Molecular characteristics of long-term epilepsy-associated tumours (LEATs) and mechanisms for tumour-related epilepsy (TRE)

Brain tumours are the second most common cause of seizures identified in epilepsy surgical series. While any tumour involving the brain has the potential to cause seizures, specific subtypes are more frequently associated with epilepsy. Tumour-related epilepsy has a profound impact on patients with brain tumours and these seizures are often refractory to anti-epileptic treatments, resulting in long-term disability and patient morbidity. Despite the drastic impact epilepsy-associated tumours have on patients, they have not traditionally enjoyed as much attention as more malignant neoplasms. However, recently a number of developments have been achieved towards furthering our understanding of the molecular and developmental backgrounds of specific epilepsy associated tumours. In addition, the past decade has seen an expansion in the literature on the pathophysiology of tumour-related epilepsy. In this review, we aim to summarise the mechanisms by which tumours may cause seizures and detail recent data regarding the pathogenesis of specific developmental epilepsy-associated tumours. This article is protected by copyright. All rights reserved

Employing the Gini coefficient to measure participation inequality in treatment-focused Digital Health Social Networks

Digital Health Social Networks (DHSNs) are common; however, there are few metrics that can be used to identify participation inequality. The objective of this study was to investigate whether the Gini coefficient, an economic measure of statistical dispersion traditionally used to measure income inequality, could be employed to measure DHSN inequality. Quarterly Gini coefficients were derived from four long-standing DHSNs. The combined data set included 625,736 posts that were generated from 15,181 actors over 18,671 days. The range of actors (8–2323), posts (29–28,684), and Gini coefficients (0.15–0.37) varied. Pearson correlations indicated statistically significant associations between number of actors and number of posts (0.527–0.835, p < .001), and Gini coefficients and number of posts (0.342–0.725, p < .001). However, the association between Gini coefficient and number of actors was only statistically significant for the addiction networks (0.619 and 0.276, p < .036). Linear regression models had positive but mixed R2 results (0.333–0.527). In all four regression models, the association between Gini coefficient and posts was statistically significant (t = 3.346–7.381, p < .002). However, unlike the Pearson correlations, the association between Gini coefficient and number of actors was only statistically significant in the two mental health networks (t = −4.305 and −5.934, p < .000). The Gini coefficient is helpful in measuring shifts in DHSN inequality. However, as a standalone metric, the Gini coefficient does not indicate optimal numbers or ratios of actors to posts, or effective network engagement. Further, mixed-methods research investigating quantitative performance metrics is required

The lectin from leaves of Japanese cycad, Cycas revoluta Thunb. (gymnosperm) is a member of the jacalin-related family

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65624/1/j.1432-1033.2002.03127.x.pd

Pkc-Mediated Stimulation of Amphibian Cftr Depends on a Single Phosphorylation Consensus Site. Insertion of This Site Confers Pkc Sensitivity to Human Cftr

Mutations of the CFTR, a phosphorylation-regulated Cl− channel, cause cystic fibrosis. Activation of CFTR by PKA stimulation appears to be mediated by a complex interaction between several consensus phosphorylation sites in the regulatory domain (R domain). None of these sites has a critical role in this process. Here, we show that although endogenous phosphorylation by PKC is required for the effect of PKA on CFTR, stimulation of PKC by itself has only a minor effect on human CFTR. In contrast, CFTR from the amphibians Necturus maculosus and Xenopus laevis (XCFTR) can be activated to similar degrees by stimulation of either PKA or PKC. Furthermore, the activation of XCFTR by PKC is independent of the net charge of the R domain, and mutagenesis experiments indicate that a single site (Thr665) is required for the activation of XCFTR. Human CFTR lacks the PKC phosphorylation consensus site that includes Thr665, but insertion of an equivalent site results in a large activation upon PKC stimulation. These observations establish the presence of a novel mechanism of activation of CFTR by phosphorylation of the R domain, i.e., activation by PKC requires a single consensus phosphorylation site and is unrelated to the net charge of the R domain

Are online support groups always beneficial? A qualitative exploration of the empowering and disempowering processes of participation within HIV/AIDS-related online support groups

BACKGROUND: Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) is one of the leading concerns in healthcare. Individuals living with HIV/AIDS are often confronted with tremendous physical and psychosocial challenges. Online support groups can provide a valuable source of information, advice and support, and a medium through which individuals living with HIV/AIDS can interact with each other and share their experiences. However, very little is known about how online support group might promote empowerment and the potential disadvantages associated with online support group use among individuals living with HIV/AIDS. OBJECTIVES: The present study explored the potential empowering and disempowering processes, and empowering outcomes of online support group use among individuals with HIV/AIDS. DESIGN, SETTINGS, PARTICIPANTS: A total of 115 HIV-positive online support group members were recruited from HIV-related online support groups. They completed an online survey exploring their experiences of online support group use. RESULTS: Thematic analysis revealed six empowering processes arising from use of online support groups: exchanging information, sharing experiences, connecting to others, encountering emotional support, finding recognition and understanding, and helping others. Six empowering outcomes were identified: increased optimism, emotional well-being, social well-being, being better informed, improved disease management, and feeling confident in the relationship with physicians. Potentially disempowering processes were also identified which included: being unable to connect physically, inappropriate behaviour online, declining real life relationships, and information overload and misinformation. CONCLUSION: Findings suggest ways through which individuals with HIV/AIDS may be empowered although some problematic features specific to the online context may also be present

Biomechanical effects of polyaxial pedicle screw fixation on the lumbosacral segments with an anterior interbody cage support

