Flexible circumferential bioelectronics to enable 360-degree recording and stimulation of the spinal cord.

The spinal cord is crucial for transmitting motor and sensory information between the brain and peripheral systems. Spinal cord injuries can lead to severe consequences, including paralysis and autonomic dysfunction. We introduce thin-film, flexible electronics for circumferential interfacing with the spinal cord. This method enables simultaneous recording and stimulation of dorsal, lateral, and ventral tracts with a single device. Our findings include successful motor and sensory signal capture and elicitation in anesthetized rats, a proof-of-concept closed-loop system for bridging complete spinal cord injuries, and device safety verification in freely moving rodents. Moreover, we demonstrate potential for human application through a cadaver model. This method sees a clear route to the clinic by using materials and surgical practices that mitigate risk during implantation and preserve cord integrity.

A multivariate physiological model of vagus nerve signalling during metabolic challenges in anaesthetised rats for diabetes treatment.

Objective.This study aims to develop a comprehensive decoding framework to create a multivariate physiological model of vagus nerve transmission that reveals the complex interactions between the nervous and metabolic systems.Approach.Vagus nerve activity was recorded in female Sprague-Dawley rats using gold hook microwires implanted around the left cervical vagus nerve. The rats were divided into three experimental cohorts (intact nerve, ligation nerve for recording afferent activation, and ligation for recording efferent activation) and metabolic challenges were administered to change glucose levels while recording the nerve activity. The decoding methodology involved various techniques, including continuous wavelet transformation, extraction of breathing rate (BR), and correlation of neural metrics with physiological signals.Main results.Decrease in glucose level was consistently negatively correlated with an increase in the firing activity of the intact vagus nerve that was found to be conveyed by both afferent and efferent pathways, with the afferent response being more similar to the one on the intact nerve. A larger variability was observed in the sensory and motor responses to hyperglycaemia. A novel strategy to extract the BR over time based on inter-burst-interval is also presented. The vagus afferent was found to encode breathing information through amplitude and firing rate modulation. Modulations of the signal amplitude were also observed due to changes in heart rate in the intact and efferent recordings, highlighting the parasympathetic control of the heart.Significance.The analytical framework presented in this study provides an integrative understanding that considers the relationship between metabolic, cardiac, and breathing signals and contributes to the development of a multivariable physiological model for the transmission of vagus nerve signals. This work progresses toward the development of closed-loop neuro-metabolic therapeutic systems for diabetes.

Functional neurological restoration of amputated peripheral nerve using biohybrid regenerative bioelectronics.

The development of neural interfaces with superior biocompatibility and improved tissue integration is vital for treating and restoring neurological functions in the nervous system. A critical factor is to increase the resolution for mapping neuronal inputs onto implants. For this purpose, we have developed a new category of neural interface comprising induced pluripotent stem cell (iPSC)-derived myocytes as biological targets for peripheral nerve inputs that are grafted onto a flexible electrode arrays. We show long-term survival and functional integration of a biohybrid device carrying human iPSC-derived cells with the forearm nerve bundle of freely moving rats, following 4 weeks of implantation. By improving the tissue-electronics interface with an intermediate cell layer, we have demonstrated enhanced resolution and electrical recording in vivo as a first step toward restorative therapies using regenerative bioelectronics.

3D Bioelectronics with a Remodellable Matrix for Long-Term Tissue Integration and Recording.

Bioelectronics hold the key for understanding and treating disease. However, achieving stable, long-term interfaces between electronics and the body remains a challenge. Implantation of a bioelectronic device typically initiates a foreign body response, which can limit long-term recording and stimulation efficacy. Techniques from regenerative medicine have shown a high propensity for promoting integration of implants with surrounding tissue, but these implants lack the capabilities for the sophisticated recording and actuation afforded by electronics. Combining these two fields can achieve the best of both worlds. Here, the construction of a hybrid implant system for creating long-term interfaces with tissue is shown. Implants are created by combining a microelectrode array with a bioresorbable and remodellable gel. These implants are shown to produce a minimal foreign body response when placed into musculature, allowing one to record long-term electromyographic signals with high spatial resolution. This device platform drives the possibility for a new generation of implantable electronics for long-term interfacing.

