Publications by authors named "Ian Simpson"

135 Publications

How Living in Vulnerable Conditions Undermines Cognitive Development: Evidence from the Pediatric Population of Guatemala.

Children (Basel) 2021 Jan 29;8(2). Epub 2021 Jan 29.

Department of Psychology, Human Neuroscience Lab, Universidad Loyola Andalucía, 41704 Sevilla, Spain.

Low-socioeconomic backgrounds represent a risk factor for children's cognitive development and well-being. Evidence from many studies highlights that cognitive processes may be adversely affected by vulnerable contexts. The aim of this study was to determine if living in vulnerable conditions affects childhood cognitive development. To achieve this, we assessed the performance of a sample of 347 Guatemalan children and adolescents aged from 6 to 17 years ( = 10.8, = 3) in a series of 10 neuropsychological tasks recently standardized for the pediatric population of this country. Two-fifths of the sample (41.5%) could be considered to have vulnerable backgrounds, coming from families with low-socioeconomic status or having had a high exposure to violence. As expected, results showed lower scores in language and attention for the vulnerable group. However, contrary to expectations, consistent systematic differences were not found in the executive function tasks. Vulnerable children obtained lower scores in cognitive flexibility compared to the non-vulnerable group, but higher scores in inhibition and problem-solving tasks. These results suggest the importance of developing pediatric standards of cognitive performance that take environmental vulnerable conditions into consideration. These findings, one of the first obtained in the Guatemalan population, also provide relevant information for specific educational interventions and public health policies which will enhance vulnerable children and adolescent cognitive development.
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http://dx.doi.org/10.3390/children8020090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912439PMC
January 2021

Diagnostic dilemma for an adrenal mass: perivascular epithelioid cell neoplasm versus adrenocortical carcinoma.

ANZ J Surg 2021 Feb 6. Epub 2021 Feb 6.

Department of Anatomical Pathology, St Vincent's Hospital, Melbourne, Victoria, Australia.

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http://dx.doi.org/10.1111/ans.16648DOI Listing
February 2021

Rare case of adult intestinal hypoganglionosis and review of the literature.

Clin J Gastroenterol 2021 Apr 27;14(2):599-607. Epub 2021 Jan 27.

Colorectal Surgery Unit, Dandenong Hospital, Monash Health, 135 David Street, Dandenong, VIC, Australia.

Intestinal hypoganglionosis is a rare condition in adults. We report a case of intestinal hypoganglionosis in the mid-distal transverse colon to splenic flexure in a 65-year-old female patient presenting with altered bowel habit and abdominal distension, and reviewed the current literature on this topic. Our patient had a medical history of neurofibromatosis type 1. A preoperative computed tomography (CT) scan demonstrated a grossly dilated transverse colon without obstruction. A laparotomy for subtotal colectomy was performed, with histopathology demonstrating intestinal hypoganglionosis.
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http://dx.doi.org/10.1007/s12328-021-01342-5DOI Listing
April 2021

Access to community support workers during hospital admission for people with spinal cord injury: a pilot study.

Spinal Cord Ser Cases 2021 Jan 19;7(1). Epub 2021 Jan 19.

Burwood Academy of Independent Living, Christchurch, New Zealand.

Study Design: A descriptive qualitative study.

Objectives: To evaluate a pilot project enabling people with spinal cord injury (SCI) to have their support workers accompany them into a non-SCI specialist/public hospital (excluding ICU) to perform selected care.

Setting: The study was conducted in New Zealand.

Methods: Interviews and focus groups with people with SCI, support workers, care agency staff, and hospital staff who participated in the pilot project.

Results: Twenty-five individuals participated in the study. Two themes captured participants' experiences of the pilot: 'Maintaining individualised care' and 'Role, tasks and responsibilities. Support workers were described as knowledgeable about SCI care needs and being better positioned to provide individualised care for people with SCI than general nursing staff. Participants with SCI felt less anxious having a support worker with them, and perceived less risk of acquiring secondary health complications during the hospital admission. Good communications is important to ensure there is a shared understanding of the role and responsibilities of having an unregistered support worker in the hospital environment.

Conclusions: Having their regular support worker during admission to public hospital improved the SCI-specific care received. Support workers reduced the demand on hospital nursing staff who did not always have the time or specialist SCI knowledge to provide individualised care. People with SCI may be more likely to access medical assistance earlier and not defer hospital admissions if they can have support workers accompany them into hospital.
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http://dx.doi.org/10.1038/s41394-020-00370-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815731PMC
January 2021

Bullous pemphigoid in a young male during treatment with adalimumab.

Australas J Dermatol 2021 Feb 27;62(1):e155-e156. Epub 2020 Sep 27.

Department of Dermatology, Monash Health, Clayton, Victoria, Australia.

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http://dx.doi.org/10.1111/ajd.13466DOI Listing
February 2021

Kimura disease of the breast: Case report and literature review of current management.

Breast J 2020 10 20;26(10):2038-2041. Epub 2020 Aug 20.

Department of Breast Surgery, Monash Health, Bentleigh East, Vic, Australia.

