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Quantifying myelin in crossing fibers using diffusion-prepared phase imaging: Theory and simulations.
PURPOSE: Myelin has long been the target of neuroimaging research. However, most available techniques can only provide a voxel-averaged estimate of myelin content. In the human brain, white matter fiber pathways connecting different brain areas and carrying different functions often cross each other in the same voxel. A measure that can differentiate the degree of myelination of crossing fibers would provide a more specific marker of myelination. THEORY AND METHODS: One MRI signal property that is sensitive to myelin is the phase accumulation. This sensitivity is used by measuring the phase accumulation of the signal remaining after diffusion-weighting, which is called diffusion-prepared phase imaging (DIPPI). Including diffusion-weighting before estimating the phase accumulation has two distinct advantages for estimating the degree of myelination: (1) It increases the relative contribution of intra-axonal water, whose phase is related linearly to the thickness of the surrounding myelin (in particular the log g-ratio); and (2) it gives directional information, which can be used to distinguish between crossing fibers. Here the DIPPI sequence is described, an approach is proposed to estimate the log g-ratio, and simulations are used and DIPPI data acquired in an isotropic phantom to quantify other sources of phase accumulation. RESULTS: The expected bias is estimated in the log g-ratio for reasonable in vivo acquisition parameters caused by eddy currents (~4%-10%), remaining extra-axonal signal (~15%), and gradients in the bulk off-resonance field (<10% for most of the brain). CONCLUSION: This new sequence may provide a g-ratio estimate per fiber population crossing within a voxel.
Improving robustness of 3D multi-shot EPI by structured low-rank reconstruction of segmented CAIPI sampling for fMRI at 7T
Three-dimensional (3D) encoding methods are increasingly being explored as alternatives to multi-slice two-dimensional (2D) acquisitions in fMRI, particularly in cases where high isotropic resolution is needed. 3D multi-shot EPI is the most popular 3D fMRI acquisition method, but is susceptible to physiological fluctuations which can induce inter-shot phase variations, and thus reducing the achievable tSNR, negating some of the benefit of 3D encoding. This issue can be particularly problematic at ultra-high fields like 7T, which have more severe off-resonance effects. In this work, we aim to improve the temporal stability of 3D multi-shot EPI at 7T by improving its robustness to inter-shot phase variations. We presented a 3D segmented CAIPI sampling trajectory (“seg-CAIPI”) and an improved reconstruction method based on Hankel structured low-rank matrix recovery. Simulation and in-vivo results demonstrate that the combination of the seg-CAIPI sampling scheme and the proposed structured low-rank reconstruction is a promising way to effectively reduce the unwanted temporal variance induced by inter-shot physiological fluctuations, and thus improve the robustness of 3D multi-shot EPI for fMRI. Highlights A 3D multi-shot EPI sampling trajectory using interleaved ordering along k z and a CAIPI blipping pattern improves robustness to inter-shot phase variations Reconstruction based on Hankel structured low-rank matrix completion can significantly improve the temporal stability of 3D multi-shot acquisitions at 7T 1.5mm resolution brain fMRI data show that ~60% improvement in mean tSNR can be obtained using the proposed method compared to the conventional method 1.8mm resolution brain fMRI data demonstrate that the proposed method allows for 4-fold acceleration without loss of tSNR compared to conventional 3D EPI Preliminary brainstem fMRI data show that ~40% improvement in mean tSNR can be obtained using the proposed sampling and reconstruction
Post-acute COVID-19 neuropsychiatric symptoms are not associated with ongoing nervous system injury.
