Host Immune Transcriptional Profiles Reflect the Variability in Clinical Disease Manifestations in Patients with Staphylococcus aureus Infections

Staphylococcus aureus infections are associated with diverse clinical manifestations leading to significant morbidity and mortality. To define the role of the host response in the clinical manifestations of the disease, we characterized whole blood transcriptional profiles of children hospitalized with community-acquired S. aureus infection and phenotyped the bacterial strains isolated. The overall transcriptional response to S. aureus infection was characterized by over-expression of innate immunity and hematopoiesis related genes and under-expression of genes related to adaptive immunity. We assessed individual profiles using modular fingerprints combined with the molecular distance to health (MDTH), a numerical score of transcriptional perturbation as compared to healthy controls. We observed significant heterogeneity in the host signatures and MDTH, as they were influenced by the type of clinical presentation, the extent of bacterial dissemination, and time of blood sampling in the course of the infection, but not by the bacterial isolate. System analysis approaches provide a new understanding of disease pathogenesis and the relation/interaction between host response and clinical disease manifestations

Hippocampal - diencephalic - cingulate networks for memory and emotion: An anatomical guide

This review brings together current knowledge from tract tracing studies to update and reconsider those limbic connections initially highlighted by Papez for their presumed role in emotion. These connections link hippocampal and parahippocampal regions with the mammillary bodies, the anterior thalamic nuclei, and the cingulate gyrus, all structures now strongly implicated in memory functions. An additional goal of this review is to describe the routes taken by the various connections within this network. The original descriptions of these limbic connections saw their interconnecting pathways forming a serial circuit that began and finished in the hippocampal formation. It is now clear that with the exception of the mammillary bodies, these various sites are multiply interconnected with each other, including many reciprocal connections. In addition, these same connections are topographically organised, creating further subsystems. This complex pattern of connectivity helps explain the difficulty of interpreting the functional outcome of damage to any individual site within the network. For these same reasons, Papez’s initial concept of a loop beginning and ending in the hippocampal formation needs to be seen as a much more complex system of hippocampal–diencephalic–cingulate connections. The functions of these multiple interactions might be better viewed as principally providing efferent information from the posterior medial temporal lobe. Both a subcortical diencephalic route (via the fornix) and a cortical cingulate route (via retrosplenial cortex) can be distinguished. These routes provide indirect pathways for hippocampal interactions with prefrontal cortex, with the preponderance of both sets of connections arising from the more posterior hippocampal regions. These multi-stage connections complement the direct hippocampal projections to prefrontal cortex, which principally arise from the anterior hippocampus, thereby creating longitudinal functional differences along the anterior–posterior plane of the hippocampus

Histologic dating of bruises in moribund infants and young children

It is generally held that leukocytes are found within bruised subcutaneous tissues within 4–12 h of injury as part of a standard cellular response to trauma. As a corollary, the absence of leukocytes is often cited as evidence of more recent injury. To investigate how long after injury it may be before a leukocyte response occurs selected bruises from three children aged 27, 11, and 3 months, respectively, were examined microscopically. All of the children had sustained lethal head trauma, with survival on life-support equipment for some time in hospital, and with bruises of at least 24-h duration confirmed by medical evaluation (at 30, 44, and 79 h from the time of initial medical evaluation to death). Histologic examination of selected lesions in all three cases revealed extravasation of red blood cells within subcutaneous tissues, but no leukocyte infiltration or other cellular reaction. Other bruises in these children exhibited a standard inflammatory response. This study has shown that selected bruises in three children were present for at least 30 h without a leukocyte infiltrate. Caution should, therefore, be exercised in assigning too rigid a time course to bruising in infants and young children based on a lack of a vital reaction, as the absence of leukocytes within soft tissues of bruised skin in these cases may not necessarily indicate that the injuries are recent. Variability in tissue response may also occur in different bruises in the same individual. Whether severe craniocerebral trauma played a role in delaying the cellular response in these particular injuries is unclear.Roger W. Byard, Regula Wick, John D. Gilbert and Terence Donal