We report a rare case of Kimura disease in a 50-year old female patient who attended our tertiary level Breast Surgery Clinic.
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http://dx.doi.org/10.1111/tbj.14026DOI Listing
October 2020

The role of neutrophils in mediating stroke injury in the diabetic db/db mouse brain following hypoxia-ischemia.

Neurochem Int 2020 10 9;139:104790. Epub 2020 Jul 9.

Dept of Neural & Behavioral Sciences, College of Medicine, Penn State University, Hershey Medical Center, Hershey, PA, USA.

Diabetic mice exhibit increased mortality and morbidity following stroke. Recent studies from our laboratory have indicated that increased morbidity in diabetic db/db mice relative to their non-diabetic db/+ littermates is associated with increased levels of MMP-9 protease activity, increased blood-brain barrier (BBB) permeability, and greater neutrophil infiltration following hypoxic/ischemic (H/I) insult. Neutrophils are a major source of proteases and reactive oxygen species and studies have reported neutrophil depletion/inhibition is protective in certain models of experimental stroke. The objective of the current study is to determine the role of neutrophils in the increased morbidity seen in db/db mice following acute ischemic stroke. In this study, we found a significant increase in circulating neutrophils in the db/db mice at 4 h post H/I, which bound to endothelial cells in the ipsilateral hemisphere and infiltrated into brain tissue by 24 h of recovery. Depletion of circulating neutrophils resulted in reduced neutrophil concentrations in blood and in the ipsilateral hemispheres of the brain of both db/+ and db/db mice and decreased the levels of MMP-9 within the infarcted area. This resulted in smaller infarct size in the db/db mice compared to non-treated controls but did not affect stroke outcome in db/+ mice. While there was a significant correlation between neutrophil number and the levels of MMP-9 in the ipsilateral hemisphere of control and diabetic mice, surprisingly, neutrophil depletion had no effect on BBB permeability in either group. Thus, the current study suggests that neutrophil depletion reduces MMP-9 protease levels and improves stroke outcome in db/db mice but not in their db/+ counterparts.
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http://dx.doi.org/10.1016/j.neuint.2020.104790DOI Listing
October 2020

Excellent outcomes of transformed lymphomas in the rituximab era without autologous stem cell transplantation: an Australian, single-centre experience.

Intern Med J 2020 Jul 1. Epub 2020 Jul 1.

Department of Clinical Haematology, Monash Health, Melbourne, Australia.

Background: Histologic transformation (HT) is an important event with adverse prognosis in the natural history of indolent lymphomas. There is minimal data on HT in the Australian setting.

Aim: To characterise patients with biopsy-proven HT and their outcomes identified at a tertiary Australian Hospital.

Methods: All patients with biopsy-proven HT during a 15-year period (2002-2017) were included. Clinico-pathological data were systematically collected from review of patient records. Survival estimates were assessed by the Kaplan-Meier method and compared using the log-rank test. Associations between variables and clinical outcomes were evaluated using Cox's proportional hazards model.

Results: A cohort of 45 patients was identified with a median age of 66 years and the majority (59%) having high-risk disease (Revised-International Prognostic Index score ≥ 3). R-CHOP induction was used in 69% with an overall response rate of 82% (complete response (CR), 75%). 61% of these induction-responders received consolidation, with autologous stem cell transplant (ASCT) performed in only 17% and rituximab maintenance given to 31%. With a median follow-up of 47 months (range: 4-136), the 5-year overall survival (OS) was 69% (95% CI: 52%, 81%). Chemotherapy-naivety at HT was associated with a superior rate of CR (84% vs. 54%, p = 0.057) and 5-year OS (82% vs. 46%, p = 0.012). Rituximab maintenance was associated with a durable progression-free survival in induction-responders.

Conclusions: Excellent OS was observed in this modern cohort of patients treated with rituximab-containing induction and low rate of consolidation by ASCT, particularly in those who were chemotherapy-naïve at HT. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/imj.14965DOI Listing
July 2020

Evidence for communication of peripheral iron status to cerebrospinal fluid: clinical implications for therapeutic strategy.

Fluids Barriers CNS 2020 Apr 16;17(1):28. Epub 2020 Apr 16.

Department of Neurology, Emory University, Atlanta, GA, USA.

Background: Iron is crucial for proper functioning of all organs including the brain. Deficiencies and excess of iron are common and contribute to substantial morbidity and mortality. Whereas iron's involvement in erythropoiesis drives clinical practice, the guidelines informing interventional strategies for iron repletion in neurological disorders are poorly defined. The objective of this study was to determine if peripheral iron status is communicated to the brain.

Methods: We used a bi-chamber cell culture model of the blood-brain-barrier to determine transcytosis of iron delivered by transferrin as a metric of iron transport. In the apical chamber (representative of the blood) we placed transferrin complexed with iron and in the basal chamber (representative of the brain) we placed human cerebrospinal fluid. Cerebrospinal fluid (CSF) samples (N = 24) were collected via lumbar puncture. The integrity of the tight junctions were monitored throughout the experiments using RITC-Dextran.

Results: We demonstrate that iron transport correlates positively with plasma hemoglobin concentrations but not serum ferritin levels.

