Integrating central nervous system metagenomics and host response for diagnosis of tuberculosis meningitis and its mimics.

The epidemiology of infectious causes of meningitis in sub-Saharan Africa is not well understood, and a common cause of meningitis in this region, Mycobacterium tuberculosis (TB), is notoriously hard to diagnose. Here we show that integrating cerebrospinal fluid (CSF) metagenomic next-generation sequencing (mNGS) with a host gene expression-based machine learning classifier (MLC) enhances diagnostic accuracy for TB meningitis (TBM) and its mimics. 368 HIV-infected Ugandan adults with subacute meningitis were prospectively enrolled. Total RNA and DNA CSF mNGS libraries were sequenced to identify meningitis pathogens. In parallel, a CSF host transcriptomic MLC to distinguish between TBM and other infections was trained and then evaluated in a blinded fashion on an independent dataset. mNGS identifies an array of infectious TBM mimics (and co-infections), including emerging, treatable, and vaccine-preventable pathogens including Wesselsbron virus, Toxoplasma gondii, Streptococcus pneumoniae, Nocardia brasiliensis, measles virus and cytomegalovirus. By leveraging the specificity of mNGS and the sensitivity of an MLC created from CSF host transcriptomes, the combined assay has high sensitivity (88.9%) and specificity (86.7%) for the detection of TBM and its many mimics. Furthermore, we achieve comparable combined assay performance at sequencing depths more amenable to performing diagnostic mNGS in low resource settings.

The role of mesenchymal-epithelial transition in endometrial function and receptivity.

OBJECTIVE: During reproductive age of a woman, endometrium undergoes frequent stuctural and functional changes. Abilities of regeneration, remodelation and differentiation are precondition of endometrial receptivity and implantation and development of an embryo. These processes are conditioned by mutual transformation between mesenchymal and epithelial fenotype of endometrial cells: epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET). The aim of this study is to present contemporary knowledge of transformation between epithelial and mesenchymal endometrial cells and its influence on human fertility. DESIGN: Review article. SETTING: Department of Obstetrics and Gynecology, Faculty of Medicine, Masaryk university and University Hospital Brno; Department of Obstetrics and Gynecology, University Hospital Faculty of Medicine, Palacky University, Olomouc. METHODS: PubMed was searched for articles in English indexed until February 2019 with terms of „endometrial receptivity“, „embryo implantation“, „endometrial regeneration“, „mesenchymal-epithelial transition/transformation“. RESULTS: It has been proved, that mesenchymal stromal cells participate on regeneration of not only the endometrial stroma, but also of the epithelium. During endometrial decidualisation under influence of ovarian steroids, the MET is under way. Stromal fibroblasts gain the morfological and functional properties of epithelial cells. During implantaion of an embryo, the trofoblast interacts with decidualised endometrium. Epithelial cells transform into mesenchymal (EMT), which mediate the growth of trofoblast. CONCLUSION: Mutual transformation between stromal and epithelial cells in essential for normal function of endometrium and implantation and development of an embryo.

Organoleptic excipients used in pediatric antibiotics.

Taste is a crucial factor that determines the palatability of the oral dosage form and patient compliance. OBJECTIVE: The aim of this work was to evaluate the organoleptic excipients in oral antibiotics for pediatric use marketed in Brazil. METHODS: The information was obtained from the GuidetoPharmacy, a reference for the pharmaceutical trade. The analysis included dosage forms for oral administration and drugs and their combination with antibacterial action. After this survey, we identified the constitution of the flavoring, sweetening, and coloring agents of each medicine. The results are presented in a descriptive form. RESULTS: Twelve drugs or associations are distributed in 70medicines. Oral suspension was the most common pharmaceutical dosage form. Sweeteners were sucrose, sodium saccharin, and sodium cyclamate. All the coloring agents observed are synthetic and the most frequent ones were yellow twilight no. 6, yellow tartrazine no. 5, and red ponceau 4R. The presence of two or more types of flavorings per medicine was observed. CONCLUSION: Antibacterials use coloring agents, flavorings, and sweeteners to facilitate the administration of medicines for children, using up to six different substances per formulation. No natural coloring agent was observed, demonstrating an issue to be explored in the future. It is important to note that, although necessary, these excipients are responsible for a high incidence of allergic reactions in children.