Development of a community-based COVID-19 intervention in rural Ghana: a document analysis.

BACKGROUND: The COVID-19 pandemic has caused the loss of millions of lives and economic breakdowns in many countries across the globe. Despite the limited availability of vaccines and the challenges of poor health infrastructure, few interventions have been developed and implemented for those who live in rural areas, particularly in sub-Saharan Africa. In response, Cocoa360, a global health nonprofit in rural Ghana designed an intervention called Cocoa360's COVID-19 Preparedness and Outbreak Prevention Plan (CoCoPOPP). This paper aimed to examine the extent to which CoCoPOPP's design aligned with the Promoting Action on Research Implementation in Health Services (PARIHS) framework. METHODS: We reviewed documents influencing CoCoPOPP's design between March and June 2021. A total of 11 documents were identified for analysis. Using the Promoting Action on Research Implementation in Health Services (PARIHS) framework as a guide, thematic analysis was done to analyze the extracted data. RESULTS: Overall, CoCoPOPP's design aligned with the evidence, context, and facilitation domains of the PARIHS framework. It positioned CoCoPOPP as an intervention that considered the unique context of a rural Ghanaian setting. It was guided by robust and high-quality published and non-published evidence and engaged external and internal stakeholders during its implementation. CoCoPOPP's context-dependent nature positions it for potential replication in sub-Saharan Africa's rural communities with similar farming contexts. Specific areas that were less well and/or not addressed were the unintended negative consequences of community engagement, the absence of primary data in the guiding evidence, and the lack of a facilitation continuum coupled with the role of power during the facilitation process. CONCLUSION: CoCoPOPP, Cocoa360's response to the COVID-19 pandemic in rural Ghana, is an evidence-driven, context-dependent public health intervention that has been designed to reduce COVID-19 infections and prevent potential deaths. This study underscores the importance of considering the unique community and cultural contexts, employing evidence, and engaging local and external actors as facilitators when designing interventions to respond to global health pandemics.

Hybrid fabrication of multimodal intracranial implants for electrophysiology and local drug delivery.

New fabrication approaches for mechanically flexible implants hold the key to advancing the applications of neuroengineering in fundamental neuroscience and clinic. By combining the high precision of thin film microfabrication with the versatility of additive manufacturing, we demonstrate a straight-forward approach for the prototyping of intracranial implants with electrode arrays and microfluidic channels. We show that the implant can modulate neuronal activity in the hippocampus through localized drug delivery, while simultaneously recording brain activity by its electrodes. Moreover, good implant stability and minimal tissue response are seen one-week post-implantation. Our work shows the potential of hybrid fabrication combining different manufacturing techniques in neurotechnology and paves the way for a new approach to the development of multimodal implants.

Chondroitin 6-sulphate is required for neuroplasticity and memory in ageing.

Perineuronal nets (PNNs) are chondroitin sulphate proteoglycan-containing structures on the neuronal surface that have been implicated in the control of neuroplasticity and memory. Age-related reduction of chondroitin 6-sulphates (C6S) leads to PNNs becoming more inhibitory. Here, we investigated whether manipulation of the chondroitin sulphate (CS) composition of the PNNs could restore neuroplasticity and alleviate memory deficits in aged mice. We first confirmed that aged mice (20-months) showed memory and plasticity deficits. They were able to retain or regain their cognitive ability when CSs were digested or PNNs were attenuated. We then explored the role of C6S in memory and neuroplasticity. Transgenic deletion of chondroitin 6-sulfotransferase (chst3) led to a reduction of permissive C6S, simulating aged brains. These animals showed very early memory loss at 11 weeks old. Importantly, restoring C6S levels in aged animals rescued the memory deficits and restored cortical long-term potentiation, suggesting a strategy to improve age-related memory impairment.

Optimization of adeno-associated viral vector-mediated transduction of the corticospinal tract: comparison of four promoters.

