The Test Your Memory for Mild Cognitive Impairment (TYM-MCI)

BACKGROUND: To validate a short cognitive test: the Test Your Memory for Mild Cognitive Impairment (TYM-MCI) in the diagnosis of patients with amnestic mild cognitive impairment or mild Alzheimer’s disease (aMCI/AD). METHODS: Two hundred and two patients with mild memory problems were recruited. All had ‘passed’ the Mini-Mental State Examination (MMSE). Patients completed the TYM-MCI, the Test Your Memory test (TYM), MMSE and revised Addenbrooke’s Cognitive Examination (ACE-R), had a neurological examination, clinical diagnostics and multidisciplinary team review. RESULTS: As a single test, the TYM-MCI performed as well as the ACE-R in the distinction of patients with aMCI/AD from patients with subjective memory impairment with a sensitivity of 0.79 and specificity of 0.91. Used in combination with the ACE-R, it provided additional value and identified almost all cases of aMCI/AD. The TYM-MCI correctly classified most patients who had equivocal ACE-R scores. Integrated discriminant improvement analysis showed that the TYM-MCI added value to the conventional memory assessment. Patients initially diagnosed as unknown or with subjective memory impairment who were later rediagnosed with aMCI/AD scored poorly on their original TYM-MCI. CONCLUSION: The TYM-MCI is a powerful short cognitive test that examines verbal and visual recall and is a valuable addition to the assessment of patients with aMCI/AD. It is simple and cheap to administer and requires minimal staff time and training.JBR was supported by the Wellcome Trust (103838)

Self-assembled dynamic perovskite composite cathodes for intermediate temperature solid oxide fuel cells

Electrode materials for intermediate temperature (500–700 ∘C) solid oxide fuel cells require electrical and mechanical stability to maintain performance during the cell lifetime. This has proven difficult to achieve for many candidate cathode materials and their derivatives with good transport and electrocatalytic properties because of reactivity towards cell components, and the fuels and oxidants. Here we present Ba0.5Sr0.5(Co0.7Fe0.3)0.6875W0.3125O3−δ (BSCFW), a self-assembled composite prepared through simple solid state synthesis, consisting of B-site cation ordered double perovskite and disordered single perovskite oxide phases, as a candidate cathode material. These phases interact by dynamic compositional change at the operating temperature, promoting both chemical stability through the increased amount of W in the catalytically active single perovskite provided from the W-reservoir double perovskite, and microstructural stability through reduced sintering of the supported catalytically active phase. This interactive catalyst-support system enabled stable high electrochemical activity through the synergic integration of the distinct properties of the two phases

The behavioural variant frontotemporal dementia phenocopy syndrome is a distinct entity - evidence from a longitudinal study.

BACKGROUND: This study aimed to i) examine the frequency of C9orf72 expansions in a cohort of patients with the behavioural variant frontotemporal dementia (bvFTD) phenocopy syndrome, ii) observe outcomes in a group of phenocopy syndrome with very long term follow-up and iii) compare progression in a cohort of patients with the phenocopy syndrome to a cohort of patients with probable bvFTD. METHODS: Blood was obtained from 16 phenocopy cases. All met criteria for possible bvFTD and were labeled as phenocopy cases if they showed no functional decline, normal cognitive performance on the Addenbrooke's Cognitive Examination-Revised (ACE-R) and a lack of atrophy on brain imaging, over at least 3 years of follow-up. In addition, we obtained very long term follow-up data in 6 cases. A mixed model analysis approach determined the pattern of change in cognition and behaviour over time in phenocopy cases compared to 27 probable bvFTD cases. RESULTS: All 16 patients were screened for the C9orf72 expansion that was present in only one (6.25%). Of the 6 cases available for very long-term follow-up (13 - 21 years) none showed progression to frank dementia. Moreover, there was a decrease in the caregiver ratings of behavioural symptoms over time. Phenocopy cases showed significantly slower rates of progression compared to probable bvFTD patients (p < 0.006). CONCLUSION: The vast majority of patients with the bvFTD phenocopy syndrome remain stable over many years. An occasional patient can harbor the C9orf72 expansion. The aetiology of the remaining cases remains unknown but it appears very unlikely to reflect a neurodegenerative syndrome due to lack of clinical progression or atrophy on imaging

Defining language impairments in a subgroup of children with autism spectrum disorder

Autism spectrum disorder (ASD) is diagnosed on the basis of core impairments in pragmatic language skills, which are found across all ages and subtypes. In contrast, there is significant heterogeneity in language phenotypes, ranging from nonverbal to superior linguistic abilities, as defined on standardized tests of vocabulary and grammatical knowledge. The majority of children are verbal but impaired in language, relative to age-matched peers. One hypothesis is that this subgroup has ASD and co-morbid specific language impairment (SLI). An experiment was conducted comparing children with ASD to children with SLI and typically developing controls on aspects of language processing that have been shown to be impaired in children with SLI: repetition of nonsense words. Patterns of performance among the children with ASD and language impairment were similar to those with SLI, and contrasted with the children with ASD and no language impairment and typical controls, providing further evidence for the hypothesis that a subgroup of children with ASD has co-morbid SLI. The findings are discussed in the context of brain imaging studies that have explored the neural bases of language impairment in ASD and SLI, and overlap in the genes associated with elevated risk for these disorders.M01 RR00533 - NCRR NIH HHS; R01 DC10290 - NIDCD NIH HHS; U19 DC03610 - NIDCD NIH HH

