On the iodination of eudesminic acid with INO3 in an aqueous methanol medium

INTRODUCTION: Both iodo-substituted aromatic hydrocarbons and their more complex derivatives (phenols, aromatic acids, carbaldehydes, and others) are currently being used with unquestionable success in organic and pharmaceutical synthesis. Rationally, the design of a wide variety of polysubstituted biphenyl, stilbene, and other derivatives can be successfully accomplished using these compounds. As a continuation of our previous work, we propose a much more convenient and feasible methodology for the synthesis of the polysubstituted diiodo-containing 2,6-diiodo-3,4,5-trimethoxybenzoic acid.AIM: The aim of this article is to demonstrate the suitability of the used reagent pair, I2/AgNO3, in the iodination of the natural 3,4,5-trimethoxybenzoic (eudesmic) acid in the presence of water.MATERIALS AND METHODS: For the synthesis of the principal, a green strategy was applied, which used the commonly available and biocompatible reagents iodine, silver nitrate, methanol, and water. The suitability of the applied synthetic methodology was determined by the purity of the reaction product. The latter was established through Fourier transform infrared (FTIR) and 1H nuclear magnetic resonance (NMR) analysis.RESULTS: The presence of a small amount of water in the reaction mixture did not alter the yield and purity of the desired reaction product, 2,6-diiodo-3,4,5-trimethoxybenzoic acid. In all probability, the in situ-formed iodine nitrate (INO3) preserved its activity in an aqueous environment. The quantitative conversion of the organic reactant used can also be taken as indirect evidence of the stability of the thus obtained INO3.CONCLUSION: The presented preparative methodology holds potential as an optimal choice in the synthesis of the target 2,6-diiodo-3,4,5-trimethoxybenzoic acid. Given its feasibility and use of commonly available reagents, the presented synthetic strategy can be easily implemented by novice chemists, including students

A global experiment on motivating social distancing during the COVID-19 pandemic

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges

A global experiment on motivating social distancing during the COVID-19 pandemic

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e. a controlling message) compared to no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly-internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared to the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly-internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing: Controlled motivation was associated with more defiance and less long-term behavioral intentions to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges

In Vitro Bioactivity of Silver-Containing Sol-Gel Glasses: FTIR Analysis

Introduction: The sol-gel glasses (BG) have been used for various biomedical applications, such as orthopedic, dental grafting and tissue engineering. The main purpose of the presented article is the preparation and evaluation of carbonate apatite formation on the BG in SiO2-CaO-P2O5-xAg2O system, where x=0,1,2 and 4wt.% Ag2O (BG/Ag), after soaking in a simulated body fluid (1.5 SBF) for 12 days in static conditions.Materials and Methods: BG/Ag were synthesized from tetraethyl orthosilicate (TEOS), calcium oxide (CaO), phosphoric acid (H3PO4) and silver nitrate (AgNO3) as sources. TEOS was stirred into the mixed solvent of C2H5OH and H2O with a very small amount of HCl in the volume ratio TEOS:C2H5OH:H2O:HCl=1:1:1:0.01. The mixture of calcium phosphate (CP) and appropriate amount of AgNO3 was added to SiO2 sol under stirring for 20h. The mixed sol obtained was gelated at 120oC for 12h and 600oC for 6h.Results: X-ray powder diffraction (XRD) of the synthesized samples showed that the presence of some crystalline phases is dependent on the gel composition. XRD proved the presence of CaCO3, wollastonite, HA and metallic Ag in accordance with gel compositions. Fourier transform infrared spectroscopy (FTIR) of the prepared BG showed the presence of basic absorption bands, corresponding to the different chemical bands and crystalline phases, in agreement with XRD results. FTIR of the examined samples, after soaking in 1.5 SBF solution for 12 days, confirmed that B-type carbonate apatite was formed preferentially on the soaked surface.Conclusions: BG in SiO2-CaO-P2O5-xAg2O system (x=0,1,2 and 4wt.% Ag2O) were synthesized via a polystep sol-gel method. After immersion of the studied BG in 1.5 SBF solutions for 12 days in static conditions, FTIR revealed the presence of some CO32- bands, i.e. after soaking carbonate apatite (CO3HA) may be formed on the surface of the prepared sol-gel glasses. On the basis of FTIR results, we can assume that B-type CO3HA preferentially formed on the soaked samples

IL-23R and TCR signaling drives the generation of neonatal Vgamma9Vdelta2 T cells expressing high levels of cytotoxic mediators and producing IFN-gamma and IL-17.

