Enhancement of visuospatial working memory by the differential outcomes procedure in Mild Cognitive Impairment and Alzheimer’s Disease

In the present study we investigated the efficacy of the differential outcome procedure (DOP) to improve visuospatial working memory in patients with Alzheimer’s disease and Mild Cognitive Impairment (MCI). The DOP associates correct responses to the to-be-remember stimulus with unique outcomes. Eleven patients diagnosed with Alzheimer’s disease, 11 participants with MCI, and 17 healthy matched controls performed a spatial delayed memory task under the DOP and a control condition (non-differential outcomes –NOP-). We found that performance (terminal accuracy) was significantly better in the DOP condition relative to the NOP condition in all three groups of participants. AD patients performed worse, and took longer to benefit from the DOP. In line with previous animal and human research, we propose that the DOP activates brain structures and cognitive mechanisms that are less affected by healthy and pathological aging, optimizing in this way the function of the cognitive system

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) due to AIRET16M mutation in a consanguineous Greek girl

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) or autoimmune polyendocrine syndrome type 1 (APS-1) is a rare autosomal recessive disease caused by mutations of the AutoImmune REgulator (AIRE) gene, an important mediator of tolerance to self-antigens. It is characterized by two out of three major components: chronic mucocutaneous candidiasis, hypoparathyroidism and Addison's disease. We present an 11-year-old girl suffering from recurrent episodes of mucocutaneous candidiasis and onychomycosis from 1 to 6years of age, and transient alopecia at the age of 4years. Hypoparathyroidism and dental enamel hypoplasia were diagnosed at 8years. Autoantibodies to thyroid and adrenal glands were not detected and all other endocrine functions have remained normal. Genetic analysis revealed that the patient was homozygous for the mutation T16M in exon 1 of the AIRE gene (p.T16M, c.47C>T). This is the first APECED case reported for carrying this mutation in homozygous form. Parents were third cousins and heterozygous carriers of this mutatio

Mycobacterium tuberculosis antigen 85B and ESAT-6 expressed as a recombinant fusion protein in Mycobacterium smegmatis elicits cell-mediated immune response in a murine vaccination model

This is the post-print version of the final paper published in Molecular Immunology. The published article is available from the link below. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. Copyright @ 2012 Elsevier B.V.In this study, we investigated the potential molecular and immunological differences of a recombinant fusion protein (Hybrid-1), comprising of the immunodominant antigens Ag85B and ESAT-6 from Mycobacterium tuberculosis, derived from two different expression systems, namely Mycobacterium smegmatis and Escherichia coli. The fusion protein was successfully expressed and purified from both bacterial hosts and analyzed for any host-dependent post-translational modifications that might affect the immunogenicity of the protein. We investigated the immunogenicity of Hybrid-1 expressed in the two host species in a murine vaccination model, together with a reference standard Hybrid-1 (expressed in E. coli) from the Statens Serum Institut. No evidence of any post-translation modification was found in the M. smegmatis-derived Hybrid-1 fusion protein, nor were there any significant differences in the T-cell responses obtained to the three antigens analyzed. In conclusion, the Hybrid-1 fusion protein was successfully expressed in a homologous expression system using M. smegmatis and this system is worth considering as a primary source for vaccination trials, as it provided protein of excellent yield, stability and free from lipopolysaccharide.European TB-VAC consortium and Brunel University

The Use of the Gaps-In-Noise Test as an Index of the Enhanced Left Temporal Cortical Thinning Associated with the Transition between Mild Cognitive Impairment and Alzheimer's Disease

Background: The known link between auditory perception and cognition is often overlooked when testing for cognition. Purpose: To evaluate auditory perception in a group of older adults diagnosed with mild cognitive impairment (MCI). Research Design: A cross-sectional study of auditory perception. Study Sample: Adults with MCI and adults with no documented cognitive issues and matched hearing sensitivity and age. Data collection: Auditory perception was evaluated in both groups, assessing for hearing sensitivity, speech in babble (SinB), and temporal resolution. Results: Mann‐Whitney test revealed significantly poorer scores for SinB and temporal resolution abilities of MCIs versus normal controls for both ears. The right-ear gap detection thresholds on the Gaps-In-Noise (GIN) Test clearly differentiated between the two groups (p < 0.001), with no overlap of values. The left ear results also differentiated the two groups (p < 0.01); however, there was a small degree of overlap ∼8-msec threshold values. With the exception of the left-ear inattentiveness index, which showed a similar distribution between groups, both impulsivity and inattentiveness indexes were higher for the MCIs compared to the control group. Conclusions: The results support central auditory processing evaluation in the elderly population as a promising tool to achieve earlier diagnosis of dementia, while identifying central auditory processing deficits that can contribute to communication deficits in the MCI patient population. A measure of temporal resolution (GIN) may offer an early, albeit indirect, measure reflecting left temporal cortical thinning associated with the transition between MCI and Alzheimer’s disease

Functionally relevant white matter degradation in multiple sclerosis: a tract-based spatial meta-analysis

