[68 Ga]Ga-FAPI uptake correlates with the state of chronic kidney disease

Purpose Kidney fibrosis leads to a progressive reduction in kidney function ultimately resulting in kidney failure. Diagnostic tools to detect kidney fibrosis are all invasive in nature requiring kidney biopsies with subsequent histological validation. In this retrospective study, the diagnostic value of three different radiotracers for the noninvasive prediction of kidney fibrosis was analyzed, taking into account the glomerular filtration rate (GFR) and the intra-renal parenchymal radiotracer uptake. Methods In 81 patients receiving either one of the following molecular imaging probes, [68 Ga]Ga-FAPI, [68 Ga]Ga-PSMA, or [68 Ga]Ga-DOTATOC, kidney function parameters were correlated with SUVmax and SUVmean of the renal parenchyma and background activity measured in lung parenchyma, myocardium, gluteal muscle, and the abdominal aorta. Patients were clustered according to their grade of chronic kidney disease (CKD), and a regression analysis and one-way ANOVA were conducted in this retrospective analysis. Results We found a negative correlation between GFR and [68 Ga]Ga-FAPI uptake for both SUVmax and SUVmean values, whereas background activity showed no correlation with GFR. [68 Ga]Ga-DOTATOC and [68 Ga]Ga-PSMA did not correlate between CKD stage and intra-renal parenchymal radiotracer uptake. Only [68 Ga]Ga-PSMA background activity exhibited a positive correlation with GFR suggesting an unspecific binding/retention potentially due to longer circulation times. Conclusion There is a significant negative correlation between renal parenchymal [68 Ga]Ga-FAPI uptake and GFR, which was not the case for [68 Ga]Ga-DOTATOC and [68 Ga]Ga-PSMA. This correlation suggests a specific binding of FAPI rather than a potential unspecific retention in the renal parenchyma, underlining the potential value of [68 Ga]Ga-FAPI for the noninvasive quantitative evaluation of kidney fibrosis.

How synaptic strength, short-term plasticity, and temporal factors contribute to neuronal spike output

To compute spiking responses, neurons integrate inputs from thousands of synapses whose strengths span an order of magnitude. Intriguingly, in mouse neocortex, the small minority of 'strong' synapses is found predominantly between similarly tuned cells, suggesting they are the synapses that determine a neuron's spike output. This raises the question of how other computational primitives, such as 'background' activity from the majority of synapses, which are 'weak', short-term plasticity, and temporal synchrony contribute to spiking. First, we combined extracellular stimulation and whole-cell recordings in mouse barrel cortex to map the distribution of excitatory postsynaptic potential (EPSP) amplitudes and paired-pulse ratios of excitatory synaptic connections converging onto individual layer 2/3 (L2/3) neurons. While generally net short-term plasticity was weak, connections with EPSPs > 2 mV displayed pronounced paired-pulse depression. EPSP amplitudes and paired-pulse ratios of connections converging onto the same neurons spanned the full range observed across L2/3 and there was no indication that strong synapses nor those with particular short-term plasticity properties were associated with particular cells, which critically constrains theoretical models of cortical filtering. To investigate how different computational primitives of synaptic information processing interact to shape spiking, we developed a computational model of a pyramidal neuron in the rodent L2/3 circuitry: firing rates and pairwise correlations of presynaptic inputs were constrained by in vivo observations, while synaptic strength and short-term plasticity were set based on our experimental data. Importantly, we found that the ability of strong inputs to evoke spiking critically depended on their high temporal synchrony and high firing rates observed in vivo and on synaptic background activity - and not primarily on synaptic strength, which in turn further enhanced information transfer. Depression of strong synapses was critical for maintaining a neuron's responsivity and prevented runaway excitation. Our results provide a holistic framework of how cortical neurons exploit complex synergies between temporal coding, synaptic properties, and noise in order to transform synaptic inputs into output firing.

Modeling spectral changes following stimulation: Is there an event-related shift in 1/f activity?