The immune system in early life is regarded as immature. However, the IL-12 family member IL-23 is highly produced upon TLR stimulation by neonatal DCs. Human adult Vγ9Vδ2 T cells can be stimulated specifically via their TCR by phosphoantigens (as the pathogen-derived HMB-PP) or agents and infections that lead to their endogenous accumulation (as the aminobisphosphonate zoledronate). As increasing evidence indicates that γδ T cells are especially important in early life, we investigated the effect of IL-23 on neonatal Vγ9Vδ2 T cells stimulated via their TCR. Zoledronate induced clear proliferation and IFN-γ production in neonatal Vγ9Vδ2 T cells. In contrast, HMB-PP did not elicit a distinct response unless at high concentrations. Addition of IL-23 to zoledronate enhanced the expression of IFN-γ and generated a distinct, IFN-γ-negative, neonatal Vγ9Vδ2 T cell population producing IL-17. Furthermore, IL-23 significantly enhanced the expression of a range of cytotoxic mediators (perforin, granzymes, granulysin). Although the costimulatory effect of IL-23 on IFN-γ and cytotoxic mediators was also observed within adult Vγ9Vδ2 T cells, the induction of an IL-17+IFN-γ- subset was unique to neonatal Vγ9Vδ2 T cells. In conclusion, neonatal DC-derived IL-23 combined with specific TCR signaling drives the generation of neonatal Vγ9Vδ2 T cells equipped with a range of cytotoxic mediators and distinct subpopulations producing IFN-γ and IL-17.Comparative StudyJournal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Molecular pathogenesis of spontaneous abortions - Whole genome copy number analysis and expression of angiogenic factors.

OBJECTIVE To study two major molecular alterations in spontaneous abortions (SA) with unexplained etiology - fetal genomic anomalies and the endometrial expression of main angiogenic factors VEGFA/VEGFR2 and chemokines SDF-1/CXCR4. MATERIALS AND METHODS Whole genome copy number analysis by arrayCGH or Next Generation Sequencing (NGS) was applied for detection of fetal genomic imbalances. The abortive decidua of SA without fetal aneuploidies was further investigated for expression levels of the abovementioned factors using real time PCR analysis. A total of 30 abortive materials were collected from spontaneous abortions after exclusion of known predisposing factors. RESULTS In 21 of 30 spontaneous abortions (70%), genomic anomalies were discovered by whole genome copy number analysis. Numerical anomalies were detected in 90% of aberrant cases, and in 10% - structural aberrations were revealed. An increased expression for essential factors of angiogenesis was identified in spontaneous abortions' tissues - 3.44 times for VEGFA and 10.29 times for VEGFR2. We found an average of 14 times increase in the expression levels of SDF-1 and 3.21 times for its receptor CXCR4. CONCLUSION We could suggest the occurrence of increased angiogenesis in SA without fetal aneuploidies, compared to the control tissues, which could lead to increased oxidative stress and fetal loss

Correlation between Cytogenetic Findings and Spermatogenic Failure in Bulgarian Infertile Men

