Treg cell-derived osteopontin promotes microglia-mediated white matter repair after ischemic stroke.

The precise mechanisms underlying the beneficial effects of regulatory T (Treg) cells on long-term tissue repair remain elusive. Here, using single-cell RNA sequencing and flow cytometry, we found that Treg cells infiltrated the brain 1 to 5 weeks after experimental stroke in mice. Selective depletion of Treg cells diminished oligodendrogenesis, white matter repair, and functional recovery after stroke. Transcriptomic analyses revealed potent immunomodulatory effects of brain-infiltrating Treg cells on other immune cells, including monocyte-lineage cells. Microglia depletion, but not T cell lymphopenia, mitigated the beneficial effects of transferred Treg cells on white matter regeneration. Mechanistically, Treg cell-derived osteopontin acted through integrin receptors on microglia to enhance microglial reparative activity, consequently promoting oligodendrogenesis and white matter repair. Increasing Treg cell numbers by delivering IL-2:IL-2 antibody complexes after stroke improved white matter integrity and rescued neurological functions over the long term. These findings reveal Treg cells as a neurorestorative target for stroke recovery.

The area rule for circulation in three-dimensional turbulence.

An important idea underlying a plausible dynamical theory of circulation in three-dimensional turbulence is the so-called area rule, according to which the probability density function (PDF) of the circulation around closed loops depends only on the minimal area of the loop, not its shape. We assess the robustness of the area rule, for both planar and nonplanar loops, using high-resolution data from direct numerical simulations. For planar loops, the circulation moments for rectangular shapes match those for the square with only small differences, these differences being larger when the aspect ratio is farther from unity and when the moment order increases. The differences do not exceed about 5% for any condition examined here. The aspect ratio dependence observed for the second-order moment is indistinguishable from results for the Gaussian random field (GRF) with the same two-point correlation function (for which the results are order-independent by construction). When normalized by the SD of the PDF, the aspect ratio dependence is even smaller ( < 2%) but does not vanish unlike for the GRF. We obtain circulation statistics around minimal area loops in three dimensions and compare them to those of a planar loop circumscribing equivalent areas, and we find that circulation statistics match in the two cases only when normalized by an internal variable such as the SD. This work highlights the hitherto unknown connection between minimal surfaces and turbulence.

Bedside tracking of functional autonomic age in preterm infants.

BACKGROUND: Preterm birth predisposes infants to adverse outcomes that, without early intervention, impacts their long-term health. To assist bedside monitoring, we developed a tool to track the autonomic maturation of the preterm by assessing heart rate variability (HRV) changes during intensive care. METHODS: Electrocardiogram (ECG) recordings were longitudinally recorded in 67 infants (26-38 weeks postmenstrual age (PMA)). Supervised machine learning was used to generate a functional autonomic age (FAA), by combining 50 computed HRV features from successive 5-minute ECG epochs (median of 23 epochs per infant). Performance of the FAA was assessed by correlation to PMA, clinical outcomes and the infant's functional brain age (FBA), an index of maturation derived from the electroencephalogram. RESULTS: The FAA was strongly correlated to PMA (r = 0.86, 95% CI: 0.83-0.93) with a mean absolute error (MAE) of 1.66 weeks and also accurately estimated FBA (MAE = 1.58 weeks, n = 54 infants). The relationship between PMA and FAA was not confounded by neurodevelopmental outcome (p = 0.18, n = 45), sex (p = 0.88, n = 56), patent ductus arteriosus (p = 0.08, n = 56), IVH (p = 0.63, n = 56) or body weight at birth (p = 0.95, n = 56). CONCLUSIONS: The FAA, an index derived from the ubiquitous ECG signal, offers direct avenues towards estimating autonomic maturation at the bedside during intensive care monitoring. IMPACT: The development of a tool to track functional autonomic age in preterm infants based on heart rate variability features in the electrocardiogram provides a rapid and specialized view of autonomic maturation at the bedside. Functional autonomic age is linked closely to postmenstrual age and central nervous system function response, as determined by its relationship to functional brain age from the electroencephalogram. Tracking functional autonomic age during neonatal intensive care unit monitoring offers a unique insight into cardiovascular health in infants born extremely preterm and their maturational trajectories to term age.