Conclusions: The clinical ramifications of these findings are several- fold. They suggest that erythropoietic demands for iron take precedence over brain requirements, and that the metric traditionally considered to be the most specific test reflecting total body iron stores and relied upon to inform treatment decisions-i.e., serum ferritin-may not be the preferred peripheral indicator when attempting to promote brain iron uptake. The future direction of this line of investigation is to identify the factor(s) in the CSF that influence iron transport at the level of the BBB.
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http://dx.doi.org/10.1186/s12987-020-00190-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161256PMC
April 2020

Foley catheter for induction of labour: a UK observational study.

J Obstet Gynaecol 2020 Nov 3;40(8):1064-1068. Epub 2019 Dec 3.

Department of Obstetrics, Poole Hospital NHS Foundation Trust, Poole, UK.

We conducted a prospective observational study of all inductions using Foley's catheter at our center between 2016 and 2018. Outcome data collected included induction to delivery time, mode of delivery, complication rates, patient and staff satisfaction. Ninety-nine women were included in our study. Median induction to delivery time was 28.3 h (IQR 19.7-34 h), 20 (20.2%) women required Caesarean section. No relevant complications were recorded. Patients and staff were satisfied with the technique overall.These results show transcervical Foley's catheter is a safe and effective method of induction of labour in the UK setting. It was shown to be feasible in the outpatient and previous Caesarean section groups.Impact statement Foley catheter as an induction agent has already been shown to be as clinically effective as slow release prostaglandins with lower costs. No study has been published on its use for routine inductions in the UK. Our results show that Foley's catheter is a safe, effective method for inducing labour in the UK. This suggests this technique should be implemented more widely in the UK.
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http://dx.doi.org/10.1080/01443615.2019.1676213DOI Listing
November 2020

MicroRNA-34a Acutely Regulates Synaptic Efficacy in the Adult Dentate Gyrus In Vivo.

Mol Neurobiol 2020 Mar 21;57(3):1432-1445. Epub 2019 Nov 21.

Department of Biomedicine, University of Bergen, Bergen, Norway.

Activity-dependent synaptic plasticity involves rapid regulation of neuronal protein synthesis on a time-scale of minutes. miRNA function in synaptic plasticity and memory formation has been elucidated by stable experimental manipulation of miRNA expression and activity using transgenic approaches and viral vectors. However, the impact of rapid miRNA modulation on synaptic efficacy is unknown. Here, we examined the effect of acute (12 min), intrahippocampal infusion of a miR-34a antagonist (antimiR) on medial perforant path-evoked synaptic transmission in the dentate gyrus of adult anesthetised rats. AntimiR-34a infusion acutely depressed medial perforant path-evoked field excitatory post-synaptic potentials (fEPSPs). The fEPSP decrease was detected within 9 min of infusion, lasted for hours, and was associated with knockdown of antimiR-34a levels. AntimiR-34a-induced synaptic depression was sequence-specific; no changes were elicited by infusion of scrambled or mismatch control. The rapid modulation suggests that a target, or set of targets, is regulated by miR-34a. Western blot analysis of dentate gyrus lysates revealed enhanced expression of Arc, a known miR-34a target, and four novel predicted targets (Ctip2, PKI-1α, TCF4 and Ube2g1). Remarkably, antimiR-34a had no effect when infused during the maintenance phase of long-term potentiation. We conclude that miR-34a regulates basal synaptic efficacy in the adult dentate gyrus in vivo. To our knowledge, these in vivo findings are the first to demonstrate acute (< 9 min) regulation of synaptic efficacy in the adult brain by a miRNA.
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http://dx.doi.org/10.1007/s12035-019-01816-1DOI Listing
March 2020

Microliths in the South Asian rainforest ~45-4 ka: New insights from Fa-Hien Lena Cave, Sri Lanka.

PLoS One 2019 2;14(10):e0222606. Epub 2019 Oct 2.

Department of Archaeology, Max Planck Institute for the Science of Human History, Jena, Germany.

Microliths-small, retouched, often-backed stone tools-are often interpreted to be the product of composite tools, including projectile weapons, and efficient hunting strategies by modern humans. In Europe and Africa these lithic toolkits are linked to hunting of medium- and large-sized game found in grassland or woodland settings, or as adaptations to risky environments during periods of climatic change. Here, we report on a recently excavated lithic assemblage from the Late Pleistocene cave site of Fa-Hien Lena in the tropical evergreen rainforest of Sri Lanka. Our analyses demonstrate that Fa-Hien Lena represents the earliest microlith assemblage in South Asia (c. 48,000-45,000 cal. years BP) in firm association with evidence for the procurement of small to medium size arboreal prey and rainforest plants. Moreover, our data highlight that the lithic technology of Fa-Hien Lena changed little over the long span of human occupation (c. 48,000-45,000 cal. years BP to c. 4,000 cal. years BP) indicating a successful, stable technological adaptation to the tropics. We argue that microlith assemblages were an important part of the environmental plasticity that enabled Homo sapiens to colonise and specialise in a diversity of ecological settings during its expansion within and beyond Africa. The proliferation of diverse microlithic technologies across Eurasia c. 48-45 ka was part of a flexible human 'toolkit' that assisted our species' spread into all of the world's environments, and the development of specialised technological and cultural approaches to novel ecological situations.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0222606PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6774521PMC
March 2020

Archaeological assessment reveals Earth's early transformation through land use.

