Preparation and Preclinical Evaluation of F-Labeled Olutasidenib Derivatives for Non-Invasive Detection of Mutated Isocitrate Dehydrogenase 1 (mIDH1).

Mutations of isocitrate dehydrogenase 1 (IDH1) are key biomarkers for glioma classification, but current methods for detection of mutated IDH1 (mIDH1) require invasive tissue sampling and cannot be used for longitudinal studies. Positron emission tomography (PET) imaging with mIDH1-selective radioligands is a promising alternative approach that could enable non-invasive assessment of the IDH status. In the present work, we developed efficient protocols for the preparation of four F-labeled derivatives of the mIDH1-selective inhibitor olutasidenib.

8-Bicycloalkyl-CPFPX derivatives as potent and selective tools for in vivo imaging of the A adenosine receptor.

Imaging of the A adenosine receptor (AR) by positron emission tomography (PET) with 8-cyclopentyl-3-(3-[F]fluoropropyl)-1-propyl-xanthine ([F]CPFPX) has been widely used in preclinical and clinical studies. However, this radioligand suffers from rapid peripheral metabolism and subsequent accumulation of radiometabolites in the vascular compartment. In the present work, we prepared four derivatives of CPFPX by replacement of the cyclopentyl group with norbornane moieties.

Radiosynthesis and In Vitro Evaluation of [C]tozadenant as Adenosine A Receptor Radioligand.

Tozadenant (4-hydroxy--(4-methoxy-7-morpholinobenzo[]thiazol-2-yl)-4-methylpiperidine-1-carboxamide) is a highly selective adenosine A receptor (AR) antagonist and a promising lead structure for the development of AR-selective positron emission tomography (PET) probes. Although several F-labelled tozadenant derivatives showed favorable in vitro properties, recent in vivo PET studies observed poor brain penetration and lower specific binding than anticipated from the in vitro data. While these findings might be attributable to the structural modification associated with F-labelling, they could also reflect inherent properties of the parent compound.

A chimeric protein-based vaccine elicits a strong IgG antibody response and confers partial protection against Shiga toxin-producing in mice.

Background: Shiga toxin-producing (STEC) is a foodborne pathogen that causes gastrointestinal infections, ranging from acute diarrhea and dysentery to life-threatening diseases such as Hemolytic Uremic Syndrome. Currently, a vaccine to prevent STEC infection is an unmet medical need.

Results: We developed a chimeric protein-based vaccine targeting seven virulence factors of STEC, including the Stx2B subunit, Tir, Intimin, EspA, Cah, OmpT, and AggA proteins.

Multiple introgressions shape mitochondrial evolutionary history in Drosophila paulistorum and the Drosophila willistoni group.

Hybridization and the consequent introgression of genomic elements is an important source of genetic diversity for biological lineages. This is particularly evident in young clades in which hybrid incompatibilities are still incomplete and mixing between species is more likely to occur. Drosophila paulistorum, a representative of the Neotropical Drosophila willistoni subgroup, is a classic model of incipient speciation.

Central Sterile Services Department: psychosocial risks related to the prescribed organization of nursing work.

Objective: The aim of this study is to investigate the characteristics of work-flow organization of the Central Sterile Services Department and analyze whether nursing workers are subject to psychosocial risks.

Method: Mixed study, carried out between November 2017 and July 2019 with nursing workers of the Department of Central Sterile Services of a university hospital. Sampling for the quantitative stage of this study consisted of 36 professionals who have filled the Prescribed Work Organization Scale form, followed by statistical analysis.

Infection with endosymbiotic Spiroplasma disrupts tsetse (Glossina fuscipes fuscipes) metabolic and reproductive homeostasis.

Tsetse flies (Glossina spp.) house a population-dependent assortment of microorganisms that can include pathogenic African trypanosomes and maternally transmitted endosymbiotic bacteria, the latter of which mediate numerous aspects of their host's metabolic, reproductive, and immune physiologies. One of these endosymbionts, Spiroplasma, was recently discovered to reside within multiple tissues of field captured and laboratory colonized tsetse flies grouped in the Palpalis subgenera.

Multiplexed Workplace Measurements in Biogas Plants Reveal Compositional Changes in Aerosol Properties.

Anaerobic digestion is an emerging technology producing energy from renewable resources or food waste. Exposure screenings, comprising hazardous substances and biological agents, at different workplaces are necessary for a comprehensive overview of potential hazards in order to assess the risk of employees in biogas plants. In order to analyse these parameters, workplace measurements were conducted in seven full-scale anaerobic digesters.

