An Open-Source 3D-Printed Hindlimb Stabilization Apparatus for Reliable Measurement of Stimulation-Evoked Ankle Flexion in Rat.

Currently there are numerous methods to evaluate peripheral nerve stimulation interfaces in rats, with stimulation-evoked ankle torque being one of the most prominent. Commercial rat ankle torque measurement systems and custom one-off solutions have been published in the literature. However, commercial systems are proprietary and costly and do not allow for customization. One-off lab-built systems have required specialized machining expertise, and building plans have previously not been made easily accessible. Here, detailed building plans are provided for a low-cost, open-source, and basic ankle torque measurement system from which additional customization can be made. A hindlimb stabilization apparatus was developed to secure and stabilize a rat's hindlimb, while allowing for simultaneous ankle-isometric torque and lower limb muscle electromyography (EMG). The design was composed mainly of adjustable 3D-printed components to accommodate anatomical differences between rat hindlimbs. Additionally, construction and calibration procedures of the rat hindlimb stabilization apparatus were demonstrated in this study. In vivo torque measurements were reliably acquired and corresponded to increasing stimulation amplitudes. Furthermore, implanted leads used for intramuscular EMG recordings complemented torque measurements and were used as an additional functional measurement in evaluating the performance of a peripheral nerve stimulation interface. In conclusion, an open-source and noninvasive platform, made primarily with 3D-printed components, was constructed for reliable data acquisition of evoked motor activity in rat models. The purpose of this apparatus is to provide researchers a versatile system with adjustable components that can be tailored to meet user-defined experimental requirements when evaluating motor function of the rat hindlimbs.

Platelets and hemostatic proteins are co-localized with chronic neuroinflammation surrounding implanted intracortical microelectrodes.

Intracortical microelectrodes induce vascular injury upon insertion into the cortex. As blood vessels rupture, blood proteins and blood-derived cells (including platelets) are introduced into the 'immune privileged' brain tissues at higher-than-normal levels, passing through the damaged blood-brain barrier. Blood proteins adhere to implant surfaces, increasing the likelihood of cellular recognition leading to activation of immune and inflammatory cells. Persistent neuroinflammation is a major contributing factor to declining microelectrode recording performance. We investigated the spatial and temporal relationship of blood proteins fibrinogen and von Willebrand Factor (vWF), platelets, and type IV collagen, in relation to glial scarring markers for microglia and astrocytes following implantation of non-functional multi-shank silicon microelectrode probes into rats. Together with type IV collagen, fibrinogen and vWF augment platelet recruitment, activation, and aggregation. Our main results indicate blood proteins participating in hemostasis (fibrinogen and vWF) persisted at the microelectrode interface for up to 8-weeks after implantation. Further, type IV collagen and platelets surrounded the probe interface with similar spatial and temporal trends as vWF and fibrinogen. In addition to prolonged blood-brain barrier instability, specific blood and extracellular matrix proteins may play a role in promoting the inflammatory activation of platelets and recruitment to the microelectrode interface. STATEMENT OF SIGNIFICANCE: Implanted microelectrodes have substantial potential for restoring function to people with paralysis and amputation by providing signals that feed into natural control algorithms that drive prosthetic devices. Unfortunately, these microelectrodes do not display robust performance over time. Persistent neuroinflammation is widely thought to be a primary contributor to the devices' progressive decline in performance. Our manuscript reports on the highly local and persistent accumulation of platelets and hemostatic blood proteins around the microelectrode interface of brain implants. To our knowledge neuroinflammation driven by cellular and non-cellular responses associated with hemostasis and coagulation has not been rigorously quantified elsewhere. Our findings identify potential targets for therapeutic intervention and a better understanding of the driving mechanisms to neuroinflammation in the brain.

Characterization and applications of evoked responses during epidural electrical stimulation.

