Overcoming Barriers Associated with Oral Delivery of Differently Sized Fluorescent Core-Shell Silica Nanoparticles.

Oral delivery, while a highly desirable form of nanoparticle-drug administration, is limited by challenges associated with overcoming several biological barriers. Here, the authors study how fluorescent and poly(ethylene glycol)-coated (PEGylated) core-shell silica nanoparticles sized 5 to 50 nm interact with major barriers including intestinal mucus, intestinal epithelium, and stomach acid. From imaging fluorescence correlation spectroscopy studies using quasi-total internal reflection fluorescence microscopy, diffusion of nanoparticles through highly scattering mucus is progressively hindered above a critical hydrodynamic size around 20 nm. By studying Caco-2 cell monolayers mimicking the intestinal epithelia, it is observed that ultrasmall nanoparticles below 10 nm diameter (Cornell prime dots, [C' dots]) show permeabilities correlated with high absorption in humans from primarily enhanced passive passage through tight junctions. Particles above 20 nm diameter exclusively show active transport through cells. After establishing C' dot stability in artificial gastric juice, in vivo oral gavage experiments in mice demonstrate successful passage through the body followed by renal clearance without protein corona formation. Results suggest C' dots as viable candidates for oral administration to patients with a proven pathway towards clinical translation and may generate renewed interest in examining silica as a food additive and its effects on nutrition and health.

Isolated Stieda Process Fracture of Talus: A Case Study.

OBJECTIVE: The purpose of this case report is to describe a patient with a fracture of the Stieda process. CLINICAL FEATURES: A 39-year-old woman presented with pain and swelling of her left ankle immediately following a boogie boarding accident a few days earlier. Her clinical presentation was similar to that of an ankle sprain. INTERVENTION AND OUTCOME: Radiographs were ordered, and a fracture of a normal variant, the Stieda process, was identified. Non-displacement of the fracture fragment was managed with conservative treatment consisting of a short-leg cast for 6 weeks. The fracture healed without complications. CONCLUSION: The importance of early recognition of this fracture helped with proper management and a favorable outcome.

Effects of Diaphragmatic Breathing Patterns on Balance: A Preliminary Clinical Trial.

OBJECTIVE: The purpose of this study was to determine the feasibility of performing a larger study to determine if training in diaphragmatic breathing influences static and dynamic balance. METHODS: A group of 13 healthy persons (8 men, 5 women), who were staff, faculty, or students at the University of Western States participated in an 8-week breathing and balance study using an uncontrolled clinical trial design. Participants were given a series of breathing exercises to perform weekly in the clinic and at home. Balance and breathing were assessed at the weekly clinic sessions. Breathing was evaluated with Liebenson's breathing assessment, static balance with the Modified Balance Error Scoring System, and dynamic balance with OptoGait's March in Place protocol. RESULTS: Improvement was noted in mean diaphragmatic breathing scores (1.3 to 2.6, P < .001), number of single-leg stance balance errors (7.1 to 3.8, P = .001), and tandem stance balance errors (3.2 to 0.9, P = .039). A decreasing error rate in single-leg stance was associated with improvement in breathing score within participants over the 8 weeks of the study (-1.4 errors/unit breathing score change, P < .001). Tandem stance performance did not reach statistical significance (-0.5 error/unit change, P = .118). Dynamic balance was insensitive to balance change, being error free for all participants throughout the study. CONCLUSION: This proof-of-concept study indicated that promotion of a costal-diaphragmatic breathing pattern may be associated with improvement in balance and suggests that a study of this phenomenon using an experimental design is feasible.

Genetic and ecotypic differentiation in a Californian plant polyploid complex (Grindelia, Asteraceae).

Studies of ecotypic differentiation in the California Floristic Province have contributed greatly to plant evolutionary biology since the pioneering work of Clausen, Keck, and Hiesey. The extent of gene flow and genetic differentiation across interfertile ecotypes that span major habitats in the California Floristic Province is understudied, however, and is important for understanding the prospects for local adaptation to evolve or persist in the face of potential gene flow across populations in different ecological settings. We used microsatellite data to examine local differentiation in one of these lineages, the Pacific Coast polyploid complex of the plant genus Grindelia (Asteraceae). We examined 439 individuals in 10 different populations. The plants grouped broadly into a coastal and an inland set of populations. The coastal group contained plants from salt marshes and coastal bluffs, as well as a population growing in a serpentine grassland close to the coast, while the inland group contained grassland plants. No evidence for hybridization was found at the single location where adjacent populations of the two groups were sampled. In addition to differentiation along ecotypic lines, there was also a strong signal of local differentiation, with the plants grouping strongly by population. The strength of local differentiation is consistent with the extensive morphological variation observed across populations and the history of taxonomic confusion in the group. The Pacific Clade of Grindelia and other young Californian plant groups warrant additional analysis of evolutionary divergence along the steep coast-to-inland climatic gradient, which has been associated with local adaptation and ecotype formation since the classic studies of Clausen, Keck, and Hiesey.

Neurologic complications including paralysis after a medication error involving implanted intrathecal catheters.

PURPOSE: Long-term continuous intrathecal infusion of medications for chronic medical problems is common. We investigated the cause of a cluster of severe neurologic complications in patients with intrathecal catheters. METHODS: We performed an epidemiologic cohort study of patients who had intrathecal catheters in place in one neurosurgical practice, to assess the presence of new neurologic complications and associated risk factors. RESULTS: The practice included 61 patients who received pain medication through implanted intrathecal catheter pumps, 19 of whom were treated with morphine, either alone or in combination with other medications. None of the 42 patients whose drug regimen did not include morphine developed a complication, whereas 8 of 13 patients who received morphine in refills of their pumps during one 4-week period experienced neurologic complications. Three persons underwent laminectomy for sterile abscesses and were left with new paralysis or leg weakness. Testing of two stock bottles from the involved pharmacy, both labeled as containing pure morphine, revealed the presence of methadone in addition to morphine. One of these bottles also contained trace ethanol. A sample of medication aspirated from the pump of a patient prescribed morphine from the same pharmacy was also found to have contained methadone and methanol. CONCLUSIONS: A variety of severe neurologic complications was associated with inadvertent administration of methadone, and perhaps other unintended substances, by means of implanted intrathecal catheters to a group of patients. Medical errors in an outpatient pharmacy led to this outbreak.