Species Differences in Microsomal Metabolism of Xanthine-Derived A Adenosine Receptor Ligands.

Tracer development for positron emission tomography (PET) requires thorough evaluation of pharmacokinetics, metabolism, and dosimetry of candidate radioligands in preclinical animal studies. Since variations in pharmacokinetics and metabolism of a compound occur in different species, careful selection of a suitable model species is mandatory to obtain valid data. This study focuses on species differences in the in vitro metabolism of three xanthine-derived ligands for the A adenosine receptor (AAR), which, in their F-labeled form, can be used to image AAR via PET.

Leadership development of nursing students in a material and sterilization center.

Objective: To analyze the experiences of Nursing students during the mandatory hospital internship at a Material and Sterilization Center with a focus on leadership development.

Method: This is an experience report of a mandatory hospital curricular internship anchored in the national curricular guidelines for Nursing, of a descriptive-reflective nature, and carried out in a general university hospital in southern Brazil, from March to June 2019.

Results: Activities were developed in order to develop leadership aspects such as people, orthotics and prosthetics management, surgical planning, conflict management, and assertive communication.

Psychometrics and cultural adaptations of the Communities That Care Youth Survey: A systematic review.

Aims: The Communities That Care Youth Survey (CTCYS) is an assessment for youth risk and protective factors focused on antisocial behaviors, drug abuse, violence, and delinquency. The systematic review aimed to analyze psychometric validations and cross-cultural adaptation processes of CTCYS to prepare its Brazilian validation.

Methods: PubMed, SpringerLink, Scopus, and Web of Science were the databases included.

Bradykinin Exerts Independent Effects on Trophoblast Invasion and Blood Pressure in Pregnant Guinea Pigs.

Introduction: The pleiotropic kininogen-kallikrein-kinin system is upregulated in pregnancy and localizes in the uteroplacental unit. To identify the systemic and local participation of the bradykinin type 2 receptor (B2R), this was antagonized by Bradyzide (BDZ) during 2 periods: from days 20 to 34 and from days 20 to 60 in pregnant guinea pigs.

Methods: Pregnant guinea pigs received subcutaneous infusions of saline or BDZ from gestational day 20 until sacrifice on day 34 (Short B2R Antagonism [SH-B2RA]) or on day 60 (Prolonged B2R Antagonism [PR-B2RA]).

Management of ophthalmic surgical instruments and processes optimization: mixed method study.

Aim: Analysis of the use of ophthalmic instruments during surgical procedures in order to propose a material management method.

Method: Mixed method study, sequential exploratory design, performed from January to June 2015, at a university hospital in southern Brazil. First, a qualitative approach was held from brainstorming and field observation.

Combined Collection and Analysis of Inorganic and Organic Gunshot Residues.

Gunshot residue (GSR) analysis and their interpretation provide crucial information on a criminal investigation involving the use of firearms. To date, several approaches have been proposed for the implementation of a combined sampling and analysis of inorganic (IGSR) and organic GSR (OGSR). However, it is not clear at this stage if concurrent analyses of both types of residue might be detrimental to the analysis of IGSR currently applied in forensic laboratories.

Parallel Sequencing of Wolbachia wCer2 from Donor and Novel Hosts Reveals Multiple Incompatibility Factors and Genome Stability after Host Transfers.

The application of Wolbachia in insect pest and vector control requires the establishment of genotypically stable host associations. The cytoplasmic incompatibility (CI) inducing Wolbachia strain wCer2 naturally occurs in the cherry fruit fly Rhagoletis cerasi as co-infection with other strains and was transferred to other fruit fly species by embryonic microinjections. We obtained wCer2 genome data from its native and three novel hosts, Drosophila simulans, Drosophila melanogaster, and Ceratitis capitata and assessed its genome stability, characteristics, and CI factor (cif) genes.

Performance of Nb/BDD material for the electrochemical advanced oxidation of prednisone in different water matrix.

Glucocorticoids are widely used to treat a variety of diseases. Consequently, these compounds have been found in water and wastewater matrix. Despite studies have proven its toxicity, just a few works investigate techniques to degrade and mineralize them.

Influence of binding affinity and blood plasma level on cerebral pharmacokinetics and PET imaging characteristics of two novel xanthine PET radioligands for the A adenosine receptor.

Introduction: The suitability of novel positron emission tomography (PET) radioligands for quantitative in vivo imaging is affected by various physicochemical and pharmacological parameters. In this study, the combined effect of binding affinity, lipophilicity, protein binding and blood plasma level on cerebral pharmacokinetics and PET imaging characteristics of three xanthine-derived A adenosine receptor (AAR) radioligands was investigated in rats.

