Wide bandgap semiconductor nanomembranes as a long-term biointerface for flexible, implanted neuromodulator.

Electrical neuron stimulation holds promise for treating chronic neurological disorders, including spinal cord injury, epilepsy, and Parkinson's disease. The implementation of ultrathin, flexible electrodes that can offer noninvasive attachment to soft neural tissues is a breakthrough for timely, continuous, programable, and spatial stimulations. With strict flexibility requirements in neural implanted stimulations, the use of conventional thick and bulky packages is no longer applicable, posing major technical issues such as short device lifetime and long-term stability. We introduce herein a concept of long-lived flexible neural electrodes using silicon carbide (SiC) nanomembranes as a faradic interface and thermal oxide thin films as an electrical barrier layer. The SiC nanomembranes were developed using a chemical vapor deposition (CVD) process at the wafer level, and thermal oxide was grown using a high-quality wet oxidation technique. The proposed material developments are highly scalable and compatible with MEMS technologies, facilitating the mass production of long-lived implanted bioelectrodes. Our experimental results showed excellent stability of the SiC/silicon dioxide (SiO2) bioelectronic system that can potentially last for several decades with well-maintained electronic properties in biofluid environments. We demonstrated the capability of the proposed material system for peripheral nerve stimulation in an animal model, showing muscle contraction responses comparable to those of a standard non-implanted nerve stimulation device. The design concept, scalable fabrication approach, and multimodal functionalities of SiC/SiO2 flexible electronics offer an exciting possibility for fundamental neuroscience studies, as well as for neural stimulation-based therapies.

Flexible Nanoarchitectonics for Biosensing and Physiological Monitoring Applications.

Flexible and implantable electronics hold tremendous promises for advanced healthcare applications, especially for physiological neural recording and modulations. Key requirements in neural interfaces include miniature dimensions for spatial physiological mapping and low impedance for recognizing small biopotential signals. Herein, a bottom-up mesoporous formation technique and a top-down microlithography process are integrated to create flexible and low-impedance mesoporous gold (Au) electrodes for biosensing and bioimplant applications. The mesoporous architectures developed on a thin and soft polymeric substrate provide excellent mechanical flexibility and stable electrical characteristics capable of sustaining multiple bending cycles. The large surface areas formed within the mesoporous network allow for high current density transfer in standard electrolytes, highly suitable for biological sensing applications as demonstrated in glucose sensors with an excellent detection limit of 1.95 µm and high sensitivity of 6.1 mA cm-2  µM-1 , which is approximately six times higher than that of benchmarking flat/non-porous films. The low impedance of less than 1 kΩ at 1 kHz in the as-synthesized mesoporous electrodes, along with their mechanical flexibility and durability, offer peripheral nerve recording functionalities that are successfully demonstrated in vivo. These features highlight the new possibilities of our novel flexible nanoarchitectonics for neuronal recording and modulation applications.

Organ of Corti size is governed by Yap/Tead-mediated progenitor self-renewal.

Precise control of organ growth and patterning is executed through a balanced regulation of progenitor self-renewal and differentiation. In the auditory sensory epithelium-the organ of Corti-progenitor cells exit the cell cycle in a coordinated wave between E12.5 and E14.5 before the initiation of sensory receptor cell differentiation, making it a unique system for studying the molecular mechanisms controlling the switch between proliferation and differentiation. Here we identify the Yap/Tead complex as a key regulator of the self-renewal gene network in organ of Corti progenitor cells. We show that Tead transcription factors bind directly to the putative regulatory elements of many stemness- and cell cycle-related genes. We also show that the Tead coactivator protein, Yap, is degraded specifically in the Sox2-positive domain of the cochlear duct, resulting in down-regulation of Tead gene targets. Further, conditional loss of the Yap gene in the inner ear results in the formation of significantly smaller auditory and vestibular sensory epithelia, while conditional overexpression of a constitutively active version of Yap, Yap5SA, is sufficient to prevent cell cycle exit and to prolong sensory tissue growth. We also show that viral gene delivery of Yap5SA in the postnatal inner ear sensory epithelia in vivo drives cell cycle reentry after hair cell loss. Taken together, these data highlight the key role of the Yap/Tead transcription factor complex in maintaining inner ear progenitors during development, and suggest new strategies to induce sensory cell regeneration.