Classical 1/3 scaling of convection holds up to Ra = 1015.

The global transport of heat and momentum in turbulent convection is constrained by thin thermal and viscous boundary layers at the heated and cooled boundaries of the system. This bottleneck is thought to be lifted once the boundary layers themselves become fully turbulent at very high values of the Rayleigh number [Formula: see text]-the dimensionless parameter that describes the vigor of convective turbulence. Laboratory experiments in cylindrical cells for [Formula: see text] have reported different outcomes on the putative heat transport law. Here we show, by direct numerical simulations of three-dimensional turbulent Rayleigh-Bénard convection flows in a slender cylindrical cell of aspect ratio [Formula: see text], that the Nusselt number-the dimensionless measure of heat transport-follows the classical power law of [Formula: see text] up to [Formula: see text] Intermittent fluctuations in the wall stress, a blueprint of turbulence in the vicinity of the boundaries, manifest at all [Formula: see text] considered here, increasing with increasing [Formula: see text], and suggest that an abrupt transition of the boundary layer to turbulence does not take place.

Microbiota links to neural dynamics supporting threat processing.

There is growing recognition that the composition of the gut microbiota influences behaviour, including responses to threat. The cognitive-interoceptive appraisal of threat-related stimuli relies on dynamic neural computations between the anterior insular (AIC) and the dorsal anterior cingulate (dACC) cortices. If, to what extent, and how microbial consortia influence the activity of this cortical threat processing circuitry is unclear. We addressed this question by combining a threat processing task, neuroimaging, 16S rRNA profiling and computational modelling in healthy participants. Results showed interactions between high-level ecological indices with threat-related AIC-dACC neural dynamics. At finer taxonomic resolutions, the abundance of Ruminococcus was differentially linked to connectivity between, and activity within the AIC and dACC during threat updating. Functional inference analysis provides a strong rationale to motivate future investigations of microbiota-derived metabolites in the observed relationship with threat-related brain processes.

Reliable induction of sleep spindles with intracranial electrical pulse stimulation.

Neocortical sleep spindles have been shown to occur more frequently following a memory task, suggesting that a method to increase spindle activity could improve memory processing. Stimulation of the neocortex can elicit a slow oscillation (SO) and a spindle, but the feasibility of this method to boost SO and spindles over time has not been tested. In rats with implanted neocortical electrodes, stimulation during slow wave sleep significantly increased SO and spindle rates compared to control rest periods before and after the stimulation session. Coordination between hippocampal sharp-wave ripples and spindles also increased. These effects were reproducible across five consecutive days of testing, demonstrating the viability of this method to increase SO and spindles.

Corticostriatal Regulation of Language Functions.

The role of corticostriatal circuits in language functions is unclear. In this review, we consider evidence from language learning, syntax, and controlled language production and comprehension tasks that implicate various corticostriatal circuits. Converging evidence from neuroimaging in healthy individuals, studies in populations with subcortical dysfunction, pharmacological studies, and brain stimulation suggests a domain-general regulatory role of corticostriatal systems in language operations. The role of corticostriatal systems in language operations identified in this review is likely to reflect a broader function of the striatum in responding to uncertainty and conflict which demands selection, sequencing, and cognitive control. We argue that this role is dynamic and varies depending on the degree and form of cognitive control required, which in turn will recruit particular corticostriatal circuits and components organised in a cognitive hierarchy.

Oscillations Modulating Power Law Exponents in Isotropic Turbulence: Comparison of Experiments with Simulations.

Inertial-range features of turbulence are investigated using data from experimental measurements of grid turbulence and direct numerical simulations of isotropic turbulence simulated in a periodic box, both at the Taylor-scale Reynolds number R_{λ}∼1000. In particular, oscillations modulating the power-law scaling in the inertial range are examined for structure functions up to sixth-order moments. The oscillations in exponent ratios decrease with increasing sample size in simulations, although in experiments they survive at a low value of 4 parts in 1000 even after massive averaging. The two datasets are consistent in their intermittent character but differ in small but observable respects. Neither the scaling exponents themselves nor all the viscous effects are consistently reproduced by existing models of intermittency.