Authors:
Lucas Stephens Dorian Fuller Nicole Boivin Torben Rick Nicolas Gauthier Andrea Kay Ben Marwick Chelsey Geralda Armstrong C Michael Barton Tim Denham Kristina Douglass Jonathan Driver Lisa Janz Patrick Roberts J Daniel Rogers Heather Thakar Mark Altaweel Amber L Johnson Maria Marta Sampietro Vattuone Mark Aldenderfer Sonia Archila Gilberto Artioli Martin T Bale Timothy Beach Ferran Borrell Todd Braje Philip I Buckland Nayeli Guadalupe Jiménez Cano José M Capriles Agustín Diez Castillo Çiler Çilingiroğlu Michelle Negus Cleary James Conolly Peter R Coutros R Alan Covey Mauro Cremaschi Alison Crowther Lindsay Der Savino di Lernia John F Doershuk William E Doolittle Kevin J Edwards Jon M Erlandson Damian Evans Andrew Fairbairn Patrick Faulkner Gary Feinman Ricardo Fernandes Scott M Fitzpatrick Ralph Fyfe Elena Garcea Steve Goldstein Reed Charles Goodman Jade Dalpoim Guedes Jason Herrmann Peter Hiscock Peter Hommel K Ann Horsburgh Carrie Hritz John W Ives Aripekka Junno Jennifer G Kahn Brett Kaufman Catherine Kearns Tristram R Kidder François Lanoë Dan Lawrence Gyoung-Ah Lee Maureece J Levin Henrik B Lindskoug José Antonio López-Sáez Scott Macrae Rob Marchant John M Marston Sarah McClure Mark D McCoy Alicia Ventresca Miller Michael Morrison Giedre Motuzaite Matuzeviciute Johannes Müller Ayushi Nayak Sofwan Noerwidi Tanya M Peres Christian E Peterson Lucas Proctor Asa R Randall Steve Renette Gwen Robbins Schug Krysta Ryzewski Rakesh Saini Vivian Scheinsohn Peter Schmidt Pauline Sebillaud Oula Seitsonen Ian A Simpson Arkadiusz Sołtysiak Robert J Speakman Robert N Spengler Martina L Steffen Michael J Storozum Keir M Strickland Jessica Thompson T L Thurston Sean Ulm M Cemre Ustunkaya Martin H Welker Catherine West Patrick Ryan Williams David K Wright Nathan Wright Muhammad Zahir Andrea Zerboni Ella Beaudoin Santiago Munevar Garcia Jeremy Powell Alexa Thornton Jed O Kaplan Marie-José Gaillard Kees Klein Goldewijk Erle Ellis

Science 2019 08;365(6456):897-902

Environmentally transformative human use of land accelerated with the emergence of agriculture, but the extent, trajectory, and implications of these early changes are not well understood. An empirical global assessment of land use from 10,000 years before the present (yr B.P.) to 1850 CE reveals a planet largely transformed by hunter-gatherers, farmers, and pastoralists by 3000 years ago, considerably earlier than the dates in the land-use reconstructions commonly used by Earth scientists. Synthesis of knowledge contributed by more than 250 archaeologists highlighted gaps in archaeological expertise and data quality, which peaked for 2000 yr B.P. and in traditionally studied and wealthier regions. Archaeological reconstruction of global land-use history illuminates the deep roots of Earth's transformation and challenges the emerging Anthropocene paradigm that large-scale anthropogenic global environmental change is mostly a recent phenomenon.
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http://dx.doi.org/10.1126/science.aax1192DOI Listing
August 2019

Transferrin and H-ferritin involvement in brain iron acquisition during postnatal development: impact of sex and genotype.

J Neurochem 2020 02 22;152(3):381-396. Epub 2019 Aug 22.

Department of Neurosurgery, Penn State College of Medicine, Hershey, Pennsylvania, USA.

Iron delivery to the developing brain is essential for energy and metabolic support needed for processes such as myelination and neuronal development. Iron deficiency, especially in the developing brain, can result in a number of long-term neurological deficits that persist into adulthood. There is considerable debate that excess access to iron during development may result in iron overload in the brain and subsequently predispose individuals to age-related neurodegenerative diseases. There is a significant gap in knowledge regarding how the brain acquires iron during development and how biological variables such as development, genetics, and sex impact brain iron status. In this study, we used a mouse model expressing a mutant form of the iron homeostatic regulator protein HFE, (Hfe H63D), the most common gene variant in Caucasians, to determine impact of the mutation on brain iron uptake. Iron uptake was assessed using Fe bound to either transferrin or H-ferritin as the iron carrier proteins. We demonstrate that at postnatal day 22, mutant mice brains take up greater amounts of iron compared with wildtype. Moreover, we introduce H-ferritin as a key protein in brain iron transport during development and identify a sex and genotype effect demonstrating female mutant mice take up more iron by transferrin, whereas male mutant mice take up more iron from H-ferritin at PND22. Furthermore, we begin to elucidate the mechanism for uptake using immunohistochemistry to profile the regional distribution and temporal expression of transferrin receptor and T-cell immunoglobulin and mucin domain 2, the latter is the receptor for H-ferritin. These data demonstrate that sex and genotype have significant effects on iron uptake and that regional receptor expression may play a large role in the uptake patterns during development. Open Science: This manuscript was awarded with the Open Materials Badge For more information see: https://cos.io/our-services/open-science-badges/ Cover Image for this issue: doi: 10.1111/jnc.14731.
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http://dx.doi.org/10.1111/jnc.14834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6980902PMC
February 2020

Specialized rainforest hunting by Homo sapiens ~45,000 years ago.