Twelve tips for using Facebook as a learning platform.

The COVID-19 pandemic has forced health educators to adapt quickly to teaching and supporting students online. Social media platforms - of which Facebook is presently the most popular worldwide-has demonstrated its utility in facilitating online learning and fostering student support. In order for educators to get the most out of the platform, they should consider adopting a systematic and evidence-based approach. This article draws upon current literature and the authors' experiences to offer practical tips for health educators wanting to use Facebook as a learning platform and support tool for their students. We offer twelve tips, organized into prescriptive steps for creating and managing a Facebook group, and suggestions for utilizing Facebook's features to foster student learning, collaboration, communication, and socialization.

Total body skeletal muscle mass estimated by magnetic resonance imaging and creatine (methyl-d3 ) dilution in athletes.

Creatine dilution (D3 -cr) is a technique for estimating total skeletal muscle mass (SMM) with practical utility, but has not been applied in athletic populations where body composition may differ to that in the normal population. This study aimed to assess the agreement between SMM derived from both D3 -cr and that obtained from whole-body magnetic resonance imaging (MRI) in 15 male and 5 female national level kayakers (stature: 182.0 ± 13.1 and 170.0 ± 9.0 cm; body mass: 80.6 ± 9.9 and 66.4 ± 6.0 kg; V̇O2 peak: 56.5 ± 7.0 and 49.6 ± 4.4 mL kg-1  min-1 , mean ± SD). SMM was determined following 60 mg of dosed D3 -cr and analysis of expelled urine collected on four subsequent days for creatine, creatinine, D3 -cr, and D3 -creatinine using liquid chromatography/mass spectroscopy. SMM was then estimated by assuming a creatine pool size of 4.3 g/kg. During the same time period, a whole-body MRI was undertaken to derive SMM from the analysis of multiple slices taken across the body. A strong positive correlation (F = 74.32; R = 0.90; P < .0001) between the two methods was observed, but the D3 -cr SMM was found to be significantly higher (43.3 ± 6.8 kg) when compared with MRI (36.3 ± 5.8 kg, P < .0001). However, the difference between the methods was removed when a higher intramuscular creatine pool (5.1 g/kg) was assumed. These data show that D3 -cr has potential utility in athletes, as referenced against MRI, but show that assumptions regarding creatine pool size need to be carefully considered.

Montmorency cherry supplementation improves 15-km cycling time-trial performance.

AIM: Montmorency cherries are rich in polyphenols that possess antioxidant, anti-inflammatory and vasoactive properties. We investigated whether 7-day Montmorency cherry powder supplementation improved cycling time-trial (TT) performance. METHODS: 8 trained male cyclists ([Formula: see text]: 62.3 ± 10.1 ml kg-1 min-1) completed 10-min steady-state (SS) cycling at ~ 65% [Formula: see text] followed by a 15-km TT on two occasions. Participants consumed 6 pills per day (Montmorency cherry powder, MC; anthocyanin 257 mg day-1 or dextrose powder, PL) for a 7-day period, 3 pills in the morning and evening. Capillary blood [lactate] was measured at baseline, post SS and post TT. Pulmonary gas exchange and tissue oxygenation index (TOI) of m. vastus lateralis via near-infrared spectroscopy, were measured throughout. RESULTS: TT completion time was 4.6 ± 2.9% faster following MC (1506 ± 86 s) supplementation compared to PL (1580 ± 102 s; P = 0.004). Blood [lactate] was significantly higher in MC after SS (PL: 4.4 ± 2.1 vs. MC: 6.7 ± 3.3 mM, P = 0.017) alongside an elevated baseline TOI (PL: 68.7 ± 2.1 vs. MC: 70.4 ± 2.3%, P = 0.018). DISCUSSION: Montmorency cherry supplementation improved 15-km cycling TT performance. This improvement in exercise performance was accompanied by enhanced muscle oxygenation suggesting that the vasoactive properties of the Montmorency cherry polyphenols may underpin the ergogenic effects.

ADAM10 and γ-secretase regulate sensory regeneration in the avian vestibular organs.

