Cutaneous Cold Weather Injuries in the US Military.

Service members of the US Military are at risk for cutaneous cold weather injuries due to the demands of military training, combat operations, and peacekeeping missions. In this article, we review common cutaneous cold weather injuries likely to be encountered in the military, including frostbite, immersion foot, pernio, Raynaud phenomenon (RP), and cold urticaria. We aim to bring awareness to these specific injuries to improve diagnostic and treatment outcomes, both in service members and civilians.

Development of a liver-targeted siRNA delivery platform with a broad therapeutic window utilizing biodegradable polypeptide-based polymer conjugates.

The greatest challenge standing in the way of effective in vivo siRNA delivery is creating a delivery vehicle that mediates a high degree of efficacy with a broad therapeutic window. Key structure-activity relationships of a poly(amide) polymer conjugate siRNA delivery platform were explored to discover the optimized polymer parameters that yield the highest activity of mRNA knockdown in the liver. At the same time, the poly(amide) backbone of the polymers allowed for the metabolism and clearance of the polymer from the body very quickly, which was established using radiolabeled polymers to demonstrate the time course of biodistribution and excretion from the body. The fast degradation and clearance of the polymers provided for very low toxicity at efficacious doses, and the therapeutic window of this poly(amide)-based siRNA delivery platform was shown to be much broader than a comparable polymer platform. The results of this work illustrate that the poly(amide) platform has a promising future in the development of a siRNA-based drug approved for human use.

An in vivo evaluation of amphiphilic, biodegradable peptide copolymers as siRNA delivery agents.

A series of amphiphilic, biodegradable polypeptide copolymers were prepared for the delivery of siRNA (short interfering ribonucleic acid). The molecular weight (or polymer chain length) of the linear polymer was controlled by reaction stoichiometry for the 11.5, 17.2, and 24.6 kDa polypeptides, and the highest molecular weight polypeptide was prepared using a sequential addition method to obtain a polypeptide having a molecular weight of 38.6 kDa. These polymers were used to prepare polymer conjugate systems designed to target and deliver an apolipoprotein B (ApoB) siRNA to hepatocyte cells and to help delineate the effect of polymer molecular weight or polymer chain length on siRNA delivery in vivo. A clear trend in increasing potency was found with increasing molecular weight of the polymers examined (at a constant polymer:siRNA (w/w) ratio), with minimal toxicity found. Furthermore, the biodegradability of these polymer conjugates was examined and demonstrates the potential of these systems as siRNA delivery vectors.

Sexually-dimorphic expression of tyrosine hydroxylase immunoreactivity in the brain of a vocal teleost fish (Porichthys notatus).

Vocal communication has emerged as a powerful model for the study of neural mechanisms of social behavior. Modulatory neurochemicals postulated to play a central role in social behavior, related to motivation, arousal, incentive and reward, include the catecholamines, particularly dopamine and noradrenaline. Many questions remain regarding the functional mechanisms by which these modulators interact with sensory and motor systems. Here, we begin to address these questions in a model system for vocal and social behavior, the plainfin midshipman fish (Porichthys notatus). We mapped the distribution of immunoreactivity for the catecholamine-synthesizing enzyme tyrosine hydroxylase (TH) in the midshipman brain. The general pattern of TH(+) cell groups in midshipman appears to be highly conserved with other teleost fish, with a few exceptions, including the apparent absence of pretectal catecholamine cells. Many components of the midshipman vocal and auditory systems were innervated by TH(+) fibers and terminals, including portions of the subpallial area ventralis, the preoptic complex, and the anterior hypothalamus, the midbrain periaqueductal gray and torus semicircularis, several hindbrain auditory nuclei, and parts of the hindbrain vocal pattern generator. These areas thus represent potential sites for catecholamine modulation of vocal and/or auditory behavior. To begin to test functionally whether catecholamines modulate vocal social behaviors, we hypothesized that male and female midshipman, which are sexually dimorphic in both their vocal-motor repertoires and in their responses to hearing conspecific vocalizations, should exhibit sexually dimorphic expression of TH immunoreactivity in their vocal and/or auditory systems. We used quantitative immunohistochemical techniques to test this hypothesis across a number of brain areas. We found significantly higher levels of TH expression in male midshipman relative to females in the TH cell population in the paraventricular organ of the diencephalon and in the TH-innervated torus semicircularis, the main teleost midbrain auditory structure. The torus semicircularis has been implicated in sexually dimorphic behavioral responses to conspecific vocalizations. Our data thus support the general idea that catecholamines modulate vocal and auditory processing in midshipman, and the specific hypothesis that they shape sexually dimorphic auditory responses in the auditory midbrain.