Nat Commun 2019 02 19;10(1):739. Epub 2019 Feb 19.

Department of Archaeology, Max Planck Institute for the Science of Human History, 07745, Jena, Germany.

Defining the distinctive capacities of Homo sapiens relative to other hominins is a major focus for human evolutionary studies. It has been argued that the procurement of small, difficult-to-catch, agile prey is a hallmark of complex behavior unique to our species; however, most research in this regard has been limited to the last 20,000 years in Europe and the Levant. Here, we present detailed faunal assemblage and taphonomic data from Fa-Hien Lena Cave in Sri Lanka that demonstrates specialized, sophisticated hunting of semi-arboreal and arboreal monkey and squirrel populations from ca. 45,000 years ago, in a tropical rainforest environment. Facilitated by complex osseous and microlithic technologies, we argue these data highlight that the early capture of small, elusive mammals was part of the plastic behavior of Homo sapiens that allowed it to rapidly colonize a series of extreme environments that were apparently untouched by its hominin relatives.
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http://dx.doi.org/10.1038/s41467-019-08623-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381157PMC
February 2019

RAN and orthographic processing: What can syllable frequency tell us about this relationship?

J Exp Child Psychol 2019 06 16;182:1-17. Epub 2019 Feb 16.

Human Neuroscience Lab, Department of Psychology, Universidad Loyola Andalucía, 41014 Sevilla, Spain.

Many explanations accounting for rapid automatized naming's (RAN) relationship with reading have been proposed. One of the most debated perspectives argues that RAN measures orthographic processing, defined as the ability to process groups of letters or entire words as single units. Given that reading familiar spelling patterns will rely on orthographic processing more than reading unfamiliar spelling patterns, manipulating orthographic syllable frequency can be a useful tool to examine RAN's relationship with orthographic familiarity. To meet this aim, RAN's concurrent and longitudinal contribution to reading speed of nonwords composed of high and low syllable frequency, as well as real words, was assessed in a sample of 142 Spanish children. RAN, phonological skills, and visual skills were measured in kindergarten and Grade 5, whereas reading speed was measured in Grade 5 only. Both longitudinal and concurrent path analyses revealed that RAN made a comparable contribution to the reading of both types of nonwords as well as to real-word reading. This suggests that the reading-related cognitive ability measured by RAN operates at a grapho-phonemic, grapho-syllabic, and whole-word level. The current results do not support the view of RAN as a measure of orthographic processing.
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http://dx.doi.org/10.1016/j.jecp.2019.01.002DOI Listing
June 2019

Mixed-species RNA-seq for elucidation of non-cell-autonomous control of gene transcription.

Nat Protoc 2018 10;13(10):2176-2199

Edinburgh Medical School, and UK Dementia Research Institute at The University of Edinburgh, Edinburgh, UK.

Transcriptomic changes induced in one cell type by another mediate many biological processes in the brain and elsewhere; however, achieving artifact-free physical separation of cell types to study them is challenging and generally allows for analysis of only a single cell type. We describe an approach using a co-culture of distinct cell types from different species that enables physical cell sorting to be replaced by in silico RNA sequencing (RNA-seq) read sorting, which is possible because of evolutionary divergence of messenger RNA (mRNA) sequences. As an exemplary experiment, we describe the co-culture of purified neurons, astrocytes, and microglia from different species (12-14 d). We describe how to use our Python tool, Sargasso, to separate the reads from conventional RNA-seq according to species and to eliminate any artifacts borne of imperfect genome annotation (10 h). We show how this procedure, which requires no special skills beyond those that might normally be expected of wet lab and bioinformatics researchers, enables the simultaneous transcriptomic profiling of different cell types, revealing the distinct influence of microglia on astrocytic and neuronal transcriptomes under inflammatory conditions.
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http://dx.doi.org/10.1038/s41596-018-0029-2DOI Listing
October 2018

What Predicts What? Self-Reported and Behavioral Impulsivity and High-Risk Patterns of Alcohol Use in Spanish Early Adolescents: A 2-Year Longitudinal Study.

Alcohol Clin Exp Res 2018 10 26;42(10):2022-2032. Epub 2018 Aug 26.

Department of Psychology, Addictive Behaviors Research Group, Universidad de Oviedo, Oviedo, Asturias, Spain.

Background: The directionality of the relationship between impulsivity and heavy drinking patterns remains unclear. Recent research suggests it could be reciprocal and depends on different facets of impulsivity and different patterns of drinking. The aim of this study was to analyze this potential reciprocal relationship between self-reported and behavioral measures of impulsivity and sensation seeking with specific patterns of heavy drinking in a sample of Spanish adolescents across 2 years.

