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Cerebral hemodynamics and metabolism are similar in sickle cell disease patients with hemoglobin SS and Sβ thalassemia phenotypes.
Ikwuanusi I, Jordan LC, Lee CA, Patel NJ, Waddle S, Pruthi S, Davis LT, Griffin A, DeBaun MR, Kassim AA, Donahue MJ
(2020) Am J Hematol 95: E66-E68
MeSH Terms: Adolescent, Adult, Anemia, Sickle Cell, Cerebrovascular Circulation, Child, Female, Hemodynamics, Hemoglobin, Sickle, Humans, Male, Thalassemia
Added March 24, 2020
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11 MeSH Terms
Temporo-frontal activation during phonological processing predicts gains in arithmetic facts in young children.
Suárez-Pellicioni M, Fuchs L, Booth JR
(2019) Dev Cogn Neurosci 40: 100735
MeSH Terms: Adolescent, Brain, Brain Mapping, Child, Female, Frontal Lobe, Humans, Male, Mathematics, Phonetics, Temporal Lobe
Show Abstract · Added March 3, 2020
Behavioral studies have shown discrepant results regarding the role of phonology in predicting math gains. The objective of this study was to use fMRI to study the role of activation during a rhyming judgment task in predicting behavioral gains on math fluency, multiplication, and subtraction skill. We focused within the left middle/superior temporal gyrus and left inferior frontal gyrus, brain areas associated with the storage of phonological representations and with their access, respectively. We ran multiple regression analyses to determine whether activation predicted gains in the three math measures, separately for younger (i.e. 10 years old) and older (i.e 12 years old) children. Results showed that activation in both temporal and frontal cortex only predicted gains in fluency and multiplication skill, and only for younger children. This study suggests that both temporal and frontal cortex activation during phonological processing are important in predicting gains in math tasks that involve the retrieval of facts that are stored as phonological codes in memory. Moreover, these results were specific to younger children, suggesting that phonology is most important in the early stages of math development. When the math task involved subtractions, which relies on quantity representations, phonological processes were not important in driving gains.
Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.
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11 MeSH Terms
Roux-en-Y gastric bypass surgery improves hepatic glucose metabolism and reduces plasma kisspeptin levels in morbidly obese patients with type 2 diabetes.
Flynn CR, Albaugh VL, Tamboli RA, Gregory JM, Bosompem A, Sidani RM, Winnick JJ
(2020) Am J Physiol Gastrointest Liver Physiol 318: G370-G374
MeSH Terms: Adolescent, Adult, Anastomosis, Roux-en-Y, Blood Glucose, Diabetes Mellitus, Type 2, Female, Glucagon, Glucose, Humans, Insulin, Kisspeptins, Liver, Male, Middle Aged, Obesity, Morbid, Treatment Outcome, Young Adult
Show Abstract · Added November 12, 2019
Roux-en-Y gastric bypass surgery (RYGB) is known to improve whole-body glucose metabolism in patients with type 2 diabetes (T2D), although the mechanisms are not entirely clear and are likely multifactorial. The aim of this study was to assess fasting hepatic glucose metabolism and other markers of metabolic activity before and after RYGB in patients with and without T2D. Methods: Metabolic characteristics of patients who are obese with T2D were compared with those without the disease (non-T2D) before and 1 and 6 mo after RYGB. Fasting plasma insulin and the insulin:glucagon ratio were markedly reduced as early as 1 mo after RYGB in both patients with T2D and without T2D. Despite this reduction, endogenous glucose production and fasting plasma glucose levels were lower in both groups after RYGB, with the reductions being much larger in T2D. Plasma kisspeptin, an inhibitor of insulin secretion, was reduced only in T2D after surgery. Improved hepatic glucose metabolism and lower plasma kisspeptin in T2D after RYGB may link improved hepatic function with enhanced insulin responsiveness after surgery. Our manuscript is the first, to the best of our knowledge, to present data showing that Roux-en-Y gastric bypass surgery (RYGB) lowers fasting kisspeptin levels in patients who are obese with type 2 diabetes. This lowering of kisspeptin is important because it could link improvements in liver glucose metabolism after RYGB with increased insulin responsiveness also seen after surgery.
