A Systematic Review of Glucose Transport Alterations in Alzheimer's Disease

From Frontiers via Jisc Publications RouterHistory: collection 2021, received 2021-01-12, accepted 2021-04-22, epub 2021-05-20Publication status: PublishedIntroduction: Alzheimer's disease (AD) is characterized by cerebral glucose hypometabolism. Hypometabolism may be partly due to reduced glucose transport at the blood-brain barrier (BBB) and across astrocytic and neuronal cell membranes. Glucose transporters (GLUTs) are integral membrane proteins responsible for moving glucose from the bloodstream to parenchymal cells where it is metabolized, and evidence indicates vascular and non-vascular GLUTs are altered in AD brains, a process which could starve the brain of glucose and accelerate cognitive decline. Here we review the literature on glucose transport alterations in AD from human and rodent studies. Methods: Literature published between 1st January 1946 and 1st November 2020 within EMBASE and MEDLINE databases was searched for the terms “glucose transporters” AND “Alzheimer's disease”. Human and rodent studies were included while reviews, letters, and in-vitro studies were excluded. Results: Forty-three studies fitting the inclusion criteria were identified, covering human (23 studies) and rodent (20 studies). Post-mortem studies showed consistent reductions in GLUT1 and GLUT3 in the hippocampus and cortex of AD brains, areas of the brain closely associated with AD pathology. Tracer studies in rodent models of AD and human AD also exhibit reduced uptake of glucose and glucose-analogs into the brain, supporting these findings. Longitudinal rodent studies clearly indicate that changes in GLUT1 and GLUT3 only occur after amyloid-β pathology is present, and several studies indicate amyloid-β itself may be responsible for GLUT changes. Furthermore, evidence from human and rodent studies suggest GLUT depletion has severe effects on brain function. A small number of studies show GLUT2 and GLUT12 are increased in AD. Anti-diabetic medications improved glucose transport capacity in AD subjects. Conclusions: GLUT1 and GLUT3 are reduced in hippocampal and cortical regions in patients and rodent models of AD, and may be caused by high levels of amyloid-β in these regions. GLUT3 reductions appear to precede the onset of clinical symptoms. GLUT2 and GLUT12 appear to increase and may have a compensatory role. Repurposing anti-diabetic drugs to modify glucose transport shows promising results in human studies of AD

Understanding the impact of heavy ions and tailoring the optical properties of large-area Monolayer WS2 using Focused Ion Beam

Focused ion beam (FIB) has been used as an effective tool for precise nanoscale fabrication. It has recently been employed to tailor defect engineering in functional nanomaterials such as two-dimensional transition metal dichalcogenides (TMDCs), providing desirable properties in TMDC-based optoelectronic devices. However, the damage caused by the FIB irradiation and milling process to these delicate atomically thin materials, especially in the extended area, has not yet been elaboratively characterised. Understanding the correlation between lateral ion beam effects and optical properties of 2D TMDCs is crucial in designing and fabricating high-performance optoelectronic devices. In this work, we investigate lateral damage in large-area monolayer WS2 caused by the gallium focused ion beam milling process. Three distinct zones away from the milling location are identified and characterised via steady-state photoluminescence (PL) and Raman spectroscopy. An unexpected bright ring-shaped emission around the milled location has been revealed by time-resolved PL spectroscopy with high spatial resolution. Our finding opens new avenues for tailoring the optical properties of TMDCs by charge and defect engineering via focused ion beam lithography. Furthermore, our study provides evidence that while some localised damage is inevitable, distant destruction can be eliminated by reducing the ion beam current. It paves the way for the use of FIB to create nanostructures in 2D TMDCs, as well as the design and realisation of optoelectrical devices on a wafer scale

Factors impacting employment for people with autism spectrum disorder: A scoping review