Modulating functional connectivity with non-invasive brain stimulation for the investigation and alleviation of age-associated declines in response inhibition: A narrative review.

Response inhibition, the ability to withhold a dominant and prepotent response following a change in circumstance or sensory stimuli, declines with advancing age. While non-invasive brain stimulation (NiBS) has shown promise in alleviating some cognitive and motor functions in healthy older individuals, NiBS research focusing on response inhibition has mostly been conducted on younger adults. These extant studies have primarily focused on modulating the activity of distinct neural regions known to be critical for response inhibition, including the right inferior frontal gyrus (rIFG) and the pre-supplementary motor area (pre-SMA). However, given that changes in structural and functional connectivity have been associated with healthy aging, this review proposes that NiBS protocols aimed at modulating the functional connectivity between the rIFG and pre-SMA may be the most efficacious approach to investigate-and perhaps even alleviate-age-related deficits in inhibitory control.

Self-Similar Subgrid-Scale Models for Inertial Range Turbulence and Accurate Measurements of Intermittency.

A class of spectral subgrid models based on a self-similar and reversible closure is studied with the aim to minimize the impact of subgrid scales on the inertial range of fully developed turbulence. In this manner, we improve the scale extension where anomalous exponents are measured by roughly 1 order of magnitude when compared to direct numerical simulations or to other popular subgrid closures at the same resolution. We find a first indication that intermittency for high-order moments is not captured by many of the popular phenomenological models developed so far.

Steep Cliffs and Saturated Exponents in Three-Dimensional Scalar Turbulence.

The intermittency of a passive scalar advected by three-dimensional Navier-Stokes turbulence at a Taylor-scale Reynolds number of 650 is studied using direct numerical simulations on a 4096^{3} grid; the Schmidt number is unity. By measuring scalar increment moments of high orders, while ensuring statistical convergence, we provide unambiguous evidence that the scaling exponents saturate to 1.2 for moment orders beyond about 12, indicating that scalar intermittency is dominated by the most singular shocklike cliffs in the scalar field. We show that the fractal dimension of the spatial support of steep cliffs is about 1.8, whose sum with the saturation exponent value of 1.2 adds up to the space dimension of 3, thus demonstrating a deep connection between the geometry and statistics in turbulent scalar mixing. The anomaly for the fourth and sixth order moments is comparable to that in the Kraichnan model for the roughness exponent of 4/3.

Effective assessments of electroencephalography during stroke recovery: contemporary approaches and considerations.

Stroke is one of the leading causes of permanent disability worldwide, relying conventionally on extended periods of physiotherapy to recover functional ability. While neuroimaging techniques and emerging neurorehabilitation paradigms have advanced our understanding of pathophysiological mechanisms underlying stroke, recent evidence has renewed focus on quantifying features of cortical activity present in electroencephalography recordings to greatly enhance our understanding of stroke treatment and recovery. This Neuro Forum article reviews these key advances and discusses the importance of quantifying electroencephalography in future assessments of stroke survivors.

Cortical burst dynamics predict clinical outcome early in extremely preterm infants.

Intermittent bursts of electrical activity are a ubiquitous signature of very early brain activity. Previous studies have largely focused on assessing the amplitudes of these transient cortical bursts or the intervals between them. Recent advances in basic neuroscience have identified the presence of scale-free 'avalanche' processes in bursting patterns of cortical activity in other clinical contexts. Here, we hypothesize that cortical bursts in human preterm infants also exhibit scale-free properties, providing new insights into the nature, temporal evolution, and prognostic value of spontaneous brain activity in the days immediately following preterm birth. We examined electroencephalographic recordings from 43 extremely preterm infants (gestational age 22-28 weeks) and demonstrated that their cortical bursts exhibit scale-free properties as early as 12 h after birth. The scaling relationships of cortical bursts correlate significantly with later mental development-particularly within the first 12 h of life. These findings show that early preterm brain activity is characterized by scale-free dynamics which carry developmental significance, hence offering novel means for rapid and early clinical prediction of neurodevelopmental outcomes.