The aim of our study was to determine the type and frequency of chromosomal aberrations and polymorphisms in men with different degrees of spermatogenic failure in comparison to men with normozoospermia, in order to find correlations between cytogenetic findings and the abnormal results of semen analysis. In our study, we performed cytogenetic analysis in 901 infertile men, divided into five groups according to semen analysis—normozoospermia (86), asthenozoospermia (394), oligoasthenozoospermia (182), severe male factor (100), and azoospermia (139). The frequency of polymorphisms was similar in all groups (11–16%, without significant differences). The frequency of numerical and structural aberrations increases with the degree of the spermatogenic failure (3.5% in normozoospermia, 5.6% in asthenozoospermia, 9.8% in oligoasthenozoospermia, 9% in severe male factor, and 13.5% in azoospermia). We found a significantly higher incidence of numerical chromosomal aberrations in severe male factor (7%) and azoospermia (9.3%). Oligoasthenozoospermia occured in 45% of cases with translocation, compared to 20% in the group with a normal karyotype. We revealed that chromosomal translocations are tightly associated with oligoasthenozoospermia, whereas numerical chromosomal aberrations—with severe male factor and azoospermia. The impact of chromosome polymorphisms on male infertility should be studied in greater detail

Ammonio Methacrylate Copolymer (Type B)-Diltiazem Interactions in Solid Dispersions and <i>Microsponge</i> Drug-Delivery Systems

This paper presents a complex analytical study on the distribution, solubility, amorphization, and compatibility of diltiazem within the composition of Eudragit RS 100-based particles of microspongeous type. For this purpose, a methodology combining attenuated total reflectance Fourier transform infrared (ATR-FTIR) absorption spectroscopy, differential scanning calorimetry (DSC), scanning electron microscopy with energy-dispersive X-ray microanalysis (SEM-EDX), and in vitro dissolution study is proposed. The correct interpretation of the FTIR and drug-dissolution results was guaranteed by the implementation of two contrasting reference models: physical drug–polymer mixtures and casting-obtained, molecularly dispersed drug–polymer composites (solid dispersions). The spectral behavior of the drug–polymer composites in the carbonyl frequency (νCO) region was used as a quality marker for the degree of their interaction/mutual solubility. A spectral-pattern similarity between the microsponge particles and the solid dispersions indicated the molecular-type dispersion of the former. The comparative drug-desorption study and the qualitative observations over the DSC and SEM-EDX results confirmed the successful synthesis of a homogeneous coamorphous microsponge-type formulation with excellent drug-loading capacity and “controlled” dissolution profile. Among them, the drug-delivery particles with 25% diltiazem content (M-25) were recognized as the most promising, with the highest population of drug molecules in the polymer bulk and the most suitable desorption profile. Furthermore, an economical and effective analytical algorithm was developed for the comprehensive physicochemical characterization of complex delivery systems of this kind

Early Pregnancy Human Decidua is Enriched with Activated, Fully Differentiated and Pro-Inflammatory Gamma/Delta T Cells with Diverse TCR Repertoires

Pregnancy is a state where high and stage-dependent plasticity of the maternal immune system is necessary in order to equilibrate between immunosuppression of harmful responses towards the fetus and ability to fight infections. TCR &gamma;&delta; cells have been implicated in the responses in infectious diseases, in the regulation of immune responses, and in tissue homeostasis and repair. The variety of functions makes &gamma;&delta; T cells a particularly interesting population during pregnancy. In this study, we investigated the proportion, phenotype and TCR &gamma; and &delta; repertoires of &gamma;&delta; T cells at the maternal&ndash;fetal interface and in the blood of pregnant women using FACS, immunohistochemistry and spectratyping. We found an enrichment of activated and terminally differentiated pro-inflammatory &gamma;&delta; T-cell effectors with specific location in the human decidua during early pregnancy, while no significant changes in their counterparts in the blood of pregnant women were observed. Our spectratyping data revealed polyclonal CDR3 repertoires of the &delta;1, &delta;2 and &delta;3 chains and &gamma;2, &gamma;3, &gamma;4 and &gamma;5 chains and oligoclonal and highly restricted CDR3&gamma;9 repertoire of &gamma;&delta; T cells in the decidua and blood of pregnant women. Early pregnancy induces recruitment of differentiated pro-inflammatory &gamma;&delta; T-cell effectors with diverse TCR repertoires at the maternal&ndash;fetal interface