Activation of inflammasomes and their effects on neuroinflammation at the microelectrode-tissue interface in intracortical implants.

Invasive neuroprosthetics rely on microelectrodes (MEs) to record or stimulate the activity of large neuron assemblies. However, MEs are subjected to tissue reactivity in the central nervous system (CNS) due to the foreign body response (FBR) that contribute to chronic neuroinflammation and ultimately result in ME failure. An endogenous, acute set of mechanisms responsible for the recognition and targeting of foreign objects, called the innate immune response, immediately follows the ME implant-induced trauma. Inflammasomes are multiprotein structures that play a critical role in the initiation of an innate immune response following CNS injuries. The activation of inflammasomes facilitates a range of innate immune response cascades and results in neuroinflammation and programmed cell death. Despite our current understanding of inflammasomes, their roles in the context of neural device implantation remain unknown. In this study, we implanted a non-functional Utah electrode array (UEA) into the rat somatosensory cortex and studied the inflammasome signaling and the corresponding downstream effects on inflammatory cytokine expression and the inflammasome-mediated cell death mechanism of pyroptosis. Our results not only demonstrate the continuous activation of inflammasomes and their contribution to neuroinflammation at the electrode-tissue interface but also reveal the therapeutic potential of targeting inflammasomes to attenuate the FBR in invasive neuroprosthetics.

Human Trafficking in Rehabilitation: What Nurses Need to Know.

ABSTRACT: Violence and human trafficking are frequently paired and violate human rights. Human trafficking is a complex, global health issue. Trafficking survivors report seeking medical care for women's services, physical abuse, mental health, and gastrointestinal issues while being held in captivity. However, the majority of healthcare providers are unaware or unprepared to intervene, thus missing the chance to identify victims during these encounters. Rehabilitation nurses are no exception. Trafficking victims may come in contact with rehabilitation nurses because of injuries or chronic diseases caused by trafficking abuse. This article shares human trafficking red flags, victims' access to services, barriers to identification, and nursing interventions and implications.

Painful temporomandibular joint overloading induces structural remodeling in the pericellular matrix of that joint's chondrocytes.

Mechanical stress to the temporomandibular joint (TMJ) is an important factor in cartilage degeneration, with both clinical and preclinical studies suggesting that repeated TMJ overloading could contribute to pain, inflammation, and/or structural damage in the joint. However, the relationship between pain severity and early signs of cartilage matrix microstructural dysregulation is not understood, limiting the advancement of diagnoses and treatments for temporomandibular joint-osteoarthritis (TMJ-OA). Changes in the pericellular matrix (PCM) surrounding chondrocytes may be early indicators of OA. A rat model of TMJ pain induced by repeated jaw loading (1 h/day for 7 days) was used to compare the extent of PCM modulation for different loading magnitudes with distinct pain profiles (3.5N-persistent pain, 2N-resolving pain, or unloaded controls-no pain) and macrostructural changes previously indicated by Mankin scoring. Expression of PCM structural molecules, collagen VI and aggrecan NITEGE neo-epitope, were evaluated at Day 15 by immunohistochemistry within TMJ fibrocartilage and compared between pain conditions. Pericellular collagen VI levels increased at Day 15 in both the 2N (p = 0.003) and 3.5N (p = 0.042) conditions compared to unloaded controls. PCM width expanded to a similar extent for both loading conditions at Day 15 (2N, p < 0.001; 3.5N, p = 0.002). Neo-epitope expression increased in the 3.5N group over levels in the 2N group (p = 0.041), indicating pericellular changes that were not identified in the same groups by Mankin scoring of the pericellular region. Although remodeling occurs in both pain conditions, the presence of pericellular catabolic neo-epitopes may be involved in the macrostructural changes and behavioral sensitivity observed in persistent TMJ pain.

The complement cascade at the Utah microelectrode-tissue interface.

Devices implanted within the central nervous system (CNS) are subjected to tissue reactivity due to the lack of biocompatibility between implanted material and the cells' microenvironment. Studies have attributed blood-brain barrier disruption, inflammation, and oxidative stress as main contributing factors that lead to electrode recording failure. The complement cascade is a part of the innate immunity that focuses on recognizing and targeting foreign objects; however, its role in the context of neural implants is substantially unknown. In this study, we implanted a non-functional 4x4 Utah microelectrode array (UEA) into the somatosensory cortex and studied the complement cascade via combined gene and immunohistochemistry quantification at acute (48-h), sub-acute (1-week), and early chronic (4-weeks) time points. The results of this study demonstrate the activation and continuation of the complement cascade at the electrode-tissue interface, illustrating the therapeutic potential of modulating the foreign body response via the complement cascade.

Surface Modifications of an Organic Polymer-Based Microwire Platform for Sustained Release of an Anti-Inflammatory Drug.