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17 MeSH Terms
Increased reporting of fatal hepatitis associated with immune checkpoint inhibitors.
Vozy A, De Martin E, Johnson DB, Lebrun-Vignes B, Moslehi JJ, Salem JE
(2019) Eur J Cancer 123: 112-115
MeSH Terms: Adolescent, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Immunological, B7-H1 Antigen, CTLA-4 Antigen, Chemical and Drug Induced Liver Injury, Child, Databases, Factual, Female, Hepatitis, Autoimmune, Humans, Ipilimumab, Male, Massive Hepatic Necrosis, Middle Aged, Neoplasms, Nivolumab, Programmed Cell Death 1 Receptor, World Health Organization, Young Adult
Added November 12, 2019
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23 MeSH Terms
DNA methylation of HPA-axis genes and the onset of major depressive disorder in adolescent girls: a prospective analysis.
Humphreys KL, Moore SR, Davis EG, MacIsaac JL, Lin DTS, Kobor MS, Gotlib IH
(2019) Transl Psychiatry 9: 245
MeSH Terms: Adolescent, CpG Islands, DNA Methylation, Depressive Disorder, Major, Epigenesis, Genetic, Female, Genotype, Humans, Hypothalamo-Hypophyseal System, Pituitary-Adrenal System, Polymorphism, Single Nucleotide, Proportional Hazards Models, Prospective Studies, Receptors, Corticotropin-Releasing Hormone, Receptors, Glucocorticoid
Show Abstract · Added March 3, 2020
The stress response system is disrupted in individuals with major depressive disorder (MDD) as well as in those at elevated risk for developing MDD. We examined whether DNA methylation (DNAm) levels of CpG sites within HPA-axis genes predict the onset of MDD. Seventy-seven girls, approximately half (n = 37) of whom were at familial risk for MDD, were followed longitudinally. Saliva samples were taken in adolescence (M age = 13.06 years [SD = 1.52]) when participants had no current or past MDD diagnosis. Diagnostic interviews were administered approximately every 18 months until the first onset of MDD or early adulthood (M age of last follow-up = 19.23 years [SD = 2.69]). We quantified DNAm in saliva samples using the Illumina EPIC chip and examined CpG sites within six key HPA-axis genes (NR3C1, NR3C2, CRH, CRHR1, CRHR2, FKBP5) alongside 59 genotypes for tagging SNPs capturing cis genetic variability. DNAm levels within CpG sites in NR3C1, CRH, CRHR1, and CRHR2 were associated with risk for MDD across adolescence and young adulthood. To rule out the possibility that findings were merely due to the contribution of genetic variability, we re-analyzed the data controlling for cis genetic variation within these candidate genes. Importantly, methylation levels in these CpG sites continued to significantly predict the onset of MDD, suggesting that variation in the epigenome, independent of proximal genetic variants, prospectively predicts the onset of MDD. These findings suggest that variation in the HPA axis at the level of the methylome may predict the development of MDD.
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15 MeSH Terms
Automatic semantic influence on early visual word recognition in the ventral occipito-temporal cortex.
