Polymicrobial sepsis is associated with immunosuppression caused by the predominance of anti-inflammatory mediators and profound loss of lymphocytes through apoptosis. Dendritic cells (DC) are potent antigen-presenting cells and play a key role in T cell activation. We tested the hypothesis that DC are involved in sepsis-mediated immunosuppression in a mouse cecal ligation and puncture (CLP) model, which resembles human polymicrobial sepsis. At different time-points after CLP, DC from the spleen and peripheral lymph nodes were characterized in terms of expression of costimulatory molecules, cytokine synthesis, and subset composition. Splenic DC strongly up-regulated CD86 and CD40 but not CD80 as soon as 8 h after CLP. In contrast, lymph node DC equally increased the expression of CD86, CD40, and CD80. However, this process of maturation occurred later in the lymph nodes than in the spleen. Splenic DC from septic mice were unable to secrete interleukin (IL)-12, even upon stimulation with CpG or lipopolysaccharide+CD40 ligand, but released high levels of IL-10 in comparison to DC from control mice. Neutralization of endogenous IL-10 could not restore IL-12 secretion by DC of septic mice. In addition, the splenic CD4+CD8- and CD4-CD8+ subpopulations were lost during sepsis, and the remaining DC showed a reduced capacity for allogeneic T cell activation associated with decreased IL-2 synthesis. Thus, during sepsis, splenic DC acquire a state of aberrant responsiveness to bacterial stimuli, and two DC subtypes are selectively lost. These changes in DC behavior might contribute to impaired host response against bacteria during sepsis.

The human hippocampus plays a key role in memory management and is one of the first structures affected by Alzheimer's disease. Ultra-high magnetic resonance imaging provides access to its inner structure in vivo. However, gradient limitations on clinical systems hinder access to its inner connectivity and microstructure. A major target of this paper is the demonstration of diffusion MRI potential, using ultra-high field (11.7 T) and strong gradients (750 mT/m), to reveal the extra-and intrahippocampal connectivity in addition to its microstructure. To this purpose, a multiple-shell diffusion-weighted acquisition protocol was developed to reach an ultra-high spatio-angular resolution with a good signal-to-noise ratio. The MRI data set was analyzed using analytical Q-Ball Imaging, Diffusion Tensor Imaging (DTI), and Neurite Orientation Dispersion and Density Imaging models. High Angular Resolution Diffusion Imaging estimates allowed us to obtain an accurate tractography resolving more complex fiber architecture than DTI models, and subsequently provided a map of the cross-regional connectivity. The neurite density was akin to that found in the histological literature, revealing the three hippocampal layers. Moreover, a gradient of connectivity and neurite density was observed between the anterior and the posterior part of the hippocampus. These results demonstrate that ex vivo ultra-high field/ultra-high gradients diffusion-weighted MRI allows the mapping of the inner connectivity of the human hippocampus, its microstructure, and to accurately reconstruct elements of the polysynaptic intra-hippocampal pathway using fiber tractography techniques at very high spatial/angular resolutions.

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IntroductionPrevious studies reported divergent results concerning the effect of gender on patient outcome after severe injury. Results suggest that women have better outcomes because they have lower rates of sepsis and multi-organ failure. The objective of this analysis was to study gender differences in a Level 1 trauma center in Germany.MethodsPatients who were admitted to hospital between 2002 and 2011 with an Injury Severity Score (ISS) ≥16 were included. Data were collected from the Trauma Registry of the German Society for Trauma Surgery and from hospital records. The effects of gender on a variety of parameters were investigated. To eliminate the influence of differences in ISS, an analysis of groups with similar ISS was performed. Also, a matched-pair analysis of 422 patients was performed.ResultsA total of 962 patients met the inclusion criteria. The mortality rate was lower in male patients (25.4% versus 36.59%). Female patients had more severe head injuries, received less fluid volume and had a lower rate of sepsis. Men were more frequently involved in motorcycle accidents and sustained more penetrating trauma. Women were more frequently involved in pedestrian accidents and sustained more falls from under 3 m. The effects of gender were reduced when the data were analyzed by matching ISS. The mortality rate was significantly different in the ISS 26 to 35 group but in mostly all groups, the mortality rate was higher in women. In the matched-pair analysis, the rate of sepsis and the length of the ICU stay were significantly lower in women and the mortality rate showed no significant difference (28.1% for male patients versus 33.01% for female patients). Women died after an average of 5.22 days, and men died after an average of 9.02 days.ConclusionsGender-based differences in patient outcome after severe trauma were observed in this study. Women are more likely to die in the first days after trauma. Upon extended hospital stay, women had a better survival rate because they had a lower rate of sepsis. No significant differences in mortality rate could be found, but there was a trend towards a higher rate in female patients.

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