Spin-glass behavior and pyroelectric anomalies in a new lithium-based oxide, Li3FeRuO5.

The results of dc and ac magnetization, heat capacity, (57)Fe Mössbauer spectroscopy, dielectric, pyroelectric current and isothermal magneto-capacitance measurements of a recently reported lithium-rich layered oxide, Li3FeRuO5, related to LiCoO2-type (rhombohedral, space group R3[combining macron]m), are presented. The results reveal that the compound undergoes spin-glass freezing at 15 K. There is a peak around 34 K in pyroelectric data, which cannot be attributed to ferroelectricity, but to the phenomenon of thermally stimulated depolarization current. As revealed by magnetocapacitance data above and below the magnetic ordering temperature, magnetic and electric dipoles appear to be coupled, thereby offering evidence for magnetodielectric coupling.

Scale-free bursting in human cortex following hypoxia at birth.

The human brain is fragile in the face of oxygen deprivation. Even a brief interruption of metabolic supply at birth challenges an otherwise healthy neonatal cortex, leading to a cascade of homeostatic responses. During recovery from hypoxia, cortical activity exhibits a period of highly irregular electrical fluctuations known as burst suppression. Here we show that these bursts have fractal properties, with power-law scaling of burst sizes across a remarkable 5 orders of magnitude and a scale-free relationship between burst sizes and durations. Although burst waveforms vary greatly, their average shape converges to a simple form that is asymmetric at long time scales. Using a simple computational model, we argue that this asymmetry reflects activity-dependent changes in the excitatory-inhibitory balance of cortical neurons. Bursts become more symmetric following the resumption of normal activity, with a corresponding reorganization of burst scaling relationships. These findings place burst suppression in the broad class of scale-free physical processes termed crackling noise and suggest that the resumption of healthy activity reflects a fundamental reorganization in the relationship between neuronal activity and its underlying metabolic constraints.

Early Detection of Preterm Intraventricular Hemorrhage From Clinical Electroencephalography.

OBJECTIVES: Intraventricular hemorrhage is a common neurologic complication of extremely preterm birth and leads to lifelong neurodevelopmental disabilities. Early bedside detection of intraventricular hemorrhage is crucial to enabling timely interventions. We sought to detect early markers of brain activity that preempt the occurrence of intraventricular hemorrhage in extremely preterm infants during the first postnatal days. DESIGN: Cross-sectional study. SETTING: Level III neonatal ICU. PATIENTS: Twenty-five extremely preterm infants (22-28 wk gestational age). MEASUREMENTS AND MAIN RESULTS: We quantitatively assessed electroencephalography in the first 72 hours of postnatal life, focusing on the electrical burst activity of the preterm. Cranial ultrasound was performed on day 1 (0-24 hr) and day 3 (48-72 hr). Outcomes were categorized into three classes: 1) no intraventricular hemorrhage (grade 0); 2) mild-moderate intraventricular hemorrhage (grades 1-2, i.e., germinal matrix hemorrhages or intraventricular hemorrhage without ventricular dilatation, respectively); and 3) severe intraventricular hemorrhage (grades 3-4, i.e., intraventricular hemorrhage with ventricular dilatation or intraparenchymal involvement). Quantitative assessment of electroencephalography burst shapes was used to preempt the occurrence and severity of intraventricular hemorrhage as detected by ultrasound. The shapes of electroencephalography bursts found in the intraventricular hemorrhage infants were significantly sharper (F = 13.78; p < 0.0001) and less symmetric (F = 6.91; p < 0.015) than in preterm infants without intraventricular hemorrhage. Diagnostic discrimination of intraventricular hemorrhage infants using measures of burst symmetry and sharpness yielded high true-positive rates (82% and 88%, respectively) and low false-positive rates (19% and 8%). Conventional electroencephalography measures of interburst intervals and burst counts were not significantly associated with intraventricular hemorrhage. CONCLUSIONS: Detection of intraventricular hemorrhage during the first postnatal days is possible from bedside measures of brain activity prior to ultrasound confirmation of intraventricular hemorrhage. Significantly, our novel automated assessment of electroencephalography preempts the occurrence of intraventricular hemorrhage in the extremely preterm. Early bedside detection of intraventricular hemorrhage holds promise for advancing individual care, targeted therapeutic trials, and understanding mechanisms of brain injury in neonates.

