Day-to-Day Test–Retest Variability of CBF, CMRO2, and OEF Measurements Using Dynamic 15O PET Studies

Contains fulltext : 169592.pdf (publisher's version ) (Open Access)PURPOSE: We assessed test-retest variability of cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rate of oxygen (CMRO(2)), and oxygen extraction fraction (OEF) measurements derived from dynamic (15)O positron emission tomography (PET) scans. PROCEDURES: In seven healthy volunteers, complete test-retest (15)O PET studies were obtained; test-retest variability and left-to-right ratios of CBF, CBV, OEF, and CMRO(2) in arterial flow territories were calculated. RESULTS: Whole-brain test-retest coefficients of variation for CBF, CBV, CMRO(2), and OEF were 8.8%, 13.8%, 5.3%, and 9.3%, respectively. Test-retest variability of CBV left-to-right ratios was <7.4% across all territories. Corresponding values for CBF, CMRO(2), and OEF were better, i.e., <4.5%, <4.0%, and <1.4%, respectively. CONCLUSIONS: The test-retest variability of CMRO(2) measurements derived from dynamic (15)O PET scans is comparable to within-session test-retest variability derived from steady-state (15)O PET scans. Excellent regional test-retest variability was observed for CBF, CMRO(2), and OEF. Variability of absolute CBF and OEF measurements is probably affected by physiological day-to-day variability of CBF

Abnormal Intracellular Accumulation and Extracellular Aβ Deposition in Idiopathic and Dup15q11.2-q13 Autism Spectrum Disorders

<div><h3>Background</h3><p>It has been shown that amyloid ß (Aβ), a product of proteolytic cleavage of the amyloid β precursor protein (APP), accumulates in neuronal cytoplasm in non-affected individuals in a cell type–specific amount.</p> <h3>Methodology/Principal Findings</h3><p>In the present study, we found that the percentage of amyloid-positive neurons increases in subjects diagnosed with idiopathic autism and subjects diagnosed with duplication 15q11.2-q13 (dup15) and autism spectrum disorder (ASD). In spite of interindividual differences within each examined group, levels of intraneuronal Aβ load were significantly greater in the dup(15) autism group than in either the control or the idiopathic autism group in 11 of 12 examined regions (p<0.0001 for all comparisons; Kruskall-Wallis test). In eight regions, intraneuronal Aβ load differed significantly between idiopathic autism and control groups (p<0.0001). The intraneuronal Aβ was mainly N-terminally truncated. Increased intraneuronal accumulation of Aβ_17–40/42 in children and adults suggests a life-long enhancement of APP processing with α-secretase in autistic subjects. Aβ accumulation in neuronal endosomes, autophagic vacuoles, Lamp1-positive lysosomes and lipofuscin, as revealed by confocal microscopy, indicates that products of enhanced α-secretase processing accumulate in organelles involved in proteolysis and storage of metabolic remnants. Diffuse plaques containing Aβ_1–40/42 detected in three subjects with ASD, 39 to 52 years of age, suggest that there is an age-associated risk of alterations of APP processing with an intraneuronal accumulation of a short form of Aβ and an extracellular deposition of full-length Aβ in nonfibrillar plaques.</p> <h3>Conclusions/Significance</h3><p>The higher prevalence of excessive Aβ accumulation in neurons in individuals with early onset of intractable seizures, and with a high risk of sudden unexpected death in epilepsy in autistic subjects with dup(15) compared to subjects with idiopathic ASD, supports the concept of mechanistic and functional links between autism, epilepsy and alterations of APP processing leading to neuronal and astrocytic Aβ accumulation and diffuse plaque formation.</p> </div

Macrophages in Alzheimer’s disease: the blood-borne identity

Alzheimer’s disease (AD) is a progressive and incurable neurodegenerative disorder clinically characterized by cognitive decline involving loss of memory, reasoning and linguistic ability. The amyloid cascade hypothesis holds that mismetabolism and aggregation of neurotoxic amyloid-β (Aβ) peptides, which are deposited as amyloid plaques, are the central etiological events in AD. Recent evidence from AD mouse models suggests that blood-borne mononuclear phagocytes are capable of infiltrating the brain and restricting β-amyloid plaques, thereby limiting disease progression. These observations raise at least three key questions: (1) what is the cell of origin for macrophages in the AD brain, (2) do blood-borne macrophages impact the pathophysiology of AD and (3) could these enigmatic cells be therapeutically targeted to curb cerebral amyloidosis and thereby slow disease progression? This review begins with a historical perspective of peripheral mononuclear phagocytes in AD, and moves on to critically consider the controversy surrounding their identity as distinct from brain-resident microglia and their potential impact on AD pathology

