Comparative genomic analysis for the presence of potential enterococcal virulence factors in the probiotic Enterococcus faecalis strain Symbioflor 1

Enterococci are members of the natural microbiota of animal and human intestinal tracts and are capable of causing opportunistic infections. They are also used as starter cultures in the food industry as well as in health supplements and probiotics by the pharmaceutical industry. This Janus-faced status requires a careful evaluation on the basis of pathogenic traits to ensure the safety of the strain used to produce food and pharmaceuticals. We performed gapped-genome sequencing of a probiotic strain Enterococcus faecalis Symbioflor 1 and present initial results deriving from comparative genome analysis with that of the previously sequenced pathogenic clinical isolate E. faecalis V583. There was strong overall conservation of synteny between both strains and a detailed analysis revealed the absence of large genomic regions from the chromosome of the probiotic strain, indicating gene loss. Genes absent from the Symbioflor 1 strain included those encoding the enterococcal cytolysin, enterococcal surface protein, and gelatinase (coccolysin) as well as hyaluronidase and the peptide antibiotic AS-48. This data was confirmed using PCR primers specific for the respective genes. However, other enterococcal determinants such as aggregation substance, collagen adhesion protein, the ability to resist oxygen anions as well as capsule formation were detected. The presence of these traits may be advantageous for the strain Symbioflor 1 since they potentially enable colonization and proliferation of the bacterium on mucosal surfaces thereby conferring on it probiotic traits.     

U-RT1 – A new model for Richter transformation

The advent of highly effective treatments targeting the disease biology of chronic lymphocytic leukemia (CLL) has transformed the therapeutic field tremendously. However, transformation into an aggressive B-cell lymphoma, called Richter syndrome (RS), remains highly challenging since the treatment options for this condition are still insufficient. Exploratory drug testing and experimental studies are restricted by the lack of satisfactory models. We have established U-RT1, a cell line derived from a highly proliferating RS clonally related to the patient''s underlying CLL. The cell line shows morphological features and an immunophenotype of RS-DLBCL (non-GCB). Molecular analysis revealed a complex karyotype with driver aberrations characteristic for RS such as loss of TP53 and CDKN2A. Furthermore, U-RT1 displays a chromosomal gain of the NOTCH1 gene locus and strong immunoreactivity for BCL-2. These features suggest that U-RT1 is the first eligible model system for investigations on the pathogenesis of RS and novel treatment options.     

Metabolism of low-dose inorganic arsenic in a central European population: influence of sex and genetic polymorphisms

BACKGROUND: There is a wide variation in susceptibility to health effects of arsenic, which, in part, may be due to differences in arsenic metabolism. Arsenic is metabolized by reduction and methylation reactions, catalyzed by reductases and methyltransferases. OBJECTIVES: Our goal in this study was to elucidate the influence of various demographic and genetic factors on the metabolism of arsenic. METHODS: We studied 415 individuals from Hungary, Romania, and Slovakia by measuring arsenic metabolites in urine using liquid chromatography with hydride generation and inductively coupled plasma mass spectrometry (HPLC-HG-ICPMS). We performed genotyping of arsenic (+III) methyltransferase (AS3MT), glutathione S-transferase omega 1 (GSTO1), and methylene-tetrahydrofolate reductase (MTHFR). RESULTS: The results show that the M287T (T-->C) polymorphism in the AS3MT gene, the A222V (C-->T) polymorphism in the MTHFR gene, body mass index, and sex are major factors that influence arsenic metabolism in this population, with a median of 8.0 microg/L arsenic in urine. Females < 60 years of age had, in general, higher methylation efficiency than males, indicating an influence of sex steroids. That might also explain the observed better methylation in overweight or obese women, compared with normal weight men. The influence of the M287T (T-->C) polymorphism in the AS3MT gene on the methylation capacity was much more pronounced in men than in women. CONCLUSIONS: The factors investigated explained almost 20% of the variation seen in the metabolism of arsenic among men and only around 4% of the variation among women. The rest of the variation is probably explained by other methyltransferases backing up the methylation of arsenic.     

Experimental determination of blood permittivity and conductivity in simple shear flow

The paper is concerned with the determination of blood permittivity and conductivity in Poiseuille and Couette simple shear flows. The experimental procedure, based on dielectric spectroscopy, evidences the sensitivity of blood electric properties to the applied frequency and local shear rate magnitude. The method evidences the possibility to correlate (for well-defined flow geometry) magnitude of shear rate, and consequently the shear stress level, with spectra permittivity of blood.     

Salmonella diskitis in a 2-year old immunocompetent child

Spine infections are uncommon in paediatrics and are generally caused by Staphylococcus aureus. Salmonella spp. are a rare cause of spine infections, usually affecting children with sickle-cell anaemia. We present a case of group C1 Salmonella diskitis in a previously healty 2-y-old child, and review the relevant literature.     

Valproate in the treatment of epilepsy in girls and women of childbearing potential

This document provides guidance on the use of valproate in girls and women of childbearing age from a joint Task Force of the Commission on European Affairs of the International League Against Epilepsy (CEA‐ILAE) and the European Academy of Neurology (EAN), following strengthened warnings from the Coordination Group for Mutual Recognition and Decentralised Procedures‐Human (CMDh) of the European Medicines Agency (EMA), which highlight the risk of malformations and developmental problems in infants who are exposed to valproate in the womb. To produce these recommendations, the Task Force has considered teratogenic risks associated with use of valproate and treatment alternatives, the importance of seizure control and of patient and fetal risks with seizures, and the effectiveness of valproate and treatment alternatives in the treatment of different epilepsies. The Task Force's recommendations include the following: (1) Where possible, valproate should be avoided in women of childbearing potential. (2) The choice of treatment for girls and women of childbearing potential should be based on a shared decision between clinician and patient, and where appropriate, the patient's representatives. Discussions should include a careful risk–benefit assessment of reasonable treatment options for the patient's seizure or epilepsy type. (3) For seizure (or epilepsy) types where valproate is the most effective treatment, the risks and benefits of valproate and other treatment alternatives should be discussed. (4) Valproate should not be prescribed as a first‐line treatment for focal epilepsy. (5) Valproate may be offered as a first‐line treatment for epilepsy syndromes where it is the most effective treatment, including idiopathic (genetic) generalized syndromes associated with tonic–clonic seizures. (6) Valproate may be offered as a first‐line treatment in situations where pregnancy is highly unlikely (e.g., significant intellectual or physical disability). (7) Women and girls taking valproate require regular follow‐up for ongoing consideration of the most appropriate treatment regimen.