In vivo evolution of an emerging zoonotic bacterial pathogen in an immunocompromised human host.

Zoonotic transfer of animal pathogens to human hosts can generate novel agents, but the genetic events following such host jumps are not well studied. Here we characterize the mechanisms driving adaptive evolution of the emerging zoonotic pathogen Bordetella hinzii in a patient with interleukin-12 receptor ß1 deficiency. Genomic sequencing of 24 B. hinzii isolates cultured from blood and stool over 45 months revealed a clonal lineage that had undergone extensive within-host genetic and phenotypic diversification. Twenty of 24 isolates shared an E9G substitution in the DNA polymerase III ε-subunit active site, resulting in a proofreading deficiency. Within this proofreading-deficient clade, multiple lineages with mutations in DNA repair genes and altered mutational spectra emerged and dominated clinical cultures for more than 12 months. Multiple enzymes of the tricarboxylic acid cycle and gluconeogenesis pathways were repeatedly mutated, suggesting rapid metabolic adaptation to the human environment. Furthermore, an excess of G:C > T:A transversions suggested that oxidative stress shaped genetic diversification during adaptation. We propose that inactivation of DNA proofreading activity in combination with prolonged, but sub-lethal, oxidative attack resulting from the underlying host immunodeficiency facilitated rapid genomic adaptation. These findings suggest a fundamental role for host immune phenotype in shaping pathogen evolution following zoonotic infection.

Pain patients' letters: The visit before the visit - A qualitative analysis of letters from patients referred to a tertiary pain center.

BACKGROUND: Pain centers manage only selected patients, and have long waiting lists. Some patients spontaneously send letters, before the visit, and these letters represent the first contact between the patients and the pain centers. We report a study of the content and format of these letters, for a patient perspective analysis. METHODS: During a 3 month-period, all newly referred patients to a tertiary pain center were considered. If a patient letter was provided, it was collected for analysis. Qualitative analyses including semantic and content analyses were performed to identify themes and categories. RESULTS: Among 138 newly referred patients, 44 had sent a letter before consultation. Content analysis of 42 letters disclosed four themes: I) pain experience; II) impact of the pain problem; III) patient history; and IV) expectations. These themes could be distributed along four pain dimensions: (1) physical; (2) psycho-affective; (3) social; and (4) temporal. This first study on patient letters reveals that a bio-psychosocial model. Patients contribute actively to their trajectory, not only as healthcare seekers but also by constructing their narrative identity. CONCLUSIONS: Patient letters constitute narrative material to be integrated into clinical analysis, alongside patient interviews, especially in pain management. Pain specialists should take account of this narrative approach to better understand the unvoiced and sometimes silent experience of pain. This may increase quality of medical care by including patient-centered data in an original method. Further studies may be valuable to analyze the possible contributions of such letters to patient management. SIGNIFICANCE: Patients' letters constitute original narrative material to be integrated into clinical analysis, especially for pain management. Patients' letters analyses may improve the patient physician relationship, by understanding patient's perspectives, beliefs and expectations.

Evaluation of trace elements released by edible clays in physicochemically simulated physiological media.

Physicochemical simulation (pH, electrolytes and temperature) of three physiological media was carried out in order to follow the release of trace elements contained in seven edible clays (mainly kaolinite, illite, muscovite and quartz) collected from the West African countries of Côte d'Ivoire, Guinée and Sénégal. These clays are ingested by pregnant women for diverse reasons that are related to their condition. Simulated oral (6.5

Effects of phenobarbital and rose bengal on the ATPases of plasma membranes of rat and rabbit liver.

The effects of drugs which change the bile-salt-independent fraction of bile flow on Na(+)K(a+) and Mg(2+) activated ATPases were studied in membrane fractions rich in bile canaliculi. The administration of phenobarbital caused no induction of these enzymes which could explain the increased bile flow observed in the rat. Rose bengal, in addition to its strong photoxidative inhibition of both ATPases, inhibits the Na(+)K(+) ATPase of rat and rabbit bile canaliculi in the absence of light. A closely related substance, uranine, inhibits neither bile flow nor Na(+)K(+)ATPase. Inhibition of this enzyme by rose bengal may therefore be responsible for the observed effects of this dye on bile flow independent of bile salts.