Donahuecurran1060

Diabetic ketoacidosis (DKA) has been associated with cognitive impairment and structural alterations in the brain. There is increased evidence supporting the role of neuroinflammation in causing these alterations. In the present study, using human microglial cell line (CHME-5), we aimed to investigate the effect of immunoglobulins (IG) on survival, activation, reactive oxygen species (ROS) and cytokine production of microglia exposed to ketone bodies. We demonstrated that high and low dose of ketone bodies induced a significant increase in ROS within 1 h after exposure to CHME-5 cells with upregulation in mitochondrial superoxide level 5 min after exposure suggestive of early and selective impairment of mitochondrial function. A significant and delayed increase of apoptosis of CHME-5 cells was observed 4 days after ketone bodies exposure. Cytokine expression reached a peak within 1 h and persisted for 3 days after exposure to ketone bodies. IG significantly reduced ROS and transiently suppressed cytokine expression of CHME-5 cells after exposure to ketone bodies. However, no effect of IG on apoptosis was observed. Overall, these results supported that ketone bodies induced microglia activation with early and selective impairment of mitochondrial function, increased cytokines expression and delayed increase in apoptosis. BzATP triethylammonium order IG suppressed microglia activation and transiently inhibited cytokines expression without affecting apoptosis. These results warrant further experimental work on the role of microglia and potential benefit of IG in brain structural changes induced by DKA.Mild traumatic brain injury (mTBI) in early childhood is prevalent, and some children may be at risk for short- and long-term difficulties that could affect quality of life (QoL). Despite growing efforts to understand associations between potential risk factors and outcomes after injury, prognosis is elusive and lacks the inclusion of genetic variables which may convey additional predictive power. This study assessed which factors contribute to pediatric QoL 6 and 18 months post-recruitment in 159 participants (mTBI = 52; orthopedic injury [OI] = 43; typically developing controls [TDC] = 64) aged 18 to 60 months at the time of injury (M = 37.50, SD = 11.69). Family environment, injury characteristics, and child cognitive-behavioral functioning were assessed at 6 months via parent questionnaires and socio-cognitive assessment. QoL was determined using the Pediatric Quality of Life Inventory at both time points. Genetic information (Brain-derived neurotrophic factor [BDNF] genotype) was collected using saliva samples. Hierarchical regression analyses testing biological, family-environmental, injury and cognitive-behavioral factors revealed that the BDNF Val66Met polymorphism was a significant independent predictor of better QoL 6 months post-injury in the mTBI group. Lower parental distress significantly and independently predicted higher QoL 18 months after mTBI, and 6 months post-recruitment in the TDC group. At 18 months, models were non-significant for both control groups. Genetic factors involved in neuroplasticity may play an important role in recovery 6 months after mTBI and contribute to outcome via their interplay with environmental factors. Over time, family factors appear to become the primary determinants of post-mTBI outcome.This study examines how across-trial (average) and trial-by-trial (variability in) amplitude and latency of the N400 event-related potential (ERP) reflect temporal integration of pitch accent and beat gesture. Thirty native English speakers viewed videos of a talker producing sentences with beat gesture co-occurring with a pitch accented focus word (synchronous), beat gesture co-occurring with the onset of a subsequent non-focused word (asynchronous), or the absence of beat gesture (no beat). Across trials, increased amplitude and earlier latency were observed when beat gesture was temporally asynchronous with pitch accenting than when it was temporally synchronous with pitch accenting or absent. Moreover, temporal asynchrony of beat gesture relative to pitch accent increased trial-by-trial variability of N400 amplitude and latency and influenced the relationship between across-trial and trial-by-trial N400 latency. These results indicate that across-trial and trial-by-trial amplitude and latency of the N400 ERP reflect temporal integration of beat gesture and pitch accent during language comprehension, supporting extension of the integrated systems hypothesis of gesture-speech processing and neural noise theories to focus processing in typical adult populations.We investigated the effect of mild traumatic brain injury (mTBI) on the glymphatic pathway using contrast-enhanced magnetic resonance imaging (CE-MRI) and quantified with kinetic parameters obtained from an advanced two-compartment model. mTBI was induced in male Wistar rats using a closed head impact. Animals with and without mTBI (n = 7/group) underwent the identical MRI protocol 10-weeks post-injury, including T2-weighted imaging and 3D T1-weighted imaging with intra-cisterna magna injection of contrast agent (Gd-DTPA). The parameters of infusion rate, clearance rate and clearance time constant, characterizing the kinetic features of glymphatic tracer transport in a living brain, were quantified in multiple brain tissue regions. In the majority of examined regions, our quantification demonstrated significantly reduced infusion and clearance rates, and significantly increased clearance time constant in the mTBI animals compared to the healthy controls. These data indicate that mTBI induces chronic changes in influx and efflux of contrast agent and glymphatic pathway dysfunction. While the reduced efficiency of glymphatic function after mTBI was apparent in brain, regional evaluation revealed heterogeneous glymphatic effects of the mTBI in different anatomical regions. The suppression of glymphatic function, rather than the presence of focal lesions, indicates a persistent injury of the brain after mTBI. Thus, dynamic CE-MRI in conjunction with advanced kinetic analysis may offer a useful methodology for an objective assessment and confirmatory diagnosis of mTBI.