The loss of sensory hair cells from the inner ear is a leading cause of hearing and balance disorders. The mammalian ear has a very limited ability to replace lost hair cells, but the inner ears of non-mammalian vertebrates can spontaneously regenerate hair cells after injury. Prior studies have shown that replacement hair cells are derived from epithelial supporting cells and that the differentiation of new hair cells is regulated by the Notch signaling pathway. The present study examined molecular influences on regeneration in the avian utricle, which has a particularly robust regenerative ability. Chicken utricles were placed in organotypic culture and hair cells were lesioned by application of the ototoxic antibiotic streptomycin. Cultures were then allowed to regenerate in vitro for seven days. Some specimens were treated with small molecule inhibitors of γ-secretase or ADAM10, proteases which are essential for transmission of Notch signaling. As expected, treatment with both inhibitors led to increased numbers of replacement hair cells. However, we also found that inhibition of both proteases resulted in increased regenerative proliferation. Subsequent experiments showed that inhibition of γ-secretase or ADAM10 could also trigger proliferation in undamaged utricles. To better understand these phenomena, we used RNA-Seq profiling to characterize changes in gene expression following γ-secretase inhibition. We observed expression patterns that were consistent with Notch pathway inhibition, but we also found that the utricular sensory epithelium contains numerous γ-secretase substrates that might regulate cell cycle entry and possibly supporting cell-to-hair cell conversion. Together, our data suggest multiple roles for γ-secretase and ADAM10 in vestibular hair cell regeneration.

A randomized, double-blind, placebo-controlled trial of camicinal in Parkinson's disease.

BACKGROUND: Delayed gastric emptying may impair l-dopa absorption, contributing to motor fluctuations. We evaluated the effect of camicinal (GSK962040), a gastroprokinetic, on the absorption of l-dopa and symptoms of PD. METHODS: Phase II, double-blind, placebo-controlled trial. Participants were randomized to receive camicinal 50 mg once-daily (n = 38) or placebo (n = 20) for 7 to 9 days. RESULTS: l-dopa exposure was similar with coadministration of camicinal compared to placebo. Median time to maximum l-dopa concentration was reduced, indicating more rapid absorption of l-dopa. Camicinal resulted in significant reduction in OFF time (-2.31 hours; 95% confidence interval: -3.71, -0.90), significant increase in ON time (+1.88 hours; 95% confidence interval: 0.28, 3.48) per day, and significant decrease in mean total MDS-UPDRS score (-12.5; 95% confidence interval: -19.67, -5.29). Camicinal treatment was generally well tolerated. CONCLUSIONS: PD symptom improvement with camicinal occurred in parallel with more rapid absorption of l-dopa. This study provides evidence of an improvement of the motor response to l-dopa in people with PD treated with camicinal 50 mg once-daily compared with placebo, which will require further evaluation. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

The Glia Response after Peripheral Nerve Injury: A Comparison between Schwann Cells and Olfactory Ensheathing Cells and Their Uses for Neural Regenerative Therapies.

The peripheral nervous system (PNS) exhibits a much larger capacity for regeneration than the central nervous system (CNS). One reason for this difference is the difference in glial cell types between the two systems. PNS glia respond rapidly to nerve injury by clearing debris from the injury site, supplying essential growth factors and providing structural support; all of which enhances neuronal regeneration. Thus, transplantation of glial cells from the PNS is a very promising therapy for injuries to both the PNS and the CNS. There are two key types of PNS glia: olfactory ensheathing cells (OECs), which populate the olfactory nerve, and Schwann cells (SCs), which are present in the rest of the PNS. These two glial types share many similar morphological and functional characteristics but also exhibit key differences. The olfactory nerve is constantly turning over throughout life, which means OECs are continuously stimulating neural regeneration, whilst SCs only promote regeneration after direct injury to the PNS. This review presents a comparison between these two PNS systems in respect to normal physiology, developmental anatomy, glial functions and their responses to injury. A thorough understanding of the mechanisms and differences between the two systems is crucial for the development of future therapies using transplantation of peripheral glia to treat neural injuries and/or disease.

An electromagnetic cell-stretching device for mechanotransduction studies of olfactory ensheathing cells.