Wang J, Deng Y, Booth JR
(2019) Neuropsychologia 133: 107188
MeSH Terms: Adolescent, Adult, China, Female, Functional Neuroimaging, Humans, Language, Magnetic Resonance Imaging, Male, Neural Pathways, Occipital Lobe, Pattern Recognition, Visual, Prefrontal Cortex, Reading, Repetition Priming, Semantics, Temporal Lobe, Young Adult
Show Abstract · Added March 3, 2020
The left ventral occipitotemporal cortex (vOT) is a critical region in reading. According to the interactive account of reading, the vOT is an interface between the lower-level visual regions and higher-level language areas. One prediction of the interactive account is that orthographic activation in vOT should be automatically influenced by semantics and phonology. In the current study, we used functional magnetic resonance imaging (fMRI) and a masked priming paradigm with a relatively short duration (150 ms) to examine whether language information automatically influences vOT during Chinese reading. Participants were asked to perform a lexical decision task on target characters. We separately tested the phonological and semantic influence on orthographic processing in vOT. Brain activation analyses showed that the activation of vOT was modulated by semantic information. In addition, a functional connectivity analysis showed stronger connectivity between vOT and the left ventral inferior frontal gyrus was modulated by semantic information. These findings provided converging evidence for the existence of an automatic semantic influence on vOT during reading, supporting the interactive account. Our study did not show a phonological effect either in the activation of or connectivity with vOT. Taken together, these results reflect the unique processes of Chinese reading, which relies more on the mapping between orthography and semantics, as compared to the orthographic to phonology mapping.
Copyright © 2019 Elsevier Ltd. All rights reserved.
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18 MeSH Terms
Advanced age adversely affects chronic rhinosinusitis surgical outcomes.
Yancey KL, Lowery AS, Chandra RK, Chowdhury NI, Turner JH
(2019) Int Forum Allergy Rhinol 9: 1125-1134
MeSH Terms: Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Chronic Disease, Endoscopy, Female, Humans, Male, Middle Aged, Nasal Surgical Procedures, Paranasal Sinuses, Prognosis, Quality of Life, Rhinitis, Sinusitis, Treatment Outcome, United States, Young Adult
Show Abstract · Added July 23, 2020
BACKGROUND - Patient-specific and disease-specific factors shape the course of chronic rhinosinusitis (CRS) and its response to treatment, with optimal management involving interventions tailored to these factors. Recent evidence suggests CRS inflammatory signatures depend on age. The objective of this study was to determine whether age also influences quality-of-life (QOL) and postoperative outcomes.
METHODS - Retrospective analysis of prospectively collected QOL data from 403 adults with medically refractory CRS who underwent functional endoscopic sinus surgery (FESS) at a tertiary care medical center between 2014 and 2018 was undertaken. Total and subdomain scores from the 22-item Sino-Nasal Outcome Test (SNOT-22) and the Short Form 8 Health Survey (SF-8) measure of general health completed at preoperative and postoperative visits were reviewed.
RESULTS - Patients were divided into young (18 to 39 years, n = 100), middle-aged (40 to 59 years, n = 172), and elderly (≥60 years, n = 131) groups. Baseline total SNOT-22 scores differed between groups (p = 0.01), with middle-aged patients having the highest symptom burden and elderly patients having the lowest. Similar patterns were observed for SNOT-22 subdomains. Elderly patients reported smaller improvements and were less likely to achieve a minimally important clinical difference. CRS patients had worse SF-8 scores compared to the general population, and elderly patients were the least likely to match population norms following surgery. Age was an independent predictor of QOL outcomes after FESS.
CONCLUSION - Age may play a significant role in CRS pathophysiology, symptom burden, and surgical outcomes. Elderly patients report smaller improvements in disease-specific and general health QOL after surgery. CRS management in the elderly population should incorporate age-dependent differences in symptom burden and expectations into treatment algorithms.
© 2019 ARS-AAOA, LLC.
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A case report of clonal EBV-like memory CD4 T cell activation in fatal checkpoint inhibitor-induced encephalitis.
