Multicenter study evaluating the Vitek MS system for identification of medically important yeasts

The optimal management of fungal infections is correlated with timely organism identification. Matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry (MS) is revolutionizing the identification of yeasts isolated from clinical specimens. We present a multicenter study assessing the performance of the Vitek MS system (bioMérieux) in identifying medically important yeasts. A collection of 852 isolates was tested, including 20 Candida species (626 isolates, including 58 C. albicans, 62 C. glabrata, and 53 C. krusei isolates), 35 Cryptococcus neoformans isolates, and 191 other clinically relevant yeast isolates; in total, 31 different species were evaluated. Isolates were directly applied to a target plate, followed by a formic acid overlay. Mass spectra were acquired using the Vitek MS system and were analyzed using the Vitek MS v2.0 database. The gold standard for identification was sequence analysis of the D2 region of the 26S rRNA gene. In total, 823 isolates (96.6%) were identified to the genus level and 819 isolates (96.1%) were identified to the species level. Twenty-four isolates (2.8%) were not identified, and five isolates (0.6%) were misidentified. Misidentified isolates included one isolate of C. albicans (n = 58) identified as Candida dubliniensis, one isolate of Candida parapsilosis (n = 73) identified as Candida pelliculosa, and three isolates of Geotrichum klebahnii (n = 6) identified as Geotrichum candidum. The identification of clinically relevant yeasts using MS is superior to the phenotypic identification systems currently employed in clinical microbiology laboratories

The Road Less Traveled: Regulation of Leukocyte Migration Across Vascular and Lymphatic Endothelium by Galectins

Leukocyte entry from the blood into inflamed tissues, exit into the lymphatics, and migration to regional lymph nodes are all crucial processes for mounting an effective adaptive immune response. Leukocytes must cross two endothelial cell layers, the vascular and the lymphatic endothelial cell layers, during the journey from the blood to the lymph node. The proteins and cellular interactions which regulate leukocyte migration across the vascular endothelium are well studied; however, little is known about the factors that regulate leukocyte migration across the lymphatic endothelium. Here, we will summarize evidence for a role for galectins, a family of carbohydrate-binding proteins, in regulating leukocyte migration across the vascular endothelium and propose that galectins are also involved in leukocyte migration across the lymphatic endothelium

The combined effect of determinants on coverage of intermittent preventive treatment of malaria during pregnancy in the Kilombero Valley, Tanzania

BACKGROUND\ud \ud Intermittent preventive treatment during pregnancy (IPTp) at routine antenatal care (ANC) clinics is an important and efficacious intervention to reduce adverse health outcomes of malaria infections during pregnancy. However, coverage for the recommended two IPTp doses is still far below the 80% target in Tanzania. This paper investigates the combined impact of pregnant women's timing of ANC attendance, health workers' IPTp delivery and different delivery schedules of national IPTp guidelines on IPTp coverage.\ud \ud METHODS\ud \ud Data on pregnant women's ANC attendance and health workers' IPTp delivery were collected from ANC card records during structured exit interviews with ANC attendees and through semi-structured interviews with health workers in south-eastern Tanzania. Women's timing of ANC visits and health worker's timing of IPTp delivery were analyzed in relation to the different national IPTp schedules and the outcome on IPTp coverage was modelled.\ud \ud RESULTS\ud \ud Among all women eligible for IPTp, 79% received a first dose of IPTp and 27% were given a second dose. Although pregnant women initiated ANC attendance late, their timing was in line with the national guidelines recommending IPTp delivery between 20-24 weeks and 28-32 weeks of gestation. Only 15% of the women delayed to the extent of being too late to be eligible for a first dose of IPTp. Less than 1% of women started ANC attendance after 32 weeks of gestation. During the second IPTp delivery period health workers delivered IPTp to significantly less women than during the first one (55% vs. 73%) contributing to low second dose coverage. Simplified IPTp guidelines for front-line health workers as recommended by WHO could lead to a 20 percentage point increase in IPTp coverage.\ud \ud CONCLUSIONS\ud \ud This study suggests that facility and policy factors are greater barriers to IPTp coverage than women's timing of ANC attendance. To maximize the benefit of the IPTp intervention, revision of existing guidelines is needed. Training on simplified IPTp messages should be consolidated as part of the extended antenatal care training to change health workers' delivery practices and increase IPTp coverage. Pregnant women's knowledge about IPTp and the risks of malaria during pregnancy should be enhanced as well as their ability and power to demand IPTp and other ANC services

Glycan labeling strategies and their use in identification and quantification

Most methods for the analysis of oligosaccharides from biological sources require a glycan derivatization step: glycans may be derivatized to introduce a chromophore or fluorophore, facilitating detection after chromatographic or electrophoretic separation. Derivatization can also be applied to link charged or hydrophobic groups at the reducing end to enhance glycan separation and mass-spectrometric detection. Moreover, derivatization steps such as permethylation aim at stabilizing sialic acid residues, enhancing mass-spectrometric sensitivity, and supporting detailed structural characterization by (tandem) mass spectrometry. Finally, many glycan labels serve as a linker for oligosaccharide attachment to surfaces or carrier proteins, thereby allowing interaction studies with carbohydrate-binding proteins. In this review, various aspects of glycan labeling, separation, and detection strategies are discussed

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)

Specialized inpatient treatment of adult anorexia nervosa: effectiveness and clinical significance of changes

Background: Previous studies have predominantly evaluated the effectiveness of inpatient treatment for anorexia nervosa at the group level. The aim of this study was to evaluate treatment outcomes at an individual level based on the clinical significance of improvement. Patients' treatment outcomes were classified into four groups: deteriorated, unchanged, reliably improved and clinically significantly improved. Furthermore, the study set out to explore predictors of clinically significant changes in eating disorder psychopathology. Methods: A total of 435 inpatients were assessed at admission and at discharge on the following measures: body-mass-index, eating disorder symptoms, general psychopathology, depression and motivation for change. Results: 20.0-32.0% of patients showed reliable changes and 34.1-55.3% showed clinically significant changes in the various outcome measures. Between 23.0% and 34.5% remained unchanged and between 1.7% and 3.0% deteriorated. Motivation for change and depressive symptoms were identified as positive predictors of clinically significant changes in eating disorder psychopathology, whereas body dissatisfaction, impulse regulation, social insecurity and education were negative predictors. Conclusions: Despite high rates of reliable and clinically significant changes following intensive inpatient treatment, about one third of anorexia nervosa patients showed no significant response to treatment. Future studies should focus on the identification of non-responders as well as on the development of treatment strategies for these patients