Notes

Using the BAT-LQ to guage TBI chance within a university student population.
How spontaneously fluctuating functional magnetic resonance imaging (fMRI) signals in different brain regions relate to behaviour has been an open question for decades. Correlations in these signals, known as functional connectivity, can be averaged over several minutes of data to provide a stable representation of the functional network architecture for an individual. However, associations between these stable features and behavioural traits have been shown to be dominated by individual differences in anatomy. Here, using kernel learning tools, we propose methods to assess and compare the relation between time-varying functional connectivity, time-averaged functional connectivity, structural brain data, and non-imaging subject behavioural traits. We applied these methods to Human Connectome Project resting-state fMRI data to show that time-varying fMRI functional connectivity, detected at time-scales of a few seconds, has associations with some behavioural traits that are not dominated by anatomy. Despite time-averaged functional connectivity accounting for the largest proportion of variability in the fMRI signal between individuals, we found that some aspects of intelligence could only be explained by time-varying functional connectivity. The finding that time-varying fMRI functional connectivity has a unique relationship to population behavioural variability suggests that it might reflect transient neuronal communication fluctuating around a stable neural architecture.Speech mental imagery is a quasi-perceptual experience that occurs in the absence of real speech stimulation. How imagined speech with higher-order structures such as words, phrases and sentences is rapidly organized and internally constructed remains elusive. To address this issue, subjects were tasked with imagining and perceiving poems along with a sequence of reference sounds with a presentation rate of 4 Hz while magnetoencephalography (MEG) recording was conducted. Giving that a sentence in a traditional Chinese poem is five syllables, a sentential rhythm was generated at a distinctive frequency of 0.8 Hz. Using the frequency tagging we concurrently tracked the neural processing timescale to the top-down generation of rhythmic constructs embedded in speech mental imagery and the bottom-up sensory-driven activity that were precisely tagged at the sentence-level rate of 0.8 Hz and a stimulus-level rate of 4 Hz, respectively. We found similar neural responses induced by the internal construction of sentences from syllables with both imagined and perceived poems and further revealed shared and distinct cohorts of cortical areas corresponding to the sentence-level rhythm in imagery and perception. This study supports the view of a common mechanism between imagery and perception by illustrating the neural representations of higher-order rhythmic structures embedded in imagined and perceived speech.The α-tocopherol-derived long-chain metabolite (α-LCM) α-13'-carboxychromanol (α-13'-COOH) is formed via enzymatic degradation of α-tocopherol (α-TOH) in the liver. In the last decade, α-13'-COOH has emerged as a new regulatory metabolite revealing more potent or even different effects compared with its vitamin precursor α-TOH. The detection of α-13'-COOH in human serum has further strengthened the concept of its physiological relevance as a potential regulatory molecule. Here, we present a new facet on the interaction of α-13'-COOH with macrophage foam cell formation. We found that α-13'-COOH (5 μM) increases angiopoietin-like 4 (ANGPTL4) mRNA expression in human THP-1 macrophages in a time- and dose-dependent manner, while α-TOH (100 μM) showed no effects. Interestingly, the mRNA level of lipoprotein lipase (LPL) was not influenced by α-13'-COOH, but α-TOH treatment led to a reduction of LPL mRNA expression. Both compounds also revealed different effects on protein level while α-13'-COOH reduced the secreted amount of LPL protein via induction of ANGPTL4 cleavage, i.e. activation, the secreted amount of LPL in the α-TOH-treated samples was diminished due to the inhibition of mRNA expression. In line with this, both compounds reduced the catalytic activity of LPL. However, α-13'-COOH but not α-TOH attenuated VLDL-induced lipid accumulation by 35%. In conclusion, only α-13'-COOH revealed possible antiatherogenic effects due to the reduction of VLDL-induced foam cell formation in THP-1 macrophages. Our results provide further evidence for the role of α-13'-COOH as a functional metabolite of its vitamin E precursor.The rationale of spinal administration of endothelin-1(ET-1) mediated anti-nociceptive effect has not been elucidated. ET-1 is reported to promote nuclear effluxion of histone deacetylase 5 (HDAC5) in myocytes, and spinal HDAC5 is implicated in modulation of pain processing. In this study, we aimed to investigate whether central ET-1 plays an anti-nociceptive role by facilitating spinal HDAC5 nuclear shuttling under neuropathic pain. Here, we demonstrate that upregulating spinal ET-1 attenuated the nociception induced by partial sciatic nerve ligation surgery and this analgesic effect mediated by ET-1 was attenuated by intrathecal injection of endothelin A receptor selective inhibitor (BQ123) or by blocking the exportation of nuclear HDAC5 by adeno-associated viruses targeting neuronal HDAC5 (AVV-HDAC5 S259/498A Mutant). Notably, ET-1 administration increased spinal glutamate acid decarboxylases (GAD65/67) expression via initiating HDAC5 nuclear exportation and increased the acetylation of histone 3 at lysine 9 (Acetyl-H3K9) in the promotor regions of spinal Gad1 and Gad2 genes. This was reversed by blocking endothelin A receptor function or by inhibiting the spinal neuronal nuclear exportation of HDAC5. Therefore, inducing spinal GABAergic neuronal HDAC5 nuclear exportation may be a novel therapeutic approach for managing neuropathic pain. PERSPECTIVE Neuropathic pain is intractable in a clinical setting, and epigenetic regulation is considered to contribute to this processing. Characterizing