Methods: The study has a cross-lagged prospective design in which participants were evaluated 3 times over 2 years (once a year). Participants were 1,430 adolescents (53.9% male; mean age at study commencement = 13.02, SD = 0.51) from 22 secondary schools in Spain. Computerized versions of the following instruments were used: 2 subscales of Impulsive Sensation Seeking, 2 behavioral measures (Stroop Test and Delay Discounting [DD] task), frequency of intoxication episodes (IE), and the Rutgers Alcohol Problem Index to evaluate alcohol-related problems (ARP). Random intercepts cross-lagged panel models of reciprocal relationships between impulsivity measures and alcohol use outcomes were used.

Results: Individual levels of self-reported impulsivity and sensation seeking significantly predicted prospective involvement in IE and ARP. Performance in behavioral measures (Stroop Test and DD) did not predict subsequent heavy drinking or alcohol problems. No measure of drinking was found to be a significant predictor of prospective changes in impulsivity.

Conclusions: Within-person levels of self-reported impulsivity and sensation seeking significantly predicted further heavy drinking from as early as 13 years old, whereas behavioral measures were not predictive. In our study, neither IE nor ARP predicted prospective changes in impulsivity. Further studies should address additional specific relationships between facets of impulsivity and specific outcomes of heavy drinking.
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http://dx.doi.org/10.1111/acer.13852DOI Listing
October 2018

Endothelial cells are critical regulators of iron transport in a model of the human blood-brain barrier.

J Cereb Blood Flow Metab 2019 11 18;39(11):2117-2131. Epub 2018 Jun 18.

Department of Neurosurgery, Penn State College of Medicine, Hershey, PA, USA.

Iron delivery to the brain is essential for multiple neurological processes such as myelination, neurotransmitter synthesis, and energy production. Loss of brain iron homeostasis is a significant factor in multiple neurological disorders. Understanding the mechanism by which the transport of iron across the blood-brain barrier (BBB) is regulated is crucial to address the impact of iron deficiency on brain development and excessive accumulation of iron in neurodegenerative diseases. Using induced pluripotent stem cell (iPSC)-derived brain endothelial cells (huECs) as a human BBB model, we demonstrate the ability of transferrin, hepcidin, and DMT1 to impact iron transport and release. Our model reveals a new function for H-ferritin to transport iron across the BBB by binding to the T-cell immunoglobulin and mucin receptor 1. We show that huECs secrete both transferrin and H-ferritin, which can serve as iron sources for the brain. Based on our data, brain iron status can exert control of iron transport across the endothelial cells that constitute the BBB. These data address a number of pertinent questions such as how brain iron uptake is regulated at the regional level, the source of iron delivery to the brain, and the clinical strategies for attempting to treat brain iron deficiency.
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http://dx.doi.org/10.1177/0271678X18783372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827128PMC
November 2019

Pharmaceutical iron formulations do not cross a model of the human blood-brain barrier.

PLoS One 2018 11;13(6):e0198775. Epub 2018 Jun 11.

Department of Neurosurgery, Penn State Hershey Medical Center, Hershey, PA, United States of America.

Whether iron formulations used therapeutically for a variety of conditions involving iron deficiency can deliver iron to the brain is a significant clinical question given the impact that iron loading has on the brain in neurodegenerative diseases. In this study, we examine the ability of 5 pharmaceutical iron formulations that are given intravenously for treatment of iron deficiency to cross an in vitro model of the blood-brain barrier. The model uses human brain endothelial cells derived from induced pluripotent stem cells. We report that, compared to the natural iron delivery proteins, transferrin and H-ferritin, the pharmaceutical iron formulations neither cross the blood-brain barrier model nor significantly load the endothelial cells with iron. Furthermore, we report that mimicking brain iron sufficiency or deficiency by exposing the endothelial cells to apo- or holo-transferrin does not alter the amount of iron compound transported by or loaded into the cells. Coupled with previous studies, we propose that pharmaceutical iron formulations must first be processed in macrophages to make iron bioavailable. The results of this study have significant clinical and mechanistic implications for the use of therapeutic iron formulations.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0198775PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5995392PMC
January 2019

Iowa Stream Nitrate, Discharge and Precipitation: 30-Year Perspective.

Environ Manage 2018 10 31;62(4):709-720. Epub 2018 May 31.

Iowa Department of Natural Resources, Des Moines, IA, USA.

We evaluated Iowa Department of Natural Resources nitrate (NO-N) and US Geological Survey hydrological data from 1987 to 2016 in nine agricultural watersheds to assess how transport of this pollutant has changed in the US state of Iowa. When the first 15 years of the 30-year water-quality record is compared to the second 15 years (1987-2001 and 2002-2016), three different metrics used to quantify NO-N transport all indicate levels of this pollutant are increasing. Yield of NO-N (kg ha) averaged 18% higher in the second 15 years, while flow-weighted average concentrations (mg L) were 12% higher. We also introduced the new metric of NO-N yield (g ha) per mm precipitation to assess differences between years and watersheds, which averaged 21 g NO-N ha per 1 mm of precipitation across all watersheds and was 13% higher during the second half of the record. These increases of NO-N occurred within a backdrop of increasing wetness across Iowa, with precipitation and discharge levels 8 and 16% higher in the last half of the record, indicating how NO-N transport is amplified by increasing precipitation levels. The implications of this are that in future climate scenarios where rainfall is more abundant, detaining water and increasing evapotranspiration within the cropping system will be necessary to control NO-N losses. Land use changes that include use of cover crops, living mulches, and perennial plants should be expanded to improve water quality and affect the water balance within agricultural basins.
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http://dx.doi.org/10.1007/s00267-018-1074-xDOI Listing
October 2018

Mental health symptoms and verbal fluency in elderly people: Evidence from the Spanish longitudinal study of aging.

