We identified 5 risk factors for nocardiosis after SOT. Low-dose cotrimoxazole was not found to prevent Nocardia infection. These findings may help improve management of transplant recipients.

Background. Solid organ transplant (SOT) recipients are at risk of nocardiosis, a rare opportunistic bacterial infection, but prognosis and outcome of these patients are poorly defined. Our objectives were to identify factors associated with 1-year mortality after nocardiosis and describe the outcome of patients receiving short-course antibiotics (≤120 days).Methods. We analyzed data from a multicenter European case-control study that included 117 SOT recipients with nocardiosis diagnosed between 2000 and 2014. Factors associated with 1-year all-cause mortality were identified using multivariable conditional logistic regression.Results. One-year mortality was 10-fold higher in patients with nocardiosis (16.2%, 19/117) than in control transplant recipients (1.3%, 3/233, P < .001). A history of tumor (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.1-1.8), invasive fungal infection (OR, 1.3; 95% CI, 1.1-1.5), and donor age (OR, 1.0046; 95% CI, 1.0007-1.0083) were independently associated with 1-year mortality. Acute rejection in the year before nocardiosis was associated with improved survival (OR, 0.85; 95% CI, 0.73-0.98). Seventeen patients received short-course antibiotics (median duration 56 [24-120] days) with a 1-year success rate (cured and surviving) of 88% and a 5.9% risk of relapse (median follow-up 49 months).Conclusions. One-year mortality was 10-fold higher in SOT patients with nocardiosis than in those without. Four factors, largely reflecting general medical condition rather than severity and/or management of nocardiosis, were independently associated with 1-year mortality. Patients who received short-course antibiotic treatment had good outcomes, suggesting that this may be a strategy for further study.

BackgroundIncreasing studies show that immigrants have different perinatal health outcomes compared to native women. Nevertheless, we lack a systematic examination of the combined effects of immigrant status and socioeconomic factors on perinatal outcomes. Our objectives were to analyse national Belgian data to determine 1) whether socioeconomic status (SES) modifies the association between maternal nationality and perinatal outcomes (low birth weight and perinatal mortality); 2) the effect of adopting the Belgian nationality on the association between maternal foreign nationality and perinatal outcomes.MethodsThis study is a population-based study using the data from linked birth and death certificates from the Belgian civil registration system. Data are related to all singleton births to mothers living in Belgium between 1998 and 2010. Perinatal mortality and low birth weight (LBW) were estimated by SES (maternal education and parental employment status) and by maternal nationality (at her own birth and at her child’s birth). We used logistic regression to estimate the odds ratios for the associations between nationality and perinatal outcomes after adjusting for and stratifying by SES.ResultsThe present study includes, for the first time, all births in Belgium; that is 1,363,621 singleton births between 1998 and 2010. Compared to Belgians, we observed an increased risk of perinatal mortality in all migrant groups (p < 0.0001), despite lower rates of LBW in some nationalities. Immigrant mothers with the Belgian nationality had similar rates of perinatal mortality to women of Belgian origin and maintained their protection against LBW (p < 0.0001). After adjustment, the excess risk of perinatal mortality among immigrant groups was mostly explained by maternal education; whereas for sub-Saharan African mothers, mortality was mainly affected by parental employment status. After stratification by SES, we have uncovered a significant protective effect of immigration against LBW and perinatal mortality for women with low SES but not for high SES.ConclusionsOur results show a protective effect of migration in relation to perinatal mortality and LBW among women of low SES. Hence, the study underlines the importance of taking into account socioeconomic status in order to understand more fully the relationship between migration and perinatal outcomes. Further studies are needed to analyse more finely the impact of socio-economic characteristics on perinatal outcomes.

SummaryBackground and objectives In 2009, the pandemic influenza A/H1N1 accounted for worldwide recommendations about vaccination. There are few data concerning the immunogenicity or the security of the adjuvanted-A/H1N1 vaccine in transplanted and hemodialyzed patients.Design, setting, participants, & measurements Sera from 21 controls, 53 hemodialyzed (HD) patients, and 111 renal transplant recipients (RT) were sampled before (T0) and 1 month after (T1) a single dose of Pandemrix® vaccine (GSK Biologicals, AS03-adjuvanted). We measured the neutralizing antibodies against A/H1N1/2009, the geometric mean (GM) titers, the GM titer ratios (T1/T0) with 95% confidence intervals, and the seroconversion rate (responders: Ն4-fold increase in titer). The HLA and MICA immunization was determined by Luminex technology. ResultsThe GM titer ratio was 38 (19 to 78), 9 (5 to 16), and 5 (3 to 6) for controls, HD patients, and RT patients, respectively (P Ͻ 0.001). The proportion of responders was 90%, 57%, and 44%, respectively (P Ͻ 0.001). In RT patients, the prevalence of histocompatibility leukocyte antigen (HLA) class I, histocompatibility leukocyte antigen class II, and MHC class I-related chain A immunization, was, respectively, 15%, 14%, and 14% before and 14%, 14%, and 11% after vaccination (P ϭ 1, 1, and 0.39). ConclusionsThe influenza A/H1N1-adjuvanted vaccine is of limited efficacy but is safe in renal disease populations. The humoral response is lower in transplanted versus hemodialyzed patients. Further studies are needed to improve the efficacy of vaccination in those populations.

