Conventional kinesin (Kinesin‐1), the founding member of the kinesin family, was discovered in the squid giant axon, where it is thought to move organelles on microtubules. In this study, we identify a second squid kinesin by searching an expressed sequence tag database derived from the ganglia that give rise to the axon. The full‐length open reading frame encodes a 1753 amino acid sequence that classifies this protein as a Kinesin‐3. Immunoblots demonstrate that this kinesin, unlike Kinesin‐1, is highly enriched in chaotropically stripped axoplasmic organelles, and immunogold electron microscopy (EM) demonstrates that Kinesin‐3 is tightly bound to the surfaces of these organelles. Video microscopy shows that movements of purified organelles on microtubules are blocked, but organelles remain attached, in the presence Kinesin‐3 antibody. Immunogold EM of axoplasmic spreads with antibody to Kinesin‐3 decorates discrete sites on many, but not all, free organelles and localizes Kinesin‐3 to organelle/microtubule interfaces. In contrast, label for Kinesin‐1 decorates microtubules but not organelles. The presence of Kinesin‐3 on purified organelles, the ability of an antibody to block their movements along microtubules, the tight association of Kinesin‐3 with motile organelles and its distribution at the interface between native organelles and microtubules suggest that Kinesin‐3 is a dominant motor in the axon for unidirectional movement of organelles along microtubules.

IMPORTANCE Photodynamic therapy (PDT) is an effective and cosmetically favorable treatment modality for actinic keratoses (AKs). However, prolonged incubation times and pain associated with treatment are burdensome to the patient and a hindrance to widespread use of PDT as standard field therapy for AK. OBJECTIVE To evaluate efficacy and pain associated with microneedle expedited PDT. DESIGN, SETTING, AND PARTICIPANTS The Microneedle Photodynamic Therapy II (MNPDT-II) study was a randomized, single-blinded, split-face controlled, 2-arm clinical trial. Thirty-three participants with AK on the face were recruited in a university dermatology outpatient clinic from 2015 to 2016, and 32 participants completed the study. INTERVENTIONS Participants were randomized into 2 incubations arms, either 10-minute or 20-minute aminolevulinic acid (ALA) incubation times, after pretreatment with a microneedle roller (200 um) vs a sham roller. They were blinded to the laterality of microneedle and sham roller assignments. After incubation, they were exposed to blue light (Blu-U, Dusa Pharmaceuticals) for 1000 seconds for a total fluence of 10 J/cm 2. MAIN OUTCOMES AND MEASURES The primary outcome was to quantitatively measure AK resolution, and the secondary outcome was to assess pain associated with microneedle pretreatment. RESULTS Thirty-three individuals were recruited and randomized to either the 20-minute or the 10-minute incubation arm. Thirty-two participants completed the study with a mean follow-up time of 34.5 days in the 20-minute group, and 30.2 days in the 10-minute group. For the 20-minute incubation arm, average AK clearance was 76% vs 58% on the sham side (P < .01), including 3 patients with complete clearance, although not statistically significant (P = .25). Pain assessment on the visual analog scale (VAS) during blue light illumination was not significantly different between the microneedle and sham sides (0.7 and 0.4; P = .28), respectively. For the 10-minute incubation arm AK clearance for the microneedle pretreated side was 43% compared with 38% on the sham side (P = .66). Pain during the blue light exposure was not significantly different between the microneedle and sham sides, 4.5 mm and 3.4 mm (P = .21), respectively. CONCLUSIONS AND RELEVANCE Photodynamic therapy with microneedle pretreatment at a 20-minute ALA incubation time significantly improved AK clearance with efficacy similar to that of a conventional 1-hour ALA incubation time. The additional advantage to expedited treatment was that the procedure was virtually painless. However, expedited exposure of a 10-minute ALA incubation time did not reach significantly different AK clearance from the sham control. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT02594644

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for trainees and health care providers based on the most common dermatologic diagnoses we identified could help alleviate the pediatric dermatology workforce shortage and improve quality of care for many children.

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