Ketone Metabolite β-Hydroxybutyrate Ameliorates Inflammation After Spinal Cord Injury by Inhibiting the NLRP3 Inflammasome

Neurochemical Research - Ketogenic diet (KD) has been shown to be beneficial in a range of neurological disorders, with ketone metabolite β-hydroxybutyrate (βOHB) reported to block the...     

Lithium Inhibits GSK3β Activity via Two Different Signaling Pathways in Neurons After Spinal Cord Injury

Spinal cord injury (SCI) is a type of long-term disability with a high morbidity rate in clinical settings for which there is no effective clinical treatment to date. Usually, lithium is used as a popular mood stabilizer. Recently, growing evidence has shown that lithium has clear neuroprotective effects after SCI, and the administration of lithium can effectively improve locomotor recovery. However, the exact neuroprotective mechanism of lithium is still not understood. Glycogen synthase kinase-3 beta (GSK3β) is a serine/threonine kinase that plays an important role in the neuroprotective effects of lithium both in vivo and in vitro. In this study, we discovered that lithium inhibits GSK3β activity through two different signaling pathways in spinal cord neurons. In the acute phase, lithium inhibited GSK3β activity by stimulating phosphorylation of AKT; in the chronic phase, we first discovered that lithium additionally upregulated the expression of Na⁺, K⁺-ATPase α1 (NKA α1), which had an inhibitory effect on GSK3β activity by inducing the expression of glucocorticoid inducible kinase 1 (SGK1). SGK1 is well known as a regulator of the GSK3β/β-catenin signaling pathway. Moreover, the suppressed activity of GSK3β increased the level of β-catenin in the cytoplasm, which gave rise to the translocation of the freely stabilized β-catenin to the nucleus. In addition, the accumulation of β-catenin in the nucleus had the benefits of neuronal survival. Hopefully our findings from this study are beneficial in revealing the neuroprotective mechanism of lithium and in offering novel targets for the development of new SCI therapeutic drugs.     

Does the Brain Detect 3G Mobile Phone Radiation Peaks? An Explorative In-Depth Analysis of an Experimental Study

This study aimed to investigate whether third generation mobile phone radiation peaks result in event related potentials. Thirty-one healthy females participated. In this single-blind, cross-over design, a 15 minute mobile phone exposure was compared to two 15 minute sham phone conditions, one preceding and one following the exposure condition. Each participant was measured on two separate days, where mobile phone placement was varied between the ear and heart. EEG activity and radiofrequency radiation were recorded jointly. Epochs of 1200ms, starting 200ms before and lasting until 1000ms after the onset of a radiation peak, were extracted from the exposure condition. Control epochs were randomly selected from the two sham phone conditions. The main a-priori hypothesis to be tested concerned an increase of the area in the 240-500ms post-stimulus interval, in the exposure session with ear-placement. Using multilevel regression analyses the placement*exposure interaction effect was significant for the frontal and central cortical regions, indicating that only in the mobile phone exposure with ear-placement an enlarged cortical reactivity was found. Post-hoc analyses based on visual inspection of the ERPs showed a second significantly increased area between 500-1000ms post-stimulus for almost every EEG location measured. It was concluded that, when a dialing mobile phone is placed on the ear, its radiation, although unconsciously, is electrically detected by the brain. The question of whether or not this cortical reactivity results in a negative health outcome has to be answered in future longitudinal experiments.     

Alternatively Activated Macrophages in Spinal Cord Injury and Remission: Another Mechanism for Repair?

Tissues within the central nervous system (CNS) have generally been regarded as immunologically privileged. However, in recent decades, it has been shown that immune reactions in the CNS continuously occur via various types of inflammation following autoimmune diseases and mechanical insults such as spinal cord injury (SCI). Among the various inflammatory cells associated with CNS disease, activated macrophages are classically known to induce detrimental consequences that are mediated by the secretion of pro-inflammatory molecules. Alternatively activated macrophages have recently been shown to modulate various types of CNS inflammation, including SCI. This review summarizes the potential roles of alternatively activated macrophages in the course of CNS inflammation in rodent SCI models.     

Are the 10 Meter and 6 Minute Walk Tests Redundant in Patients with Spinal Cord Injury?

