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

Goodbye Hartmann trial: a prospective, international, multicenter, observational study on the current use of a surgical procedure developed a century ago

Background: Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann's procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA. Methods: This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up. Results: 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6 years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P < 0.001). 30-day mortality was higher in HP patients (13.7%), especially in case of bowel perforation and diffused peritonitis. 1-year follow-up showed no differences on ostomy reversal rate between HP and RPA. (P = 0.127). A backward likelihood logistic regression model showed that RPA was preferred in younger patients, having low ASA score (≤ 3), in case of large bowel obstruction, absence of colonic ischemia, longer time from admission to surgery, operating early at the day working hours, by a surgeon who performed more than 50 colorectal resections. Conclusions: After 100 years since the first Hartmann's procedure, HP remains the most common treatment for left-sided colorectal emergencies. Treatment's choice depends on patient characteristics, the time of surgery and the experience of the surgeon. RPA should be considered as the gold standard for surgery, with HP being an exception

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

New Aromatic Iodine Derivatives – Synthesis, Structure, Properties // Нови ароматни йодопроизводни - синтез, структура, свойства

Halogen-substituted aromatic compounds have been used with undoubted success in organic and pharmaceutical synthesis. Rationally, the "design" of a wide variety of polysubstituted biphenyls, stilbenes and other derivatives can be successfully realised using this class of compounds. A number of halogenated compounds are also used for diagnostic purposes or the preparation of so-called tissue-imitating materials. Therefore, this thesis focuses on the synthesis and detailed structural characterisation of new iodo-, bromo- and mixed halogen-substituted aromatic compounds – compounds with great potential in pharmaceutical synthesis and imaging. Significant emphasis is placed on the methods of growing monocrystals from each received compound, which undoubtedly prove their structure. In this regard, the toxicity of some of the resulting compounds has been determined. Separately, the possibility of making their real physical phantoms with application in contrast-enhanced mammography has been evaluated.Халогенозаместените ароматни съединения се използват с безспорен успех в органичния и фармацевтичния синтез. Рационално, "дизайнът" на голямо разнообразие от полизаместени бифенили, стилбени и други производни може да бъде успешно реализиран с помощта на този клас съединения. Редица халогенозаместени съединения се използват и за диагностични цели или получаването на т. нар. тъканно-имитиращи материали. Ето защо, темата на настоящия дисертационен труд е насочена към синтеза и детайлното структурно охарактеризиране на нови йодо-, бромо- и смесено халогенозаместени ароматни съединения. Последните притежават особено голям потенциал в полето на фармацевтичния синтез, а също и в образната диагностика. Акцент е поставен и върху методите, за израстване на монокристали от всяко получено съединение, с които безспорно доказваме и тяхната структура. В тази връзка е определена токсичността на някои от новосинтезираните съединения. Отделно е оценена възможността за изработване на техни реални, физични фантоми с приложение в контрастно-усилената мамография

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

HLA-G Expression/Secretion and T-Cell Cytotoxicity in Missed Abortion in Comparison to Normal Pregnancy

The main role of HLA-G is to protect the semi-allogeneic embryo from immune rejection by proper interaction with its cognate receptors on the maternal immune cells. Spontaneous abortion is the most common adverse pregnancy outcome, with an incidence rate between 10% and 15%, with immunologic dysregulation being thought to play a role in some of the cases. In this study, we aimed to detect the membrane and soluble HLA-G molecule at the maternal–fetal interface (MFI) and in the serum of women experiencing missed abortion (asymptomatic early pregnancy loss) in comparison to the women experiencing normal early pregnancy. In addition, the proportion of T cells and their cytotoxic profile was evaluated. We observed no difference in the spatial expression of HLA-G at the MFI and in its serum levels between the women with missed abortions and those with normal early pregnancy. In addition, comparable numbers of peripheral blood and decidual total T and γδT cells were found. In addition, as novel data we showed that missed abortion is not associated with altered extravilous invasion into uterine blood vessels and increased cytotoxicity of γδT cells. A strong signal for HLA-G on non-migrating extravilous trophoblast in the full-term normal placental bed was detected. In conclusion, HLA-G production at the MFI or in the blood of the women could not be used as a marker for normal pregnancy or missed abortions

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