Neural activity contains oscillatory components (i.e., narrowband oscillations) and non-oscillatory components (e.g., event-related potentials [ERPs] and 1/f-like background activity). Here, surface-level EEG data was analyzed to investigate how the spectral content of neural activity below 25 Hz changes from before to after an event. We focused on changes in non-oscillatory background activity, a spectral component often assumed to be static across time in time-frequency analyses. During a simple auditory perception task (n = 46) and an auditory oddball task (n = 23), we found an apparent increase in the offset and a decrease in the slope of 1/f activity from before to after a tone. Importantly, however, these changes in non-oscillatory background activity were almost completely accounted for by the emergence of ERPs in response to the stimulus in frequencies below the alpha range (8-12 Hz). Our findings suggest that post-event spectral changes below 25 Hz can be modelled as the sum of pre-event non-oscillatory activity, the spectrum of the ERP, and an independent alpha component that is modulated in amplitude, but not elicited, by the event. Theta activity (4-8 Hz), however, was not present before the event and appeared to be phase-locked to it. The theoretical and methodological implications of our findings regarding the nature and origin of 1/f activity, and the interpretation of low-frequency activity in the time-frequency domain are discussed.

Short latency stretch reflexes depend on the balance of activity in agonist and antagonist muscles during ballistic elbow movements

The spinal stretch reflex is a fundamental building block of motor function, modulating sensitivity across tasks to augment volitional control. Stretch reflex sensitivity can vary continuously during movement and changes between movement and posture. While there have been many demonstrations of reflex modulation and investigations into the underlying mechanisms, there have been few attempts to provide simple, quantitative descriptions of the relationship between the volitional control and stretch reflex sensitivity throughout tasks that require the coordinated activity of several muscles. Here we develop such a description and use it to test the hypothesis that the modulation of stretch reflex sensitivity during movement can be explained by the balance of activity within the relevant agonist and antagonist muscles better than by the activity only in the muscle homonymous with the elicited reflex. We applied continuous pseudo-random perturbations of elbow angle as subjects completed approximately 500 movements in elbow flexion and extension. Measurements were averaged across the repeated movements to obtain continuous estimates of stretch reflex amplitude and background muscle activity. We also ran a control experiment on a subset of subjects performing postural tasks at muscle activity levels matched to those measured in the movement task. For both experiments, we assessed the relationship between background activity in the agonist and antagonist muscles controlling elbow movement and the stretch reflexes elicited in them. We found that modulation in the stretch reflexes during movement can be described by modulation of the background activity in the agonist and antagonist muscles, and that models incorporating agonists and antagonists are significantly better than those considering only the homonymous muscle. Increases in agonist muscle activity enhanced stretch reflex sensitivity whereas increases in antagonist activity suppressed reflex activity. Surprisingly, the magnitude of these effects was similar, suggesting a balance of control between agonists and antagonist that is very different than the dominance of sensitivity to agonist activity during postural tasks. This greater relative sensitivity to antagonist background activity during movement is due to a large decrease in sensitivity to homonymous muscle activity during movement rather than substantial changes in the influence of antagonist muscle activity.

Automatic Cyclic Alternating Pattern (CAP) analysis: Local and multi-trace approaches

The Cyclic Alternating Pattern (CAP) is composed of cycles of two different electroencephalographic features: an activation A-phase followed by a B-phase representing the background activity. CAP is considered a physiological marker of sleep instability. Despite its informative nature, the clinical applications remain limited as CAP analysis is a time-consuming activity. In order to overcome this limit, several automatic detection methods were recently developed. In this paper, two new dimensions were investigated in the attempt to optimize novel, efficient and automatic detection algorithms: 1) many electroencephalographic leads were compared to identify the best local performance, and 2) the global contribution of the concurrent detection across several derivations to CAP identification. The developed algorithms were tested on 41 polysomnographic recordings from normal (n = 8) and pathological (n = 33) subjects. In comparison with the visual CAP analysis as the gold standard, the performance of each algorithm was evaluated. Locally, the detection on the F4-C4 derivation showed the best performance in comparison with all other leads, providing practical suggestions of electrode montage when a lean and minimally invasive approach is preferable. A further improvement in the detection was achieved by a multi-trace method, the Global Analysis—Common Events, to be applied when several recording derivations are available. Moreover, CAP time and CAP rate obtained with these algorithms positively correlated with the ones identified by the scorer. These preliminary findings support efficient automated ways for the evaluation of the sleep instability, generalizable to both normal and pathological subjects affected by different sleep disorders.