Rotating turbulence under "precession-like" perturbation.

The effects of changing the orientation of the rotation axis on homogeneous turbulence is considered. We perform direct numerical simulations on a periodic box of 1024(3) grid points, where the orientation of the rotation axis is changed (a) at a fixed time instant (b) regularly at time intervals commensurate with the rotation time scale. The former is characterized by a dominant inverse energy cascade whereas in the latter, the inverse cascade is stymied due to the recurrent changes in the rotation axis resulting in a strong forward energy transfer and large-scale structures that resemble those of isotropic turbulence.

S.O.S. - Save our supplies: Understanding reasons to tackle the challenge of wasted returned blood products.

OBJECTIVES: To evaluate the return of blood components across different hospital areas, reasons for the same and suggest preventive strategies which might reduce out of controlled temperature storage (CTS) blood logistics and wastage. MATERIAL AND METHODS: A retrospective audit was carried out in the department of Transfusion Medicine from January 2019 to December 2022. Data related to returned blood components was compiled using departmental records and blood centre software entries. RESULTS: A total of 218 instances of returned components were noted and the total number of components returned were 442 (0.4% of all issued components) (38.4% (170) packed red blood cells, 16.2% (72) single donor cryoprecipitate concentrate, 19.6% (87) platelet concentrate and 25.5% (113) fresh frozen plasma). Components were returned back within 30 mins in only 27% (59/218) of all instances . Wards followed by high dependency units/intensive care units were noted to have the highest number of instances (86 (39.4%) and 69 (31.6%) respectively) with emergency department having the least,comprising 19 instances (8.7%). 77.9% (170/218) instances were observed for routine transfusion requests and 44.5% (97/218) of all instances could have been prevented by an appropriate clinical status assessment of the patient. CONCLUSION: Stakeholders such as clinicians, transfusion laboratory professional and nursing staff must take consolidated efforts to eliminate wastage of blood components. Instances of returned blood components can be targeted by the hospital quality team as a quality improvement project.

Attention Please! Unravelling the Link Between Brain Network Connectivity and Cognitive Attention Following Acquired Brain Injury: A Systematic Review of Structural and Functional Measures.

Traumatic brain injury (TBI) and stroke are the most common causes of acquired brain injury (ABI), annually affecting 69 million and 15 million people, respectively. Following ABI, the relationship between brain network disruption and common cognitive issues including attention dysfunction is heterogenous. Using PRISMA guidelines, we systematically reviewed 43 studies published by February 2023 that reported correlations between attention and connectivity. Across all ages and stages of recovery, following TBI, greater attention was associated with greater structural efficiency within/between executive control network (ECN), salience network (SN), and default mode network (DMN) and greater functional connectivity (fc) within/between ECN and DMN, indicating DMN interference. Following stroke, greater attention was associated with greater structural connectivity (sc) within ECN; or greater fc within the dorsal attention network (DAN). In childhood ABI populations, decreases in structural network segregation were associated with greater attention. Longitudinal recovery from TBI was associated with normalization of DMN activity, and in stroke, normalization of DMN and DAN activity. Results improve clinical understanding of attention-related connectivity changes after ABI. Recommendations for future research include increased use of electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) to measure connectivity at the point of care, standardized attention and connectivity outcome measures and analysis pipelines, detailed reporting of patient symptomatology, and casual analysis of attention-related connectivity using brain stimulation.