Brain machine interfaces (BMIs), introduced into the daily lives of individuals with injuries or disorders of the nervous system such as spinal cord injury, stroke, or amyotrophic lateral sclerosis, can improve the quality of life. BMIs rely on the capability of microelectrode arrays to monitor the activity of large populations of neurons. However, maintaining a stable, chronic electrode-tissue interface that can record neuronal activity with a high signal-to-noise ratio is a key challenge that has limited the translation of such technologies. An electrode implant injury leads to a chronic foreign body response that is well-characterized and shown to affect the electrode-tissue interface stability. Several strategies have been applied to modulate the immune response, including the application of immunomodulatory drugs applied both systemically and locally. While the use of passive drug release at the site of injury has been exploited to minimize neuroinflammation, this strategy has all but failed as a bolus of anti-inflammatory drugs is released at predetermined times that are often inconsistent with the ongoing innate inflammatory process. Common strategies do not focus on the proper anchorage of soft hydrogel scaffolds on electrode surfaces, which often results in delamination of the porous network from electrodes. In this study, we developed a microwire platform that features a robust yet soft biocompatible hydrogel coating, enabling long-lasting drug release via formation of drug aggregates and dismantlement of hydrophilic biodegradable three-dimensional polymer networks. Facile surface chemistry is developed to functionalize polyimide-coated electrodes with the covalently anchored porous hydrogel network bearing large numbers of highly biodegradable ester groups. Exponential long-lasting drug release is achieved using such hydrogels. We show that the initial state of dexamethasone (Dex) used to formulate the hydrogel precursor solution plays a cardinal role in engineering hydrophilic networks that enable a sustained and long-lasting release of the anti-inflammatory agent. Furthermore, utilization of a high loading ratio that exceeds the solubility of Dex leads to the encapsulation of Dex aggregates that regulate the release of this anti-inflammatory agent. To validate the anti-inflammatory effect of the hydrogel-functionalized Dex-loaded microwires, an in vivo preliminary study was performed in adult male rats (n = 10) for the acute time points of 48 h and 7 days post implant. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to assess the mRNA expression of certain inflammatory-related genes. In general, a decrease in fold-change expression was observed for all genes tested for Dex-loaded wires compared with controls (functionalized but no drug). The engineering of hybrid microwires enables a sustained release of the anti-inflammatory agent over extended periods of time, thus paving the way to fabricate neuroprosthetic devices capable of attenuating the foreign body response.

Distribution of a New Invasive Species, Sipha maydis (Heteroptera: Aphididae), on Cereals and Wild Grasses in the Southern Plains and Rocky Mountain States.

Sipha maydis Passerini (Heteroptera: Aphididae) is a cereal pest with an extensive geographical range that includes countries in Europe, Asia, Africa, and South America. Reports of S. maydis in the United States have been infrequent since it was first detected in California, 2007. Two studies, focused (NW CO) and multistate (OK, TX, NM, CO, UT, WY), were conducted to determine the distribution and host range of S. maydis in the Rocky Mountain and Southern Plains states over a 3-yr period, 2015-2017. In 2015, focused sampling in NW Colorado found S. maydis at 59% of the 37 sites, primarily on wheat. Sipha maydis did not survive extreme winter temperatures from late December 2015 to early January 2016 that ranged from -9.0 to -20.9°C over a 9-d period, which resulted in no aphids detected in 2016. In the multistate study, S. maydis occurred in 14.6% of 96 sites sampled in 2015, 8% of 123 sites in 2016, and 9% of 85 sites in 2017 at wide range of altitudes from 1,359 to 2,645 m. Sipha maydis occurred mainly in NW and SW Colorado and NE New Mexico along with a few sites in NE Colorado, SE Utah, and SE Wyoming. This aphid mainly infested wheat followed by a variety of eight wild grass species. No parasites, predators, sexual morphs, or significant plant damage occurred at the sites. Sipha maydis utilized 14 hosts in the United States including 8 new host records, which expands its host range to 52 plant species worldwide. Sipha maydis may be of concern to wheat, barley, and sorghum production in the United States if its populations continue to increase.

Nutrient signaling: evolutionary origins of the immune-modulating effects of dietary fat.

Many dietary fatty acids (FA) have potent effects on inflammation, which is not only energetically costly, but also contributes to a range of chronic diseases. This presents an evolutionary paradox: Why should the host initiate a costly and damaging response to commonly encountered nutrients? We propose that the immune system has evolved a capacity to modify expenditure on inflammation to compensate for the effects of dietary FA on gut microorganisms. In a comprehensive literature review, we show that the body preferentially upregulates inflammation in response to saturated FA that promote harmful microbes. In contrast, the host opften reduces inflammation in response to the many unsaturated FA with antimicrobial properties. Our model is supported by contrasts involving shorter-chain FA and omega-3 FA, but with less consistent evidence for trans fats, which are a recent addition to the human diet. Our findings support the idea that the vertebrate immune system has evolved a capacity to detect diet-driven shipfts in the composition of gut microbiota from the profile of FA consumed and to calibrate the costs of inflammation in response to these cues. We conclude by extending the nutrient signaling model to other nutrients, and consider implications for drug discovery and public health.