BACKGROUND: Epidural electrical stimulation (EES) of the spinal cord has been FDA approved and used therapeutically for decades. However, there is still not a clear understanding of the local neural substrates and consequently the mechanism of action responsible for the therapeutic effects. METHOD: Epidural spinal recordings (ESR) are collected from the electrodes placed in the epidural space. ESR contains multi-modality signal components such as the evoked neural response (due to tonic or BurstDR™ waveforms), evoked muscle response, stimulation artifact, and cardiac response. The tonic stimulation evoked compound action potential (ECAP) is one of the components in ESR and has been proposed recently to measure the accumulative local potentials from large populations of neuronal fibers during EES. RESULT: Here, we first review and investigate the referencing strategies, as they apply to ECAP component in ESR in the domestic swine animal model. We then examine how ECAP component can be used to sense lead migration, an adverse outcome following lead placement that can reduce therapeutic efficacy. Lastly, we show and isolate concurrent activation of local back and leg muscles during EES, demonstrating that the ESR obtained from the recording contacts contain both ECAP and EMG components. CONCLUSION: These findings may further guide the implementation of recording and reference contacts in an implantable EES system and provide preliminary evidence for the utility of ECAP component in ESR to detect lead migration. We expect these results to facilitate future development of EES methodology and implementation of use of different components in ESR to improve EES therapy.

Optic nerve sheath fenestration for treating papilloedema in the era of cerebral venous sinus stenting.

BACKGROUND: Pseudotumour cerebri (PTC) is the syndrome of intracranial hypertension without intracranial mass or hydrocephalus and is the commonest cause of papilloedema seen in many eye clinics. In the last 10 years, we have increasingly used TSS in patients whose papilloedema was not well controlled with medical treatment and have done fewer ONSFs. Here, we review our experience at Royal Prince Alfred Hospital Sydney with ONSF in 35 patients over the period 2002-2021. METHODS: Retrospective case series of 35 patients, 30 of whom had primary PTC [i.e., idiopathic intracranial hypertension (IIH)] and 5 with secondary PTC. RESULTS: Eighteen patients had bilateral ONSF and 17 patients unilateral ONSF, in each case of the worse eye. Thirteen patients then underwent transverse sinus stenting (TSS), in each case following ONSF. The primary outcome measures were visual acuity (VA) and mean deviation (MD) on visual field (VF) testing. MD improved by 5 dB or more in 34 of 70 total eyes (48.6%); VA improved by 0.2 logMAR (two lines on Snellen chart) or more in 21 eyes (30%), and by both in 15 eyes (21.4%). Final MD was -10 dB or better in 38 eyes (54.3%); final VA was 0.3 (6/12) or better in 54 eyes (77.1%), and both in 39 eyes (55.7%). CONCLUSIONS: The results confirm that ONSF can relieve papilloedoema in both eyes and improve both VF and VA, even in cases of fulminant PTC with severe acute visual impairment.

Measuring the Resting Energy Expenditure in Children on Extracorporeal Membrane Oxygenation: A Prospective Pilot Study.

Both overfeeding and underfeeding critically ill children are problematic. This prospective pilot study evaluated the resting energy expenditure in infants and children requiring extracorporeal membrane oxygenation (ECMO) support. An indirect calorimeter was used to measure oxygen consumption (VO 2 ) and carbon dioxide production (VCO 2 ) from the mechanical ventilator. Blood gases were used to determine VO 2 and VCO 2 from the ECMO circuit. Values from the mechanical ventilator and ECMO circuit were added, and the resting energy expenditure (REE) (Kcal/kg/day) was calculated. Measurements were obtained > 24 hours after ECMO support was initiated (day 2 of ECMO), 1 day before ECMO discontinuation or transfer, and 1 day after decannulation. Data were compared with the predicted energy expenditure. Seven patients aged 3 months to 13 years were included. The REE varied greatly both above and below predicted values, from 26 to 154 KCal/kg/day on day 2 of ECMO support. In patients with septic shock, the REE was > 300% above the predicted value on day 2 of ECMO. Before ECMO discontinuation, two of six (33%) children continued to have a REE > 110% of predicted. Three patients had measurements after decannulation, all with a REE < 90% of predicted. REE measurements can be obtained by indirect calorimetry in children receiving ECMO support. ECMO may not provide metabolic rest for all children as a wide variation in REE was observed. For optimal care, individual testing should be considered to match calories provided with the metabolic demand.