Adeno-associated viral vectors are widely used as vehicles for gene transfer to the nervous system. The promoter and viral vector serotype are two key factors that determine the expression dynamics of the transgene. A previous comparative study has demonstrated that AAV1 displays efficient transduction of layer V corticospinal neurons, but the optimal promoter for transgene expression in corticospinal neurons has not been determined yet. In this paper, we report a side-by-side comparison between four commonly used promoters: the short CMV early enhancer/chicken ß actin (sCAG), human cytomegalovirus (hCMV), mouse phosphoglycerate kinase (mPGK) and human synapsin (hSYN) promoter. Reporter constructs with each of these promoters were packaged in AAV1, and were injected in the sensorimotor cortex of rats and mice in order to transduce the corticospinal tract. Transgene expression levels and the cellular transduction profile were examined after 6 weeks. The AAV1 vectors harbouring the hCMV and sCAG promoters resulted in transgene expression in neurons, astrocytes and oligodendrocytes. The mPGK and hSYN promoters directed the strongest transgene expression. The mPGK promoter did drive expression in cortical neurons and oligodendrocytes, while transduction with AAV harbouring the hSYN promoter resulted in neuron-specific expression, including perineuronal net expressing interneurons and layer V corticospinal neurons. This promoter comparison study contributes to improve transgene delivery into the brain and spinal cord. The optimized transduction of the corticospinal tract will be beneficial for spinal cord injury research.

Dimensions of authentic leadership and patient care quality.

PURPOSE: The purpose of this study is to investigate the causal relationships between the dimensions of authentic leadership and patient care quality in the nursing profession of Ghana. DESIGN/METHODOLOGY/APPROACH: The study used explanatory and cross-sectional survey designs. The data were obtained from 400 respondents, consisting of 200 nurses and 200 patients in selected general hospitals. The analysis was done using descriptive statistics, correlation and multi-linear regression techniques. FINDINGS: The study found that all four dimensions of authentic leadership, namely, self-awareness, internalized moral perspective, balanced processing and relational transparency positively correlated with patient care quality, however, only internalized moral perspective and self-awareness have positive significant association with patient care quality and internalized moral perspective being the highest predictor. Thus, the results suggest that authentic leadership can positively predict patient care quality. PRACTICAL IMPLICATIONS: The study contributes to the understanding of how dimensions of authentic leadership practices affect patient care quality. This understanding is relevant to academics in general and Ghanaian policymakers in particular. ORIGINALITY/VALUE: The research makes a significant contribution to the existing authentic leadership literature by establishing that the dimensions of authentic leadership predict patient care quality with an internalized moral perspective being the highest predictor followed by self-awareness. Furthermore, the authors anticipate that the outcomes of this research, which so far is the first study in the Ghanaian context, can significantly shape nursing leadership discourse, practices and policies in Ghana and in other developing countries to improve patient care quality.

Antibody recognizing 4-sulfated chondroitin sulfate proteoglycans restores memory in tauopathy-induced neurodegeneration.

Chondroitin sulfate proteoglycans (CSPGs) are the main active component of perineuronal nets (PNNs). Digestion of the glycosaminoglycan chains of CSPGs with chondroitinase ABC or transgenic attenuation of PNNs leads to prolongation of object recognition memory and activation of various forms of plasticity in the adult central nervous system. The inhibitory properties of the CSPGs depend on the pattern of sulfation of their glycosaminoglycans, with chondroitin 4-sulfate (C4S) being the most inhibitory form. In this study, we tested a number of candidates for functional blocking of C4S, leading to selection of an antibody, Cat316, which specifically recognizes C4S and blocks its inhibitory effects on axon growth. It also partly blocks binding of semaphorin 3A to PNNs and attenuates PNN formation. We asked whether injection of Cat316 into the perirhinal cortex would have the same effects on memory as chondroitinase ABC treatment. We found that masking C4S with the Cat316 antibody extended long-term object recognition memory in normal wild-type mice to 24 hours, similarly to chondroitinase or transgenic PNN attenuation. We then tested Cat316 for restoration of memory in a neurodegeneration model. Mice expressing tau with the P301S mutation showed profound loss of object recognition memory at 4 months of age. Injection of Cat316 into the perirhinal cortex normalized object recognition at 3 hours in P301S mice. These data indicate that Cat316 binding to C4S in the extracellular matrix can restore plasticity and memory in the same way as chondroitinase ABC digestion. Our results suggest that antibodies to C4S could be a useful therapeutic to restore memory function in neurodegenerative disorders.