Johnson DB, McDonnell WJ, Gonzalez-Ericsson PI, Al-Rohil RN, Mobley BC, Salem JE, Wang DY, Sanchez V, Wang Y, Chastain CA, Barker K, Liang Y, Warren S, Beechem JM, Menzies AM, Tio M, Long GV, Cohen JV, Guidon AC, O'Hare M, Chandra S, Chowdhary A, Lebrun-Vignes B, Goldinger SM, Rushing EJ, Buchbinder EI, Mallal SA, Shi C, Xu Y, Moslehi JJ, Sanders ME, Sosman JA, Balko JM
(2019) Nat Med 25: 1243-1250
MeSH Terms: Adolescent, Adult, Aged, Aged, 80 and over, CD4-Positive T-Lymphocytes, Encephalitis, Female, Herpesvirus 4, Human, Humans, Immunologic Memory, Lymphocyte Activation, Male, Middle Aged, Programmed Cell Death 1 Receptor, Young Adult
Show Abstract · Added November 12, 2019
Checkpoint inhibitors produce durable responses in numerous metastatic cancers, but immune-related adverse events (irAEs) complicate and limit their benefit. IrAEs can affect organ systems idiosyncratically; presentations range from mild and self-limited to fulminant and fatal. The molecular mechanisms underlying irAEs are poorly understood. Here, we report a fatal case of encephalitis arising during anti-programmed cell death receptor 1 therapy in a patient with metastatic melanoma. Histologic analyses revealed robust T cell infiltration and prominent programmed death ligand 1 expression. We identified 209 reported cases in global pharmacovigilance databases (across multiple cancer types) of encephalitis associated with checkpoint inhibitor regimens, with a 19% fatality rate. We performed further analyses from the index case and two additional cases to shed light on this recurrent and fulminant irAE. Spatial and multi-omic analyses pinpointed activated memory CD4 T cells as highly enriched in the inflamed, affected region. We identified a highly oligoclonal T cell receptor repertoire, which we localized to activated memory cytotoxic (CD45ROGZMBKi67) CD4 cells. We also identified Epstein-Barr virus-specific T cell receptors and EBV lymphocytes in the affected region, which we speculate contributed to neural inflammation in the index case. Collectively, the three cases studied here identify CD4 and CD8 T cells as culprits of checkpoint inhibitor-associated immune encephalitis.
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Irritability and brain volume in adolescents: cross-sectional and longitudinal associations.
Dennis EL, Humphreys KL, King LS, Thompson PM, Gotlib IH
(2019) Soc Cogn Affect Neurosci 14: 687-698
MeSH Terms: Adolescent, Brain, Cerebral Cortex, Child, Cross-Sectional Studies, Female, Humans, Irritable Mood, Longitudinal Studies, Magnetic Resonance Imaging, Male, Stress, Psychological, Young Adult
Show Abstract · Added March 3, 2020
Irritability is garnering increasing attention in psychiatric research as a transdiagnostic marker of both internalizing and externalizing disorders. These disorders often emerge during adolescence, highlighting the need to examine changes in the brain and in psychological functioning during this developmental period. Adolescents were recruited for a longitudinal study examining the effects of early life stress on the development of psychopathology. The 151 adolescents (73 M/78 F, average age = 11.5 years, standard deviation = 1.1) were scanned with a T1-weighted MRI sequence and parents completed reports of adolescent irritability using the Affective Reactivity Index. Of these 151 adolescents, 94 (46 M/48 F) returned for a second session (average interval = 1.9 years, SD = 0.4). We used tensor-based morphometry to examine cross-sectional and longitudinal associations between irritability and regional brain volume. Irritability was associated with brain volume across a number of regions. More irritable individuals had larger hippocampi, insula, medial orbitofrontal cortex and cingulum/cingulate cortex and smaller putamen and internal capsule. Across the brain, more irritable individuals also had larger volume and less volume contraction in a number of areas that typically decrease in volume over the developmental period studied here, suggesting delayed maturation. These structural changes may increase adolescents' vulnerability for internalizing and externalizing disorders.
© The Author(s) 2019. Published by Oxford University Press.
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Slow graded reintroduction of oxcarbazepine for delayed maculopapular eruption.
Rukasin CRF, Phillips EJ, Norton AE
(2019) Ann Allergy Asthma Immunol 123: 411-412
MeSH Terms: Adolescent, Anticonvulsants, Desensitization, Immunologic, Drug Hypersensitivity, Exanthema, Female, Humans, Oxcarbazepine, Stevens-Johnson Syndrome
Added March 30, 2020
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