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Substantia nigra (SN) hyperechogenicity, viewed with transcranial ultrasound, is a risk marker for Parkinson's disease. We hypothesized that SN hyperechogenicity in healthy adults aged 50 – 70 years is associated with reduced short-interval intracortical inhibition in primary motor cortex, and that the reduced intracortical inhibition is associated with neurochemical markers of activity in the pre-supplementary motor area (pre-SMA). Short-interval intracortical inhibition and intracortical facilitation in primary motor cortex was assessed with paired-pulse transcranial magnetic stimulation in 23 healthy adults with normal (n = 14; 61 ± 7 yrs) or abnormally enlarged (hyperechogenic; n = 9; 60 ± 6 yrs) area of SN echogenicity. Thirteen of these participants (7 SN − and 6 SN+) also underwent brain magnetic resonance spectroscopy to investigate pre-SMA neurochemistry. There was no relationship between area of SN echogenicity and short-interval intracortical inhibition in the ipsilateral primary motor cortex. There was a significant positive relationship, however, between area of echogenicity in the right SN and the magnitude of intracortical facilitation in the right (ipsilateral) primary motor cortex (p = .005; multivariate regression), evidenced by the amplitude of the conditioned motor evoked potential (MEP) at the 10 – 12 ms interstimulus interval. This relationship was not present on the left side. Pre-SMA glutamate did not predict primary motor cortex inhibition or facilitation. The results suggest that SN hyperechogenicity in healthy older adults may be associated with changes in excitability of motor cortical circuitry. The results advance understanding of brain changes in healthy older adults at risk of Parkinson's disease.

Background: Adequate identification and testing of people at risk for HIV is fundamental for the HIV care continuum. A key strategy to improve timely testing is HIV indicator condition (IC) guided testing. Aim: To evaluate the uptake of HIV testing recommendations in HIV IC-specific guidelines in European countries. Methods: Between 2019 and 2021, European HIV experts reviewed guideline databases to identify all national guidelines of 62 HIV ICs. The proportion of HIV IC guidelines recommending HIV testing was reported, stratified by subgroup (HIV IC, country, eastern/western Europe, achievement of 90- 90-90 goals and medical specialty). Results: Of 30 invited European countries, 15 participated. A total of 791 HIV IC guidelines were identified: median 47 (IQR: 38-68) per country. Association with HIV was reported in 69% (545/791) of the guidelines, and 46% (366/791) recommended HIV testing, while 42% (101/242) of the AIDS-defining conditions recommended HIV testing. HIV testing recommendations were observed more frequently in guidelines in eastern ( 53%) than western (42%) European countries and in countries yet to achieve the 90-90- 90 goals ( 52%) compared to those that had ( 38%). The medical specialties internal medicine, neurology/neurosurgery, ophthalmology, pulmonology and gynaecology/obstetrics had an HIV testing recommendation uptake below the 46% average. None of the 62 HIV ICs, countries or medical specialties had 100% accurate testing recommendation coverage in all their available HIV IC guidelines. Conclusion: Fewer than half the HIV IC guidelines recommended HIV testing. This signals an insufficient adoption of this recommendation in non-HIV specialty guidelines across Europe.

Background: Adequate identification and testing of people at risk for HIV is fundamental for the HIV care continuum. A key strategy to improve timely testing is HIV indicator condition (IC) guided testing. Aim: To evaluate the uptake of HIV testing recommendations in HIV IC-specific guidelines in European countries. Methods: Between 2019 and 2021, European HIV experts reviewed guideline databases to identify all national guidelines of 62 HIV ICs. The proportion of HIV IC guidelines recommending HIV testing was reported, stratified by subgroup (HIV IC, country, eastern/western Europe, achievement of 90-90-90 goals and medical specialty). Results: Of 30 invited European countries, 15 participated. A total of 791 HIV IC guidelines were identified: median 47 (IQR: 38-68) per country. Association with HIV was reported in 69% (545/791) of the guidelines, and 46% (366/791) recommended HIV testing, while 42% (101/242) of the AIDS-defining conditions recommended HIV testing. HIV testing recommendations were observed more frequently in guidelines in eastern (53%) than western (42%) European countries and in countries yet to achieve the 90-90-90 goals (52%) compared to those that had (38%). The medical specialties internal medicine, neurology/neurosurgery, ophthalmology, pulmonology and gynaecology/obstetrics had an HIV testing recommendation uptake below the 46% average. None of the 62 HIV ICs, countries or medical specialties had 100% accurate testing recommendation coverage in all their available HIV IC guidelines. Conclusion: Fewer than half the HIV IC guidelines recommended HIV testing. This signals an insufficient adoption of this recommendation in non-HIV specialty guidelines across Europe.