Objective

To evaluate the relationship and redundancy between gait speeds measured by the 10 Meter Walk Test (10MWT) and 6 Minute Walk Test (6MWT) after motor incomplete spinal cord injury (iSCI). To identify gait speed thresholds supporting functional ambulation as measured with the Spinal Cord Injury Functional Ambulation Inventory (SCI-FAI).

Design

Prospective observational cohort.

Setting

Seven outpatient rehabilitation centers from the Christopher and Dana Reeve Foundation NeuroRecovery Network (NRN).

Participants

249 NRN patients with American Spinal Injury Association Impairment Scale (AIS) level C (n = 20), D (n = 179) and (n = 50) iSCI not AIS evaluated, from February 2008 through April 2011.

Interventions

Locomotor training using body weight support and walking on a treadmill, overground and home/community practice.

Main Outcome Measure(s)

10MWT and 6MWT collected at enrollment, approximately every 20 sessions, and upon discharge.

Results

The 10MWT and 6MWT speeds were highly correlated and the 10MWT speeds were generally faster. However, the predicted 6MWT gait speed from the 10MWT, revealed increasing error with increased gait speed. Regression lines remained significantly different from lines of agreement, when the group was divided into fast (≥0.44 m/s) and slow walkers (<0.44 m/s). Significant differences between 6MWT and 10MWT gait speeds were observed across SCI-FAI walking mobility categories (Wilcoxon sign rank test p<.001), and mean speed thresholds for limited community ambulation differed for each measure. The smallest real difference for the 6MWT and 10MWT, as well as the minimally clinically important difference (MCID) values, were also distinct for the two tests.

Conclusions

While the speeds were correlated between the 6MWT and 10MWT, redundancy in the tests using predictive modeling was not observed. Different speed thresholds and separate MCIDs were defined for community ambulation for each test.     

Preventive Role of Magnesium on Skeletal Muscle Ischemia–Reperfusion Injury—an Experimental Study

The present study aims to explore whether Mg infusion has a preventive effect on ischemia–reperfusion injury in rats. A total of 20 Sprague-Dawley-type adult male rats were used. In group 1 (control), 0.9% isotonic solution was administered. In group 2 (experiment), magnesium sulfate (0.5 mg per 100 g) was administered. Ischemia was induced for 15 min for the two groups. Magnesium (Mg), interleukin 8 (IL-8), and malondialdehyde levels were analyzed in blood, while edema, neutrophil infiltration, eosinophilia, loss of striation, and nucleolization were evaluated in histopathological examination. Mg levels in the experiment group were higher than those in the control group after ischemia–reperfusion (p < 0.05). In the control group, postischemia and postreperfusion IL-8 values were higher than preoperative values (p < 0.05). As for eosinophilia and loss of striation values, these were higher in the experiment group after ischemia–reperfusion than the values in the control group (p < 0.05). Histopathologically, Mg infusion cannot prevent the tissue injury triggered in ischemia–reperfusion periods. Eosinophilia can be one of the major and earliest markers of ischemia–reperfusion injury.     

Does Facilitation of Faunal Recruitment Benefit Ecosystem Restoration? An Experimental Study of Invertebrate Assemblages in Wetland Mesocosms

We used wetland mesocosms (1) to experimentally assess whether inoculating a restored wetland site with vegetation/sediment plugs from a natural wetland would alter the development of invertebrate communities relative to unaided controls and (2) to determine if stocking of a poor invertebrate colonizer could further modify community development beyond that due to simple inoculation. After filling mesocosms with soil from a drained and cultivated former wetland and restoring comparable hydrology, mesocosms were randomly assigned to one of three treatments: control (a reference for unaided community development), inoculated (received three vegetation/sediment cores from a natural wetland), and stocked + inoculated (received three cores and were stocked with a poorly dispersing invertebrate group—gastropods). All mesocosms were placed 100 m from a natural wetland and allowed to colonize for 82 days. Facilitation of invertebrate colonization led to communities in inoculated and stocked + inoculated treatments that contrasted strongly with those in the unaided control treatment. Control mesocosms had the highest taxa richness but the lowest diversity due to high densities and dominance of Tanytarsini (Diptera: Chironomidae). Community structure in inoculated and stocked + inoculated mesocosms was more similar to that of a nearby natural wetland, with abundance more evenly distributed among taxa, leading to diversity that was higher than in the control treatment. Inoculated and stocked + inoculated communities were dominated by non‐aerial invertebrates, whereas control mesocosms were dominated by aerial invertebrates. These results suggest that facilitation of invertebrate recruitment does indeed alter invertebrate community development and that facilitation may lead to a more natural community structure in less time under conditions simulating wetland restoration.     

