[Bullet and shrapnel injuries in the face and neck regions. Current aspects of wound ballistics]

A basic understanding of the ballistic behaviour of projectiles or fragments after entering the human body is essential for the head and neck surgeon in the military environment in order to anticipate the diagnostic and therapeutic consequences of this type of injury. Although a large number of factors influence the missile in flight and after penetration of the body, the most important factor is the amount of energy transmitted to the tissue. Long guns (rifles or shotguns) have a much higher muzzle energy compared to handguns, explaining why the remote effects beyond the bullet track play a major role. While most full metal jacket bullets release their energy after 12-20 cm (depending on the calibre), soft point bullets release their energy immediately after entry into the human body. This results in a major difference in extremity wounds, but not so much in injuries with long bullet paths (e.g. diagonal shots). Shrapnel wounds are usually produced with similarly high kinetic energy to those caused by hand- and long guns. However, fragments tend to dissipate the entire amount of energy within the body, which increases the degree of tissue disruption. Of all relevant injuries in the head and neck region, soft tissue injuries make up the largest proportion (60%), while injuries to the face are seen three times more often than injuries to the neck. Concomitant intracranial or spinal injury is seen in 30% of cases. Due to high levels of wound contamination, the infection rate is approximately 15%, often associated with a complicated and/or multiresistant spectrum of germs.

Fluids and barriers of the CNS establish immune privilege by confining immune surveillance to a two-walled castle moat surrounding the CNS castle

Neuronal activity within the central nervous system (CNS) strictly depends on homeostasis and therefore does not tolerate uncontrolled entry of blood components. It has been generally believed that under normal conditions, the endothelial blood-brain barrier (BBB) and the epithelial blood-cerebrospinal fluid barrier (BCSFB) prevent immune cell entry into the CNS. This view has recently changed when it was realized that activated T cells are able to breach the BBB and the BCSFB to perform immune surveillance of the CNS. Here we propose that the immune privilege of the CNS is established by the specific morphological architecture of its borders resembling that of a medieval castle. The BBB and the BCSFB serve as the outer walls of the castle, which can be breached by activated immune cells serving as messengers for outside dangers. Having crossed the BBB or the BCSFB they reach the castle moat, namely the cerebrospinal fluid (CSF)-drained leptomeningeal and perivascular spaces of the CNS. Next to the CNS parenchyma, the castle moat is bordered by a second wall, the glia limitans, composed of astrocytic foot processes and a parenchymal basement membrane. Inside the castle, that is the CNS parenchyma proper, the royal family of sensitive neurons resides with their servants, the glial cells. Within the CSF-drained castle moat, macrophages serve as guards collecting all the information from within the castle, which they can present to the immune-surveying T cells. If in their communication with the castle moat macrophages, T cells recognize their specific antigen and see that the royal family is in danger, they will become activated and by opening doors in the outer wall of the castle allow the entry of additional immune cells into the castle moat. From there, immune cells may breach the inner castle wall with the aim to defend the castle inhabitants by eliminating the invading enemy. If the immune response by unknown mechanisms turns against self, that is the castle inhabitants, this may allow for continuous entry of immune cells into the castle and lead to the death of the castle inhabitants, and finally members of the royal family, the neurons. This review will summarize the molecular traffic signals known to allow immune cells to breach the outer and inner walls of the CNS castle moat and will highlight the importance of the CSF-drained castle moat in maintaining immune surveillance and in mounting immune responses in the CNS.

Proteins encoded in genomic regions associated with immune-mediated disease physically interact and suggest underlying biology

Genome-wide association studies (GWAS) have defined over 150 genomic regions unequivocally containing variation predisposing to immune-mediated disease. Inferring disease biology from these observations, however, hinges on our ability to discover the molecular processes being perturbed by these risk variants. It has previously been observed that different genes harboring causal mutations for the same Mendelian disease often physically interact. We sought to evaluate the degree to which this is true of genes within strongly associated loci in complex disease. Using sets of loci defined in rheumatoid arthritis (RA) and Crohn's disease (CD) GWAS, we build protein-protein interaction (PPI) networks for genes within associated loci and find abundant physical interactions between protein products of associated genes. We apply multiple permutation approaches to show that these networks are more densely connected than chance expectation. To confirm biological relevance, we show that the components of the networks tend to be expressed in similar tissues relevant to the phenotypes in question, suggesting the network indicates common underlying processes perturbed by risk loci. Furthermore, we show that the RA and CD networks have predictive power by demonstrating that proteins in these networks, not encoded in the confirmed list of disease associated loci, are significantly enriched for association to the phenotypes in question in extended GWAS analysis. Finally, we test our method in 3 non-immune traits to assess its applicability to complex traits in general. We find that genes in loci associated to height and lipid levels assemble into significantly connected networks but did not detect excess connectivity among Type 2 Diabetes (T2D) loci beyond chance. Taken together, our results constitute evidence that, for many of the complex diseases studied here, common genetic associations implicate regions encoding proteins that physically interact in a preferential manner, in line with observations in Mendelian disease.

Interhemispheric connections shape subjective experience of bistable motion

The right and left visual hemifields are represented in different cerebral hemispheres and are bound together by connections through the corpus callosum. Much has been learned on the functions of these connections from split-brain patients [1-4], but little is known about their contribution to conscious visual perception in healthy humans. We used diffusion tensor imaging and functional magnetic resonance imaging to investigate which callosal connections contribute to the subjective experience of a visual motion stimulus that requires interhemispheric integration. The "motion quartet" is an ambiguous version of apparent motion that leads to perceptions of either horizontal or vertical motion [5]. Interestingly, observers are more likely to perceive vertical than horizontal motion when the stimulus is presented centrally in the visual field [6]. This asymmetry has been attributed to the fact that, with central fixation, perception of horizontal motion requires integration across hemispheres whereas perception of vertical motion requires only intrahemispheric processing [7]. We are able to show that the microstructure of individually tracked callosal segments connecting motion-sensitive areas of the human MT/V5 complex (hMT/V5+; [8]) can predict the conscious perception of observers. Neither connections between primary visual cortex (V1) nor other surrounding callosal regions exhibit a similar relationship.

Occurrence, finger printing and ecological risk assessment of polycyclic aromatic hydrocarbons (PAHs) in the Chenab River, Pakistan

Seventeen polycyclic aromatic hydrocarbons (PAHs) were studied in surface waters (including particulate phase) from the Chenab River, Pakistan and ranged from 289-994 and 437-1290 ng l-1 in summer and winter (2007-09), respectively. Concentrations for different ring-number PAHs followed the trend: 3-rings > 2-rings > 4-rings > 5-rings > 6-rings. The possible sources of PAHs are identified by calculating the indicative ratios; appropriating petrogenic sources of PAHs in urban and sub-urban regions with pyrogenic sources in agricultural region. Factor analysis based on principal component analysis identified the origins of PAHs from industrial activities, coal and trash burning in agricultural areas and municipal waste disposal from surrounding urban and sub-urban areas via open drains into the riverine ecosystem. Water quality guidelines and toxic equivalent factors highlighted the potential risk of low molecular weight PAHs to the aquatic life of the Chenab River. The flux estimated for PAHs contaminants from the Chenab River to the Indus River was >50 tons/year.