Methods: A comparative evaluation of two novel cyclobutyl-substituted xanthine derivatives, 8-cyclobutyl-3-(3-[F]fluoropropyl)-1-propylxanthine ([F]CBX) and 3-(3-[F]fluoropropyl)-8-(1-methylcyclobutyl)-1-propylxanthine ([F]MCBX), with the reference AAR radioligand 8-cyclopentyl-3-(3-[F]fluoropropyl)-1-propylxanthine ([F]CPFPX) was conducted.

Spatio-temporal distribution of Spiroplasma infections in the tsetse fly (Glossina fuscipes fuscipes) in northern Uganda.

Tsetse flies (Glossina spp.) are vectors of parasitic trypanosomes, which cause human (HAT) and animal African trypanosomiasis (AAT) in sub-Saharan Africa. In Uganda, Glossina fuscipes fuscipes (Gff) is the main vector of HAT, where it transmits Gambiense disease in the northwest and Rhodesiense disease in central, southeast and western regions.

The effect of Wolbachia on gene expression in Drosophila paulistorum and its implications for symbiont-induced host speciation.

Background: The Neotropical fruit fly Drosophila paulistorum (Diptera: Drosophilidae) is a species complex in statu nascendi comprising six reproductively isolated semispecies, each harboring mutualistic Wolbachia strains. Although wild type flies of each semispecies are isolated from the others by both pre- and postmating incompatibilities, mating between semispecies and successful offspring development can be achieved once flies are treated with antibiotics to reduce Wolbachia titer. Here we use RNA-seq to study the impact of Wolbachia on D.

Relevance of In Vitro Metabolism Models to PET Radiotracer Development: Prediction of In Vivo Clearance in Rats from Microsomal Stability Data.

The prediction of in vivo clearance from in vitro metabolism models such as liver microsomes is an established procedure in drug discovery. The potentials and limitations of this approach have been extensively evaluated in the pharmaceutical sector; however, this is not the case for the field of positron emission tomography (PET) radiotracer development. The application of PET radiotracers and classical drugs differs greatly with regard to the amount of substance administered.

Electrooxidation Using Nb/BDD as Post-Treatment of a Reverse Osmosis Concentrate in the Petrochemical Industry.

This work evaluated the performance of an electrochemical oxidation process (EOP), using boron-doped diamond on niobium substrate (Nb/BDD), for the treatment of a reverse osmosis concentrate (ROC) produced from a petrochemical wastewater. The effects of applied current density (5, 10, or 20 mA·cm) and oxidation time (0 to 5 h) were evaluated following changes in chemical oxygen demand (COD) and total organic carbon (TOC). Current efficiency and specific energy consumption were also evaluated.

Bradykinin Exerts Independent Effects on Trophoblast Invasion and Blood Pressure in Pregnant Guinea Pigs.

Introduction:: The pleiotropic kininogen-kallikrein-kinin system is upregulated in pregnancy and localizes in the uteroplacental unit. To identify the systemic and local participation of the bradykinin type 2 receptor (B2R), this was antagonized by Bradyzide (BDZ) during 2 periods: from days 20 to 34 and from days 20 to 60 in pregnant guinea pigs.

Methods:: Pregnant guinea pigs received subcutaneous infusions of saline or BDZ from gestational day 20 until sacrifice on day 34 (Short B2R Antagonism [SH-B2RA]) or on day 60 (Prolonged B2R Antagonism [PR-B2RA]).

Influence of incubation conditions on microsomal metabolism of xanthine-derived A adenosine receptor ligands.

Introduction: In vitro metabolism models such as liver microsomes represent an important tool for the development of novel radioligands. Comparability and physiological relevance of in vitro metabolism data critically depend on the careful evaluation and optimization of assay protocols. We therefore investigated the influence of incubation conditions on the microsomal stability of xanthine-derived A adenosine receptor (AAR) ligands which have been developed for positron emission tomography (PET).

High-sensitivity detection of cryptic Wolbachia in the African tsetse fly (Glossina spp.).

Background: In African tsetse flies Glossina, spp. detection of bacterial symbionts such as Wolbachia is challenging since their prevalence and distribution are patchy, and natural symbiont titers can range at levels far below detection limit of standard molecular techniques. Reliable estimation of symbiont infection frequency, especially with regard to interrelations between symbionts and their potential impact on host biology, is of pivotal interest in the context of future applications for the control and eradication of Glossina-vectored African trypanosomosis.