A proportion of patients infected with severe acute respiratory syndrome coronavirus 2 experience a range of neuropsychiatric symptoms months after infection, including cognitive deficits, depression and anxiety. The mechanisms underpinning such symptoms remain elusive. Recent research has demonstrated that nervous system injury can occur during COVID-19. Whether ongoing neural injury in the months after COVID-19 accounts for the ongoing or emergent neuropsychiatric symptoms is unclear. Within a large prospective cohort study of adult survivors who were hospitalized for severe acute respiratory syndrome coronavirus 2 infection, we analysed plasma markers of nervous system injury and astrocytic activation, measured 6 months post-infection: neurofilament light, glial fibrillary acidic protein and total tau protein. We assessed whether these markers were associated with the severity of the acute COVID-19 illness and with post-acute neuropsychiatric symptoms (as measured by the Patient Health Questionnaire for depression, the General Anxiety Disorder assessment for anxiety, the Montreal Cognitive Assessment for objective cognitive deficit and the cognitive items of the Patient Symptom Questionnaire for subjective cognitive deficit) at 6 months and 1 year post-hospital discharge from COVID-19. No robust associations were found between markers of nervous system injury and severity of acute COVID-19 (except for an association of small effect size between duration of admission and neurofilament light) nor with post-acute neuropsychiatric symptoms. These results suggest that ongoing neuropsychiatric symptoms are not due to ongoing neural injury.
The Sleep of Shift Workers in a UK Financial Organisation and Associations with Mental, Physical, Social and Cognitive Health
Shift workers are vulnerable to circadian misalignment, sleep disturbance and increased risk of impaired health. Studies concerning the sleep and health of individuals working shifts in the financial sector are lacking. We investigated sleep quality, sleep duration and associations with health in a UK financial organisation. Employees (n = 178; 61% male) completed an online survey comprising the SSI, PSQI, GAD-7, PHQ-9, WAFCS, EMQ-R and BMI. Three-quarters of employees reported poor sleep quality. Poorer sleep quality and shorter sleep duration were both associated with greater anxiety and depression symptoms. However, sleep quality demonstrated greater explained variance with symptom severity (anxiety: Rs2 difference = 13.2%; depression: Rs2 difference = 21.8%). Poorer sleep quality was associated with higher BMI, greater work-to-family conflict and poorer everyday memory (rs = 0.26–0.29), while shorter sleep duration was only significantly associated with higher BMI. Sleep quality did not differ depending on the nightshift type (“permanent”/“other”). Sleep achieved was shorter than perceived sleep-need for all consecutive shift types—especially night shifts (40 min–1 h 24 min). This preliminary study suggests that sleep quality, and to a lesser extent sleep duration, are associated with a range of health outcomes for shift workers within the financial sector, highlighting the need to increase organisational awareness of the importance of sleep for employee health.
Author Correction: Development and validation of an expanded antibody toolset that captures alpha-synuclein pathological diversity in Lewy body diseases (npj Parkinson's Disease, (2023), 9, 1, (161), 10.1038/s41531-023-00604-y)
Correction to: npj Parkinson’s Disease, published online 07 December 2023 In this article, the wrong slot blots of LASH-BL34-45 and BL 4B12 were presented in Figure 2a; the figure should have appeared as shown below. The original article has been corrected. (Figure presented.).
Hydrocortisone Differentially Affects Reinstatement of Pain-related Responses in Patients With Chronic Back Pain and Healthy Volunteers.
Despite the crucial role of effective and sustained extinction of conditioned pain-related fear in cognitive-behavioral treatment approaches for chronic pain, experimental research on extinction memory retrieval in chronic pain remains scarce. In healthy populations, extinction efficacy of fear memory is affected by stress. Therefore, we investigated the effects of oral hydrocortisone administration on the reinstatement of pain-related associations in 57 patients with non-specific chronic back pain (CBP) and 59 healthy control (HC) participants in a differential pain-related conditioning paradigm within a placebo-controlled, randomized, and double-blind design. Participants' skin conductance responses indicate hydrocortisone-induced reinstatement effects in HCs but no observable reinstatement in HCs receiving placebo treatment. Interestingly, these effects were reversed in patients with CBP, that is, reinstatement responses were only observed in the placebo and not in the hydrocortisone group. Our findings corroborate previous evidence of stress-induced effects on extinction efficacy and reinstatement of fear memory in HCs, extending them into the pain context, and call for more research to clarify the role of stress in fear extinction and return of fear phenomena possibly contributing to treatment failure in chronic pain treatment. PERSPECTIVE: Opposing effects in HCs and patients with non-specific CBP may be associated with changes in the patients' stress systems. These findings could be of relevance to optimizing psychological, extinction-based treatment approaches.