The aim of this study is to holistically synthesise the extent and range of literature relating to the employment of individuals with autism spectrum disorder. Database searches of Medline, CINAHL, PsychINFO, Scopus, ERIC, Web of Science and EMBASE were conducted. Studies describing adults with autism spectrum disorder employed in competitive, supported or sheltered employment were included. Content analysis was used to identify the strengths and abilities in the workplace of employees with autism spectrum disorder. Finally, meaningful concepts relating to employment interventions were extracted and linked to the International Classification of Functioning, Disability and Health Core Sets for autism spectrum disorder. The search identified 134 studies for inclusion with methodological quality ranging from limited to strong. Of these studies, only 36 evaluated employment interventions that were coded and linked to the International Classification of Functioning, Disability and Health, primarily focusing on modifying autism spectrum disorder characteristics for improved job performance, with little consideration of the impact of contextual factors on work participation. The International Classification of Functioning, Disability and Health Core Sets for autism spectrum disorder are a useful tool in holistically examining the employment literature for individuals with autism spectrum disorder. This review highlighted the key role that environmental factors play as barriers and facilitators in the employment of people with autism spectrum disorder and the critical need for interventions which target contextual factors if employment outcomes are to be improved

A global spectral library to characterize the world's soil

Soil provides ecosystem services, supports human health and habitation, stores carbon and regulates emissions of greenhouse gases. Unprecedented pressures on soil from degradation and urbanization are threatening agro-ecological balances and food security. It is important that we learn more about soil to sustainably manage and preserve it for future generations. To this end, we developed and analyzed a global soil visible-near infrared (vis-NIR) spectral library. It is currently the largest and most diverse database of its kind. We show that the information encoded in the spectra can describe soil composition and be associated to land cover and its global geographic distribution, which acts as a surrogate for global climate variability. We also show the usefulness of the global spectra for predicting soil attributes such as soil organic and inorganic carbon, clay, silt, sand and iron contents, cation exchange capacity, and pH. Using wavelets to treat the spectra, which were recorded in different laboratories using different spectrometers and methods, helped to improve the spectroscopic modelling. We found that modelling a diverse set of spectra with a machine learning algorithm can find the local relationships in the data to produce accurate predictions of soil properties. The spectroscopic models that we derived are parsimonious and robust, and using them we derived a harmonized global soil attribute dataset, which might serve to facilitate research on soil at the global scale. This spectroscopic approach should help to deal with the shortage of data on soil to better understand it and to meet the growing demand for information to assess and monitor soil at scales ranging from regional to global. New contributions to the library are encouraged so that this work and our collaboration might progress to develop a dynamic and easily updatable database with better global coverage. We hope that this work will reinvigorate our community's discussion towards larger, more coordinated collaborations. We also hope that use of the database will deepen our understanding of soil so that we might sustainably manage it and extend the research outcomes of the soil, earth and environmental sciences towards applications that we have not yet dreamed of

Polymorphisms in the RNASE3 Gene Are Associated with Susceptibility to Cerebral Malaria in Ghanaian Children

BACKGROUND: Cerebral malaria (CM) is the most severe outcome of Plasmodium falciparum infection and a major cause of death in children from 2 to 4 years of age. A hospital based study in Ghana showed that P. falciparum induces eosinophilia and found a significantly higher serum level of eosinophil cationic protein (ECP) in CM patients than in uncomplicated malaria (UM) and severe malaria anemia (SA) patients. Single nucleotide polymorphisms (SNPs) have been described in the ECP encoding-gene (RNASE3) of which the c.371G>C polymorphism (rs2073342) results in an arginine to threonine amino acid substitution p.R124T in the polypeptide and abolishes the cytotoxicity of ECP. The present study aimed to investigate the potential association between polymorphisms in RNASE3 and CM. METHODOLOGY/PRINCIPAL FINDINGS: The RNASE3 gene and flanking regions were sequenced in 206 Ghanaian children enrolled in a hospital based malaria study. An association study was carried out to assess the significance of five SNPs in CM (n=45) and SA (n=56) cases, respectively. The two severe case groups (CM and SA) were compared with the non-severe control group comprising children suffering from UM (n=105). The 371G allele was significantly associated with CM (p=0.00945, OR=2.29, 95% CI=1.22-4.32) but not with SA. Linkage disequilibrium analysis demonstrated significant linkage between three SNPs and the haplotype combination 371G/*16G/*94A was strongly associated with susceptibility to CM (p=0.000913, OR=4.14, 95% CI=1.79-9.56), thus, defining a risk haplotype. The RNASE3 371GG genotype was found to be under frequency-dependent selection. CONCLUSIONS/SIGNIFICANCE: The 371G allele of RNASE3 is associated with susceptibility to CM and forms part of a risk associated haplotype GGA defined by the markers: rs2073342 (G-allele), rs2233860 (G-allele) and rs8019343 (A-allele) respectively. Collectively, these results suggest a hitherto unrecognized role for eosinophils in CM pathogenesis

