Surface Pressures in Lower Extremity Splints: A Biomechanical Study.

Background: Though ubiquitously used in orthopaedic trauma, lower extremity splints may have associated iatrogenic risk of morbidity. Although clinicians pad bony prominences to minimize skin pressure, the effect of joint position on skin pressure and, more specifically, changing joint position, is understudied. The purpose of this biomechanical study is to determine the effect of various short-leg splint application techniques on anterior ankle surface pressure in the development of iatrogenic skin pressure ulcers. Methods: Various constructs of lower extremity, short-leg splints were applied to 3 healthy subjects (6 limbs total) with an underlying pressure transducer (Tekscan I-Scan system) on the skin surface centered on the tibialis anterior tendon at the level of the ankle. All subjects underwent anterior ankle surface pressure assessment when padding was applied in maximum plantar flexion and neutral position for conventional short-leg splints application in clinically relevant patient scenarios. Percentage change from initial contact pressure centered on the tibialis anterior with cast padding were calculated. Results: The percentage change in anterior ankle contact pressure when padding was applied in maximum plantar flexion (PF) and then definitively placed in neutral was increased at least 2-fold without the addition of plaster in lower extremity short-leg splints. Removing anterior ankle padding following final splint application in neutral reduced contact forces at the anterior ankle 46% and 59% in splints applied in maximum PF and neutral ankle position, respectively. Conclusion: The present study is the first of its kind to underscore and quantify clinically relevant technical pearls that can be useful in reducing risk of iatrogenic risk of skin breakdown at the anterior ankle when placing short-leg splints, mainly, that it is imperative to apply padding in the intended final splint position and to remove anterior ankle padding following splint application when able. Level of Evidence: Level IV, biomechanical study with clear hypothesis.

Oral and dermal toxicity of alkenones extracted from Isochrysis species.

Isochrysis is commercially available marine algae used for animal feed, human nutrient supplements, and biodiesel. The Isochrysis species is one of five genera of haptophytes that produces unique, long-chain lipids known as alkenones that are promising new ingredients for green cosmetics, personal care products and pharmaceutical delivery. However, there is a lack of toxicity data for alkenones in animals, thus limiting their use in humans. In this study, we performed acute oral, acute dermal, and repeated 28-day dermal toxicity studies, using female SAS Sprague Dawley Rats. Our behavioral studies indicated that the specific alkenones had no overt behavioural effects at oral doses up to 4000 mg/kg. In the acute and chronic dermal toxicity studies, the alkenones produced less irritation and did not significantly damage the skin based on the Draize skin reaction scale and trans-epidermal water loss readings compared to the positive control, 1% sodium lauryl sulfate. Overall, our results indicated that alkenones are safe in Sprague Dawley rats, suggesting that they could be used for both oral and dermal formulations, although additional studies will be required.

Human TUBB3 Mutations Disrupt Netrin Attractive Signaling.

Heterozygous missense mutations in human TUBB3 gene result in a spectrum of brain malformations associated with defects in axon guidance, neuronal migration and differentiation. However, the molecular mechanisms underlying mutation-related axon guidance abnormalities are unclear. Recent studies have shown that netrin-1, a canonical guidance cue, induced the interaction of TUBB3 with the netrin receptor deleted in colorectal cancer (DCC). Furthermore, TUBB3 is required for netrin-1-induced axon outgrowth, branching and pathfinding. Here, we provide evidence that TUBB3 mutations impair netrin/DCC signaling in the developing nervous system. The interaction of DCC with most TUBB3 mutants (eight out of twelve) is significantly reduced compared to the wild-type TUBB3. TUBB3 mutants R262C and A302V exhibit decreased subcellular colocalization with DCC in the growth cones of primary neurons. Netrin-1 increases the interaction of endogenous DCC with wild-type human TUBB3, but not R262C or A302V, in primary neurons. Netrin-1 also increases co-sedimentation of DCC with polymerized microtubules (MTs) in primary neurons expressing the wild-type TUBB3, but not R262C or A302V. Expression of either R262C or A302V not only suppresses netrin-1-induced neurite outgrowth, branching and attraction in vitro, but also causes defects in spinal cord commissural axon (CA) projection and pathfinding in ovo. Our study reveals that missense TUBB3 mutations specifically disrupt netrin/DCC-mediated attractive signaling.