Background Adequate identification and testing of people at risk for HIV is fundamental for the HIV care continuum. A key strategy to improve timely testing is HIV indicator condition (IC) guided testing. Aim To evaluate the uptake of HIV testing recommendations in HIV IC-specific guidelines in European countries. Methods Between 2019 and 2021, European HIV experts reviewed guideline databases to identify all national guidelines of 62 HIV ICs. The proportion of HIV IC guidelines recommending HIV testing was reported, stratified by subgroup (HIV IC, country, eastern/western Europe, achievement of 90–90–90 goals and medical specialty). Results Of 30 invited European countries, 15 participated. A total of 791 HIV IC guidelines were identified: median 47 (IQR: 38–68) per country. Association with HIV was reported in 69% (545/791) of the guidelines, and 46% (366/791) recommended HIV testing, while 42% (101/242) of the AIDS-defining conditions recommended HIV testing. HIV testing recommendations were observed more frequently in guidelines in eastern (53%) than western (42%) European countries and in countries yet to achieve the 90–90–90 goals (52%) compared to those that had (38%). The medical specialties internal medicine, neurology/neurosurgery, ophthalmology, pulmonology and gynaecology/obstetrics had an HIV testing recommendation uptake below the 46% average. None of the 62 HIV ICs, countries or medical specialties had 100% accurate testing recommendation coverage in all their available HIV IC guidelines. Conclusion Fewer than half the HIV IC guidelines recommended HIV testing. This signals an insufficient adoption of this recommendation in non-HIV specialty guidelines across Europe., SCOPUS: ar.j, info:eu-repo/semantics/published

PURPOSE: Heating of gradient coils and passive shim components is a common cause of instability in the B0 field, especially when gradient intensive sequences are used. The aim of the study was to set a benchmark for typical drift encountered during MR spectroscopy (MRS) to assess the need for real-time field-frequency locking on MRI scanners by comparing field drift data from a large number of sites.METHOD: A standardized protocol was developed for 80 participating sites using 99 3T MR scanners from 3 major vendors. Phantom water signals were acquired before and after an EPI sequence. The protocol consisted of: minimal preparatory imaging; a short pre-fMRI PRESS; a ten-minute fMRI acquisition; and a long post-fMRI PRESS acquisition. Both pre- and post-fMRI PRESS were non-water suppressed. Real-time frequency stabilization/adjustment was switched off when appropriate. Sixty scanners repeated the protocol for a second dataset. In addition, a three-hour post-fMRI MRS acquisition was performed at one site to observe change of gradient temperature and drift rate. Spectral analysis was performed using MATLAB. Frequency drift in pre-fMRI PRESS data were compared with the first 5:20 minutes and the full 30:00 minutes of data after fMRI. Median (interquartile range) drifts were measured and showed in violin plot. Paired t-tests were performed to compare frequency drift pre- and post-fMRI. A simulated in vivo spectrum was generated using FID-A to visualize the effect of the observed frequency drifts. The simulated spectrum was convolved with the frequency trace for the most extreme cases. Impacts of frequency drifts on NAA and GABA were also simulated as a function of linear drift. Data from the repeated protocol were compared with the corresponding first dataset using Pearson's and intraclass correlation coefficients (ICC).RESULTS: Of the data collected from 99 scanners, 4 were excluded due to various reasons. Thus, data from 95 scanners were ultimately anal

