Error self-regulation following traumatic brain injury: A single case study evaluation of metacognitive skills training and behavioural practice interventions

The objective of the study was to evaluate the effects of metacognitive skills training (MST) and behavioural practice on error self-regulation during a naturalistic task after traumatic brain injury (TBI). A single-case study design was used and three participants (two males, one female) aged 26–43 years with severe TBI were included in the study. In the first study, after a four-session baseline of behavioural practice, two participants received eight MST sessions followed by four maintenance sessions. In the second study, a third participant received 16 sessions of behavioural practice to assess the extent to which error self-regulation improves through long-term task practice and therapist corrections. Participants prepared two different meals with a novel meal introduced later to examine skills generalisation. Behavioural outcomes included error frequency, checking and self-corrections. Data analysis involved a combination of visual analysis and two standard deviation (2-SD) band analysis. In the MST study, the two participants demonstrated a 38% and 76% reduction in error frequency (p < .05), a significant decrease in checks (p < .05), and a significant increase in self-corrections (p < .05) relative to baseline. In the behavioural practice study, the participant demonstrated reduced errors (25%), although this was not statistically significant, and a significant increase in checks (p < .05), but self-corrections did not significantly change (p > .05). This exploratory research suggests that, firstly, by targeting error self-regulation MST can potentially promote independence on complex everyday tasks; and secondly, although behavioural practice alone may facilitate some functional gains, it fails to promote more independent self-regulatory behaviours.     

Influence of Intra- and Extracellular Acidification on Free Radical Formation and Mitochondria Membrane Potential in Rat Brain Synaptosomes

Brain ischemia is accompanied by lowering of intra- and extracellular pH. Stroke often leads to irreversible damage of synaptic transmission by unknown mechanism. We investigated an influence of lowering of pH_i and pH_o on free radical formation in synaptosomes. Three models of acidosis were used: (1) pH_o 6.0 corresponding to pH_i decrease down to 6.04; (2) pH_o 7.0 corresponding to the lowering of pH_i down to 6.92: (3) 1 mM amiloride corresponding to pH_i decrease down to 6.65. We have shown that both types of extracellular acidification, but not intracellular acidification, increase 2′,7′-dichlorodihydrofluorescein diacetate fluorescence that reflects free radical formation. These three treatments induce the rise of the dihydroethidium fluorescence that reports synthesis of superoxide anion. However, the impact of amiloride on superoxide anion synthesis was less than that induced by moderate extracellular acidification. Superoxide anion synthesis at pH_o 7.0 was almost completely eliminated by mitochondrial uncoupler carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone. Furthermore, using fluorescent dyes JC-1 and rhodamine-123, we confirmed that pH_o lowering, but not intracellular acidification, led to depolarization of intrasynaptosomal mitochondria. We have shown that pH_o but not pH_i lowering led to oxidative stress in neuronal presynaptic endings that might underlie the long-term irreversible changing in synaptic transmission.     

The Importance of astrocyte‐derived purines in the modulation of sleep

Sleep is an evolutionarily conserved phenomenon that is clearly essential for survival, but we have limited understanding of how and why it is so important. Adenosine triphosphate (ATP)/adenosine signaling has been known to be important in the regulation of sleep and recent evidence suggests a critical role for gliotransmission in the modulation of sleep homeostasis. Herein, we review the regulation of ATP/adenosine in the nervous system and provide evidence of a critical role for astrocyte‐derived adenosine in the regulation of sleep homeostasis and the modulation of synaptic transmission. Further understanding of the role of glial cells in the regulation of sleep may provide new targets for pharmaceutical intervention in the treatment of brain dysfunctions, specifically those that are comorbid with sleep disruptions. © 2012 Wiley Periodicals, Inc     

Metaphor Comprehension in Individuals with Autism Spectrum Disorder: Core Language Skills Matter

Journal of Autism and Developmental Disorders - Poor metaphor comprehension was considered a hallmark of autism spectrum disorder (ASD), but recent research has questioned the extent and the...     