Does Innovation Success Influence Social Interactions? An Experimental Test in House Sparrows

In group‐living animals, individuals may benefit from the presence of an innovative group‐mate because new resources made available by innovators can be exploited, for example by scrounging or social learning. As a consequence, it may pay off to take the group‐mates' problem‐solving abilities into account in social interactions such as aggression or spatial association, for example because dominance over an innovative group‐mate can increase scrounging success, while spatial proximity may increase the chance of both direct exploitation and social learning. In this study, we tested whether the individuals' innovation success influences their social interactions with group‐mates in small captive flocks of house sparrows (Passer domesticus). First, we measured the birds' actual problem‐solving success in individual food‐extracting tasks. Then, we manipulated their apparent problem‐solving success in one task (by allowing or not allowing them to open a feeder repeatedly) while a new, unfamiliar group‐member (focal individual) had the opportunity to witness their performance. After this manipulation, we observed the frequency and intensity of aggression and the frequency of spatial associations between the focal individuals and their manipulated flock‐mates. Although flock‐mates behaved according to their treatments during manipulations, their apparent problem‐solving success did not affect significantly the focal individuals' agonistic behaviour or spatial associations. These results do not support that sparrows take flock‐mates' problem‐solving abilities into account during social interactions. However, focal individuals attacked those flock‐mates more frequently that had higher actual problem‐solving success (not witnessed directly by the focal individuals), although aggression intensity and spatial association by the focal birds were unrelated to the flock‐mates' actual success. If this association between flock‐mates' actual innovativeness and focal individuals' aggression is not due to confounding effects, it may imply that house sparrows can use more subtle cues to assess the group‐mates' problem‐solving ability than direct observation of their performance in simple foraging tasks.     

Does Anthropomorphism of Dogs Affect Pain Perception in Animal-Assisted Interventions? An Exploratory Study

The purpose of this exploratory study was to determine the effects of anthropomorphism of a therapy dog on pain perception during an animal-assisted intervention. Participants were 32 college women who were randomly assigned to the anthropomorphism condition or the control condition. All participants engaged in a pretest cold pressor task to measure base-line individual differences in pain tolerance and perceptions of pain intensity and pain unpleasantness. After completing this task, participants in the anthropomorphism group engaged in a task intended to prime them to view a therapy dog anthropomorphically. Specifically, they rated photos of dogs on a series of humanlike traits (e.g., “this dog would be a good listener”). Participants in the control condition rated photos of dogs on a series of canine traits (e.g., “this dog would make a good watchdog”). After this experimental manipulation, participants engaged in a second cold pressor task in the presence of a therapy dog and the therapy dog handler. We hypothesized that participants in the anthropomorphism group would demonstrate greater pain tolerance and report lower levels of pain intensity and pain unpleasantness during the second cold pressor task than participants in the control group. Results provide partial support for these hypotheses. Participants in the anthropomorphism group reported lower posttest pain intensity than participants in the control group. In addition, they demonstrated greater posttest pain tolerance than participants in the control group—but only under conditions of medium or high pretest pain tolerance. The two groups did not differ with respect to posttest pain unpleasantness. The results of this exploratory study provide preliminary evidence that prompting individuals to view a therapy dog anthropomorphically may augment their experience of pain relief from a therapy dog visit.     

