ABSTRACT
We present a case of laboratory-acquired Salmonella Typhi, resulting in hospitalization of a technician. Blood and stool cultures revealed a S. Typhi strain, identical to the strain with which the employee had recently worked, confirmed using core-genome multilocus sequence typing. The incident occurred despite working in a biosafety cabinet.
Subject(s)
Salmonella typhi , Typhoid Fever , Humans , Salmonella typhi/genetics , Typhoid Fever/diagnosis , Multilocus Sequence Typing/methods , LaboratoriesABSTRACT
We provide incidences (cases/10 million persons) in the Netherlands during 2009-2019 for pathogens listed as potential bioterrorism agents. We included pathogens from the highest categories of the European Medicines Agency or the US Centers for Disease Control and Prevention. Notifiable diseases and recently published data were used to calculate the average annual incidence. Coxiella burnetii had the highest incidence because of a Q fever epidemic during 2007-2010. Incidence then decreased to 10.8 cases/. Pathogens with an incidence >1 were Brucella spp. (2.5 cases), Francisella tularensis (1.3 cases), and Burkholderia pseudomallei (1.1 cases). Pathogens with an incidence <1 were hemorrhagic fever viruses (0.3 cases), Clostridium botulinum (0.2 cases), and Bacillus anthracis (0.1 cases). Variola major and Yersinia pestis were absent. The generally low incidences make it unlikely that ill-meaning persons can isolate these pathogens from natural sources in the Netherlands. However, the pathogens are stored in laboratories, underscoring the need for biosecurity measures.
Subject(s)
Bacillus anthracis , Francisella tularensis , Biological Warfare Agents , Bioterrorism/prevention & control , Netherlands/epidemiologyABSTRACT
INTRODUCTION: Bloodstream infections (BSIs) cause treatment-related mortality in pediatric acute leukemia. We explored the potential of intestinal microbiota and fecal volatile organic compounds (VOCs) analyses to predict BSI. METHODS: In this case-control study, fecal samples of pediatric acute leukemia patients were collected. Microbiota composition and fecal VOC profiles of BSI cases and matched non-BSI controls were compared. RESULTS: In total, 6 patients were included, of which 1 developed BSI and 1 neutropenic fever. Both showed reduced microbial diversity and stability of Bacteroidetes. In the BSI case, Pantoea was identified 15 days before BSI. Significant differences in fecal VOC profiles were measured between the case and controls. CONCLUSION: Microbiota and fecal VOC could serve as biomarkers to predict BSI in pediatric leukemia.
Subject(s)
Feces , Gastrointestinal Microbiome , Leukemia, Myeloid, Acute , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Sepsis/blood , Adolescent , Child , Child, Preschool , Feces/chemistry , Feces/microbiology , Female , Humans , Leukemia, Myeloid, Acute/blood , Leukemia, Myeloid, Acute/microbiology , Male , Pilot Projects , Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood , Precursor Cell Lymphoblastic Leukemia-Lymphoma/microbiology , Volatile Organic CompoundsABSTRACT
The nonspecific divalent cation channel TRPM7 (transient receptor potential-melastatin-like 7) is involved in many Ca2+ and Mg2+-dependent cellular processes, including survival, proliferation and migration. TRPM7 expression predicts metastasis and recurrence in breast cancer and several other cancers. In cultured cells, it can induce an invasive phenotype by promoting Ca2+-mediated epithelial-mesenchymal transition. We previously showed that in neuroblastoma cells that overexpress TRPM7 moderately, stimulation with Ca2+-mobilizing agonists leads to a characteristic sustained influx of Ca2+. Here we report that sustained influx through TRPM7 is abruptly abrogated by elevating intracellular levels of cyclic adenosine monophosphate (cAMP). Using pharmacological inhibitors and overexpression studies we show that this blockage is mediated by the cAMP effector Protein Kinase A (PKA). Mutational analysis demonstrates that the Serine residue S1269, which is present proximal to the coiled-coil domain within the protein c-terminus, is responsible for sensitivity to cAMP.
Subject(s)
Calcium/metabolism , Cyclic AMP-Dependent Protein Kinases/metabolism , Cyclic AMP/metabolism , Neurons/metabolism , TRPM Cation Channels/metabolism , Animals , Calcium Signaling/drug effects , Cell Line, Tumor , Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors , Isoquinolines/pharmacology , Mice , Neurons/drug effects , Phosphorylation/drug effects , Protein Kinase Inhibitors/pharmacology , Sulfonamides/pharmacologyABSTRACT
Single Molecule Localization super-resolution Microscopy (SMLM) has become a powerful tool to study cellular architecture at the nanometer scale. In SMLM, single fluorophore labels are made to repeatedly switch on and off ("blink"), and their exact locations are determined by mathematically finding the centers of individual blinks. The image quality obtainable by SMLM critically depends on efficacy of blinking (brightness, fraction of molecules in the on-state) and on preparation longevity and labeling density. Recent work has identified several combinations of bright dyes and imaging buffers that work well together. Unfortunately, different dyes blink optimally in different imaging buffers, and acquisition of good quality 2- and 3-color images has therefore remained challenging. In this study we describe a new imaging buffer, OxEA, that supports 3-color imaging of the popular Alexa dyes. We also describe incremental improvements in preparation technique that significantly decrease lateral- and axial drift, as well as increase preparation longevity. We show that these improvements allow us to collect very large series of images from the same cell, enabling image stitching, extended 3D imaging as well as multi-color recording.