Aging Ment Health 2019 06 10;23(6):670-679. Epub 2018 Apr 10.

b Department of Developmental and Educational Psychology, University of Granada , Granada , Spain.

Objectives: Depression and loneliness are highly prevalent in old age. Moreover these mental health symptoms adversely affect the verbal fluency of the elderly. We examined the relationship between depression and loneliness with verbal fluency in people aged 50 years or older.

Method: Research data were collected during the pilot study of the Longitudinal Aging Study in Spain (ELES) in which a representative sample of non-institutionalized Spanish older people was assessed. Here, the cross-sectional data for 962 participants were analysed using hierarchical regressions, controlling for age, education level, overall cognitive functioning, social networks and satisfaction with family.

Results: Higher levels of cognitive functioning were associated with higher verbal fluency. Females showed higher levels of phonological fluency. Neither depression nor loneliness were significant predictors of phonological fluency but loneliness was a significant predictor of semantic fluency. For mild levels of loneliness, the rate of decline in semantic fluency slows in the oldest ages. In contrast, for severe loneliness the rate of decline in semantic fluency increases in the oldest ages.

Conclusions: Depressive symptoms, loneliness and cognitive impairment are all prominent in ageing and therefore their impact on ageing needs to be better understood. Early detection of loneliness, along with the implementation of intervention for individuals diagnosed with loneliness is advisable in order to avoid negative repercussions for the verbal fluency of these individuals.
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http://dx.doi.org/10.1080/13607863.2018.1448969DOI Listing
June 2019

Large Paediatric Central Osteoma with Osteoblastoma-Like Features in the Mandible.

Head Neck Pathol 2019 Jun 5;13(2):264-269. Epub 2018 Mar 5.

Consultant Oral and Maxillofacial Surgeon, Monash Health, Melbourne, VIC, Australia.

The diagnosis of osteomas in the paediatric population can pose a challenge to pathologists in excluding malignant bony tumours. We present the case of a 10-year old male presenting with a large left mandibular radiopaque lesion. This paper discusses the case of a central osteoma with osteoblastoma-like features, literature review, differential diagnosis of radiopaque lesions of the maxilla and mandible as well as a detailed discussion of the pathology of the lesion. Although similar lesions have been described in the sino-orbital region, this is believed to be the first report of this pathological entity in the mandible.
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http://dx.doi.org/10.1007/s12105-018-0900-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6514206PMC
June 2019

The role of HFE genotype in macrophage phenotype.

J Neuroinflammation 2018 Feb 1;15(1):30. Epub 2018 Feb 1.

Department of Neurosurgery, The Pennsylvania State University College of Medicine, M.S. Hershey Medical Center, Hershey, PA, 17033, USA.

Background: Iron regulation is essential for cellular energy production. Loss of cellular iron homeostasis has critical implications for both normal function and disease progression. The H63D variant of the HFE gene is the most common gene variant in Caucasians. The resulting mutant protein alters cellular iron homeostasis and is associated with a number of neurological diseases and cancer. In the brain, microglial and infiltrating macrophages are critical to maintaining iron homeostasis and modulating inflammation associated with the pathogenic process in multiple diseases. This study addresses whether HFE genotype affects macrophage function and the implications of these findings for disease processes.

Methods: Bone marrow macrophages were isolated from wildtype and H67D HFE knock-in mice. The H67D gene variant in mice is the human equivalent of the H63D variant. Upon differentiation, the macrophages were used to analyze iron regulatory proteins, cellular iron release, migration, phagocytosis, and cytokine expression.

Results: The results of this study demonstrate that the H67D HFE genotype significantly impacts a number of critical macrophage functions. Specifically, fundamental activities such as proliferation in response to iron exposure, L-ferritin expression in response to iron loading, secretion of BMP6 and cytokines, and migration and phagocytic activity were all found to be impacted by genotype. Furthermore, we demonstrated that exposure to apo-Tf (iron-poor transferrin) can increase the release of iron from macrophages. In normal conditions, 70% of circulating transferrin is unsaturated. Therefore, the ability of apo-Tf to induce iron release could be a major regulatory mechanism for iron release from macrophages.

Conclusions: These studies demonstrate that the HFE genotype impacts fundamental components of macrophage phenotype that could alter their role in degenerative and reparative processes in neurodegenerative disorders.
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http://dx.doi.org/10.1186/s12974-018-1057-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5796391PMC
February 2018

Oral vocabulary training program for Spanish third-graders with low socio-economic status: A randomized controlled trial.

PLoS One 2017 29;12(11):e0188157. Epub 2017 Nov 29.

Department of Developmental and Educational Psychology, Universidad de Granada, Granada, Spain.