Apparent Defective Abduction Without Diplopia.

Sixth nerve palsies present with horizontal diplopia and typically have a neurological or neurovascular aetiology. They can be confirmed by clinically evaluating the velocity of the abducting saccade, which is slowed. Three cases are presented in which the patients had apparent defective abduction of one eye, resulting from not only neurological causes but also orbital causes. Clinicians should have a high index of suspicion in patients with defective abduction without diplopia and should include apparent defective abduction without diplopia (ADAD) in the list of potential differential diagnoses, considering not only neurological involvement but also orbital involvement.

Characterization of a Temporary Peripheral Nerve Stimulation Electrode Utilizing a Bioabsorbable Suture Substrate.

Electrical stimulation after peripheral nerve injury (PNI) has the potential to promote more rapid and complete recovery of damaged fiber tracts. While permanently implanted devices are commonly used to treat chronic or persistent conditions, they are not ideal solutions for transient medical therapies due to high costs, increased risk of surgical injury, irritation, infection, and persistent inflammation at the site of the implant. Furthermore, removal of temporary leads placed on or around peripheral nerves may have unacceptable risk for nerve injury, which is counterproductive in developing therapies for PNI treatment. Transient devices which provide effective clinical stimulation while being capable of harmless bioabsorption may overcome key challenges in these areas. However, current bioabsorbable devices are limited in their robustness and require complex fabrication strategies and novel materials which may complicate their clinical translation pathway. In this study, we present a simple bioabsorbable / biodegradable electrode fabricated by modifying standard absorbable sutures, and we present data characterizing our prototype's stability in vitro and in vivo.

Why Australia should move towards nationally consistent mental health legislation?

OBJECTIVE: Mental Health Acts (MHAs) are important pieces of legislation which include essential definitions of mental illness and mental disorder and are used to guide decision-making regarding treatment, including involuntary admissions. In Australia, responsibility for reviewing this legislation falls under the jurisdiction of State and Territory Governments, resulting in interstate variations of legislative definitions and care requirements. In this paper, we outline some of the main differences between MHAs, and argue that it is time for Australia to enact nationally consistent Mental Health Legislation. CONCLUSIONS: Substantial divergence exists between definitions of mental illness and mental disorder, differing criteria for involuntary treatment and discrepancies between treatment requirements for Indigenous Australians. While variations between MHAs are understandable considering the historical context, in an increasingly integrated society, it is time for Australia to enact nationally consistent mental health legislation.

Renal Nerve Activity and Arterial Depressor Responses Induced by Neuromodulation of the Deep Peroneal Nerve in Spontaneously Hypertensive Rats.

Hypertension is a main cause of death in the United States with more than 103 million adults affected. While pharmacological treatments are effective, blood pressure (BP) remains uncontrolled in 50-60% of resistant hypertensive subjects. Using a custom-wired miniature electrode, we previously reported that deep peroneal nerve stimulation (DPNS) elicited acute cardiovascular depressor responses in anesthetized spontaneously hypertensive rats (SHRs). Here, we further study this effect by implementing a wireless system and exploring different stimulation parameters to achieve a maximum depressor response. Our results indicate that DPNS consistently induces a reduction in BP and suggests that renal sympathetic nerve activity (RSNA) is altered by this bioelectronic treatment. To test the acute effect of DPNS in awake animals, we developed a novel miniaturized wireless microchannel electrode (w-µCE), with a Z-shaped microchannel through which the target nerves slide and lock into the recording/stimulation chamber. Animals implanted with w-µCE and BP telemetry systems for 3 weeks showed an average BP of 150 ± 14 mmHg, which was reduced significantly by an active DPNS session to 135 ± 8 mmHg (p < 0.04), but not in sham-treated animals. The depressor response in animals with an active w-µCE was progressively returned to baseline levels 14 min later (164 ± 26 mmHg). This depressor response was confirmed in restrained fully awake animals that received DPNS for 10 days, where tail-cuff BP measurements showed that systolic BP in SHR lowered 10% at 1 h and 16% 2 h after the DPNS when compared to the post-implantation baseline. Together, these results support the use of DPN neuromodulation as a possible strategy to lower BP in drug-resistant hypertension.

