Digital Commons Network^™

Sex-Specific Alterations In Hepatic Cholesterol Metabolism In Low Birth Weight Adult Guinea Pigs., Ousseynou Sarr, Katherine E Mathers, Christina Vanderboor, Kristina Wiggers, Aditya Devgan, Daniel B Hardy, Lin Zhao, Timothy Regnault

Paediatrics Publications

BACKGROUND: Intrauterine growth restriction and low birth weight (LBW) have been widely reported as an independent risk factor for adult hypercholesterolaemia and increased hepatic cholesterol in a sex-specific manner. However, the specific impact of uteroplacental insufficiency (UPI), a leading cause of LBW in developed world, on hepatic cholesterol metabolism in later life, is ill defined and is clinically relevant in understanding later life liver metabolic health trajectories.

METHODS: Hepatic cholesterol, transcriptome, cholesterol homoeostasis regulatory proteins, and antioxidant markers were studied in UPI-induced LBW and normal birth weight (NBW) male and female guinea pigs at 150 days.

RESULTS: Hepatic free and …

Developing And Implementing A Novel Mentorship Model (4+ 1) For Maternal, Newborn And Child Health In Rwanda, Anaclet Ngabonzima, Cynthia Kenyon, Celestin Hategeka, Aimee Josephine Utuza, Paulin Ruhato Banguti, Isaac Luginaah, David F Cechetto

Paediatrics Publications

BACKGROUND: There are a number of factors that may contribute to high mortality and morbidity of women and newborns in low-income countries. These include a shortage of competent health care providers (HCP) and a lack of sufficient continuous professional development (CPD) opportunities. Strengthening the skills and building the capacity of HCP involved in the provision of maternal, newborn and child health (MNCH) is essential to ensure quality care for mothers, newborns and children. To address this challenge in Rwanda, mentorship of HCPs was identified as an approach that could help build capacity, improve the provision of care and accelerate the …

Treatment De-Escalation For Hpv-Associated Oropharyngeal Squamous Cell Carcinoma With Radiotherapy Vs. Trans-Oral Surgery (Orator2): Study Protocol For A Randomized Phase Ii Trial., Anthony C Nichols, Pencilla Lang, Eitan Prisman, Eric Berthelet, Eric Tran, Sarah Hamilton, Jonn Wu, Kevin Fung, John R De Almeida, Andrew Bayley, David P Goldstein, Antoine Eskander, Zain Husain, Houda Bahig, Apostolos Christopoulous, Michael Hier, Khalil Sultanem, Keith Richardson, Alex Mlynarek, Suren Krishnan, Hien Le, John Yoo, S Danielle Macneil, Adrian Mendez, Eric Winquist, Nancy Read, Varagur Venkatesan, Sara Kuruvilla, Andrew Warner, Sylvia Mitchell, Martin Corsten, Murali Rajaraman, Stephanie Johnson-Obaseki, Libni Eapen, Michael Odell, Shamir Chandarana, Robyn Banerjee, Joseph Dort, T Wayne Matthews, Robert Hart, Paul Kerr, Samuel Dowthwaite, Michael Gupta, Han Zhang, Jim Wright, Christina Parker, Bret Wehrli, Keith Kwan, Julie Theurer, David A Palma

Paediatrics Publications

BACKGROUND: Patients with human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPC) have substantially better treatment response and overall survival (OS) than patients with HPV-negative disease. Treatment options for HPV+ OPC can involve either a primary radiotherapy (RT) approach (± concomitant chemotherapy) or a primary surgical approach (± adjuvant radiation) with transoral surgery (TOS). These two treatment paradigms have different spectrums of toxicity. The goals of this study are to assess the OS of two de-escalation approaches (primary radiotherapy and primary TOS) compared to historical control, and to compare survival, toxicity and quality of life (QOL) profiles between the two approaches. …

