The Frequency and Utility of Drug Cessation Trials in Older Adults With Chronic Eczematous Dermatitis of Unknown Etiology: A Retrospective Cohort Study.

Background: Eczematous dermatitis is a major cause of recalcitrant pruritic eruptions in older adults. Although some medications have been implicated, there are limited data demonstrating the utility of medication changes. Objective: To investigate the utility and possible harms of drug cessation trials (DCTs) in chronic eczematous eruptions in the aging (CEEA). Methods: This is a retrospective cohort study utilizing electronic health records of DCTs in adults older than 65 years with CEEA. Results: We identified 646 patients >65 years with new onset eczematous eruptions, 89 (14%) of whom had no identifiable etiology. In this cohort, 35 patients underwent a total of 40 DCTs. Although there was mention of improvement in 17.5% (7/40), all patients sought tertiary care for their persistent rash. Negative outcomes occurred in 45% (18/40), all of which were due to exacerbation of a comorbidity that the medication was prescribed to treat. Conclusion: Our experience suggests that patients with CEEA undergo DCTs that do not improve their dermatitis and can lead to dangerous worsening of underlying conditions. Further study of the etiology of CEEA is needed.

3D in vitro modeling of the central nervous system.

There are currently more than 600 diseases characterized as affecting the central nervous system (CNS) which inflict neural damage. Unfortunately, few of these conditions have effective treatments available. Although significant efforts have been put into developing new therapeutics, drugs which were promising in the developmental phase have high attrition rates in late stage clinical trials. These failures could be circumvented if current 2D in vitro and in vivo models were improved. 3D, tissue-engineered in vitro systems can address this need and enhance clinical translation through two approaches: (1) bottom-up, and (2) top-down (developmental/regenerative) strategies to reproduce the structure and function of human tissues. Critical challenges remain including biomaterials capable of matching the mechanical properties and extracellular matrix (ECM) composition of neural tissues, compartmentalized scaffolds that support heterogeneous tissue architectures reflective of brain organization and structure, and robust functional assays for in vitro tissue validation. The unique design parameters defined by the complex physiology of the CNS for construction and validation of 3D in vitro neural systems are reviewed here.

Bioengineered functional brain-like cortical tissue.

The brain remains one of the most important but least understood tissues in our body, in part because of its complexity as well as the limitations associated with in vivo studies. Although simpler tissues have yielded to the emerging tools for in vitro 3D tissue cultures, functional brain-like tissues have not. We report the construction of complex functional 3D brain-like cortical tissue, maintained for months in vitro, formed from primary cortical neurons in modular 3D compartmentalized architectures with electrophysiological function. We show that, on injury, this brain-like tissue responds in vitro with biochemical and electrophysiological outcomes that mimic observations in vivo. This modular 3D brain-like tissue is capable of real-time nondestructive assessments, offering previously unidentified directions for studies of brain homeostasis and injury.

Semi-automatic quantification of neurite fasciculation in high-density neurite images by the neurite directional distribution analysis (NDDA).

BACKGROUND: Bundling of neurite extensions occur during nerve development and regeneration. Understanding the factors that drive neurite bundling is important for designing biomaterials for nerve regeneration toward the innervation target and preventing nociceptive collateral sprouting. High-density neuron cultures including dorsal root ganglia explants are employed for in vitro screening of biomaterials designed to control directional outgrowth. Although some semi-automated image processing methods exist for quantification of neurite outgrowth, methods to quantify axonal fasciculation in terms of direction of neurite outgrowth are lacking. NEW METHOD: This work presents a semi-automated program to analyze micrographs of high-density neurites; the program aims to quantify axonal fasciculation by determining the orientational distribution function of the tangent vectors of the neurites and calculating its Fourier series coefficients ('c' values). RESULTS: We found that neurite directional distribution analysis (NDDA) of fasciculated neurites yielded 'c' values of ≥∼0.25 whereas branched outgrowth led to statistically significant lesser values of <∼0.2. The 'c' values correlated directly to the width of neurite bundles and indirectly to the number of branching points. COMPARISON WITH EXISTING METHODS: Information about the directional distribution of outgrowth is lost in simple counting methods or achieved laboriously through manual analysis. The NDDA supplements previous quantitative analyses of axonal bundling using a vector-based approach that captures new information about the directionality of outgrowth. CONCLUSION: The NDDA is a valuable addition to open source image processing tools available to biomedical researchers offering a robust, precise approach to quantification of imaged features important in tissue development, disease, and repair.

The behavior of neuronal cells on tendon-derived collagen sheets as potential substrates for nerve regeneration.

Peripheral nervous system injuries result in a decreased quality of life, and generally require surgical intervention for repair. Currently, the gold standard of nerve autografting, based on the use of host tissue such as sensory nerves is suboptimal as it results in donor-site loss of function and requires a secondary surgery. Nerve guidance conduits fabricated from natural polymers such as collagen are a common alternative to bridge nerve defects. In the present work, tendon sections derived through a process named bioskiving were studied for their potential for use as a substrate to fabricate nerve guidance conduits. We show that cells such as rat Schwann cells adhere, proliferate, and align along the fibrous tendon substrate which has been shown to result in a more mature phenotype. Additionally we demonstrate that chick dorsal root ganglia explants cultured on the tendon grow to similar lengths compared to dorsal root ganglia cultured on collagen gels, but also grow in a more oriented manner on the tendon sections. These results show that tendon sections produced through bioskiving can support directional nerve growth and may be of use as a substrate for the fabrication of nerve guidance conduits.