Resolution of Diplopia and Torsion Following Yttrium Aluminum Garnet (YAG) Laser Capsulotomy in a Patient With the Ocular Tilt Reaction.

The ocular tilt reaction is a rare neuro-ophthalmological phenomenon commonly occurring due to an injury to the vestibulo-ocular pathway, or a thalamic, brainstem, or cerebellar lesion. Most ocular tilt reactions are transient and demonstrate spontaneous recovery. This report documents the immediate resolution of diplopia and the patient's ocular tilt reaction following visual recovery from left yttrium aluminum garnet laser capsulotomy.

Lessons From Management: Perioperative Phacoemulsification Planning Following Resolution of Acute Angle Closure.

Patients with loose zonular apparatus after acute angle closure may require phacoemulsification cataract surgery. The authors' experience from management of such patients provides excellent instruction on the surgical intervention for their cataracts. This is because patients who have recovered from acute angle closure glaucoma may not have evident zonular laxity preoperatively, as the iris may be taut secondary to the effects of associated ischaemia. If the surgeon's preoperative planning is directed to the possibility of loose zonular apparatus, then appropriate preoperative, intraoperative, and postoperative planning and management can be effected. This may permit preoperative patient counselling regarding the potentially increased complexity of the case. Intraoperatively, deliberately gentle capsulorrhexis, the use of iris hooks or a pupil expander to dilate the pupil, iris hooks to support the capsular bag, and the employment of a capsular tension ring may be helpful. Postoperatively, due to the previous ocular ischaemia, intraocular pressure elevation may ensue, and should be actively managed. The authors provide a summary of factors that require consideration in patients undergoing cataract surgery following acute angle closure.

Five-Year Outcomes of Trabeculectomy and Phacotrabeculectomy.

Purpose The purpose of this study is to examine five-year outcomes of trabeculectomy and compare the stand-alone procedure when combined with phacoemulsification. Patients and methods This study included 123 eyes of 109 patients, with 79 patients in the trabeculectomy group and 44 patients in the phacotrabeculectomy group. Non-randomized comparative cohort study with data collected retrospectively from an existing database compiled by a single surgeon operating in Sydney, Australia from 2007 to 2019. The primary outcome measure was intraocular pressure. Secondary outcome measures were a number of glaucoma medications, treatment success rates, best-corrected visual acuity, bleb morphology, post-operative complications, and re-operation rate. Results The mean intraocular pressure was 10.6 ± 2.7 mm Hg in the trabeculectomy group (pre-operative mean intraocular pressure of 28.0 ± 9.8) and 12.0 ± 3.0 mm Hg in the phacotrabeculectomy group (pre-operative mean intraocular pressure of 23.4 ± 7.9) after five years (P = 0.052). The number of glaucoma medications required was 0.3 ± 0.7 in the trabeculectomy group (pre-operative mean of 3.7 ± 1.1) and 1.3 ± 1.2 in the phacotrabeculectomy group (pre-operative mean of 3.1 ± 1.0, P < 0.001). Conclusions Intraocular pressure reduction post-operatively over five years was similar between trabeculectomy and phacotrabeculectomy as determined by mean intraocular pressure, and intraocular pressure reduction from baseline. However, fewer supplemental glaucoma medications were required following trabeculectomy as compared to the combined procedure.

Risk Factors for Hemolysis During Extracorporeal Life Support for Congenital Diaphragmatic Hernia.