Despite the clinical effectiveness of transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS), the comparability of these interventions in neurophysiological aspects have not been thoroughly investigated. Thus, we aimed to directly compare the electrophysiological effects of single-session tDCS and gamma-tACS in healthy subjects, matching the intervention protocol as closely as possible.

This was a randomized, double-blinded, and active-controlled study. Sixty healthy college students were enrolled in the study. Both tACS with, at 40Hz frequency, and tDCS have the same current intensity (2mA, 30min) within the same target area (right and left dorsolateral prefrontal cortex). Resting-state electroencephalography (EEG) was recorded before and after single-session stimulation.

Significant differences in theta, alpha, low-beta, and gamma frequencies were found between tDCS, tACS, and the sham groups. Low-beta source activity of the middle temporal gyrus was deced light on their potential clinical benefits and distinctive neuropathology in various clinical symptoms.

. The goal of the study was to test the effects of photobiomodulation therapy (PBMT) and intra-spinal injection of chondroitinase ABC (chABC) both alone and combined on pain induced by spinal cord injury (SCI) in rats.

SCI was induced by compression using an aneurysm clip. PBMT used a 660 nm laser starting at 30 minutes after SCI and then daily for 2 week, and at the end of 1-week ChABC was injected into the spinal cord. Allodynia (mechanical and cold), hyperalgesia (mechanical and thermal) and functional recovery were measured. Molecular levels of IL6, BDNF, GDNF and Gad65 were evaluated.

. Both ChABC, PBMT and the combination reduced allodynia and thermal hyperalgesia and improved functional recovery, but did not reduce mechanical hyperalgesia. Pain-related factors (BDNF and IL6) were decreased and anti-nociceptive factors (Gad65 and GDNF) were increased.

. Treatment of SCI by PBM is a non-invasive technique, and could be improved by ChABC injection to reduce neuropathic pain and improve movement.

. Treatment of SCI by PBM is a non-invasive technique, and could be improved by ChABC injection to reduce neuropathic pain and improve movement.During a range expansion, deleterious mutations can "surf" on the colonization front. The resultant decrease in fitness is known as expansion load. An Allee effect is known to reduce the loss of genetic diversity of expanding populations, by changing the nature of the expansion from "pulled" to "pushed". We study the impact of an Allee effect on the formation of an expansion load with a new model, in which individuals have the genetic structure of a Muller's ratchet. A key feature of Muller's ratchet is that the population fatally accumulates deleterious mutations due to the stochastic loss of the fittest individuals, an event called a click of the ratchet. We observe fast clicks of the ratchet at the colonization front owing to small population size, followed by a slow fitness recovery due to migration of fit individuals from the bulk of the population, leading to a transient expansion load. For large population size, we are able to derive quantitative features of the expansion wave, such as the wave speed and the frequency of individuals carrying a given number of mutations. Using simulations, we show that the presence of an Allee effect reduces the rate at which clicks occur at the front, and thus reduces the expansion load.An inverse relationship between bone marrow (BM) adiposity and bone mass has been described in different physiological and pathological conditions, including osteoporosis (OP). In osteoporotic patients, lower bone mass density is indeed associated with higher BM fat content, suggesting a potential role for bone lipids in the OP pathogenesis. Nevertheless, some questions remain. Is that BM adiposity a cause or a consequence of the bone loss? What kinds of lipids are involved? Human data are somehow contradictories regarding bone lipid signature related to OP, and animal data are needed to support on one or another way the human observations. Bone lipid signature associated to OP needs to be clarified if we want to understand better their roles in OP. In that context, by using an ovariectomy-induced OP murine model and looking at lipids in two bone compartments BM and mineralized tissue (MT), our first challenge was to identify local lipid changes in relation to OP, in view to explore later the mechanisms by which those compounds could alter bone quality, particularly during the mineralization process. As the most striking data, long-term OP resulted in an accumulation of triglycerides, reduced levels of arachidonic and docosahexaenoic acids, an increase of stearoyl-CoA desaturase indices and a reduction of sphingomyelin in the MT, and potential consequences on bone properties and cell activities are discussed. The reader will appreciate that we are at an early stage of understanding the roles of lipids in the OP development and more investigations will be necessary.