Seven-Valent Pneumococcal Conjugate Vaccine and Nasopharyngeal Microbiota in Healthy Children

Seven-valent pneumococcal conjugate vaccine (PCV-7) is effective against vaccine serotype disease and carriage. Nevertheless, shifts in colonization and disease toward nonvaccine serotypes and other potential pathogens have been described. To understand the extent of these shifts, we analyzed nasopharyngeal microbial profiles of 97 PCV-7–vaccinated infants and 103 control infants participating in a randomized controlled trial in the Netherlands. PCV-7 immunization resulted in a temporary shift in microbial community composition and increased bacterial diversity. Immunization also resulted in decreased presence of the pneumococcal vaccine serotype and an increase in the relative abundance and presence of nonpneumococcal streptococci and anaerobic bacteria. Furthermore, the abundance of Haemophilus and Staphylococcus bacteria in vaccinees was increased over that in controls. This study illustrates the much broader effect of vaccination with PCV-7 on the microbial community than currently assumed, and highlights the need for careful monitoring when implementing vaccines directed against common colonizers.     

PET/CT and MR imaging biomarker of lipid-rich plaques using [Cu]-labeled scavenger receptor (CD68-Fc)

Continued uptake of modified low-density lipoproteins (LDL) by the scavenger receptor, CD68, of activated macrophages is a crucial process in the development of atherosclerotic plaques and leads to the formation of foam cells. Eight-weeks-old male Apolipoprotein E-deficient (ApoE^-/-) mice (n=6) were fed a high-fat diet for 12 weeks. C57BL/6J wildtype (WT) mice served as controls (n=6). Positron emission tomography (PET) with an acquisition time of 1800s (NanoPET/CT scanner; Mediso, Hungary & Bioscan, USA) was carried out 24h after intravenous tail vein administration of 50µl ⁶⁴Cu-CD68-Fc (~20-30µg labeled protein/mouse containing approximately 10-12MBq ⁶⁴Cu-CD68-Fc per mouse). Three days after PET/CT, all mice received an intravenous administration of 0.2 mmol/kg body weight of a gadolinium-based elastin-binding contrast agent to assess plaque burden and vessel wall remodeling. Two hours after injection, mice were imaged in a 3T clinical MR scanner (Philips Healthcare, Best, NL) using a dedicated single loop surface coil (23mm). Enhanced ⁶⁴Cu-CD68-Fc uptake was found in the aortic arches of ApoE^-/- compared to WT mice (ApoE^-/- mice:10.5±1.5Bq/cm³ vs. WT mice: 2.1±0.3Bq/cm³; P=0.002). Higher gadolinium-based elastin-binding contrast agent uptake was also detected in the aortic arch of ApoE^-/- compared to WT mice using R¹ maps (R¹=1.47±0.06 s^-1 vs. 0.92±0.05 s^-1; P <0.001). Radiolabeled scavenger receptor (⁶⁴Cu-CD68-Fc) may help to target foam cell rich plaques with high content of oxidized LDL. This novel imaging biomarker tool may have potential to identify unstable plaques and for risk stratification.     

Opposing effects of oxytocin on moral judgment in males and females

Current perspectives on the evolutionary roots of human morality suggest it arose to incentivize social cooperation by promoting feelings of disgust toward selfish behavior, although the underlying neural mechanisms remain unclear. To investigate whether the ancient mammalian neuropeptide oxytocin (OXT) influences self‐referential processing in the domains of emotion evaluation and moral decision making, we conducted a pharmaco‐functional magnetic resonance imaging (fMRI) and a behavioral experiment involving 157 healthy women and men who were treated with either OXT (24 IU) or placebo (PLC) intranasally. Our results show that OXT facilitated cortical midline responses during self‐processing of disgust and selectively promoted self‐interest moral judgments in men. In contrast, in women OXT increased the reaction time difference between accepted and rejected moral dilemmas and led them to suppress their self‐interest and respond more altruistically for the benefit of others. Taken together, these findings suggest an OXT‐related sexual dimorphism in human moral behavior which evolved adaptively to optimize both protection and nurturing of offspring by promoting selfish behavior in men and altruistic behavior in women. Hum Brain Mapp 35:6067–6076, 2014. © 2014 Wiley Periodicals, Inc.     

Early acute antibody-mediated rejection of a negative flow crossmatch 3rd kidney transplant with exclusive disparity at HLA-DP

Donor-specific alloantibodies (DSA) to HLA-DP may cause antibody-mediated rejection (AMR), especially in re-transplants. We describe the immunization history of a patient who received 3 kidney transplants; the 3rd kidney was completely matched except at DPA1 and DPB1. Prior to the 3rd transplant, single antigen bead analysis (SAB) showed DSA reactivity against DPA1 shared by the 1st and 3rd donors, but B and T flow crossmatch (FXM) results were negative. Within 11 days the 3rd transplant underwent acute C4d+ AMR which coincided with the presence of complement (C1q)-binding IgG1 DSA against donor DPA1 and DPB1. Using HLAMatchmaker and SAB, we provide evidence that eplet (epitope) spreading on DPA1 and eplet sharing on differing DPB1 alleles of the 1st and 3rd transplants was associated with AMR. Since weak DSA to DPA1/DPB1 may induce acute AMR with negative FXM, donor DPA1/DPB1 high resolution typing should be considered in sensitized patients with DP-directed DSA.