Safe Opioid Storage and Disposal: A Survey of Patient Beliefs and Practices.

OBJECTIVE: To evaluate knowledge, practices, and beliefs of US patients receiving prescription opioids regarding opioid storage, disposal, and diversion. DESIGN: Internet-based, cross-sectional survey conducted between September and October 2018. Fisher's exact tests and Kendall's Tau-c were used to assess associations with storage and disposal outcomes. PARTICIPANTS: Patients aged ≥18 years with acute (n=250) or chronic noncancer (n=250) pain were prescribed an oral opioid within 90 days of the survey. RESULTS: Mean (SD) patient age was 48 (14.7) years, 57.2% were female, 82.6% lived with ≥1 person in the home, and 28.0% had remaining/unused pills. One-third of all patients received safe opioid storage (35.2%) and/or disposal (31.4%) counseling from a healthcare provider, while 50.0% received neither storage nor disposal information. Only 27.4% of all patients stored their opioids in a locked location, and 17.9% of those with remaining/unused pills disposed of their medication. Patients who received any opioid counseling were more likely to keep their medication in a locked location compared with those who did not (42.4% vs 12.4%, respectively; P<0.0001), as were those who perceived any risk of opioid diversion in the home compared with those who perceived no risk or were unsure (53.7% vs 24.2%, respectively; P<0.0001). Disposal rates did not differ based on counseling received (20.8% counseled vs 16.1% not counseled; P=0.5011) or perceived diversion risk (27.8% perceived any risk vs 16.4% perceived no risk or unsure; P=0.3166). CONCLUSION: The proportion of patients receiving prescription opioids who receive safe storage/disposal counseling from a healthcare provider appears suboptimal. Further research is warranted to develop effective ways to improve patient opioid storage/disposal education and practices.

Crosstalk between developing vasculature and optogenetically engineered skeletal muscle improves muscle contraction and angiogenesis.

Capillary networks surrounding skeletal muscle play an important role in not only supplying oxygen and nutrients but also in regulating the myogenesis and repair of skeletal muscle tissues. Herein, we model the early stages of 3D vascularized muscle fiber formation in vitro using a sequential molding technique to investigate interactions between angiogenesis of endothelial cells and myogenesis of skeletal muscle cells. Channelrhodopsin-2 C2C12 muscle fiber bundles and 3D vascular structures (600 µm diameter) were formed at 500 µm intervals in a collagen gel. Endothelial cells exhibited an emergent angiogenic sprouting behavior over several days, which was modulated by the muscle fiber bundle through the secretion of angiopoietin-1. Through a reciprocal response, myogenesis was also upregulated by interactions with the vascular cells, improving muscle contraction via angiopoetin-1/neuregulin-1 signaling. Moreover, continuous training of muscle tissue by optical stimulation induced significantly more angiogenic sprouting. This in vitro model could be used to better understand the formation of vascularized muscle tissues and to test the interactions between muscle growth, repair or training and angiogenesis for applications in tissue engineering and regenerative medicine.

Engineered 3D vascular and neuronal networks in a microfluidic platform.

Neurovascular coupling plays a key role in the pathogenesis of neurodegenerative disorders including motor neuron disease (MND). In vitro models provide an opportunity to understand the pathogenesis of MND, and offer the potential for drug screening. Here, we describe a new 3D microvascular and neuronal network model in a microfluidic platform to investigate interactions between these two systems. Both 3D networks were established by co-culturing human embryonic stem (ES)-derived MN spheroids and endothelial cells (ECs) in microfluidic devices. Co-culture with ECs improves neurite elongation and neuronal connectivity as measured by Ca2+ oscillation. This improvement was regulated not only by paracrine signals such as brain-derived neurotrophic factor secreted by ECs but also through direct cell-cell interactions via the delta-notch pathway, promoting neuron differentiation and neuroprotection. Bi-directional signaling was observed in that the neural networks also affected vascular network formation under perfusion culture. This in vitro model could enable investigations of neuro-vascular coupling, essential to understanding the pathogenesis of neurodegenerative diseases including MNDs such as amyotrophic lateral sclerosis.

Vascularized microfluidic organ-chips for drug screening, disease models and tissue engineering.

Vascularization of micro-tissues in vitro has enabled formation of tissues larger than those limited by diffusion with appropriate nutrient/gas exchange as well as waste elimination. Furthermore, angiocrine signaling from the vasculature may be essential in mimicking organ-level functions in these micro-tissues. In drug screening applications, the presence of an appropriate blood-organ barrier in the form of a vasculature and its supporting cells (pericytes, appropriate stromal cells) may be essential to reproducing organ-scale drug delivery pharmacokinetics. Cutting-edge techniques including 3D bioprinting and in vitro angiogenesis and vasculogenesis could be applied to vascularize a range of tissues and organoids. Herein, we describe the latest developments in vascularization and prevascularization of micro-tissues and provide an outlook on potential future strategies.

In Vitro Microfluidic Models for Neurodegenerative Disorders.

Microfluidic devices enable novel means of emulating neurodegenerative disease pathophysiology in vitro. These organ-on-a-chip systems can potentially reduce animal testing and substitute (or augment) simple 2D culture systems. Reconstituting critical features of neurodegenerative diseases in a biomimetic system using microfluidics can thereby accelerate drug discovery and improve our understanding of the mechanisms of several currently incurable diseases. This review describes latest advances in modeling neurodegenerative diseases in the central nervous system and the peripheral nervous system. First, this study summarizes fundamental advantages of microfluidic devices in the creation of compartmentalized cell culture microenvironments for the co-culture of neurons, glial cells, endothelial cells, and skeletal muscle cells and in their recapitulation of spatiotemporal chemical gradients and mechanical microenvironments. Then, this reviews neurodegenerative-disease-on-a-chip models focusing on Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Finally, this study discusses about current drawbacks of these models and strategies that may overcome them. These organ-on-chip technologies can be useful to be the first line of testing line in drug development and toxicology studies, which can contribute significantly to minimize the phase of animal testing steps.

Effect of bunching of cilia and their interplay on muco-ciliary transport.

Cilia are hair-like organelles projecting from a eukaryotic cell, used either for locomotion or as sensors. Cilia commonly occur in patches. To take this into consideration, we represent cilia in multiple patches, instead of the conventional 'dense mat' representation. We focus on the combined action and interplay of these patches. The effects of varying the frequency, spacing and phase lag of the beating of one cilia bunch with respect to the beating of adjacent patches are studied. We model the Airway Surface Liquid (ASL) as a three-layer structure. The possibility of an optimum frequency of beating is noted and the change of mucous flow under different spacing and phase differences are observed.