Olfactory ensheathing cells (OECs) are primary candidates for cell transplantation therapy to repair spinal cord injury (SCI). However, the post transplantation survival of these cells remains a major hurdle for a success using this therapy. Mechanical stimuli may contribute to the maintenance of these cells and thus, mechanotransduction studies of OECs may serve as a key benefit to identify strategies for improvement in cell transplantation. We developed an electromagnetic cell stretching device based on a single sided uniaxial stretching approach to apply tensile strain to OECs in culture. This paper reports the design, simulation and characterisation of the stretching device with preliminary experimental observations of OECs in vitro. The strain field of the deformable membrane was investigated both experimentally and numerically. Heterogeneity of the device provided an ideal platform for establishing strain requirement for the OEC culture. The cell stretching system developed may serve as a tool in exploring the mechanobiology of OECs for future SCI transplantation research.

The effect of camicinal (GSK962040), a motilin agonist, on gastric emptying and glucose absorption in feed-intolerant critically ill patients: a randomized, blinded, placebo-controlled, clinical trial.

BACKGROUND: The promotility agents currently available to treat gastroparesis and feed intolerance in the critically ill are limited by adverse effects. The aim of this study was to assess the pharmacodynamic effects and pharmacokinetics of single doses of the novel gastric promotility agent motilin agonist camicinal (GSK962040) in critically ill feed-intolerant patients. METHODS: A prospective, randomized, double-blind, parallel-group, placebo-controlled, study was performed in mechanically ventilated feed-intolerant patients [median age 55 (19-84), 73 % male, APACHE II score 18 (5-37) with a gastric residual volume ≥200 mL]. Gastric emptying and glucose absorption were measured both pre- and post-treatment after intragastric administration of 50 mg (n = 15) camicinal and placebo (n = 8) using the (13)C-octanoic acid breath test (BTt1/2), acetaminophen concentrations, and 3-O-methyl glucose concentrations respectively. RESULTS: Following 50 mg enteral camicinal, there was a trend to accelerated gastric emptying [adjusted geometric means: pre-treatment BTt1/2 117 minutes vs. post- treatment 76 minutes; 95 % confidence intervals (CI; 0.39, 1.08) and increased glucose absorption (AUC240min pre-treatment: 28.63 mmol.min/L vs. post-treatment: 71.63 mmol.min/L; 95 % CI (1.68, 3.72)]. When two patients who did not have detectable plasma concentrations of camicinal were excluded from analysis, camicinal accelerated gastric emptying (adjusted geometric means: pre-treatment BTt1/2 121 minutes vs. post-treatment 65 minutes 95 % CI (0.32, 0.91) and increased glucose absorption (AUC240min pre-treatment: 33.04 mmol.min/L vs. post-treatment: 74.59 mmol.min/L; 95 % CI (1.478, 3.449). In those patients receiving placebo gastric emptying was similar pre- and post-treatment. CONCLUSIONS: When absorbed, a single enteral dose of camicinal (50 mg) accelerates gastric emptying and increases glucose absorption in feed-intolerant critically ill patients. TRIAL REGISTRATION: The study protocol was registered with the US NIH clinicaltrials.gov on 23 December 2009 (Identifier NCT01039805 ).

Sensory perturbations using suture and sutureless repair of transected median nerve in rats.

The effects of changes to cold, mechanical, and heat thresholds following median nerve transection with repair by sutures (Su) or Rose Bengal adhesion (RA) were compared to sham-operated animals. Both nerve-injured groups showed a transient, ipsilateral hyposensitivity to mechanical and heat stimuli followed by a robust and long-lasting hypersensitivity (6-7 weeks) with gradual recovery towards pre-injury levels by 90 days post-repair. Both tactile and thermal hypersensitivity were seen in the contralateral limb that was similar in onset but differed in magnitude and resolved more rapidly compared to the injured limb. Prior to injury, no animals showed any signs of aversion to cold plate temperatures of 4-16 °C. After injury, animals showed cold allodynia, lasting for 7 weeks in RA-repaired rats before recovering towards pre-injury levels, but were still present at 12 weeks in Su-repaired rats. Additionally, sensory recovery in the RA group was faster compared to the Su group in all behavioural tests. Surprisingly, sham-operated rats showed similar bilateral behavioural changes to all sensory stimuli that were comparable in onset and magnitude to the nerve-injured groups but resolved more quickly compared to nerve-injured rats. These results suggest that nerve repair using a sutureless approach produces an accelerated recovery with reduced sensorimotor disturbances compared to direct suturing. They also describe, for the first time, that unilateral forelimb nerve injury produces mirror-image-like sensory perturbations in the contralateral limb, suggesting that the contralateral side is not a true control for sensory testing. The potential mechanisms involved in this altered behaviour are discussed.