Growth Hormone Deficiency In Megalencephaly-Capillary Malformation Syndrome: An Association With Activating Mutations In Pik3ca, Shanlee Davis, Meredith A Ware, Jordan Zeiger, Matthew A Deardorff, Katheryn Grand, Adda Grimberg, Stephanie Hsu, Megan Kelsey, Shideh Majidi, Revi P Matthew, Melanie Napier, Natalie Nokoff, Chitra Prasad, Andrew C Riggs, Margaret L Mckinnon, Ghayda Mirzaa

Paediatrics Publications

Megalencephaly-capillary malformation syndrome (MCAP) is a brain overgrowth disorder characterized by cortical malformations (specifically polymicrogyria), vascular anomalies, and segmental overgrowth secondary to somatic activating mutations in the PI3K-AKT-MTOR pathway (PIK3CA). Cases of growth failure and hypoglycemia have been reported in patients with MCAP, raising the suspicion for unappreciated growth hormone (GH) deficiency. Here we report an observational multicenter study of children with MCAP and GH deficiency. Eleven participants were confirmed to have GH deficiency, all with very low or undetectable circulating concentrations of insulin-like growth factor-1 and insulin-like growth factor binding protein-3. Seven underwent GH stimulation testing and all had …

Phenytoin Activates Smad3 Phosphorylation And Periostin Expression In Drug-Induced Gingival Enlargement., Shawna S Kim, Georgia Nikoloudaki, Mark Darling, Michael J Rieder, Douglas W Hamilton

Paediatrics Publications

Drug-induced gingival enlargement (DIGE) is a fibrotic condition associated with systemic administration of the anti-epileptic drug, phenytoin. We have previously demonstrated that periostin, which is transforming growth factor-beta (TGF-β) inducible gene, is upregulated in various fibrotic conditions including gingival enlargement associated with nifedipine. The objective of this study was to assess periostin expression in phenytoin-induced gingival enlargement (PIGE) tissues and to investigate the mechanisms underlying periostin expression. Human PIGE tissues were assessed using Masson's trichrome, with cell infiltration and changes in extracellular matrix composition characterized through labeling with antibodies to periostin, phospho-SMAD 3, TGF-β, as well as the macrophage markers …

Modified Origins Of Cortical Projections To The Superior Colliculus In The Deaf: Dispersion Of Auditory Efferents., Blake E Butler, Julia K Sunstrum, Stephen G Lomber

Brain and Mind Institute Researchers' Publications

Following the loss of a sensory modality, such as deafness or blindness, crossmodal plasticity is commonly identified in regions of the cerebrum that normally process the deprived modality. It has been hypothesized that significant changes in the patterns of cortical afferent and efferent projections may underlie these functional crossmodal changes. However, studies of thalamocortical and corticocortical connections have refuted this hypothesis, instead revealing a profound resilience of cortical afferent projections following deafness and blindness. This report is the first study of cortical outputs following sensory deprivation, characterizing cortical projections to the superior colliculus in mature cats (