Purpose To identify statistical consensus between published studies for distribution and functional relevance of tract white matter (WM) degradation in multiple sclerosis (MS). Materials and Methods By systematically searching online databases, tract-based spatial statistics studies were identified that compared fractional anisotropy (FA; a marker for WM integrity) in MS patients to healthy control subjects, correlated FA in MS patients with physical disability, or correlated FA in MS patients with cognitive performance. Voxelwise meta-analysis was performed by using the Signed Differential Mapping method for each comparison. Moderating effects of mean age, mean physical disability score, imager magnet strength, lesion load, and number of diffusion directions were assessed by means of meta-regression. Results Meta-analysis was performed on data from 495 patients and 253 control subjects across 12 studies. MS diagnosis was significantly associated with widespread lower tract FA (nine studies; largest cluster, 4379 voxels; z = 7.1; P < .001). Greater physical disability was significantly associated with lower FA in the right posterior cingulum, left callosal splenium, right inferior fronto-occipital fasciculus, and left fornix crus (six studies; 323 voxels; z = 1.7; P = .001). Impaired cognition was significantly associated with lower FA in the callosal genu, thalamus, right posterior cingulum, and fornix crus (seven studies; largest cluster, 980 voxels; z = 2.5; P < .001). Conclusion WM damage is widespread in MS with differential and only minimally overlapping distributions of low FA that relates to physical disability and cognitive impairment. The higher number of clusters of lower FA in relation to cognition and their higher z scores suggest that cerebral WM damage may have a greater relevance to cognitive dysfunction than physical disability in MS, and that low anterior callosal and thalamic FA have specific importance to cognitive status

Glucocorticoid-related genetic susceptibility for Alzheimer's disease

Because glucocorticoid excess increases neuronal vulnerability, genetic variations in the glucocorticoid system may be related to the risk for Alzheimer's disease (AD). We analyzed single-nucleotide polymorphisms in 10 glucocorticoid-related genes in a population of 814 AD patients and unrelated control subjects. Set-association analysis revealed that a rare haplotype in the 5′ regulatory region of the gene encoding 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1) was associated with a 6-fold increased risk for sporadic AD. Results of a reporter-gene assay indicated that the rare risk-associated haplotype altered HSD11B1 transcription. HSD11B1 controls tissue levels of biologically active glucocorticoids and thereby influences neuronal vulnerability. Our results indicate that a functional variation in the glucocorticoid system increases the risk for AD, which may have important implications for the diagnosis and treatment of this diseas

Visualization of Nd3+-doped Laf3 Nanoparticles For Near Infrared Bioimaging via Upconversion Luminescence at Multiphoton Excitation Microscopyvisualization of Nd3+-doped Laf3 Nanoparticles For Near Infrared Bioimaging via Upconversion Luminescence at Multiphoton Excitation Microscopy

Recent developments in the field of biophotonics facilitate the raise of interest to inorganic nanoparticles (NPs) doped with Nd 3+ ions, because of their near-infrared (NIR) absorption. These NPs are interesting bioimaging probes for deep tissue visualization, while they can also act as local thermometers in biological tissues. Despite the good possibilities for visualization of NPs with Nd 3+ ions in NIR spectral range, difficulties arise when studying the cellular uptake of these NPs using commercially available fluorescence microscopy systems, since the selection of suitable luminescence detectors is limited. However, Nd 3+ ions are able to convert NIR radiation into visible light, showing upconversion properties. In this paper we found optimal parameters to excite upconversion luminescence of Nd 3+ :LaF 3 NPs in living cells and to compare the distribution of the NPs inside the cell culture of human macrophages THP-1 obtained by two methods. Firstly, by detecting the upconversion luminescence of the NPs in VIS under NIR multiphoton excitation using laser scanning confocal microscopy and secondly, using transmission electron microscopy

Pathological Mineralisation

Pathological mineralisation is a well-known phenomenon in the medical field as it relates to a wide range of diseases, including cancer, neurodegenerative dis-eases, aortic valve stenosis, and atherosclerosis. Despite this, the direct study of pathological minerals has been rare, as most research focuses on the study of the organic components of these pathologies and the microenvironment the minerals are observed in. Even though material science methods have been used for the study of biomaterials, hard tissues, and other biological systems; they have not been widely used in the research of pathological mineralisation. This work is, subsequently, con-centrating on the direct study of the minerals found in cardiovascular, breast, and brain tissues aiming to provide a full physicochemical characterization. The presence of in-organic material in these soft tissues has been long observed in relation to several diseases, but the relationship between their properties and specific pathologies is not fully understood. Therefore, through the direct investigation of the minerals present, this study aims to provide new insights into the association of unique mineral proper-ties to specific disease characteristics. In addition, the data on the mineral properties will then be evaluated to gain information on the mineral formation processes, in order to identify proteins, cells, or vesicles, which might be involved. Finally, a range of bio-chemical assays will be used, aiming to directly investigate the presence of biological markers in the inorganic material to give new insights on the mineralisation mecha-nisms