Genetic Risk for Alzheimer\u27s Disease Alters the Five-Year Trajectory of Semantic Memory Activation in Cognitively Intact Elders

Healthy aging is associated with cognitive declines typically accompanied by increased task-related brain activity in comparison to younger counterparts. The Scaffolding Theory of Aging and Cognition (STAC) (Park and Reuter-Lorenz, 2009; Reuter-Lorenz and Park, 2014) posits that compensatory brain processes are responsible for maintaining normal cognitive performance in older adults, despite accumulation of aging-related neural damage. Cross-sectional studies indicate that cognitively intact elders at genetic risk for Alzheimer\u27s disease (AD) demonstrate patterns of increased brain activity compared to low risk elders, suggesting that compensation represents an early response to AD-associated pathology. Whether this compensatory response persists or declines with the onset of cognitive impairment can only be addressed using a longitudinal design. The current prospective, 5-year longitudinal study examined brain activation in APOE ε4 carriers (N = 24) and non-carriers (N = 21). All participants, ages 65–85 and cognitively intact at study entry, underwent task-activated fMRI, structural MRI, and neuropsychological assessments at baseline, 18, and 57 months. fMRI activation was measured in response to a semantic memory task requiring participants to discriminate famous from non-famous names. Results indicated that the trajectory of change in brain activation while performing this semantic memory task differed between APOE ε4 carriers and non-carriers. The APOE ε4 group exhibited greater activation than the Low Risk group at baseline, but they subsequently showed a progressive decline in activation during the follow-up periods with corresponding emergence of episodic memory loss and hippocampal atrophy. In contrast, the non-carriers demonstrated a gradual increase in activation over the 5-year period. Our results are consistent with the STAC model by demonstrating that compensation varies with the severity of underlying neural damage and can be exhausted with the onset of cognitive symptoms and increased structural brain pathology. Our fMRI results could not be attributed to changes in task performance, group differences in cerebral perfusion, or regional cortical atrophy

The rebelion of Anōš Āzād

This article analyses the sources of the Rebellion of Anōš Āzād, son of Xusrō Anōšīrvān. The truth of what happ ened during this imp ortant p eriod of Iranian history may never be known. But historical sources have transmitted fragments of the story from various differ ent perspectives –often in lacunary form. Reading the relevant sources together, and analysing them, allows us to determine why some sources are fragmentary or deliberately misleading. It is possible to infer why certain authors, such as Procopius and Dinawari, might have been motivated to suppress or distort certain details also

James Howard-Johnston. The Sasanians’ Strategic Dilemma

Cet article traite, comme le suggère le titre, des dilemmes stratégiques auxquels les Sassanides étaient confrontés : la série de guerres contre les Romains, celle contre les Hephtalites, la montée du pouvoir des Turcs pendant le règne de Ḫosrow Anūšīrvān, et la succession de crises annonçant la chute de l’empire sassanide. Dans son style inimitable, l’A. décrit et analyse l’histoire de la grande offensive militaire lancée par Ḫosrow II contre l’empire romain et la sévère contre-attaque menée..

A brief military history of the later reign of Šāpur II

This is a brief history of the wars of Šāpur II from the middle of the fourth century to the death of that king in the year 379. These conflicts represent the military operations of the Sasanid state at its height before a gradual decline under the successor to Šāpur I

Nutritional deficiencies in homeless persons with problematic drinking:A systematic review

BACKGROUND: A significant proportion of homeless people drink alcohol excessively and this can lead to malnutrition and consequent medical problems. The aim of this review was to assess the evidence on the range of nutritional deficiencies in the homeless problem-drinking populations. METHODS: We conducted a comprehensive search of nine scientific literature databases and 13 grey literature sources. We included studies of any design that included homeless population with problem-drinking and reported measures of nutritional deficiencies in urine or blood. Study selection and data extraction was done by one reviewer and checked by another. Data on malnutrition profile were summarized narratively. RESULTS: We found nine studies reporting nutritional deficiencies in homeless populations with problem-drinking. The oldest study was from the 1950s and the most recent from 2013. The following nutrients were reported across studies: vitamins B1, B2, B6, B9, B12, C, A, and E; haemoglobin; and albumin. The most common deficiencies reported were of vitamin B1 (prevalence of deficiency was 0, 2, 6, 45, and 51% in five studies) and vitamin C (29, 84, and 95% in three studies). None of the studies were assessed to be at a low risk of bias. CONCLUSIONS: The limited, low quality and relatively old evidence suggests that homeless people who drink heavily may be deficient in vitamin C, thiamine, and other nutrients. New, well conducted studies are needed in order to optimally inform public health interventions aimed at improving deficiencies in this population