BACKGROUND: Lumbosacral fusion is a relatively common procedure that is used in the management of an unstable spine. The anterior interbody cage has been involved to enhance the stability of a pedicle screw construct used at the lumbosacral junction. Biomechanical differences between polyaxial and monoaxial pedicle screws linked with various rod contours were investigated to analyze the respective effects on overall construct stiffness, cage strain, rod strain, and contact ratios at the vertebra-cage junction. METHODS: A synthetic model composed of two ultrahigh molecular weight polyethylene blocks was used with four titanium pedicle screws (two in each block) and two rods fixation to build the spinal construct along with an anterior interbody cage support. For each pair of the construct fixed with polyaxial or monoaxial screws, the linked rods were set at four configurations to simulate 0°, 7°, 14°, and 21° lordosis on the sagittal plane, and a compressive load of 300 N was applied. Strain gauges were attached to the posterior surface of the cage and to the central area of the left connecting rod. Also, the contact area between the block and the cage was measured using prescale Fuji super low pressure film for compression, flexion, lateral bending and torsion tests. RESULTS: Our main findings in the experiments with an anterior interbody cage support are as follows: 1) large segmental lordosis can decrease the stiffness of monoaxial pedicle screws constructs; 2) polyaxial screws rather than monoaxial screws combined with the cage fixation provide higher compression and flexion stiffness in 21° segmental lordosis; 3) polyaxial screws enhance the contact surface of the cage in 21° segmental lordosis. CONCLUSION: Polyaxial screws system used in conjunction with anterior cage support yields higher contact ratio, compression and flexion stiffness of spinal constructs than monoaxial screws system does in the same model when the spinal segment is set at large lordotic angles. Polyaxial pedicle screw fixation performs nearly equal percentages of vertebra-cage contact among all constructs with different sagittal alignments, therefore enhances the stabilization effect of interbody cages in the lumbosacral area

Androgen Excess Produces Systemic Oxidative Stress and Predisposes to β-Cell Failure in Female Mice

In women, excess production of the male hormone, testosterone (T), is accompanied by insulin resistance. However, hyperandrogenemia is also associated with β-cell dysfunction and type 2 diabetes raising the possibility that androgen receptor (AR) activation predisposes to β-cell failure. Here, we tested the hypothesis that excess AR activation produces systemic oxidative stress thereby contributing to β-cell failure. We used normal female mice (CF) and mice with androgen resistance by testicular feminization (Tfm). These mice were exposed to androgen excess and a β-cell stress induced by streptozotocin (STZ). We find that following exposure to T, or the selective AR-agonist dehydrotestosterone (DHT), CF mice challenged with STZ, which are normally protected, are prone to β-cell failure and insulin-deficient diabetes. Conversely, T-induced predisposition to β-cell failure is abolished in Tfm mice. We do not observe any proapoptotic effect of DHT alone or in the presence of H2O2 in cultured mouse and human islets. However, we observe that exposure of CF mice to T or DHT provokes systemic oxidative stress, which is eliminated in Tfm mice. This work has significance for hyperandrogenic women; excess activation of AR by testosterone may provoke systemic oxidative stress. In the presence of a prior β-cell stress, this may predispose to β-cell failure

Flexible Cognitive Strategies during Motor Learning

Visuomotor rotation tasks have proven to be a powerful tool to study adaptation of the motor system. While adaptation in such tasks is seemingly automatic and incremental, participants may gain knowledge of the perturbation and invoke a compensatory strategy. When provided with an explicit strategy to counteract a rotation, participants are initially very accurate, even without on-line feedback. Surprisingly, with further testing, the angle of their reaching movements drifts in the direction of the strategy, producing an increase in endpoint errors. This drift is attributed to the gradual adaptation of an internal model that operates independently from the strategy, even at the cost of task accuracy. Here we identify constraints that influence this process, allowing us to explore models of the interaction between strategic and implicit changes during visuomotor adaptation. When the adaptation phase was extended, participants eventually modified their strategy to offset the rise in endpoint errors. Moreover, when we removed visual markers that provided external landmarks to support a strategy, the degree of drift was sharply attenuated. These effects are accounted for by a setpoint state-space model in which a strategy is flexibly adjusted to offset performance errors arising from the implicit adaptation of an internal model. More generally, these results suggest that strategic processes may operate in many studies of visuomotor adaptation, with participants arriving at a synergy between a strategic plan and the effects of sensorimotor adaptation

Human Uterine Wall Tension Trajectories and the Onset of Parturition

Uterine wall tension is thought to be an important determinant of the onset of labor in pregnant women. We characterize human uterine wall tension using ultrasound from the second trimester of pregnancy until parturition and compare preterm, term and twin pregnancies. A total of 320 pregnant women were followed from first antenatal visit to delivery during the period 2000–2004 at the John Hunter Hospital, NSW, Australia. The uterine wall thickness, length, anterior-posterior diameter and transverse diameter were determined by serial ultrasounds. Subjects were divided into three groups: women with singleton pregnancies and spontaneous labor onset, either preterm or term and women with twin pregnancies. Intrauterine pressure results from the literature were combined with our data to form trajectories for uterine wall thickness, volume and tension for each woman using the prolate ellipsoid method and the groups were compared at 20, 25 and 30 weeks gestation. Uterine wall tension followed an exponential curve, with results increasing throughout pregnancy with the site of maximum tension on the anterior wall. For those delivering preterm, uterine wall thickness was increased compared with term. For twin pregnancies intrauterine volume was increased compared to singletons (), but wall thickness was not. There was no evidence for increased tension in those delivering preterm or those with twin gestations. These data are not consistent with a role for high uterine wall tension as a causal factor in preterm spontaneous labor in singleton or twin gestations. It seems likely that hormonal differences in multiple gestations are responsible for increased rates of preterm birth in this group rather than increased tension