Sleep and immune function

Sleep and the circadian system exert a strong regulatory influence on immune functions. Investigations of the normal sleep–wake cycle showed that immune parameters like numbers of undifferentiated naïve T cells and the production of pro-inflammatory cytokines exhibit peaks during early nocturnal sleep whereas circulating numbers of immune cells with immediate effector functions, like cytotoxic natural killer cells, as well as anti-inflammatory cytokine activity peak during daytime wakefulness. Although it is difficult to entirely dissect the influence of sleep from that of the circadian rhythm, comparisons of the effects of nocturnal sleep with those of 24-h periods of wakefulness suggest that sleep facilitates the extravasation of T cells and their possible redistribution to lymph nodes. Moreover, such studies revealed a selectively enhancing influence of sleep on cytokines promoting the interaction between antigen presenting cells and T helper cells, like interleukin-12. Sleep on the night after experimental vaccinations against hepatitis A produced a strong and persistent increase in the number of antigen-specific Th cells and antibody titres. Together these findings indicate a specific role of sleep in the formation of immunological memory. This role appears to be associated in particular with the stage of slow wave sleep and the accompanying pro-inflammatory endocrine milieu that is hallmarked by high growth hormone and prolactin levels and low cortisol and catecholamine concentrations

The delivery site of a monovalent influenza vaccine within the respiratory tract impacts on the immune response

Pulmonary vaccination is a promising immunization route. However, there still remains a crucial need to characterize the different parameters affecting the efficacy of inhaled vaccination. This study aimed at assessing the impact of antigen distribution within the respiratory tract on the immune response to a monovalent A/Panama/2007/99 H3N2 influenza split virus vaccine administered to BALB/c mice. Varying the administration technique allowed the targeting of the vaccine to different sites of the mouse respiratory tract, i.e. the nasal cavity, the upper or central airways, or the deep lung. This targeting was verified by using ovalbumin as a tracer compound. The immune responses generated following influenza vaccine administration to the different respiratory tract sites were compared to each other and to those elicited by intramuscular and peroral intragastric immunization. Delivery of the vaccine to the different respiratory regions generated systemic, local and cellular virus-specific immune responses, which increased with the depth of vaccine deposition, culminating in deep-lung vaccination. The latter induced virus-specific serum immunoglobulin G and neutralizing antibody titres as elevated as intramuscular vaccination, whereas the production of mucosal secretory immunoglobulin A was significantly superior in deep-lung-vaccinated animals. The analysis of cytokines secreted by mononuclear cells during an in vitro recall response indicated that deep-lung vaccination induced a local shift of the cellular immune response towards a T helper type 1 phenotype as compared to intramuscular vaccination. In conclusion, antigen distribution within the respiratory tract has a major effect on the immune response, with the deep lung as the best target for inhaled influenza vaccination

Ex Vivo Biomechanics of Kirschner-Ehmer External Skeletal Fixation Applied to Canine Tibiae

peer reviewedThe purpose of this study was to determine the respective contribution of each of the following parameters to the compressive, bending, and torsional rigidity of the Kirschner-Ehmer (KE) external fixation splint as applied to canine tibiae with an osteotomy gap: bilateral versus unilateral splints; increasing the number of fixation pins; altering the diameter of fixation pins and side bars; decreasing side bar distances from the bone; increasing pin separation distances in each pin group; decreasing distances between pin groups; altering pin clamp orientation; and altering side bar conformation. Bilateral splints were 100% (mean) stiffer than unilateral splints, with stiffness enhanced to the greatest extent in mediolateral bending and torsion. Increasing pin numbers stiffened both bilateral (mean, 41%; 8 versus 4) and unilateral splints (mean, 14%; 8 versus 4). Medium KE splints were 85% (mean) stiffer than small KE splints. Decreasing side bar distances to the bone from 1.5 cm to 1.0 cm to 0.5 cm increased stiffness of both bilateral and unilateral splints by a mean of 13% to 35%. Widening pin spacing from 1.67 cm to 2.5 cm increased stiffness in craniocaudal bending only (56% increase, bilateral splints; 73% increase, unilateral splints). Decreasing the distance between pin groups from 5.84 cm to 2.5 cm increased stiffness in torsion between 23% (unilateral splints) and 45% (bilateral splints) and decreased stiffness of unilateral splints by 29% in craniocaudal bending. Altering pin clamp configuration so that the bolts of the clamp were inside the side bar rather than outside the side bar increased stiffness in axial compression only (73% increase, bilateral splints; 54% increase, unilateral splints). Conforming the lateral side bar to the tibiae increased only axial compressive stiffness by 77% but was no different than placing the clamps inside the side bars of an unconformed bilateral splint. These results quantify the relative importance of specific parameters affecting KE splint rigidity as applied to unstable fractures in the dog

Recent Developments In Interior-Point Methods

The modern era of interior-point methods dates to 1984, when Karmarkar proposed his algorithm for linear programming. In the years since then, algorithms and software for linear programming have become quite sophisticated, while extensions to more general classes of problems, such as convex quadratic programming, semidefinite programming, and nonconvex and nonlinear problems, have reached varying levels of maturity. Interior-point methodology has been used as part of the solution strategy in many other optimization contexts as well, including analytic center methods and column-generation algorithms for large linear programs. We review some core developments in the area and discuss their impact on these other problem areas