Does Speaking Two Dialects in Daily Life Affect Executive Functions? An Event-Related Potential Study

Whether using two languages enhances executive functions is a matter of debate. Here, we take a novel perspective to examine the bilingual advantage hypothesis by comparing bi-dialect with mono-dialect speakers’ performance on a non-linguistic task that requires executive control. Two groups of native Chinese speakers, one speaking only the standard Chinese Mandarin and the other also speaking the Southern-Min dialect, which differs from the standard Chinese Mandarin primarily in phonology, performed a classic Flanker task. Behavioural results showed no difference between the two groups, but event-related potentials recorded simultaneously revealed a number of differences, including an earlier P2 effect in the bi-dialect as compared to the mono-dialect group, suggesting that the two groups engage different underlying neural processes. Despite differences in the early ERP component, no between-group differences in the magnitude of the Flanker effects, which is an index of conflict resolution, were observed in the N2 component. Therefore, these findings suggest that speaking two dialects of one language does not enhance executive functions. Implications of the current findings for the bilingual advantage hypothesis are discussed.     

Does the Effect of Micro-Environmental Factors on a Street’s Appeal for Adults’ Bicycle Transport Vary across Different Macro-Environments? An Experimental Study

Background

Characteristics of the physical environment can be classified into two broad categories: macro- (“raw” urban planning features influenced on a regional level) and micro- (features specifically within a streetscape influenced on a neighborhood level) environmental factors. In urban planning applications, it is more feasible to modify conditions at the neighborhood level than at the regional level. Yet for the promotion of bicycle transport we need to know whether relationships between micro-environmental factors and bicycle transport depend on different types of macro-environments. This study aimed to identify whether the effect of three micro-environmental factors (i.e., evenness of the cycle path surface, speed limits and type of separation between cycle path and motorized traffic) on the street’s appeal for adults’ bicycle transport varied across three different macro-environments (i.e., low, medium and high residential density street).

Methods

In total, 389 middle-aged adults completed a web-based questionnaire consisting of socio-demographic characteristics and a series of choice tasks with manipulated photographs, depicting two possible routes to cycle along. Conjoint analysis was used to analyze the data.

Results

Although the magnitude of the overall effects differed, in each macro-environment (i.e., low, medium and high residential density), middle-aged adults preferred a speed limit of 30 km/h, an even cycle path surface and a hedge as separation between motorized traffic and the cycle path compared to a speed limit of 50 or 70 km/h, a slightly uneven or uneven cycle path surface and a curb as separation or no separation between motorized traffic and the cycle path.

Conclusions

Our results suggest that irrespective of the macro-environment, the same micro-environmental factors are preferred in middle-aged adults concerning the street’s appeal for bicycle transport. The controlled environment simulations in the experimental choice task have the potential to inform real life environmental interventions and suggest that micro-environmental changes can have similar results in different macro-environments.     

Why Do People Not Attend for Treatment for Trachomatous Trichiasis in Ethiopia? A Study of Barriers to Surgery

Background

Trachomatous trichiasis (TT) surgery is provided free or subsidised in most trachoma endemic settings. However, only 18–66% of TT patients attend for surgery. This study analyses barriers to attendance among TT patients in Ethiopia, the country with the highest prevalence of TT in the world.

Methodology/Principal Findings

Participants with previously un-operated TT were recruited at 17 surgical outreach campaigns in Amhara Region, Ethiopia. An interview was conducted to ascertain why they had not attended for surgery previously. A trachoma eye examination was performed by an ophthalmologist. 2591 consecutive individuals were interviewed. The most frequently cited barriers to previous attendance for surgery were lack of time (45.3%), financial constraints (42.9%) and lack of an escort (35.5% in females, 19.6% in males). Women were more likely to report a fear of surgery (7.7% vs 3.2%, p<0.001) or be unaware of how to access services (4.5% vs 1.0% p<0.001); men were more frequently asymptomatic (19.6% vs 10.1%, p<0.001). Women were also less likely to have been previously offered TT surgery than men (OR = 0.70, 95%CI 0.53–0.94).

Conclusions/Significance

The major barriers to accessing surgery from the patients'' perspective are the direct and indirect costs of surgery. These can to a large extent be reduced or overcome through the provision of free or low cost surgery at the community level.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00522860","term_id":"NCT00522860"}}NCT00522860 and {"type":"clinical-trial","attrs":{"text":"NCT00522912","term_id":"NCT00522912"}}NCT00522912