Predictive Value For Cardiovascular Events Of Common Carotid Intima Media Thickness And Its Rate Of Change In Individuals At High Cardiovascular Risk - Results From The Prog-Imt Collaboration, Matthias W Lorenz, Lu Gao, Kathrin Ziegelbauer, Giuseppe Danilo Norata, Jean Philippe Empana, Irene Schmidtmann, Hung-Ju Lin, Stela Mclachlan, Lena Bokemark, Kimmo Ronkainen, Mauro Amato, Ulf Schminke, Sathanur R Srinivasan, Lars Lind, Shuhei Okazaki, Coen D A Stehouwer, Peter Willeit, Joseph F Polak, Helmuth Steinmetz, Dirk Sander, Holger Poppert, Moise Desvarieux, M Arfan Ikram, Stein Harald Johnsen, Daniel Staub, Cesare R Sirtori, Bernhard Iglseder, Oscar Beloqui, Gunnar Engström, Alfonso Friera, Francesco Rozza, Wuxiang Xie, Grace Parraga, Liliana Grigore, Matthieu Plichart, Stefan Blankenberg, Ta-Chen Su, Caroline Schmidt, Tomi-Pekka Tuomainen, Fabrizio Veglia, Henry Völzke, Giel Nijpels, Johann Willeit, Ralph L Sacco, Oscar H Franco, Heiko Uthoff, Bo Hedblad, Carmen Suarez, Raffaele Izzo, Dong Zhao, Thapat Wannarong, Alberico Catapano, Pierre Ducimetiere, Christine Espinola-Klein, Kuo-Liong Chien, Jackie F Price, Göran Bergström, Jussi Kauhanen, Elena Tremoli, Marcus Dörr, Gerald Berenson, Kazuo Kitagawa, Jacqueline M Dekker, Stefan Kiechl, Matthias Sitzer, Horst Bickel, Tatjana Rundek, Albert Hofman, Ellisiv B Mathiesen, Samuela Castelnuovo, Manuel F Landecho, Maria Rosvall, Rafael Gabriel, Nicola De Luca, Jing Liu, Damiano Baldassarre, Maryam Kavousi, Eric De Groot, Michiel L Bots, David N Yanez, Simon G Thompson

Medical Biophysics Publications

AIMS: Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk.

METHODS AND RESULTS: From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of …

A Quantitative Comparison Of The Hemispheric, Areal, And Laminar Origins Of Sensory And Motor Cortical Projections To The Superior Colliculus Of The Cat., Blake E Butler, Nicole Chabot, Stephen G Lomber

Brain and Mind Institute Researchers' Publications

The superior colliculus (SC) is a midbrain structure central to orienting behaviors. The organization of descending projections from sensory cortices to the SC has garnered much attention; however, rarely have projections from multiple modalities been quantified and contrasted, allowing for meaningful conclusions within a single species. Here, we examine corticotectal projections from visual, auditory, somatosensory, motor, and limbic cortices via retrograde pathway tracers injected throughout the superficial and deep layers of the cat SC. As anticipated, the majority of cortical inputs to the SC originate in the visual cortex. In fact, each field implicated in visual orienting behavior makes a …

Functional Differences Between Statistical Learning With And Without Explicit Training., Laura J Batterink, Paul J Reber, Ken A Paller

Brain and Mind Institute Researchers' Publications

Humans are capable of rapidly extracting regularities from environmental input, a process known as statistical learning. This type of learning typically occurs automatically, through passive exposure to environmental input. The presumed function of statistical learning is to optimize processing, allowing the brain to more accurately predict and prepare for incoming input. In this study, we ask whether the function of statistical learning may be enhanced through supplementary explicit training, in which underlying regularities are explicitly taught rather than simply abstracted through exposure. Learners were randomly assigned either to an explicit group or an implicit group. All learners were exposed to …

Self-Injurious Behaviours Are Associated With Alterations In The Somatosensory System In Children With Autism Spectrum Disorder., Emma G Duerden, Dallas Card, S Wendy Roberts, Kathleen M Mak-Fan, M Mallar Chakravarty, Jason P Lerch, Margot J Taylor

Brain and Mind Institute Researchers' Publications

Children with autism spectrum disorder (ASD) frequently engage in self-injurious behaviours, often in the absence of reporting pain. Previous research suggests that altered pain sensitivity and repeated exposure to noxious stimuli are associated with morphological changes in somatosensory and limbic cortices. Further evidence from postmortem studies with self-injurious adults has indicated alterations in the structure and organization of the temporal lobes; however, the effect of self-injurious behaviour on cortical development in children with ASD has not yet been determined. Thirty children and adolescents (mean age = 10.6 ± 2.5 years; range 7-15 years; 29 males) with a clinical diagnosis of …

Links Between White Matter Microstructure And Cortisol Reactivity To Stress In Early Childhood: Evidence For Moderation By Parenting., Haroon I Sheikh, Marc F Joanisse, Sarah M Mackrell, Katie R Kryski, Heather J Smith, Shiva M Singh, Elizabeth P Hayden

