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Fildes, J.

Publications and source records attributed to Fildes, J..

3 recordsLinked to original sources

Beta-band dynamics during a naturalistic motor task: an OPM-MEG study

Beta oscillations are a fundamental feature of brain activity, linked to long-range connectivity within canonical networks, inhibition of sensorimotor cortices and the maintenance of a stable sensorimotor state in situations where the external world is predictable. The importance of beta oscillations in brain function is underscored by observations of their perturbation in neurological and psychiatric disorders. However, the precise role played by beta activity, particularly in mediating complex or skilful movements, remains incompletely understood. Here, we used a newly developed wearable optically pumped magnetometer-based magnetoencephalography (OPM-MEG) system to measure beta dynamics as participants learned to play a musical instrument. Twenty-two novice players took part in a study in which OPM-MEG data were recorded during two scanning sessions, while participants attempted to play a tune on a violin. Between the two sessions, participants received a violin lesson from an expert teacher. Results showed that robust data could be acquired during this naturalistic task, with beta oscillations decreasing in amplitude during movement and increasing upon movement cessation, as expected. Moreover, beta power whilst playing, in the motor and pre-motor areas, was significantly elevated after the lesson compared to before, and the movement-related modulation of beta amplitude was more pronounced after the lesson. These findings align with predictive coding models which suggest that beta amplitude should increase when individuals have greater certainty over the movements they carry out. Our study adds to an expanding literature on the role of beta oscillations and provides further evidence for the utility of OPM-MEG in naturalistic neuroscience.

neuroscience↗

Developing a safe 15-hour preservation protocol of donor kidneys using normothermic machine perfusion

IntroductionO_ST_ABSBackgroundC_ST_ABSNormothermic machine perfusion (NMP) offers a superior alternative to existing hypothermic preservation strategies but is currently limited to 1-3 hours. Extending the time a kidney can be sustained using this technology could electivise transplantation, and enable physiological assessments of renal function. We aimed to develop a protocol that allows the safe preservation of donor kidneys for 12 hours using this technique. MethodsPorcine kidneys (n=20) were retrieved and flushed with 1L preservation solution before being stored on ice. Following a cold ischaemic time of 3.5 hours, kidneys were placed onto a NMP circuit and perfused for 12 hours. Renal haemodynamics, biochemistry and urine output were recorded and analysed. At the end of perfusion, kidneys were scored based on the clinical assessment score and their suitability for transplant determined. Biopsies were collected at the end for histological assessment. ResultsAll kidneys were successfully perfused with immediate recordable renal blood flow (RBF). RBF continually improved over the course of the perfusions, peaking at 12 hours, and negatively correlated with intra-renal resistance. Perfusate sodium concentrations remained stable and within physiological parameters. Sodium bicarbonate increased over time with a corresponding decrease in lactate concentrations, demonstrating active renal gluconeogenesis and Cori cycle processes. Urine production began immediately in all kidneys and was sustained throughout, indicating active renal function. Under the clinical perfusion assessment score, all kidneys received a score of 1 and would be considered suitable for transplantation. Histological assessment revealed kidneys were injury free with REMUZZI scores of 0 in all samples. ConclusionWe have developed an NMP protocol that safely preserves donor kidneys for over 15 hours. Successful perfusion was achieved with stable haemodynamics, blood-perfusate biochemistry, and maintained urine output. Importantly, kidneys remained in optimal health, with no evidence of injury. This protocol may enable the electivisation of transplantation, while reducing ischaemic injury associated with static cold storage.

physiology↗

Polysulfide Nanoparticles Ameliorate Ischaemia Reperfusion Injury in Renal Transplantation and Improve Kidney Function Post-Transplantation

Ischemia-reperfusion injury (IRI) is a significant complication in kidney transplantation, often affecting the viability and function of organs. Normothermic machine perfusion (NMP) is a technique used to improve the condition of organs prior to transplantation. In this study, we show that incorporating antioxidant poly(propylene sulfide) nanoparticles (PPS-NPs) during cold-storage and NMP significantly enhances its efficacy in reducing IRI upon porcine kidney transplantation. We found that by scavenging reactive oxygen species, PPS-NPs reduced oxidative stress and inflammation that occurs during ischemia-reperfusion with oxidized DNA reduced 5.3x and both TNF- and complement activation approximately halved. Our studies show that this approach led to significantly improved hemodynamics, better renal function, and tissue health compared to NMP alone. The results suggest that incorporating PPS-NPs into transplantation protocols may expand the pool of kidneys suitable for transplantation and enhance overall transplantation success rates. The broader impact of this work could extend to other organ transplants, suggesting a wider application for nanoantioxidant technologies in organ preservation.

synthetic biology↗