Genetic characterization of tick-borne flaviviruses: new insights into evolution, pathogenetic determinants and taxonomy

Here, we analyze the complete coding sequences of all recognized tick-borne flavivirus species, including Gadgets Gully, Royal Farm and Karshi virus, seabird-associated flaviviruses, Kadam virus and previously uncharacterized isolates of Kyasanur Forest disease virus and Omsk hemorrhagic fever virus. Significant taxonomic improvements are proposed, e.g. the identification of three major groups (mammalian, seabird and Kadam tick-borne flavivirus groups), the creation of a new species (Karshi virus) and the assignment of Tick-borne encephalitis and Louping ill viruses to a unique species (Tick-borne encephalitis virus) including four viral types (i.e. Western Tick-borne encephalitis virus, Eastern Tick-borne encephalitis virus, Turkish sheep Tick-borne encephalitis virus and Louping ill Tick-borne encephalitis virus). The analyses also suggest a complex relationship between viruses infecting birds and those infecting mammals. Ticks that feed on both categories of vertebrates may constitute the evolutionary bridge between the three distinct identified lineages.     

Investigation of the in vitro toxicological properties of the synthetic cannabimimetic drug CP-47,497-C8

Cannabicyclohexanol (CP-47,497-C8) is a representative of a group of cannabimimetic cyclohexylphenols which is added to herbal mixtures as a cannabis substitute since 2008. Although in the beginning CP-47,497-C8 was the main ingredient of “Spice” and similar products, it was partly replaced by aminoalkylindole-type cannabinoid receptor agonists like JWH-018, JWH-073 or JWH-250, but never completely disappeared from the market. Since information on its toxicological properties is scarce, we investigated the effects of the drug in human derived cell lines. The cytotoxic effects were studied in a panel of assays (SRB, XTT, LDHe and NR tests) in a buccal derived (TR146) and a liver derived (HepG2) cell line. The strongest effects were seen in the two former assays at levels ≥ 7.5 μM indicating that the compound interferes with protein synthesis and causes membrane damage. In additional comet assays, DNA damage was detected at levels ≥ 10 μM. Experiments with lesion specific enzymes showed that these effects are not due to oxidative damage of DNA bases. The negative findings obtained in Salmonella/microsome assays and the positive results of micronucleus tests with the cell lines indicate that the compound does not cause gene mutations but acts on the chromosomal level. In contrast to other synthetic cannabinoids, no indication for estrogenic/antiestrogenic properties was seen in a luciferase assay with bone marrow derived U2-OS cells. In conclusion, our findings show that the drug has only weak cytotoxic properties. However, the induction of chromosomal damage indicates that it may cause adverse effects in users due to its impact on the stability of the genetic material.     

Tumor-Targeted Responsive Nanoparticle-Based Systems for Magnetic Resonance Imaging and Therapy

Purpose

Design and synthesis of a tumor responsive nanoparticle-based system for imaging and treatment of various cancers.

Methods

Manganese oxide nanoparticles (Mn₃O₄ NPs) were synthesized and modified with LHRH targeting peptide or anti-melanoma antibodies (cancer targeting moieties) and a MMP2 cleavable peptide (a possible chemotactic factor). Nanostructured lipid carriers (NLCs) were used to entrap the BRAF inhibitor, vemurafenib, and enhance cytotoxicity of the drug. Size distribution, stability, drug entrapment, cytotoxicity and genotoxicity of synthesized nanoparticles were studied in vitro. Enhancement of MRI signal by nanoparticles and their body distribution were examined in vivo on mouse models of melanoma, ovarian and lung cancers.

Results

Uniform, stable cancer-targeted nanoparticles (PEGylated water-soluble Mn₃O₄ NPs and NLCs) were synthesized. No signs of cyto-,genotoxicity and DNA damage were detected for nanoparticles that do not contain an anticancer drug. Entrapment of vemurafenib into nanoparticles significantly enhanced drug toxicity in cancer cells with targeted V600E mutation. The developed nanoparticles containing LHRH and MMP2 peptides showed preferential accumulation in primary and metastatic tumors increasing the MRI signal in mice with melanoma, lung and ovarian cancers.

Conclusions

The proposed nanoparticle-based systems provide the foundation for building an integrated MRI diagnostic and therapeutic approach for various types of cancer.