Computational analysis reveals increased blood deposition following repeated mild traumatic brain injury.

Mild traumatic brain injury (mTBI) has become an increasing public health concern as subsequent injuries can exacerbate existing neuropathology and result in neurological deficits. This study investigated the temporal development of cortical lesions using magnetic resonance imaging (MRI) to assess two mTBIs delivered to opposite cortical hemispheres. The controlled cortical impact model was used to produce an initial mTBI on the right cortex followed by a second injury induced on the left cortex at 3 (rmTBI 3d) or 7 (rmTBI 7d) days later. Histogram analysis was combined with a novel semi-automated computational approach to perform a voxel-wise examination of extravascular blood and edema volumes within the lesion. Examination of lesion volume 1d post last injury revealed increased tissue abnormalities within rmTBI 7d animals compared to other groups, particularly at the site of the second impact. Histogram analysis of lesion T2 values suggested increased edematous tissue within the rmTBI 3d group and elevated blood deposition in the rm TBI 7d animals. Further quantification of lesion composition for blood and edema containing voxels supported our histogram findings, with increased edema at the site of second impact in rmTBI 3d animals and elevated blood deposition in the rmTBI 7d group at the site of the first injury. Histological measurements revealed spatial overlap of regions containing blood deposition and microglial activation within the cortices of all animals. In conclusion, our findings suggest that there is a window of tissue vulnerability where a second distant mTBI, induced 7d after an initial injury, exacerbates tissue abnormalities consistent with hemorrhagic progression

Queue-Based Random-Access Algorithms: Fluid Limits and Stability Issues

We use fluid limits to explore the (in)stability properties of wireless networks with queue-based random-access algorithms. Queue-based random-access schemes are simple and inherently distributed in nature, yet provide the capability to match the optimal throughput performance of centralized scheduling mechanisms in a wide range of scenarios. Unfortunately, the type of activation rules for which throughput optimality has been established, may result in excessive queue lengths and delays. The use of more aggressive/persistent access schemes can improve the delay performance, but does not offer any universal maximum-stability guarantees. In order to gain qualitative insight and investigate the (in)stability properties of more aggressive/persistent activation rules, we examine fluid limits where the dynamics are scaled in space and time. In some situations, the fluid limits have smooth deterministic features and maximum stability is maintained, while in other scenarios they exhibit random oscillatory characteristics, giving rise to major technical challenges. In the latter regime, more aggressive access schemes continue to provide maximum stability in some networks, but may cause instability in others. Simulation experiments are conducted to illustrate and validate the analytical results

Identification of N-benzyltetrahydroisoquinolines as novel anti-neuroinflammatory agents

A series of simplified berberine analogs was designed, synthesized, and evaluated for anti-inflammatory activity. SAR studies identified N-benzyltetrahydroisoquinoline 7d as a potent berberine analog. 7d suppressed LPS-induced inflammatory cytokine levels in both BV2 cells and primary microglia. Taken together, our results suggest that simplified BB analogs have therapeutic potential as a novel class of anti-neuroinflammatory agents

Effect of thermal treatments on optical properties of bis-acryl resins

Tese de mestrado, Medicina Dentária, Universidade de Lisboa, Faculdade de Medicina Dentária, 2018Aim: The purpose of this study was to evaluate the effect of various thermal treatments on the chromatic stability of two bis-acrylic resins, after 24h and 7d. Materials and Methods: Ten experimental groups (n=10) were set according to the several possible combinations between the bis-acrylic resin (Protemp 4, P4; Structur 3, S3) and post-polymerization thermal treatment (without any post-polymerization treatment, nt; post-polymerization in a water bath at 60°C for 5 minutes, wb5; microwave at 750W for 1 minute, mw1; water bath at 60°C for 1 minute, wb1; conventional hairdryer for 1 minute, hd1). Thirty minutes after the polymerization, the baseline color values were measured, and all the specimens were immersed in the staining solution (coffee). After 24h and 7d new measurements were taken and ΔE calculated. A ΔE higher than 3.7 was considered clinically unacceptable. After confirming the normality and homogeneity of the data with Shapiro-Wilk and Levene’s testes (p>0.05), the ΔE data were submitted to a 2-way ANOVA, followed by 1-way ANOVA and Tukey post-hoc tests for each material (α=0.05). Results: The ΔE ranged between 5.9 and 13.0, at 24h, and between 9.1 and 24.7, after 7d. The ΔE was statistically (p0.05) ΔE than nt group. At 7d, no differences were found between S3 groups. In the P4 specimens, the wb5 showed a lower ΔE than nt, and only the wb1 and the hd1 obtained a ΔE higher than nt. Conclusion: Both, bis-acrylic resin and post-polymerization treatments, influence the ΔE, at 24h and 7d