In kidney transplantation, operational tolerance and almost tolerance are infrequent findings associated with excellent long-term death-censored graft survival.

A structural model of BgK, a sea anemone toxin, complexed with the S5-S6 region of Kv1.1, a voltage-gated potassium channel, was determined by flexible docking under distance restraints identified by a double mutant cycles approach. This structure provides the molecular basis for identifying the major determinants of the BgKKv1.1 channel interactions involving the BgK dyad residues Lys 25 and Tyr 26 . These interactions are (i) electrostatic interactions between the extremity of Lys 25 side chain and carbonyl oxygen atoms of residues from the channel selectivity filter that may be strengthened by solvent exclusion provided by (ii) hydrophobic interactions involving BgK residues Tyr 26 and Phe 6 and Kv1.1 residue Tyr 379 whose side chain protrudes in the channel vestibule. In other Kv1 channel-BgK complexes, these interactions are likely to be conserved, implicating both conserved and variable residues from the channels. The data suggest that the conservation in sea anemone and scorpion potassium channel blockers of a functional dyad composed of a lysine, and a hydrophobic residue reflects their use of convergent binding solutions based on a crucial interplay between these important conserved interactions.Although most biological processes are governed by proteinprotein recognition phenomena, the molecular determinants of the specificity of these interactions are yet poorly understood. In particular, one protein ligand can bind multiple receptors and a receptor can be bound by several protein ligands of similar or even different structures (l-3), and the molecular mechanisms underlying these multiple bindings are not well understood. Kv1 voltage-gated potassium channels and toxins from scorpions, snakes, sea anemones, and conus that block currents through these channels offer an appropriate mean to investigate the molecular basis of such pleiotropic aspects of protein-protein interactions. Indeed, a potassium channel can be blocked by different toxins of similar or different folds, and conversely a toxin can bind to several members of Kv1 channels (3). Two lines of evidence suggest that the four groups of toxins use a convergent solution to block Kv1 channels. First, despite their unrelated structures, they all exert their function by binding to the same P-region of the channels, comprised between transmembrane segments S5 and S6 (4 -12). Second, the binding sites of all these toxins contain a functional dyad composed of a lysine and a hydrophobic residue that might constitute a minimal functional core for the toxins to bind Kv1 channels, whereas additional residues might provide each toxin with a specific binding profile (3,(13)(14)(15)(16)(17).To get further insights into the toxin-channel interactions and in particular into the role of the dyad residues, we used double mutant cycle analysis to identify proximities between residues of BgK, a sea anemone toxin, and Kv1.1. Then, these proximities were used to determine the structure of BgK complexed with the S5-S6 region of Kv1.1. Analysis of this model provides ...

SummaryPopA is released by type III secretion from the bacterial plant pathogen Ralstonia solanacearum and triggers the hypersensitive response (HR) in tobacco. The function of PopA remains obscure, mainly because mutants lacking this protein are not altered in their ability to interact with plants. In an attempt to identify the site of PopA activity in plant cells, we generated transgenic tobacco plants expressing the popA gene under the control of an inducible promoter. Immunocytologic analysis revealed that the HR phenotype of these plants correlated with the presence of PopA at the plant plasma membrane. Membrane localization was observed irrespective of whether the protein was designed to accumulate in the cytoplasm or to be secreted by the plant cell, suggesting a general lipidbinding ability. We found that the protein had a high affinity for sterols and sphingolipids in vitro and that it required Ca 2+ + + + for both lipid binding and oligomerization. In addition, the protein was integrated into liposomes and membranes from Xenopus laevis oocytes where it formed ion-conducting pores. These characteristics suggest that PopA is part of a system that aims to attach the host cell plasma membrane and to allow molecules cross this barrier.

(J. Coussement). y The members of the Bacteriuria in Renal Transplantation (BiRT) study group are listed in the Appendix.