Nerve repair: toward a sutureless approach.

Peripheral nerve repair for complete section injuries employ reconstructive techniques that invariably require sutures in their application. Sutures are unable to seal the nerve, thus incapable of preventing leakage of important intraneural fluids from the regenerating nerve. Furthermore, sutures are technically demanding to apply for direct repairs and often induce detrimental scarring that impedes healing and functional recovery. To overcome these limitations, biocompatible and biodegradable glues have been used to seal and repair peripheral nerves. Although creating a sufficient seal, they can lack flexibility and present infection risks or cytotoxicity. Other adhesive biomaterials have recently emerged into practice that are usually based on proteins such as albumin and collagen or polysaccharides like chitosan. These adhesives form their union to nerve tissue by either photothermal (tissue welding) or photochemical (tissue bonding) activation with laser light. These biomaterial adhesives offer significant advantages over sutures, such as their capacity to unite and seal the epineurium, ease of application, reduced invasiveness and add the potential for drug delivery in situ to facilitate regeneration. This paper reviews a number of different peripheral nerve repair (or reconstructive) techniques currently used clinically and in experimental procedures for nerve injuries with or without tissue deficit.

Severe length-dependent peripheral polyneuropathy in a patient with subacute combined spinal cord degeneration secondary to recreational nitrous oxide abuse: A case report and literature review.

Nitrous oxide abuse can have detrimental effects on the central and peripheral nervous systems. This case study report aims to demonstrate a combination of severe generalized sensorimotor polyneuropathy and cervical myelopathy related to vitamin B12 deficiency following nitrous oxide abuse. We present a clinical case study and literature review examining primary research-published between 2012 and 2022-reporting nitrous oxide abuse affecting the spinal cord (myelopathy) and peripheral nerves (polyneuropathy); 35 articles were included in the review with a total of 96 patients, where the mean "patients" age was 23.9 years and were in a 2:1 male/female ratio. Of the 96 cases, within the review, 56% of patients were diagnosed with polyneuropathy, most commonly impacting the nerves of the lower limb (62%), while 70% of patients were diagnosed with myelopathy, most commonly impacting the cervical region (78%) on the spinal cord. In our clinical case study, a 28-year-old male underwent a multitude of diagnostic investigations for bilateral "foot drop" and sense of lower limb stiffness as ongoing complications of a vitamin B12 deficiency secondary to recreational nitrous oxide abuse. Both the literature review and our case report emphasize the dangers of recreational nitrous oxide inhalation, colloquially termed "nanging" and the risks it presents to both the central and peripheral nervous systems, which is erroneously considered by many recreational drug users to be less harmful than other illicit substances.

Can we provide quality #MedEd on social media?

In 2020, universities shut their doors and educators uploaded educational content onto online learning management systems. Two years later, students and academics are returning to campus, but many have decided to maintain the delivery of online classes. Now, with education firmly situated online, the focus has transitioned to identifying best practice, refining online delivery, and considering nontraditional platforms. Here, we highlight how social media can provide accessible, quality medical education experiences.

Histological, immunohistochemical, and morphometric analysis of negative pressure-assisted in-vivo nerve stretch-growth.

Axons respond well to mechanical stimuli and can be stretched mechanically to increase their growth rate. Although stretch growth of axons and their transient lengthening ex-vivo has been discussed in literature extensively, however, real applications of this phenomenon are scarcely found. This work presents a technique to translate ex-vivo axonal stretch growth to in-vivo nerve stretch growth. By establishing a rat model of completely transected sciatic nerve injury, the regrowth rate of the proximal nerve stump was examined under the effect of a stretching force developed by negative pressure. In this manuscript, results have been presented based on quantitative and qualitative analysis of the stained nerve tissues. Gross observations have explicitly confirmed that the proximal stump of a whole sectioned sciatic nerve of a Wistar rat stretched in a T-shaped nerve prosthesis using a controlled amount of negative pressure displayed a better outcome in terms of an increase in the total length of proximal nerve stump post-treatment and a higher number of blood vessels with respect to control. The histological and morphometric analyses confirmed that negative pressure-assisted nerve growth provides an alluring control over nerve's regrowth rate. Immunohistochemical staining also supported the existence of a positive correlation between nerve growth and in-vivo application of axial stress on it. This work presents the first holistic evidence on growing nerves in the continuum of in-vivo nerve stretch growth using negative pressure and concludes that systematic and controlled negative pressure applied directly to the resected ends of a sciatic nerve resulted in the enhanced growth rate of regenerating nerve fibres.