Mutual information rate and bounds for it

The amount of information exchanged per unit of time between two nodes in a dynamical network or between two data sets is a powerful concept for analysing complex systems. This quantity, known as the mutual information rate (MIR), is calculated from the mutual information, which is rigorously defined only for random systems. Moreover, the definition of mutual information is based on probabilities of significant events. This work offers a simple alternative way to calculate the MIR in dynamical (deterministic) networks or between two data sets (not fully deterministic), and to calculate its upper and lower bounds without having to calculate probabilities, but rather in terms of well known and well defined quantities in dynamical systems. As possible applications of our bounds, we study the relationship between synchronisation and the exchange of information in a system of two coupled maps and in experimental networks of coupled oscillators

Mechanism of active K + secretion by flounder urinary bladder

We investigated the mechanism of active K + transport by the urinary bladder of the winter flounder by measuring transepithelial properties in Ussing Chambers and by determining the cellular electrical potential profile using conventional microelectrodes. In the absence of transmural electrochemical potential gradients isolated bladders can exhibit a serosa-to-mucosa short circuit which is due entirely to net K + secretion. The properties of transcellular K + movement can be adequately described by a model which provides for active K + uptake across the basolateral membrane via an electrogenic Na/K ATPase and K + exit from the cell across the apical membrane down an electrochemical potential gradient via K + channels which are blocked by mucosal barium. The conductance of the apical membranes of the transporting cells appears to be due almost solely to K + while that of the basolateral membrane may be due largely to Cl − .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47455/1/424_2004_Article_BF00585048.pd

RNA editing signature during myeloid leukemia cell differentiation

Adenosine deaminases acting on RNA (ADARs) are key proteins for hematopoietic stem cell self-renewal and for survival of differentiating progenitor cells. However, their specific role in myeloid cell maturation has been poorly investigated. Here we show that ADAR1 is present at basal level in the primary myeloid leukemia cells obtained from patients at diagnosis as well as in myeloid U-937 and THP1 cell lines and its expression correlates with the editing levels. Upon phorbol-myristate acetate or Vitamin D3/granulocyte macrophage colony-stimulating factor (GM-CSF)-driven differentiation, both ADAR1 and ADAR2 enzymes are upregulated, with a concomitant global increase of A-to-I RNA editing. ADAR1 silencing caused an editing decrease at specific ADAR1 target genes, without, however, interfering with cell differentiation or with ADAR2 activity. Remarkably, ADAR2 is absent in the undifferentiated cell stage, due to its elimination through the ubiquitin–proteasome pathway, being strongly upregulated at the end of the differentiation process. Of note, peripheral blood monocytes display editing events at the selected targets similar to those found in differentiated cell lines. Taken together, the data indicate that ADAR enzymes play important and distinct roles in myeloid cells

Promotion of breast cancer by β-Hexachlorocyclohexane in MCF10AT1 cells and MMTV-neu mice

<p>Abstract</p> <p>Background</p> <p>Exposure to β-Hexachlorocyclohexane (β-HCH), a contaminant of the hexachlorohexane pesticide lindane, has been implicated as a risk factor in the development of breast cancers in epidemiological studies. Previous studies in our laboratory have demonstrated the ability of β-HCH to elicit its actions via a ligand-independent activation of the estrogen receptor through increased c-Neu (= erbB₂or HER-2) expression and kinase activation in both the BG-1 and MCF-7 cell lines. In addition, long term exposure (33 passages) to β-HCH was shown to promote the selection of MCF-7 cells which exhibit a more metastatic phenotype.</p> <p>Methods</p> <p>In this current study, we decided to investigate the long-term effects of β-HCH in both the MCF10AT1 cell line which was derived from a normal epithelial cell line by stably transfecting a mutated c-Ha-ras and a MMTV-Neu mouse model for mammary cancer <it>in vivo</it>. MCF10AT1 cells were exposed for 20 passages with β-HCH, 4-OH-Tamoxifen (Tam), or 17-β-estradiol (E₂) after which cells were analyzed for proliferation rates and mRNA expression by RT-PCR. In our <it>in vivo </it>studies, MMTV-Neu mice were injected with β-HCH and observed for tumor formation over a 70 week period.</p> <p>Results</p> <p>β-HCH and Tam selected MCF10AT1 cells demonstrated increased mRNA expression of MMP-13 (collagenase-3) a marker of increased invasiveness. β-HCH treatment was also seen to increase the expression in a number of proto-oncogenes (c-Neu, Cyclin D1, p27), cell status markers (Met-1, CK19), and the inflammatory marker NFκB. Previous studies, have demonstrated the role of these markers as evidence of malignant transformations, and further illustrate the ability of β-HCH to be carcinogenic. To demonstrate β-HCH's tumorigenic properties in an <it>in vivo </it>system, we used an MMTV-Neu mouse model.</p> <p>MMTV-Neu is a c-Neu overexpressing strain which has been shown to spontaneously develop mammary tumors at later stages of aging. In this experiment, β-HCH exposure was shown to both accelerate the appearance (~8 weeks for median tumor-free period) and incidence (~25% increase at the end of the test period) of tumors when compared to control mice receiving only the corn-oil vehicle.</p> <p>Conclusion</p> <p>Based upon these results, it was concluded that β-HCH does act as a breast cancer promoter which exerts its tumorigenic activity via increased c-Neu expression.</p