Although the importance of vocabulary training in English speaking countries is well recognized and has been extensively studied, the same is not true for Spanish-few evidence based vocabulary studies for Spanish-speaking children have been reported. Here, two rich oral vocabulary training programs (definition and context), based on literature about vocabulary instruction for English-speaking children, were developed and applied in a sample of 100 Spanish elementary school third-graders recruited from areas of predominantly low socio-economic status (SES). Compared to an alternative read-aloud method which served as the control, both explicit methods were more effective in teaching word meanings when assessed immediately after the intervention. Nevertheless, five months later, only the definition group continued to demonstrate significant vocabulary knowledge gains. The definition method was more effective in specifically teaching children word meanings and, more broadly, in helping children organize and express knowledge of words. We recommend the explicit and rich vocabulary instruction as a means to fostering vocabulary knowledge in low SES children.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0188157PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5706695PMC
December 2017

X-Linked Lissencephaly With Absent Corpus Callosum and Abnormal Genitalia: An Evolving Multisystem Syndrome With Severe Congenital Intestinal Diarrhea Disease.

Child Neurol Open 2017 Jan-Dec;4:2329048X17738625. Epub 2017 Nov 7.

Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Victoria, Australia.

X-linked lissencephaly with abnormal genitalia is a rare and devastating syndrome. The authors present an infant with a multisystem phenotype where the intestinal manifestations were as life limiting as the central nervous system features. Severe chronic diarrhea resulted in failure to thrive, dehydration, electrolyte derangements, long-term hospitalization, and prompted transition to palliative care. Other multisystem manifestations included megacolon, colitis, pancreatic insufficiency hypothalamic dysfunction, hypothyroidism, and hypophosphatasia. A novel aristaless-related homeobox gene mutation, c.1136G>T/p.R379L, was identified. This case contributes to the clinical, histological, and molecular understanding of the multisystem nature of this disorder, especially the role of in the development of the enteroendocrine system.
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http://dx.doi.org/10.1177/2329048X17738625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5680935PMC
November 2017

Multi-organ vaso-occlusive disease: Buerger's or Kohlmeier-Degos disease?

Pathology 2017 Dec 31;49(7):798-801. Epub 2017 Oct 31.

Department of Nephrology, Monash Health, Melbourne, Australia; Centre for Inflammatory Diseases, Department of Medicine, Monash University, Clayton, Vic, Australia.

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http://dx.doi.org/10.1016/j.pathol.2017.06.008DOI Listing
December 2017

Regulatory mechanisms for iron transport across the blood-brain barrier.

Biochem Biophys Res Commun 2017 12 17;494(1-2):70-75. Epub 2017 Oct 17.

Department of Neurosurgery, Penn State Hershey Medical Center, Hershey, PA, United States. Electronic address:

Many critical metabolic functions in the brain require adequate and timely delivery of iron. However, most studies when considering brain iron uptake have ignored the iron requirements of the endothelial cells that form the blood-brain barrier (BBB). Moreover, current models of BBB iron transport do not address regional regulation of brain iron uptake or how neurons, when adapting to metabolic demands, can acquire more iron. In this study, we demonstrate that both iron-poor transferrin (apo-Tf) and the iron chelator, deferoxamine, stimulate release of iron from iron-loaded endothelial cells in an in vitro BBB model. The role of the endosomal divalent metal transporter 1 (DMT1) in BBB iron acquisition and transport has been questioned. Here, we show that inhibition of DMT1 alters the transport of iron and Tf across the endothelial cells. These data support an endosome-mediated model of Tf-bound iron uptake into the brain and identifies mechanisms for local regional regulation of brain iron uptake. Moreover, our data provide an explanation for the disparity in the ratio of Tf to iron transport into the brain that has confounded the field.
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http://dx.doi.org/10.1016/j.bbrc.2017.10.083DOI Listing
December 2017

Neurons and neuronal activity control gene expression in astrocytes to regulate their development and metabolism.

Nat Commun 2017 05 2;8:15132. Epub 2017 May 2.

Deanery of Biomedical Sciences, Edinburgh Medical School, University of Edinburgh, Edinburgh EH8 9XD, UK.

The influence that neurons exert on astrocytic function is poorly understood. To investigate this, we first developed a system combining cortical neurons and astrocytes from closely related species, followed by RNA-seq and in silico species separation. This approach uncovers a wide programme of neuron-induced astrocytic gene expression, involving Notch signalling, which drives and maintains astrocytic maturity and neurotransmitter uptake function, is conserved in human development, and is disrupted by neurodegeneration. Separately, hundreds of astrocytic genes are acutely regulated by synaptic activity via mechanisms involving cAMP/PKA-dependent CREB activation. This includes the coordinated activity-dependent upregulation of major astrocytic components of the astrocyte-neuron lactate shuttle, leading to a CREB-dependent increase in astrocytic glucose metabolism and elevated lactate export. Moreover, the groups of astrocytic genes induced by neurons or neuronal activity both show age-dependent decline in humans. Thus, neurons and neuronal activity regulate the astrocytic transcriptome with the potential to shape astrocyte-neuron metabolic cooperation.
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http://dx.doi.org/10.1038/ncomms15132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5418577PMC
May 2017