Waist circumference and risk of elevated blood pressure in children: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Increasing childhood obesity has become a major health threat. This cross-sectional study reports associations between schoolchildren's waist circumference (WC) and risk of elevated blood pressure.</p> <p>Methods</p> <p>We measured height, weight, neck and waist circumference, and blood pressure in regular health examinations among children in grade 1 (ages 6-7 years) at six elementary schools in Taipei County, Taiwan. Elevated blood pressure was defined in children found to have mean systolic or diastolic blood pressure greater than or equal to the gender-, age-, and height-percentile-specific 95th-percentile blood pressure value.</p> <p>Results</p> <p>All 2,334 schoolchildren were examined (response rate was 100% in the six schools). The mean of systolic and diastolic blood pressure increased as WC quartiles increased (p < 0.0001). The prevalence of elevated blood pressure for boys and girls within the fourth quartile of waist circumference was 38.9% and 26.8%, respectively. In the multivariate logistic regression analyses, the adjusted odds ratios of elevated blood pressure were 1.78 (95% confidence interval [CI] = 1.13-2.80), 2.45 (95% CI = 1.56-3.85), and 6.03 (95% CI = 3.59-10.1) for children in the second, third, and fourth waist circumference quartiles compared with the first quartile. The odds ratios for per-unit increase and per increase of standard deviation associated with elevated blood pressure were 1.14 (95% CI = 1.10-1.18) and 2.22 (95% CI = 1.76-2.78), respectively.</p> <p>Conclusions</p> <p>Elevated blood pressure in children was associated with waist circumference. Not only is waist circumference easier to measure than blood pressure, but it also provides important information on metabolic risk. Further research is needed on effective interventions to identify and monitor children with increased waist circumference to reduce metabolic and blood pressure risks.</p

Beyond the therapeutic: a Habermasian view of self-help groups’ place in the public sphere

Self-help groups in the United Kingdom continue to grow in number and address virtually every conceivable health condition, but they remain the subject of very little theoretical analysis. The literature to date has predominantly focused on their therapeutic effects on individual members. And yet they are widely presumed to fulfil a broader civic role and to encourage democratic citizenship. The article uses Habermas’ model of the public sphere as an analytical tool with which to reconsider the literature on self-help groups in order to increase our knowledge of their civic functions. In doing this it also aims to illustrate the continuing relevance of Habermas’ work to our understanding of issues in health and social care. We consider, within the context of current health policies and practices, the extent to which self-help groups with a range of different forms and functions operate according to the principles of communicative rationality that Habermas deemed key to democratic legitimacy. We conclude that self-help groups’ civic role is more complex than is usually presumed and that various factors including groups’ leadership, organisational structure and links with public agencies can affect their efficacy within the public sphere

Pain neuroimaging in humans: a primer for beginners and non-imagers

The field of human pain neuroimaging has exploded in the last two decades. During this time, the broader neuroimaging community has continued to investigate and refine methods. Another key to progress is exchange with clinicians and pain scientists working with other model systems and approaches. These collaborative efforts require that non-imagers be able to evaluate and assess the evidence provided in these papers. Likewise, new trainees must design rigorous and reliable pain imaging experiments. Here, we provide a guideline for designing, reading, evaluating, analyzing, and reporting results of a pain neuroimaging experiment, with a focus on functional and structural MRI. We focus in particular on considerations that are unique to neuroimaging studies of pain in humans, including study design and analysis, inferences that can be drawn from these studies, and the strengths and limitations of the approach. This article provides an overview of the concepts and considerations of structural and functional MRI neuroimaging studies. The primer is written for those who are not familiar with brain imaging. We review key concepts related to recruitment and study sample, experimental design, data analysis and data interpretation. [Abstract copyright: Copyright © 2018. Published by Elsevier Inc.

Mapping 123 million neonatal, infant and child deaths between 2000 and 2017

Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations