Relationships Between Markers of Iron Status and Hematological Parameters in Patients With Sickle Cell Disease.

Based on the relationship between the intracellular concentration of sickle hemoglobin S (HbS) and the delay that occurs prior to the onset of sickling following deoxygenation, targeting the intracellular HbS concentration is a recognized therapeutic approach for sickle cell disease (SCD). We and others have shown that restricting iron by dietary or pharmacologic means improves hematologic parameters, inflammation, and organ damage in mouse models of SCD. Clinical evidence corroborating these findings is confined to case reports and small case series studies, none of which account for treatment or -thalassemia.

Neuropsychiatric Symptoms and Alzheimer Disease Biomarkers Independently Predict Progression to Incident Cognitive Impairment.

Objectives: To investigate the effect of neuropsychiatric symptoms and depression symptoms, respectively, and Alzheimer disease (AD) biomarkers (cerebrospinal fluid [CSF] or Positron Emission Tomography [PET] imaging) on the progression to incident cognitive impairment among cognitively normal older adults.

Design: Prospective, observation, longitudinal study.

Setting: Knight Alzheimer Disease Research Center (ADRC) at Washington University School of Medicine.

Adverse driving behaviors increase over time as a function of preclinical Alzheimer's disease biomarkers.

Introduction: We investigated the relationship between preclinical Alzheimer's disease (AD) biomarkers and adverse driving behaviors in a longitudinal analysis of naturalistic driving data.

Methods: Naturalistic driving data collected using in-vehicle dataloggers from 137 community-dwelling older adults (65+) were used to model driving behavior over time. Cerebrospinal fluid (CSF) biomarkers were used to identify individuals with preclinical AD.

Neuropsychological Correlates of Changes in Driving Behavior Among Clinically Healthy Older Adults.

Objectives: To determine the extent to which cognitive domain scores moderate change in driving behavior in cognitively healthy older adults using naturalistic (Global Positioning System-based) driving outcomes and to compare against self-reported outcomes using an established driving questionnaire.

Methods: We analyzed longitudinal naturalistic driving behavior from a sample (N = 161, 45% female, mean age = 74.7 years, mean education = 16.

Strategic adaptation to dual-task in verbal working memory: Potential routes for theory integration.

How working memory supports dual-task performance is the focus of a long-standing debate. Most previous research on this topic has focused on participant performance data. In three experiments, we investigated whether changes in participant-reported strategies across single- and dual-task conditions might help resolve this debate by offering new insights that lead to fruitful integration of theories rather than perpetuating debate by attempting to identify which theory best fits the data.

Driving, Social Distancing, Protective, and Coping Behaviors of Older Adults Before and During COVID-19.

A thorough understanding of individual characteristics of older adults during the COVID-19 pandemic is critical for managing the ongoing pandemic course and planning for the future pandemics. Here, we explore the impact of the COVID-19 pandemic on driving, social distancing, protective, and coping behaviors of older adults. This study reports data on participants aged above 65 whose driving behaviors are being monitored using Global Positioning System (GPS) devices.

Naturalistic driving measures of route selection associate with resting state networks in older adults.

Our objective was to identify functional brain changes that associate with driving behaviors in older adults. Within a cohort of 64 cognitively normal adults (age 60+), we compared naturalistic driving behavior with resting state functional connectivity using machine learning. Functional networks associated with the ability to interpret and respond to external sensory stimuli and the ability to multi-task were associated with measures of route selection.

Adverse driving behaviors are associated with sleep apnea severity and age in cognitively normal older adults at risk for Alzheimer's disease.

Alzheimer's disease (AD) pathology accumulates for decades before the onset of cognitive decline. Cognitively normal individuals with biomarker evidence of AD brain pathology (i.e.

Longitudinal Changes in Anger, Anxiety, and Fatigue Are Associated with Cerebrospinal Fluid Biomarkers of Alzheimer's Disease.

Alzheimer's disease (AD) studies in cognitively normal (CN) older adults age≥65 suggest depression is associated with molecular biomarkers (imaging and cerebrospinal fluid [CSF]). This study used linear mixed models (covariance pattern model) to assess whether baseline CSF biomarkers (Aβ42/Aβ40, t-Tau/Aβ42, p-Tau/Aβ42) predicted changes in non-depressed mood states in CN older adults (N = 248), with an average of three follow-up years. Participants with higher levels of CSF biomarkers developed more anger, anxiety, and fatigue over time compared to those with more normal levels.

Exploring the influence of temporal factors on age differences in working memory dual task costs.

Working memory is defined by many as the system that allows us to simultaneously store information over brief time periods while engaging in other information processing activities. In a previous study (Rhodes, Jaroslawska et al. (2019) Journal of Experimental Psychology: General, 148, 1204-1227.

What affects the magnitude of age-related dual-task costs in working memory? The role of stimulus domain and access to semantic representations.

Although there is evidence that the effect of including a concurrent processing demand on the storage of information in working memory is disproportionately larger for older than younger adults, not all studies show this age-related impairment, and the critical factors responsible for any such impairment remain elusive. Here we assess whether domain overlap between storage and processing activities, and access to semantic representations, are important determinants of performance in a sample of younger and older adults ( = 119). We developed four versions of a processing task by manipulating the type of stimuli involved (either verbal or non-verbal) and the decision that participants had to make about the stimuli presented on the screen.

How Do Scientific Views Change? Notes From an Extended Adversarial Collaboration.

There are few examples of an extended adversarial collaboration, in which investigators committed to different theoretical views collaborate to test opposing predictions. Whereas previous adversarial collaborations have produced single research articles, here, we share our experience in programmatic, extended adversarial collaboration involving three laboratories in different countries with different theoretical views regarding working memory, the limited information retained in mind, serving ongoing thought and action. We have focused on short-term memory retention of items (letters) during a distracting task (arithmetic), and effects of aging on these tasks.

Storage and processing in working memory: Assessing dual-task performance and task prioritization across the adult lifespan.

There is a theoretical disagreement in the working memory literature, with some proposing that the storage and processing of information rely on distinct parts of the cognitive system and others who posit that they rely, to some extent, on a shared attentional capacity. This debate is mirrored in the literature on working memory and aging, where there have been mixed findings on the ability of older adults to perform simultaneous storage and processing tasks. We assess the overlap between storage and processing and how this changes with age using a procedure in which both tasks have been carefully adjusted to produce comparable levels of single-task performance across a sample (N = 164) of participants aged 18-81.

Dual-task costs in working memory: An adversarial collaboration.

[Correction Notice: An Erratum for this article was reported in Vol 45(9) of (see record 2019-48991-001). In the article, the copyright attribution was incorrectly listed and should have published under the Creative Commons CC-BY license. The correct copyright is "© 2018 The Author(s).

Resource-sharing in multiple-component working memory.

Working memory research often focuses on measuring the capacity of the system and how it relates to other cognitive abilities. However, research into the structure of working memory is less concerned with an overall capacity measure but rather with the intricacies of underlying components and their contribution to different tasks. A number of models of working memory structure have been proposed, each with different assumptions and predictions, but none of which adequately accounts for the full range of data in the working memory literature.

Item response theory analysis of cognitive tests in people with dementia: a systematic review.

Background: Performance on psychometric tests is key to diagnosis and monitoring treatment of dementia. Results are often reported as a total score, but there is additional information in individual items of tests which vary in their difficulty and discriminatory value. Item difficulty refers to an ability level at which the probability of responding correctly is 50%.

Hepatic steatosis, inflammation, and ER stress in mice maintained long term on a very low-carbohydrate ketogenic diet.

Low-carbohydrate diets are used to manage obesity, seizure disorders, and malignancies of the central nervous system. These diets create a distinctive, but incompletely defined, cellular, molecular, and integrated metabolic state. Here, we determine the systemic and hepatic effects of long-term administration of a very low-carbohydrate, low-protein, and high-fat ketogenic diet, serially comparing these effects to a high-simple-carbohydrate, high-fat Western diet and a low-fat, polysaccharide-rich control chow diet in C57BL/6J mice.

Sorting mouse jejunal epithelial cells with CD24 yields a population with characteristics of intestinal stem cells.

Intestinal stem cells (ISCs) have been studied for more than three decades; however, their isolation has remained a challenge. We hypothesized that, just as for stem cells of other tissues, one or more membrane markers would allow positive selection of ISCs by antibody-based sorting. To explore this hypothesis, microarray data of putative ISC fractions generated by side population sorting and laser capture microdissection were subjected to bioinformatic analysis to identify common membrane antigens.

The transcription factor MIST1 is a novel human gastric chief cell marker whose expression is lost in metaplasia, dysplasia, and carcinoma.

The lack of reliable molecular markers for normal differentiated epithelial cells limits understanding of human gastric carcinogenesis. Recognized precursor lesions for gastric adenocarcinoma are intestinal metaplasia and spasmolytic polypeptide expressing metaplasia (SPEM), defined here by ectopic CDX2 and TFF2 expression, respectively. In mice, expression of the bHLH transcription factor MIST1, normally restricted to mature chief cells, is down-regulated as chief cells undergo experimentally induced metaplasia.

Adaptation of myocardial substrate metabolism to a ketogenic nutrient environment.

Heart muscle is metabolically versatile, converting energy stored in fatty acids, glucose, lactate, amino acids, and ketone bodies. Here, we use mouse models in ketotic nutritional states (24 h of fasting and a very low carbohydrate ketogenic diet) to demonstrate that heart muscle engages a metabolic response that limits ketone body utilization. Pathway reconstruction from microarray data sets, gene expression analysis, protein immunoblotting, and immunohistochemical analysis of myocardial tissue from nutritionally modified mouse models reveal that ketotic states promote transcriptional suppression of the key ketolytic enzyme, succinyl-CoA:3-oxoacid CoA transferase (SCOT; encoded by Oxct1), as well as peroxisome proliferator-activated receptor alpha-dependent induction of the key ketogenic enzyme HMGCS2.

Regulation of mouse embryonic stem cell neural differentiation by retinoic acid.

Pluripotent mouse embryonic stem cells (ESCs) derived from the early blastocyst can differentiate in vitro into a variety of somatic cell types including lineages from all three embryonic germ layers. Protocols for ES cell neural differentiation typically involve induction by retinoic acid (RA), or by exposure to growth factors or medium conditioned by other cell types. A serum-free differentiation (SFD) medium completely lacking exogenous retinoids was devised that allows for efficient conversion of aggregated mouse ESCs into neural precursors and immature neurons.

A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity.

Natural killer (NK) cells are classically viewed as lymphocytes that provide innate surveillance against virally infected cells and tumour cells through the release of cytolytic mediators and interferon (IFN)-gamma. In humans, blood CD56(dim) NK cells specialize in the lysis of cell targets. In the lymph nodes, CD56(bright) NK cells secrete IFN-gamma cooperating with dendritic cells and T cells in the generation of adaptive responses.

Diverse adult stem cells share specific higher-order patterns of gene expression.

Adult tissue stem cells (SCs) share functional properties regardless of their tissue of residence. It had been thought that SCs might also share expression of certain "stemness" genes, although early investigations for such genes were unsuccessful. Here, we show that SCs from diverse tissues do preferentially express certain types of genes and that SCs resemble other SCs in terms of global gene expression more than they resemble the differentiated cells (DCs) of the tissues that they supply.