Electrode surface treatment and electrochemical impedance spectroscopy study on carbon/carbon supercapacitors

Power improvement in supercapacitors is mainly related to lowering the internal impedance. The real part of the impedance at a given frequency is called ESR (equivalent series resistance). Several contributions are included in the ESR: the electrolyte resistance (including the separator), the active material resistance (with both ionic and electronic parts) and the active material/current collector interface resistance. The first two contributions have been intensively described and studied by many authors. The first part of this paper is focused on the use of surface treatments as a way to decrease the active material/current collector impedance. Al current collector foils have been treated following a two-step procedure: electrochemical etching and sol-gel coating by a highly-covering, conducting carbonaceous material. It aims to increase the Al foil/active material surface contact leading to lower resistance. In a second part, carbon-carbon supercapacitor impedance is discussed in term of complex capacitance and complex power from electrochemical impedance spectroscopy data. This representation permits extraction of a relaxation time constant that provides important information on supercapacitor behaviour. The influence of carbon nanotubes addition on electrochemical performance of carbon/carbon supercapacitors has also been studied by electrochemical impedance spectroscopy

Chlorophylls, ligands and assembly of light-harvesting complexes in chloroplasts

Chlorophyll (Chl) b serves an essential function in accumulation of light-harvesting complexes (LHCs) in plants. In this article, this role of Chl b is explored by considering the properties of Chls and the ligands with which they interact in the complexes. The overall properties of the Chls, not only their spectral features, are altered as consequences of chemical modifications on the periphery of the molecules. Important modifications are introduction of oxygen atoms at specific locations and reduction or desaturation of sidechains. These modifications influence formation of coordination bonds by which the central Mg atom, the Lewis acid, of Chl molecules interacts with amino acid sidechains, as the Lewis base, in proteins. Chl a is a versatile Lewis acid and interacts principally with imidazole groups but also with sidechain amides and water. The 7-formyl group on Chl b withdraws electron density toward the periphery of the molecule and consequently the positive Mg is less shielded by the molecular electron cloud than in Chl a. Chl b thus tends to form electrostatic bonds with Lewis bases with a fixed dipole, such as water and, in particular, peptide backbone carbonyl groups. The coordination bonds are enhanced by H-bonds between the protein and the 7-formyl group. These additional strong interactions with Chl b are necessary to achieve assembly of stable LHCs

Can\u27t Hold Me Back! Constraint-Induced Movement Therapy for Children with CP: Evidence Based Review

Children with cerebral palsy (CP) have various functional impairments impacting participation in meaningful occupations. While Constraint-Induced Movement Therapy (CIMT) is a widely used intervention for adult populations, a modified version of this technique is a relatively new practice in pediatrics (Charles et al., 2006). Occupational therapy intervention, such as CIMT, can support functional goal attainment to enhance participation and quality of life (Boyd et al., 2010). The purpose of this presentation is to synthesize results of a comprehensive evidence-based review and identify treatment characteristics that impact efficacious use of mCIMT on children with hemiplegic CP. Practitioners will learn about best practice strategies according to current literature. After formulation of a clinical research question, a systematic search of 3 databases was conducted, yielding 15 articles. A rigorous screening process was used with specific inclusion and exclusion criteria. These articles were critiqued to identify the effectiveness of mCIMT. Using Law and MacDermid’s (2008) Appendix M, each article was reviewed by a primary rater with input from a secondary rater. Findings were synthesized and will be discussed in this presentation. The literature review indicated overall positive results for the use of mCIMT with pediatric CP populations. The majority of studies have found statistically significant results, however, there are mixed conclusions regarding clinical effect. A variety of protocol durations and types of constraints have been investigated, and demonstrate that a minimum of 1-2 hours of constraint wear time for 10-14 consecutive days may be effective in a clinic or home environment. Evidence suggests that the most effective mCIMT protocol involves a child-friendly approach using functional and age-appropriate tasks. Both preparatory and occupation-based activities were assessed utilizing a variety of standardized outcome measures. This presentation impacts clinical practice by providing evidence about the most effective intervention characteristics for implementing mCIMT as a useful and feasible treatment approach. Overall, children who received mCIMT by a trained interventionist improved functionally regardless of the protocol. Findings suggest less restrictive methods may be comparable to more intensive mCIMT interventions. Therefore, interventionists can tailor a specific mCIMT approach to meet the unique needs of each child. References: Boyd, R., Sakzewski, L., Ziviani, J., Abbott, D. F., Badawy, R., Gilmore, R., . . . Jackson, G. D. (2010). INCITE: A randomised trial comparing constraint induced movement therapy and bimanual training in children with congenital hemiplegia. BMC Neurology, 10, 1-15. doi:10.1186/1471-2377-10-4 Charles, J. R., Wolf, S. L., Schneider, J. A., & Gordon, A. M. (2006). Efficacy of a child-friendly form of constraint-induced movement therapy in hemiplegic cerebral palsy: A randomized control trial. Developmental Medicine and Child Neurology, 48(8), 635-642. doi:10.1017/S0012162206001356 Law, M. & MacDermid, J. (2008). Appendix M: Effectiveness Study Quality Checklist. In Evidence-based rehabilitation: A guide to practice (413-423). Thorofare, NJ: Slack, Inc

