-disubstituted 1,2,3-triazols in a regiospecific fashion. The complete collection of 64 compounds was tested on chloroquine -sensitive, Sierra Leone (D6), and the chloroquine-resistant, Indochina (W2), strains of Plasmodium falciparum and those compounds which were not previously reported were also tested against Leishmania donovani , the causative agent for visceral leishmaniasis. Thirteen analogs displayed antimalarial activity with IC50 below 10 uM, while the antileishmanial activity was less potent than the previously reported analogs. The cytotoxicity assay against Vero cells revealed that none of the compounds was cytotoxic up to concentrations of 4.75 ug/mL. Compounds 1o and 1r were identified as the most promising antimalarial drug leads with IC50 below 3.0 uM for both CQ-sensitive and resistant P. falciparum strains. Finally, a chemoinformatic in silico analysis was performed to evaluate physicochemical parameters, cytotoxicity risk and drug score. The validation of a bifunctional farnesyl/geranylgeranyl diphosphate synthase PfFPPS/GGPPS as the potential target of the antimalarial activity of selected analogs should be further investigated.

The Livre d'Airs et de Simphonies Meslés de Quelques Fragmens d’Opéra 1697 of Pierre Gillier: An Edition and Study

<p>The Livre d’Airs et de Simphonies meslés de quelques fragmens d’Opéra de la Composition de P. Gillier (Book of Airs and Instrumental Pieces mixed with some operatic fragments composed by Pierre Gillier) was published in Paris in 1697. Its contents are dedicated to the twenty-three year-old Philippe duc de Chartres (son of Philippe I duc d’Orléans, only brother of Louis XIV). Of the life of Pierre Gillier (1665- died after 1713), we know only that he possessed an haute-contre voice, and was employed as a chamber musician in the households of Philippe I duc d’Orléans and of his son, Philippe II. The Parisian courts of the Dauphin, and of Philippe I supported the secular arts that Louis XIV (self-exiled at Versailles), had rejected. There was an insatiable appetite for amateur music making in late seventeenthcentury France, notably in the broader societal context of airs: the salons. Composers generally wrote individual airs (of the serious and drinking types), complete operas, or theatre works. In such a context, Gillier’s publication is unique: his declared aim was to assemble a collection of serious songs linked together tonally in suites with instrumental pieces by means of their keys, for chamber music performance. As a precursor to the arrival in France of the multi-movement sonata and cantata, Gillier’s grouping together of instrumental and vocal movements to make larger musical entities has exceptional interest. His procedure has close links with theatrical practice. The thesis includes a critical edition of Gillier's complete collection made from the copy preserved in the Bibliothèque Nationale de France as F-Pn/ Rés. Vm7 305. The edition is prefaced by a study of performance practices in vocal and instrumental music in late seventeenth-century France.</p>

The Livre d'Airs et de Simphonies Meslés de Quelques Fragmens d’Opéra 1697 of Pierre Gillier: An Edition and Study

<p>The Livre d’Airs et de Simphonies meslés de quelques fragmens d’Opéra de la Composition de P. Gillier (Book of Airs and Instrumental Pieces mixed with some operatic fragments composed by Pierre Gillier) was published in Paris in 1697. Its contents are dedicated to the twenty-three year-old Philippe duc de Chartres (son of Philippe I duc d’Orléans, only brother of Louis XIV). Of the life of Pierre Gillier (1665- died after 1713), we know only that he possessed an haute-contre voice, and was employed as a chamber musician in the households of Philippe I duc d’Orléans and of his son, Philippe II. The Parisian courts of the Dauphin, and of Philippe I supported the secular arts that Louis XIV (self-exiled at Versailles), had rejected. There was an insatiable appetite for amateur music making in late seventeenthcentury France, notably in the broader societal context of airs: the salons. Composers generally wrote individual airs (of the serious and drinking types), complete operas, or theatre works. In such a context, Gillier’s publication is unique: his declared aim was to assemble a collection of serious songs linked together tonally in suites with instrumental pieces by means of their keys, for chamber music performance. As a precursor to the arrival in France of the multi-movement sonata and cantata, Gillier’s grouping together of instrumental and vocal movements to make larger musical entities has exceptional interest. His procedure has close links with theatrical practice. The thesis includes a critical edition of Gillier's complete collection made from the copy preserved in the Bibliothèque Nationale de France as F-Pn/ Rés. Vm7 305. The edition is prefaced by a study of performance practices in vocal and instrumental music in late seventeenth-century France.</p>

