The impact of topical treatment for chalazia on the odds of procedural management.

Chalazia in pediatric patients are often treated with topical antibiotics or steroids, although no strong evidence supports their use. This retrospective review of pediatric patients with chalazia did not find a decreased odds of undergoing procedural treatment (incision and curettage and/or intralesional steroid injection) with initial topical antibiotics and/or steroids compared to conservative measures. Inflamed chalazia may benefit from topical treatment, but small sample size limits this subgroup analysis. Shorter pre-topical treatment chalazion duration correlated with a lower risk of procedural intervention. Regimens that included steroids were not found to be more effective than topical antibiotics alone.

Evaluation of the Content of Ophthalmology Fellowship Program Web sites.

Purpose To assess the availability and content of fellowship program Web sites (FPWs) among ophthalmology subspecialties. Design This is a cross-sectional study. Subjects Web sites of all Association of University Professors of Ophthalmology-accredited fellowship programs in five subspecialties (i.e., surgical retina and vitreous; cornea, external disease, and refractive surgery; glaucoma; neuro-ophthalmology; and pediatric ophthalmology). Methods FPWs were assessed for the presence of 26 key content criteria encompassing program demographics ( n = 13), features ( n = 10), and social life ( n = 3). The presence of each content criterion as well as the content criteria groups were compared across subspecialties. Main Outcome Measures The main outcome measured is the average percentage of key content criteria present among ophthalmology fellowship Web sites. Results Among 266 accredited fellowship programs, 240 (90.2%) had Web sites. On average, Web sites reported 14.9 of 26 key content criteria (57.2%), 8.29 of 13 demographic criteria (63.8%), 5.84 of the 10 program features criteria (58.4%), and 0.705 of the 3 social life criteria (23.5%). Significant differences were identified among subspecialties in the presence of program description ( p = 0.046), hospital affiliation ( p < 0.001), names of current fellows ( p = 0.004), case diversity ( p = 0.001), and surgical statistics ( p = 0.015). The average number of key criteria differed between subspecialties ( p < 0.001). Conclusion There is significant heterogeneity in program fellowship Web site content among ophthalmology subspecialties. Information regarding social life, such as wellness programs and community information, was largely absent across all disciplines. Addressing missing information on ophthalmology FPWs may help optimize program-applicant fit.

Paclitaxel increases axonal localization and vesicular trafficking of Nav1.7.

The microtubule-stabilizing chemotherapy drug paclitaxel (PTX) causes dose-limiting chemotherapy-induced peripheral neuropathy (CIPN), which is often accompanied by pain. Among the multifaceted effects of PTX is an increased expression of sodium channel Nav1.7 in rat and human sensory neurons, enhancing their excitability. However, the mechanisms underlying this increased Nav1.7 expression have not been explored, and the effects of PTX treatment on the dynamics of trafficking and localization of Nav1.7 channels in sensory axons have not been possible to investigate to date. In this study we used a recently developed live imaging approach that allows visualization of Nav1.7 surface channels and long-distance axonal vesicular transport in sensory neurons to fill this basic knowledge gap. We demonstrate concentration and time-dependent effects of PTX on vesicular trafficking and membrane localization of Nav1.7 in real-time in sensory axons. Low concentrations of PTX increase surface channel expression and vesicular flux (number of vesicles per axon). By contrast, treatment with a higher concentration of PTX decreases vesicular flux. Interestingly, vesicular velocity is increased for both concentrations of PTX. Treatment with PTX increased levels of endogenous Nav1.7 mRNA and current density in dorsal root ganglion neurons. However, the current produced by transfection of dorsal root ganglion neurons with Halo-tag Nav1.7 was not increased after exposure to PTX. Taken together, this suggests that the increased trafficking and surface localization of Halo-Nav1.7 that we observed by live imaging in transfected dorsal root ganglion neurons after treatment with PTX might be independent of an increased pool of Nav1.7 channels. After exposure to inflammatory mediators to mimic the inflammatory condition seen during chemotherapy, both Nav1.7 surface levels and vesicular transport are increased for both low and high concentrations of PTX. Overall, our results show that PTX treatment increases levels of functional endogenous Nav1.7 channels in dorsal root ganglion neurons and enhances trafficking and surface distribution of Nav1.7 in sensory axons, with outcomes that depend on the presence of an inflammatory milieu, providing a mechanistic explanation for increased excitability of primary afferents and pain in CIPN.

A gain-of-function sodium channel ß2-subunit mutation in painful diabetic neuropathy.

Diabetes mellitus is a global challenge with many diverse health sequelae, of which diabetic peripheral neuropathy is one of the most common. A substantial number of patients with diabetic peripheral neuropathy develop chronic pain, but the genetic and epigenetic factors that predispose diabetic peripheral neuropathy patients to develop neuropathic pain are poorly understood. Recent targeted genetic studies have identified mutations in α-subunits of voltage-gated sodium channels (Navs) in patients with painful diabetic peripheral neuropathy. Mutations in proteins that regulate trafficking or functional properties of Navs could expand the spectrum of patients with Nav-related peripheral neuropathies. The auxiliary sodium channel ß-subunits (ß1-4) have been reported to increase current density, alter inactivation kinetics, and modulate subcellular localization of Nav. Mutations in ß-subunits have been associated with several diseases, including epilepsy, cancer, and diseases of the cardiac conducting system. However, mutations in ß-subunits have never been shown previously to contribute to neuropathic pain. We report here a patient with painful diabetic peripheral neuropathy and negative genetic screening for mutations in SCN9A, SCN10A, and SCN11A-genes encoding sodium channel α-subunit that have been previously linked to the development of neuropathic pain. Genetic analysis revealed an aspartic acid to asparagine mutation, D109N, in the ß2-subunit. Functional analysis using current-clamp revealed that the ß2-D109N rendered dorsal root ganglion neurons hyperexcitable, especially in response to repetitive stimulation. Underlying the hyperexcitability induced by the ß2-subunit mutation, as evidenced by voltage-clamp analysis, we found a depolarizing shift in the voltage dependence of Nav1.7 fast inactivation and reduced use-dependent inhibition of the Nav1.7 channel.