CNS Infiltration of Peripheral Immune Cells: D-Day for Neurodegenerative Disease?

While the central nervous system (CNS) was once thought to be excluded from surveillance by immune cells, a concept known as “immune privilege,” it is now clear that immune responses do occur in the CNS—giving rise to the field of neuroimmunology. These CNS immune responses can be driven by endogenous (glial) and/or exogenous (peripheral leukocyte) sources and can serve either productive or pathological roles. Recent evidence from mouse models supports the notion that infiltration of peripheral monocytes/macrophages limits progression of Alzheimer's disease pathology and militates against West Nile virus encephalitis. In addition, infiltrating T lymphocytes may help spare neuronal loss in models of amyotrophic lateral sclerosis. On the other hand, CNS leukocyte penetration drives experimental autoimmune encephalomyelitis (a mouse model for the human demyelinating disease multiple sclerosis) and may also be pathological in both Parkinson's disease and human immunodeficiency virus encephalitis. A critical understanding of the cellular and molecular mechanisms responsible for trafficking of immune cells from the periphery into the diseased CNS will be key to target these cells for therapeutic intervention in neurodegenerative diseases, thereby allowing neuroregenerative processes to ensue

Multiple nonprimary motor areas in the human cortex.

We measured the distribution of regional cerebral blood flow with positron emission tomography while three subjects moved their hand, shoulder, or leg. The images were coregistered with each individual's anatomic magnetic resonance scans. The data were analyzed for each individual to avoid intersubject averaging and so to preserve individual gyral anatomy. Instead of inspecting all pixels, we prospectively restricted the data analysis to particular areas of interest. These were defined on basis of the anatomic and physiological literature on nonhuman primates. By examining only a subset of areas, we strengthened the power of the statistical analysis and thereby increased the confidence in reporting single subject data. On the lateral convexity, motor related activity was found for all three subjects in the primary motor cortex, lateral premotor cortex, and an opercular area within the premotor cortex. In addition, there was activation of somatosensory cortex (SI), the supplementary somatosensory area (SII) in the Sylvian fissure, and parietal association areas (Brodmann areas 5 and 40). There was also activation in the insula. We suggest that the activation in the dorsal premotor cortex may correspond with dorsal premotor area (PMd) as described in the macaque brain. We propose three hypotheses as to the probable location of vental premotor area (PMv) in the human brain. On the medial surface, motor-related activity was found for all three subjects in the leg areas of the primary motor cortex and somatosensory cortex and also activity for the hand, shoulder, and leg in the supplementary motor area (SMA) on the dorsal medial convexity and in three areas in the cingulate sulcus. We suggest that the three cingulate areas may correspond with rostral cingulate premotor area, dorsal cingulate motor area (CMAd), and ventral cingulate motor area (CMAv) as identified in the macaque brain. Somatotopic mapping was demonstrated in the primary motor and primary somatosensory cortex. In all three subjects, the arm region lay anterior to the leg region in parietal area 5. Also in all three subjects, the arm region lay anterior to the leg region in the supplementary motor cortex