The impact of dark exposure on the feeding behaviour, production, and gastrointestinal tract segment and content weights of broiler chickens

Broiler feeding behaviour was observed at two ages to quantify how varying durations of darkness alter behaviour and impact productivity and alterations in the gastrointestinal tract (GIT) over 24 h. The impact of dark exposure on productivity, GIT segment and content weights and feeding behaviour of Ross 308 broilers (7-31d) was studied. Four lighting programs were used (23L:1D (1D), 20L:4D (4D), 17L:7D (7D), and 14L:10D (10D). The birds (n=4000) were housed in 8 rooms with 8 pens per room (2 replications per lighting treatment and 4 replications per gender per room). The GIT data were collected on d 27-28 (6 males per lighting program, euthanized at 2 h intervals for 24 h). Production data were analyzed using SAS Proc Mixed as a 4 (dark) x 2 (gender) factorial arrangement and GIT segment data as a 4 (dark) x 12 (time) factorial arrangement, with lighting program nested within room. Dark data were analyzed using regression analyses and analysis of variance. Differences were significant when P≤0.05. At 31 d, regression analyses showed no effect on body weight, however numerically birds raised on 4D and 7D were heaviest. The highest feed consumption was observed under 4D. Birds on 10D were the most feed efficient (linear response). A quadratic effect on mortality was found, with the highest mortalities under 4D and 7D. Birds on 10D had the heaviest empty crops (% of body weight (BW). Crop content (% BW) changed quadratically, with peaks prior to dark under 4D, 7D, and 10D, suggesting anticipation of darkness. The empty gizzard weight (% BW) increased linearly as dark increased. Behaviour was examined as a 4 (dark) x 2 (age (2, 4 wk) x 2 (gender) factorial arrangement with lighting program nested within room. Five males and females per room were marked and focally observed. Statistical analyses were performed similar to the production data. As dark increased, feeding bout frequency increased and feeding bout interval decreased linearly. Total time spent at the feeder decreased linearly as dark increased. As birds aged, feeding frequency decreased and feed bout length and interval increased. Males visited the feeder more frequently and had shorter bout intervals. Birds anticipated dark periods >4 h and increased their feeding activity prior to dark. Broilers adapt their feeding behaviour in response to dark exposure, which alters GIT segment and content weights, and likely feed passage rates, in turn affecting feed efficiency and digestibility

A shared neural ensemble links distinct contextual memories encoded close in time.

Recent studies suggest that a shared neural ensemble may link distinct memories encoded close in time. According to the memory allocation hypothesis, learning triggers a temporary increase in neuronal excitability that biases the representation of a subsequent memory to the neuronal ensemble encoding the first memory, such that recall of one memory increases the likelihood of recalling the other memory. Here we show in mice that the overlap between the hippocampal CA1 ensembles activated by two distinct contexts acquired within a day is higher than when they are separated by a week. Several findings indicate that this overlap of neuronal ensembles links two contextual memories. First, fear paired with one context is transferred to a neutral context when the two contexts are acquired within a day but not across a week. Second, the first memory strengthens the second memory within a day but not across a week. Older mice, known to have lower CA1 excitability, do not show the overlap between ensembles, the transfer of fear between contexts, or the strengthening of the second memory. Finally, in aged mice, increasing cellular excitability and activating a common ensemble of CA1 neurons during two distinct context exposures rescued the deficit in linking memories. Taken together, these findings demonstrate that contextual memories encoded close in time are linked by directing storage into overlapping ensembles. Alteration of these processes by ageing could affect the temporal structure of memories, thus impairing efficient recall of related information

let-7 microRNAs regulate microglial function and suppress glioma growth through Toll-like receptor 7

Microglia express Toll-like receptors (TLRs) that sense pathogen- and host-derived factors, including single-stranded RNA. In the brain, let-7 microRNA (miRNA) family members are abundantly expressed, and some have recently been shown to serve as TLR7 ligands. We investigated whether let-7 miRNA family members differentially control microglia biology in health and disease. We found that a subset of let-7 miRNA family members function as signaling molecules to induce microglial release of inflammatory cytokines, modulate antigen presentation, and attenuate cell migration in a TLR7-dependent manner. The capability of the let-7 miRNAs to control microglial function is sequence specific, mapping to a let-7 UUGU motif. In human and murine glioblastoma/glioma, let-7 miRNAs are differentially expressed and reduce murine GL261 glioma growth in the same sequence-specific fashion through microglial TLR7. Taken together, these data establish let-7 miRNAs as key TLR7 signaling activators that serve to regulate the diverse functions of microglia in health and glioma