Endothelial Jagged1 levels and distribution are post-transcriptionally controlled by ZFP36 decay proteins.
Vascular morphogenesis requires a delicate gradient of Notch signaling controlled, in part, by the distribution of ligands (Dll4 and Jagged1). How Jagged1 (JAG1) expression is compartmentalized in the vascular plexus remains unclear. Here, we show that Jag1 mRNA is a direct target of zinc-finger protein 36 (ZFP36), an RNA-binding protein involved in mRNA decay that we find robustly induced by vascular endothelial growth factor (VEGF). Endothelial cells lacking ZFP36 display high levels of JAG1 and increase angiogenic sprouting in vitro. Furthermore, mice lacking Zfp36 in endothelial cells display mispatterned and increased levels of JAG1 in the developing retinal vascular plexus. Abnormal levels of JAG1 at the sprouting front alters NOTCH1 signaling, increasing the number of tip cells, a phenotype that is rescued by imposing haploinsufficiency of Jag1. Our findings reveal an important feedforward loop whereby VEGF stimulates ZFP36, consequently suppressing Jag1 to enable adequate levels of Notch signaling during sprouting angiogenesis.
Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses.
To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1-11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely.
A Behaviorally Informed Mobile App to Improve the Nutritional Quality of Grocery Shopping (SwapSHOP): Feasibility Randomized Controlled Trial.
BACKGROUND: Interventions targeting the nutritional quality of grocery shopping have the potential to help improve diet and health outcomes. OBJECTIVE: This study aims to assess the feasibility and acceptability of receiving advice on healthier food purchases through SwapSHOP, a behaviorally informed smartphone app that allows users to scan barcodes of grocery products from the United Kingdom, providing nutritional information and personalized swap suggestions to encourage healthier purchases. METHODS: We randomized adult volunteers in a 6-arm parallel-group controlled feasibility trial. Participants used the SwapSHOP app to record their grocery shopping during a 2-week run-in period and were individually randomized in a 3:1 ratio to either intervention or control arms within 3 strata related to a nutrient of concern of their choice: saturated fat (SFA), sugar, or salt. Participants randomized to the intervention received the SwapSHOP app with a healthier swap function, goal setting, and personalized feedback. Participants in the control group were instructed to use a simpler version of the app to log all their food purchases without receiving any guidance or advice. The primary outcome was the feasibility of progression to a full trial, including app use and follow-up rates at 6 weeks. The secondary outcomes included other feasibility outcomes, process and qualitative measures, and exploratory effectiveness outcomes to assess changes in the nutrient content of the purchased foods. RESULTS: A total of 112 participants were randomized into 3 groups: SFA (n=38 intervention and n=13 control), sugar (n=40 intervention and n=15 control), and salt (n=5 intervention and n=1 control, not analyzed). The 2 progression criteria were met for SFA and sugar: 81% (30/37) and 87% (34/39) of intervention participants in the SFA and sugar groups, respectively, used the app to obtain healthier swaps, and 89% (68/76) of intervention participants and 96% (23/24) of control participants completed follow-up by scanning all purchases over the follow-up period. The process and qualitative outcomes suggested that the intervention was acceptable and has the potential to influence shopping behaviors. There were reductions of -0.56 g per 100 g (95% CI -1.02 to -0.19) in SFA and -1 g per 100 g (95% CI -1.97 to -0.03) in total sugars across all food purchases in the intervention groups. CONCLUSIONS: People were willing to use the SwapSHOP app to help reduce sugar and SFA (but not salt) in their grocery shopping. Adherence and follow-up rates suggest that a full trial is feasible. Given the suggestive evidence indicating that the intervention resulted in reductions in sugars and SFA, a definitive trial is necessary to target improvements in health outcomes. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number ISRCTN13022312; https://doi.org/10.1186/ISRCTN13022312.