Tuneable separation of gold by selective precipitation using a simple and recyclable diamide

The efficient separation of metals from ores and secondary sources such as electronic waste is necessary to realising circularity in metal supply. Precipitation processes are increasingly popular and are reliant on designing and understanding chemical recognition to achieve selectivity. Here we show that a simple tertiary diamide precipitates gold selectively from aqueous acidic solutions, including from aqua regia solutions of electronic waste. The X-ray crystal structure of the precipitate displays an infinite chain of diamide cations interleaved with tetrachloridoaurate. Gold is released from the precipitate on contact with water, enabling ligand recycling. The diamide is highly selective, with its addition to 29 metals in 2 M HCl resulting in 70% gold uptake and minimal removal of other metals. At 6 M HCl, complete collection of gold, iron, tin, and platinum occurs, demonstrating that adaptable selective metal precipitation is controlled by just one variable. This discovery could be exploited in metal refining and recycling processes due to its tuneable selectivity under different leaching conditions, the avoidance of organic solvents inherent to biphasic extraction, and the straightforward recycling of the precipitant.

The Story of how Vladimir Sergeevich Took Offense at Faivel Bentsilovich. An Unpublished V.S. Solovyov’s Letter to F.B. Getz

An analysis of the manuscript legacy of V.S. Solovyov is of the greatest importance for the study of his views, creativity, and biography, especially in connection with the ongoing pro-ject of publishing a complete collection of his works and letters. Even well-known and al-ready published texts, including those that appeared in newspapers and journals, need careful comparison with the manuscripts that have come down to us. This is particularly true of Solovyov's correspondence that at the time were carefully selected and, in some cases, edited before publication. This is demonstrated by the example of one of the philosopher’s letters that was intentionally published in a noticeably shortened form. The letter to his friend F.B. Getz was written in the summer of 1891 and reflects a dramatic episode in the lives of both and led to a break between Solovyov and the editorial board of the Petersburg newspaper Novosti. The article also presents a short story about Faivel Getz (1853–1932), a journalist, social activist, and the addressee of the letter with whom Solovyov engaged on the Jewish issue. This article also analyzes at length the events of 1891, which led to a small scandal that served as the reason for writing this letter. V.S. Solovyov could be suspected of cheating and self-promotion as a result of a misunderstanding that arose from the fact that two different authors published in the same newspaper at that time under the same pseudonym. The appendix contains the full text of Solovyov's letter to Getz with the necessary commentary.

Real-time quantitation of thyroidal radioiodine uptake in thyroid disease with monitoring by a collar detection device

Radioactive iodine (RAI) is safe and effective in most patients with hyperthyroidism but not all individuals are cured by the first dose, and most develop post-RAI hypothyroidism. Postoperative RAI therapy for remnant ablation is successful in 80–90% of thyroid cancer patients and sometimes induces remission of nonresectable cervical and/or distant metastatic disease but the effective tumor dose is usually not precisely known and must be moderated to avoid short- and long-term adverse effects on other tissues. The Collar Therapy Indicator (COTI) is a radiation detection device embedded in a cloth collar secured around the patient’s neck and connected to a recording and data transmission box. In previously published experience, the data can be collected at multiple time points, reflecting local cervical RAI exposure and correlating well with conventional methods. We evaluated the real-time uptake of RAI in patients with hyperthyroid Graves’ disease and thyroid cancer. We performed a pilot feasibility prospective study. Data were analyzed using R© (version 4.0.3, The R Foundation for Statistical Computing, 2020), and Python (version 3.6, Matplotlib version 3.0.3). The COTI was able to provide a quantitative temporal pattern of uptake within the thyroid in persons with Graves’ disease and lateralized the remnant tissue in persons with thyroid cancer. The study has demonstrated that the portable collar radiation detection device outside of a healthcare facility is accurate and feasible for use after administration of RAI for diagnostic studies and therapy to provide a complete collection of fractional target radioactivity data compared to that traditionally acquired with clinic-based measurements at one or two time-points.Clinical Trials Registration NCT03517579, DOR 5/7/2018.