the anti-nociceptive effect of ET-1 and investigating the associated epigenetic mechanisms in animal models may lead to the development of new therapeutic strategies and targets for treating neuropathic pain.Complex regional pain syndrome (CRPS) is a neuropathic pain condition that is difficult to treat. For behavioral interventions, graded motor imagery (GMI) showed relevant effects, but underlying neural substrates in patient groups have not been investigated yet. A previous study investigating differences in the representation of a left/right hand judgment task demonstrated less recruitment of subcortical structures, such as the putamen, in CRPS patients than in healthy controls. In healthy volunteers, the putamen activity increased after a hand judgment task training. In order to test for longitudinal effects of GMI training, we investigated 20 CRPS patients in a wait-list crossover design with 3 evaluation time points. Patients underwent a 6 week GMI treatment and a 6 week waiting period in a randomized group assignment and treatment groups were evaluated by a blinded rater. When compared to healthy matched controls at baseline, CRPS patients showed less functional activation in areas processing visual input, left sensorimotor cortex, and right putamen. Only GMI treatment, but not the waiting period showed an effect on movement pain and hand judgment task performance. Regression analyses revealed positive associations of movement pain with left anterior insula activation at baseline. Right intraparietal sulcus activation change during GMI was associated with a gain in performance of the hand judgment task. The design used here is reliable for investigating the functional representation of the hand judgment task in an intervention study. PERSPECTIVE Twenty chronic CRPS patients underwent a 6 week GMI intervention in a randomized wait-list crossover design. functional MRI was tested pre and post for the hand lateralization task which improved over GMI but not over WAITING. Performance gain was positively related to right parietal functional MRI activation.Fibromyalgia syndrome (FMS) is a chronic widespread pain condition of unknown aetiology. The role of temperature in FMS pain has not been reviewed systematically. The goal of this study was to review the influences of temperature on pain in FMS, from meteorological and quantitative sensory testing (QST) studies. The review was registered with Prospero ID-CRD42020167687, and followed PRISMA guidance. Databases interrogated were MEDLINE (via OVID), EMBASE, PubMed, Web of Science, ScienceDirect, CINAHL, and ProQuest (Feb'20). Exclusion criteria were age less then 18, animal studies, non-English, and noncontrolled articles. Thirteen studies pertaining to ambient temperature and FMS pain were identified; 9 of these found no uniform relationship. Thirty-five QST studies were identified, 17 of which assessed cold pain thresholds (CPTs). All studies showed numerically reduced CPTs in patients, ranging from 10.9°C to 26.3°C versus 5.9°C to 13.5°C in controls; this was statistically significant in 14/17. Other thermal thresholds were often abnormal. We conclude that the literature provides consistent evidence for an abnormal sensitization of FMS patients' temperature-sensation systems. Additional work is required to elucidate the factors that determine why a subgroup of patients perceive low ambient temperatures as painful, and to characterize that group. PERSPECTIVE Patients often report increased pain with changes in ambient temperature; even disabling, extreme temperature sensitivity in winter. read more Understanding this phenomenon may help clinicians provide reassurance and advice to patients and may guide research into the everyday impact of such hypersensitivity, whilst directing future work into the pathophysiology of FMS.Superoxide produced by mitochondria has been implicated in numerous physiologies and pathologies. Eleven different mitochondrial sites that can produce superoxide and/or hydrogen peroxide (O2.-/H2O2) have been identified in vitro, but little is known about their contributions in vivo. We introduce novel variants of S1QELs and S3QELs (small molecules that suppress O2.-/H2O2 production specifically from mitochondrial sites IQ and IIIQo, respectively, without compromising bioenergetics), that are suitable for use in vivo. When administered by intraperitoneal injection, they achieve total tissue concentrations exceeding those that are effective in vitro. We use them to study the engagement of sites IQ and IIIQo in mice lacking functional manganese-superoxide dismutase (SOD2). Lack of SOD2 is expected to elevate superoxide levels in the mitochondrial matrix, and leads to severe pathologies and death about 8 days after birth. Compared to littermate wild-type mice, 6-day-old Sod2-/- mice had significantly lower bodyn Sod2-/- mice.Cardiovascular disease (CVD) continues to be the number one killer in the aging population. Heart failure (HF) is also an important cause of morbidity and mortality in patients with congenital heart disease (CHD). Novel therapeutic approaches that could restore stable heart function are much needed in both paediatric and adult patients. Regenerative medicine holds promises to provide definitive solutions for correction of congenital and acquired cardiac defects. In this review article, we recap some important aspects of cardiovascular cell therapy. First, we report quantifiable data regarding the scientific advancements in the field and how this has been translated into tangible outcomes according clinical studies and related meta-analyses. We then comment on emerging trends and technologies, such as the use of second-generation cell products, including pericyte-like vascular progenitors, and reprogramming of cells by different approaches including modulation of oxidative stress. The more affordable and feasible strategy of repurposing clinically available drugs to awaken the intrinsic healing potential of the heart will be discussed in the light of current social, financial, and ethical context.
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