BACKGROUND: Neonates receiving extracorporeal life support (ECLS) for congenital diaphragmatic hernia (CDH) require prolonged support compared with neonates with other forms of respiratory failure. Hemolysis is a complication that can be seen during ECLS and can lead to renal failure and potentially to worse outcomes. The purpose of this study was to identify risk factors for the development of hemolysis in CDH patients treated with ECLS. METHODS: The Extracorporeal Life Support Organization database was used to identify infants with CDH (2000-2015). The primary outcome was hemolysis (plasma-free hemoglobin >50 mg/dL). Potentially associated variables were identified in the data set. Descriptive statistics and a series of nested multivariable logistic regression models were used to identify associations between hemolysis and demographic, pre-ECLS, and on-ECLS factors. RESULTS: There were 4576 infants with a mortality of 52.5%. The overall mean rate of hemolysis was 10.5% during the study period. In earlier years (2000-2005), the hemolysis rates were 6.3% and 52.7% for roller versus centrifugal pumps, whereas in later years (2010-2015), they were 2.9% and 26.5%, respectively. The fully adjusted model demonstrated that the use of centrifugal pumps was a strong predictor of hemolysis (odds ratio: 6.67, 95% confidence interval: 5.14-8.67). In addition, other risk factors for hemolysis included low 5-min Apgar score, on-ECLS complications (renal, metabolic, and cardiovascular), and duration of ECLS. CONCLUSIONS: In our cohort of CDH patients receiving ECLS over 15 y, the use of centrifugal pumps increased over time, along with the rate of hemolysis. Patient- and treatment-level risk factors were identified contributing to the development of hemolysis.

Wireless And Portable Daily Soundscape Monitoring System For Auditory Profiling: Diagnostic Tool For Alzheimer's Disease.

The purpose of this paper is to develop an inexpensive, wearable, and portable monitoring system with wireless capabilities for signal acquisition of the user's surrounding soundscape and electroencephalography (EEG). The end-goal of this device is to monitor high-risk populations that are developing into earlier stages of Alzheimer's Disease (AD). Currently, the development of such device is still within preliminary phase and has only been tested in healthy individuals. Future applications of our monitoring system may be used as a non-invasive and inexpensive diagnostic tool for early detection of AD, potentially paving a new platform for therapeutic intervention. The system consists of low-weight bearing components, including an analog front-end and a single-board computer. The analog front-end contains three independent EEG, reference, bias, and auditory recording channels. The single-board computer timestamps and encrypts the incoming channels prior to local or "cloud" storage. Cloud storage provides ease-of-access and offline data analysis without the need to physically extract the data from the monitoring system. A portable/rechargeable battery provides power to the entire monitoring system for over 4 hours of operation. A graphical user-interface (GUI) was developed for secured remote access to data, parameter settings, and system configurations. The performance of the system was tested by measuring the frequency following response (FFR) in the captured EEG signals with respect to periodic auditory stimuli.

Value of Indocyanine Green Angiography to Guide Wound Management and Prevent Necrosis in a Robotic Surgical Procedure.

Background: Inguinal lymph node dissection is performed in penile cancers and has a high complication rate with mostly wound-related complications. This case study demonstrates the use of robotic technique, tissue perfusion assessment, and negative pressure wound dressing to minimize wound-related complications. Case Presentation: A 67-year-old Maltese man was diagnosed with squamous cell carcinoma (SCC) in situ on biopsy of a self-detected penile lump. The patient underwent a partial penectomy and histopathology report confirmed moderately differentiated SCC with clear surgical margins. A positron emission tomography/CT scan was performed preoperatively, which showed several nodes in the right inguinal region with increased metabolic activity and nonspecific findings in the left inguinal region. The patient had a robotic right inguinal node dissection the following month. Assessment of the skin flap was performed using indocyanine green (ICG) angiography with the SPY system and there was excellent vascularity. Further treatment was performed 3 months later with a robotic left inguinal node dissection. Again, assessment of the skin flap was performed using the SPY system but showed an area of poor perfusion in the left femoral triangle, which suggested a high risk of inadequate wound healing and tissue necrosis. The clinical decision to use the negative pressure PICO dressing was made intraoperatively to enhance perfusion of the skin. When the PICO dressing was removed it revealed excellent tissue viability and vascularity of the skin flap. Histopathology analysis showed no evidence of malignancy in the nodes removed and patient was discharged to the outpatient care of their urologist. Conclusion: This case study demonstrates that the use of a tissue perfusion assessment tool avoided a potentially poor clinical outcome for the patient. Robotic inguinal lymph node dissection was performed in coordination with ICG angiography to guide the use of negative pressure wound therapy and facilitate good wound healing.