DIGITAL TOOLS FOR THE KNOWLEDGE AND ENHANCEMENT OF WWII HERITAGE. THE CASE STUDY OF BOSA IN THE WEST COAST OF SARDINIA (ITALY)

The essay shows some results of a research aimed at building a digital database of Sardinian military architectures of Second World War. Following an activity of cataloguing entrusted to integrated digital survey methods already applied in other case studies of the region, this contribute analyses the built heritage placed in territory of Bosa, a centre located in the west coast of the island, in which 33 bunkers have been founded, most of them represented in the IGM military historical maps.These “modern sentinels”, positioned along the coastline, the main roads and the railway leading to the actual urban context, are designed in reinforced concrete, also integrated with local stone, with a frequently use of square and circle shape often combined or modified and adapted to achieve a complete mimesis in the landscape that hosts them.The survey, applied at architecture and landscape scale, has produced a complete collection of data functional to realize an interoperable digital database, a necessary tool for a deepened knowledge and enhancement of a lost WWII heritage.

LEONE X E LEOPOLDO DE’ MEDICI COMMITTENTI E COLLEZIONISTI DI RAFFAELLO: TRE ESEMPI

Leo X and Leopoldo de ‘Medici, patrons and collectors of Raphael: three examples. Today, the great majority of Raphael’s works in the Uffizi exist thanks to the Medici art collections of the early 1500s to the early 1670s. It is therefore possible to assert that this Florentine family had a particular taste for Raphael’s works. However, not all the paintings collected in that time reflect the Medicis’ artistic interests, as many of them came from expropriations or bequests and inheritances. Despite this, one artistic genre, more than others, appears to be particularly representative of the Medici family’s interest: the portrait. The aim of this paper is to identify some trends concerning the Medicis’ taste in the portrait and self-portrait. In doing so, three artworks – preserved in the Gallerie degli Uffizi – will be examined here: the Portrait of Leo X with Cardinals Giulio de ‘Medici and Luigi de’ Rossi; the Portrait of Tommaso Inghirami, known as Fedra; and Raphael’s self-portrait. These examples show how the artistic execution of Raphael’s artworks, or their later inclusion in the Medici collection (following Raphael’s death), depended on two main Medici personalities, namely Leo X and the prince and cardinal Leopoldo. Moreover, such portraits also reflect the three main recurrent circumstances under which works would usually be included in the Medici collection. The first concerned the creation of the artwork through a direct relationship between patron and artist (and, here, reciprocal incentives from one to the other can be seen). The second had to do with a consolidated taste of the Medicis in creating a collection of artistic portraits and, here, the acquisition of the artwork perfectly reflects this artistic taste. In the third case, we will see how the desire for a complete collection of artistic self-portraits sometimes brought the collector to acquire artworks that did not exactly correspond to their tastes.