β-Hydroxybutyrate (3-hydroxybutyric acid; CH3CHOHCH2COOH; βOHB) is a ketone body oxidised as brain fuel with direct and collateral effects. It can be produced in astrocytes from the oxidation of fatty acids or catabolism of amino acids and is metabolised in the mitochondria of all brain cell types. The thesis presented here investigates βOHB brain metabolism using 1H/13C nuclear magnetic resonance spectroscopy in guinea pig cortical brain slice model. The thesis initially evaluates metabolism of increasing concentrations of [U-13C]D-βOHB in conjunction with [1-13C]D-glucose. The thesis then compares the effects of βOHB on brain metabolism to AMP-activated protein kinase (AMPK) activators. The thesis then investigates the effect of ATP-citrate lyase (ACLY) inhibition, a key enzyme generating cytosolic acetyl-CoA and oxaloacetate from citrate, on the metabolism of [U-13C]D-βOHB, [1-13C]D-glucose, [3-13C]pyruvate, [3-13C]L-lactate, and [1,2-13C]acetate.[U-13C]D-βOHB at low concentrations (0.25 and 1.25 mmol/L) stimulated mitochondrial metabolism but did not substitute for glucose as a substrate. The effect of both direct and indirect AMPK activators (A769662, PF-06409577, AICAR, and metformin) showed an overall increase in brain metabolism but was not similar to the effect of βOHB on brain metabolism. Inhibition of ACLY using BMS-303141 with pyruvate, lactate, or βOHB as substrates resulted in increased incorporation of 13C label into Krebs cycle intermediates. When [1-13C]D-glucose was the sole substrate, total metabolite pools, and net flux of 13C into Krebs cycle intermediates and glycolytic by-products were significantly reduced. This flux of [1-13C]D-glucose was “rescued” when brain slices were supplemented with [1,2-13C]acetate increasing incorporation of label from both glucose and acetate. These results indicate that the impact of ACLY activity on Krebs cycle flux is significant, although it is currently not a part of most models of brain metabolism. In summary

Muscle performance is closely related to the structure and function of tendons and aponeuroses, the sheet-like, intramuscular parts of tendons. The architecture of aponeuroses has been difficult to study with magnetic resonance imaging (MRI) because these thin, collagen-rich connective tissues have very short transverse relaxation (T2) times and therefore provide a weak signal with conventional MRI sequences. Here, we validated measurements of aponeurosis dimensions from two MRI sequences commonly used in muscle-tendon research (mDixon and T1-weighted images), and an ultrashort echo time (UTE) sequence designed for imaging tissues with short T2 times. MRI-based measurements of aponeurosis width, length, and area of 20 sheep leg muscles were compared to direct measurements made with three-dimensional (3D) quantitative microdissection. The errors in measurement of aponeurosis width relative to the mean width were 1.8% for UTE, 3.7% for T1, and 18.8% for mDixon. For aponeurosis length, the errors were 7.6% for UTE, 1.9% for T1, and 21.0% for mDixon. Measurements from T1 and UTE scans were unbiased, but mDixon scans systematically underestimated widths, lengths, and areas of the aponeuroses. Using the same methods, we then found high inter-rater reliability (intraclass correlation coefficients >0.92 for all measures) of measurements of the dimensions of the central aponeurosis of the human tibialis anterior muscle from T1-weighted scans. We conclude that valid and reliable measurements of aponeurosis dimensions can be obtained from UTE and from T1-weighted scans. When the goal is to study the macroscopic architecture of aponeuroses, UTE does not hold an advantage over T1-weighted imaging.

It has long been thought that severe chronic pain conditions, such as complex regional pain syndrome (CRPS), are not only associated with, but even maintained by a reorganization of the somatotopic representation of the affected limb in primary somatosensory cortex (S1). This notion has driven treatments that aim to restore S1 representations in CRPS patients, such as sensory discrimination training and mirror therapy. However, this notion is based on both indirect and incomplete evidence obtained with imaging methods with low spatial resolution. Here, we used fMRI to characterize the S1 representation of the affected and unaffected hand in humans (of either sex) with unilateral CRPS. The cortical area, location, and geometry of the S1 representation of the CRPS hand were largely comparable with those of both the unaffected hand and healthy controls. We found no differential relation between affected versus unaffected hand map measures and clinical measures (pain severity, upper limb disability, disease duration). Thus, if any map reorganization occurs, it does not appear to be directly related to pain and disease severity. These findings compel us to reconsider the cortical mechanisms underlying CRPS and the rationale for interventions that aim to "restore" somatotopic representations to treat pain.SIGNIFICANCE STATEMENT This study shows that the spatial map of the fingers in somatosensory cortex is largely preserved in chronic complex regional pain syndrome (CRPS). These findings challenge the treatment rationale for restoring somatotopic representations in complex regional pain syndrome patients.