Directed-evolution of translation system for efficient unnatural amino acids incorporation and generalizable synthetic auxotroph construction

Site-specific incorporation of unnatural amino acids (UAAs) with similar incorporation efficiency to that of natural amino acids (NAAs) and low background activity is extremely valuable for efficient synthesis of proteins with diverse new chemical functions and design of various synthetic auxotrophs. However, such efficient translation systems remain largely unknown in the literature. Here, we describe engineered chimeric phenylalanine systems that dramatically increase the yield of proteins bearing UAAs, through systematic engineering of the aminoacyl-tRNA synthetase and its respective cognate tRNA. These engineered synthetase/tRNA pairs allow single-site and multi-site incorporation of UAAs with efficiencies similar to those of NAAs and high fidelity. In addition, using the evolved chimeric phenylalanine system, we construct a series of E. coli strains whose growth is strictly dependent on exogenously supplied of UAAs. We further show that synthetic auxotrophic cells can grow robustly in living mice when UAAs are supplemented.

Designing for unpredictable uses: A case study on cargo handling

BACKGROUND: Activity ergonomics aims to include work variability into design process to enable various dimensions of use in projects. As design evolves with use, understanding its characteristics is essential to decipher real working requirements. However, situated design can be pluralistic and may lead to different interpretations than initially intended. OBJECTIVE: This paper aims at understanding the relationship between the designing phase of work systems and the situated task design in high uncertainty operations. METHODS: In an ergonomic work analysis, cargo handling operations were observed at offshore platforms, followed by discussions with workers. Two case studies were selected for the intervention process to demonstrate how workers dealt with high uncertainty tasks on site. RESULTS: Situated task design exhibited three main characteristics: (1) the project emerges from the situation; (2) it has an intentional and original character; and (3) it is situated in time and space to solve local problems. CONCLUSIONS: This combination is the essence of a microproject, which is a concept proposed in this paper. The design must provide resources not only to execute work but also to redesign the task on site.

Method to Determine the Statistical Technical Variability of SUV Parameters

Background: Some of the parameters used for the quantification of Positron Emission Tomography (PET) images are the Standardized Uptake Value (SUV)Max, SUVMean and SUVPeak. In order to assess the significance of an increasing or decreasing of these parameters for diagnostic purposes it is relevant to know their standard deviation. The sources of the standard deviation can be divided in biological and technical. In this study we present a method to determine the technical variation of the SUV in PET images.Results: This method was tested on images of a NEMA quality phantom with spheres of various diameters with full-length acquisition time of 150 s per bed position and foreground to background activity ratio of F18-2-fluoro-2-deoxy-D-glucose (FDG) of 10:1. Our method is based on dividing the full-length 150 s acquisition into subsets of shorter time length and reconstructing the images in the subsets. The SUVMax, Mean and Peak were calculated for each reconstructed image in a subset. The coefficient of deviation of the SUV parameters within each subset has then been used to estimate the expected standard deviation between images at 150 s reconstruction length. We report the largest technical variation of the SUV parameters for the smallest sphere, and the smallest variation for the largest sphere. The expected variation at 150 s reconstruction length does not exceed 6% for the smallest sphere and 2% for the largest sphere. Conclusions: With the presented method we are able to determine the technical variation of SUV. The method enables us to evaluate the effect of parameter selection and lesion size on the technical variation, and therefore to evaluate its relevance on the total variation of the SUV value between studies.

Background Activity Findings in End-Stage Renal Disease With and Without Comorbid Diabetes: An Electroencephalogram Study

Renal failure and diabetes can induce cerebral complications, including encephalopathy, for which attentional and cognitive impairment are common symptoms. It is possible that renal failure with comorbid diabetes may induce more severe encephalopathy due to multiple pathogenic mechanisms. This concept was supported by the main findings of this study, which showed that EEG background activity between end-stage renal disease with and without comorbid diabetes was significantly different in relative power of delta in the eyes-open condition in frontoparietal regions; theta in the eyes-closed condition in all regions; beta in the parieto-occipital regions in both eye conditions; the delta/theta ratio in both eye conditions in frontoparietal regions; and the theta/beta ratio in all regions in the eyes-closed condition. These findings may increase awareness of comorbid cerebral complications in clinical practice. Moreover, the delta/theta ratio is recommended as an optimal feature to possibly determine the severity of encephalopathy.