FORMATION OF THE DOMESTIC MARKET OF LACTOSE-FREE AND LOW-LACTOSE DAIRY PRODUCTS

Background. The problem of lactose intolerance is becoming widespread, especially in Ukraine it affects 15–35 % of the population. Dairy products are a valuable source of essential nutrients, that’s why it is impossible to completely rule out them from the diet. To solve this problem, it is important to develop technology for dairy products that are free of lactose or with reduced content. The aim of thework is to analyze the world market of low-lactose dairy products and to identify the factors which influence on the formation of such a market in Ukraine. Materials and methods. The subject of the study is the market segment of lactose-free and low-lactose dairy products. Methods of analysis and synthesis, statistical methods of evaluation, scientific generalization and comparison of data are used. Results. The formation of a healthy food market is characterized by gro­wing demand for special food products with regulated nutrient composition, in particular for dairy products, lactose-free or with its reduced content. However, in Ukraine, this market is still in its infancy. Today in country there are 160 units of lactose-free and low-lactose dairy pro­ducts. The volume of imported products in the general range is 68.13%. Kefir and sour cream have the largest share in the formation of the domestic market of low- and lactose-free dairy products, and domestic yogurts have the smallest part. Therefore, the saturation of the market with domestic yogurt, free of lactose, or with its reduced content, is an important area of the development of the Ukraine’s dairy industry. The restriction of natural food resources negatively affects the formation of the domestic market of low-lactose dairy products. In 2020, milk production decreased by about 7 %, due to the unstable economic situation caused by quarantine restrictions in the context of the COVID-19 pandemic. That’s why today the problem of complete collection and rational use of secondary raw milk in the production of food products dominates., especially dairy products of the "free-from" category. Conclusion. The need to create new technologies for low-lactose dairy products using local bioavailable raw materials is essentially due to their high demand and a narrow range of domestic products. The priority directions of development of the domestic market of low-lactose and lac­tose-free dairy products are offered in the context of the state policy of introduction of resource-saving and increase of volumes of high-quality production of domestic production.

POS1144 SERUM URIC ACID TO CREATININE RATIO IS ASSOCIATED WITH URINARY URIC ACID EXCRETION IN PATIENTS WITH GOUT

Background:Underexcretion of uric acid is the dominant mechanism leading to hyperuricemia [1] and the 24-hour urinary uric acid excretion is an important measurement. However, it is inconvenient due to accurate timing and complete collection of the specimen.Objectives:The aim of this study was to investigate the relationship between serum uric acid to creatinine ratio (sUACR) and 24-hour urinary uric acid excretion in gout patients.Methods:A total of 110 gout patients fulfilling 2015 ACR/EULAR classification criteria from Guangdong Second Provincial General Hospital from January 2019 to January 2021 were retrospectively enrolled in this study. Patients were divided into underexcretion group (<3600 μmol/24h) and non-underexcretion group (≥3600 μmol/24h). The correlation between sUACR and 24-hour urinary uric acid excretion was analyzed by the Pearson’s correlations analysis. Receiver operation characteristic (ROC) curves were performed to assess the utility of sUACR for discriminating between underexcretion group and non-underexcretion group. Furthermore, the risk factors of uric acid underexcretion were evaluated using binary logistic regression analysis.Results:sUACR in the underexcretion group was significantly lower than the non-underexcretion group (p=0.0001). Besides, sUACR was positively correlated with 24-hour urinary uric acid excretion (r=0.4833, p<0.0001). Furthermore, ROC suggested that the area under the curve (AUC) of sUACR was 0.728, which was higher that of serum uric acid and creatinine. The optimal cutoff point of sUACR was 5.2312, with a sensitivity and specificity of 71.9% and 67.9%. Logistic analysis results revealed that decreased sUACR (<5.2312) was an independent risk factor of underexcretion of uric acid (OR =5.510, 95% CI: 1.952-15.550, P=0.001).Conclusion:sUACR is lower in gout patients with underexcretion of uric acid and may serve as a useful and convenient marker of assessing underexcretion of uric acid in gout patients.References:[1]Perez-Ruiz F, Calabozo M, Erauskin GG, Ruibal A, Herrero-Beites AM. Renal underexcretion of uric acid is present in patients with apparent high urinary uric acid output. Arthritis Rheum 2002; 47: 610–13.Figure 1.A. Comparison of serum uric acid to creatinine ratio between underexcretion group and non-underexcretion group. B. Correlation between serum uric acid to creatinine ratio and 24h uric acid excretion.Disclosure of Interests:None declared.