Single spin asymmetry for p↑p→πXp^{\uparrow}p \to \pi X in perturbative QCD

Within the QCD-improved parton model and assuming the factorization theorem to hold in the helicity basis and for higher twist contributions, we show how non zero single spin asymmetries in hadron-hadron high energy and moderately large $p_T$ inclusive processes can be obtained, even in massless perturbative QCD, provided the quark intrinsic motion is taken into account. A simple model is constructed which reproduces the main features of the data on the single spin asymmetry observed in inclusive pion production in $p\,p$ collisions.Comment: 11 pages + 1 figure, plain LaTeX, figure appended as uuencoded, compressed postscript file. Revised version, to be published in Phys. Lett. B; extensive changes in Sections 1 and 2, new References added, results and conclusions essentially unchange

Inflammatory Pathway Analytes Predicting Rapid Cognitive Decline in MCI stage of Alzheimer’s disease

Objective: To determine the inflammatory analytes that predict clinical progression and evaluate their performance against biomarkers of neurodegeneration. Methods: A longitudinal study of MCI-AD patients in a Discovery cohort over 15 months, with replication in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) MCI cohort over 36 months. Fifty-three inflammatory analytes were measured in the CSF and plasma with a RBM multiplex analyte platform. Inflammatory analytes that predict clinical progression on Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) and Mini Mental State Exam scores were assessed in multivariate regression models. To provide context, key analyte results in ADNI were compared against biomarkers of neurodegeneration, hippocampal volume, and CSF neurofilament light (NfL), in receiver operating characteristic (ROC) analyses evaluating highest quartile of CDR-SB change over two years (≥3 points). Results: Cerebrospinal fluid inflammatory analytes in relation to cognitive decline were best described by gene ontology terms, natural killer cell chemotaxis, and endothelial cell apoptotic process and in plasma, extracellular matrix organization, blood coagulation, and fibrin clot formation described the analytes. CSF CCL2 was most robust in predicting rate of cognitive change and analytes that correlated to CCL2 suggest IL-10 pathway dysregulation. The ROC curves for ≥3 points change in CDR-SB over 2 years when comparing baseline hippocampal volume, CSF NfL, and CCL2 were not significantly different. Interpretation: Baseline levels of immune cell chemotactic cytokine CCL2 in the CSF and IL-10 pathway dysregulation impact longitudinal cognitive and functional decline in MCI-AD. CCL2’s utility appears comparable to biomarkers of neurodegeneration in predicting rapid decline

Protein transport in intact, purified pea etioplasts

We have developed a method to isolate intact, purified pea etioplasts. These etioplasts were capable of recognizing, transporting, and processing the precursor form of the small subunit of the ribulose-1,5-bisphosphate carboxylase, a protein which is not detectable at this developmental stage. Transport of proteins was completely dependent on ATP and could not be substituted for or stimulated by light. The transported precursor protein was processed to its proper molecular weight. The mature form of the small subunit was assembled with the large subunit of the ribulose-1,5-bisphosphate carboxylase already present at this stage to form an oligomer. Protein transport was completely abolished using the phosphatase inhibitor sodium fluoride. This is the first time protein transport has been demonstrated in isolated, purified etioplasts

Quasi-Elastic Scattering in the Inclusive (3^3He, t) Reaction

The triton energy spectra of the charge-exchange $^{12}$C($^3$He,t) reaction at 2 GeV beam energy are analyzed in the quasi-elastic nucleon knock-out region. Considering that this region is mainly populated by the charge-exchange of a proton in $^3$He with a neutron in the target nucleus and the final proton going in the continuum, the cross-sections are written in the distorted-wave impulse approximation. The t-matrix for the elementary exchange process is constructed in the DWBA, using one pion- plus rho-exchange potential for the spin-isospin nucleon- nucleon potential. This t-matrix reproduces the experimental data on the elementary pn $\rightarrow$np process. The calculated cross-sections for the $^{12}$C($^3$He,t) reaction at $2^o$ to $7^o$ triton emission angle are compared with the corresponding experimental data, and are found in reasonable overall accord.Comment: 19 pages, latex, 11 postscript figures available at [email protected], submitted to Phy.Rev.