Designing accessible educational resources for people living with spinal cord injury.

Context/objective: To identify themes of interest for the production of educational resources for people with spinal cord injury (SCI).Design: A mixed-method study.Setting: Outpatient SCI community in Australia.Participants: Individuals with a SCI, or carers, family & friends of people who live with a SCI (n = 116).Interventions: Not applicable.Outcome measures: Quantify themes of interest perceived within the Australian SCI community as necessary for the development of SCI educational resources.Results: All seven individuals from the focus-group interviews suggested that educational resources on body physiology, secondary complications, injury pathophysiology, and health and wellbeing maintenance would be most pertinent for development. These themes (among others) were further explored and quantitatively evaluated via an online survey which demonstrated that interviewees ranked 'Your injury' as being of highest importance for the production of educational resources. Within each theme, the sub-categories; 'Bowel/bladder' and 'What equipment is covered in the National Disability Insurance Scheme (NDIS)' were ranked as being of highest importance for the production of educational resources.Conclusion: We have identified multiple areas of interest in the design and production of educational resources for individuals with SCI.

Integrated, Transparent Silicon Carbide Electronics and Sensors for Radio Frequency Biomedical Therapy.

The integration of micro- and nanoelectronics into or onto biomedical devices can facilitate advanced diagnostics and treatments of digestive disorders, cardiovascular diseases, and cancers. Recent developments in gastrointestinal endoscopy and balloon catheter technologies introduce promising paths for minimally invasive surgeries to treat these diseases. However, current therapeutic endoscopy systems fail to meet requirements in multifunctionality, biocompatibility, and safety, particularly when integrated with bioelectronic devices. Here, we report materials, device designs, and assembly schemes for transparent and stable cubic silicon carbide (3C-SiC)-based bioelectronic systems that facilitate tissue ablation, with the capability for integration onto the tips of endoscopes. The excellent optical transparency of SiC-on-glass (SoG) allows for direct observation of areas of interest, with superior electronic functionalities that enable multiple biological sensing and stimulation capabilities to assist in electrical-based ablation procedures. Experimental studies on phantom, vegetable, and animal tissues demonstrated relatively short treatment times and low electric field required for effective lesion removal using our SoG bioelectronic system. In vivo experiments on an animal model were conducted to explore the versatility of SoG electrodes for peripheral nerve stimulation, showing an exciting possibility for the therapy of neural disorders through electrical excitation. The multifunctional features of SoG integrated devices indicate their high potential for minimally invasive, cost-effective, and outcome-enhanced surgical tools, across a wide range of biomedical applications.

Isolated systolic hypertension in young males: a scoping review.

Isolated systolic hypertension typically occurs in young males; however, its clinical significance is unknown. Given the prevalence of the hypertension and its contribution to global morbidity and mortality, a synthesis of the most recent available evidence around isolated systolic hypertension is warranted. This review aims firstly to review the haemodynamic and physical characteristics indicative of cardiovascular risk in young males (aged 18 to 30 years) with isolated systolic hypertension, and secondly to synthesize the associated clinical management recommendations reported in the literature. Six databases were systematically searched for all relevant peer-reviewed literature examining isolated systolic hypertension in young males. Search results were screened and examined for validity, those that did not meet the inclusion criteria were removed. A total of 20 articles were appropriate for inclusion. Key factors indicative of cardiovascular risk in isolated systolic hypertension were characterized by several distinctive haemodynamic parameters and physical characteristics. After the literature was synthesized based around these key factors, two distinct cohorts (healthy and unhealthy) were highlighted. The healthy cohort of younger males with isolated systolic hypertension was associated with a decreased cardiovascular risk and therefore no medical interventions were recommended. The second (unhealthy) cohort was, however, associated with an increased cardiovascular risk and may therefore, benefit from antihypertensive therapy.