Brain and Mind Institute Researchers' Publications

Activity of the hypothalamic-pituitary-adrenal axis (measured via cortisol reactivity) may be a biological marker of risk for depression and anxiety, possibly even early in development. However, the structural neural correlates of early cortisol reactivity are not well known, although these would potentially inform broader models of mechanisms of risk, especially if the early environment further shapes these relationships. Therefore, we examined links between white matter architecture and young girls' cortisol reactivity and whether early caregiving moderated these links. We recruited 45 6-year-old girls based on whether they had previously shown high or low cortisol reactivity to a stress task at …

Resting-State Connectivity Identifies Distinct Functional Networks In Macaque Cingulate Cortex., R Matthew Hutchison, Thilo Womelsdorf, Joseph S Gati, L Stan Leung, Ravi S Menon, Stefan Everling

Brain and Mind Institute Researchers' Publications

Subregions of the cingulate cortex represent prominent intersections in the structural networks of the primate brain. The relevance of the cingulate to the structure and dynamics of large-scale networks ultimately requires a link to functional connectivity. Here, we map fine-grained functional connectivity across the complete extent of the macaque (Macaca fascicularis) cingulate cortex and delineate subdivisions pertaining to distinct identifiable networks. In particular, we identified 4 primary networks representing the functional spectrum of the cingulate: somatomotor, attention-orienting, executive, and limbic. The cingulate nodes of these networks originated from separable subfields along the rostral-to-caudal axis and were characterized by positive and …

Resting-State Connectivity Identifies Distinct Functional Networks In Macaque Cingulate Cortex., R Matthew Hutchison, Thilo Womelsdorf, Joseph S Gati, L Stan Leung, Ravi S Menon, Stefan Everling

Physiology and Pharmacology Publications

Subregions of the cingulate cortex represent prominent intersections in the structural networks of the primate brain. The relevance of the cingulate to the structure and dynamics of large-scale networks ultimately requires a link to functional connectivity. Here, we map fine-grained functional connectivity across the complete extent of the macaque (Macaca fascicularis) cingulate cortex and delineate subdivisions pertaining to distinct identifiable networks. In particular, we identified 4 primary networks representing the functional spectrum of the cingulate: somatomotor, attention-orienting, executive, and limbic. The cingulate nodes of these networks originated from separable subfields along the rostral-to-caudal axis and were characterized by positive and …

Encoding Of Sensory Prediction Errors In The Human Cerebellum., John Schlerf, Richard B Ivry, Jörn Diedrichsen

Brain and Mind Institute Researchers' Publications

A central tenet of motor neuroscience is that the cerebellum learns from sensory prediction errors. Surprisingly, neuroimaging studies have not revealed definitive signatures of error processing in the cerebellum. Furthermore, neurophysiologic studies suggest an asymmetry, such that the cerebellum may encode errors arising from unexpected sensory events, but not errors reflecting the omission of expected stimuli. We conducted an imaging study to compare the cerebellar response to these two types of errors. Participants made fast out-and-back reaching movements, aiming either for an object that delivered a force pulse if intersected or for a gap between two objects, either of which …

Eye Position Signal Modulates A Human Parietal Pointing Region During Memory-Guided Movements., J F Desouza, S P Dukelow, J S Gati, R S Menon, R A Andersen, T Vilis

Brain and Mind Institute Researchers' Publications

Using functional magnetic resonance imaging, we examined the signal in parietal regions that were selectively activated during delayed pointing to flashed visual targets and determined whether this signal was dependent on the fixation position of the eyes. Delayed pointing activated a bilateral parietal area in the intraparietal sulcus (rIPS), rostral/anterior to areas activated by saccades. During right-hand pointing to centrally located targets, the left rIPS region showed a significant increase in activation when the eye position was rightward compared with leftward. As expected, activation in motor cortex showed no modulation when only eye position changed. During pointing to retinotopically identical …