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Prématurity And Brain

Marzia Bianchi, Melania Manco
Prolyl isomerases (Peptidylprolyl isomerase, PPIases) are enzymes that catalyze the isomerization between the cis / trans Pro conformations. Three subclasses belong to the class: FKBP (FK506 binding protein family), Cyclophilin and Parvulin family (Pin1 and Par14). Among Prolyl isomerases, Pin1 presents as distinctive feature, the ability of binding to the motif pSer/pThr-Pro that is phosphorylated by kinases. Modulation of Pin1 is implicated in cellular processes such as mitosis, differentiation and metabolism: The enzyme is dysregulated in many diverse pathological conditions, i...
August 8, 2018: International Journal of Molecular Sciences
Adolf Pfefferbaum, Natalie M Zahr, Stephanie A Sassoon, Dongjin Kwon, Kilian M Pohl, Edith V Sullivan
BACKGROUND: Life expectancy of successfully treated human immunodeficiency virus (HIV)-infected individuals is approaching normal longevity. The growing HIV population ≥50 years of age is now at risk of developing HIV-associated neurocognitive disorder, acquiring coinfection with the hepatitis C virus (HCV), and engaging in hazardous drinking or drug consumption that can adversely affect trajectories of the healthy aging of brain structures. METHODS: This cross-sectional/longitudinal study quantified regional brain volumes from 1101 magnetic resonance imaging scans collected over 14 years in 549 participants (25 to 75 years of age): 68 HIV-infected individuals without alcohol dependence, 60 HIV-infected individuals with alcohol dependence, 222 alcohol-dependent individuals, and 199 control subjects...
July 4, 2018: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
Rajendra K Diwakar, Omesh Khurana
Background: Premature newborn infants are exposed to a wide spectrum of brain lesions which are clinically silent supporting a possible role of cerebral ultrasound screening. Aim of the study is to describe the pattern of cranial ultrasound abnormalities in preterm infants defining the short term and long term neurologic outcomes. Material and Methods: A hospital-based bedside cranial ultrasound was carried out at day 1, 3, 7 and follow-up scan at 3-6 months in the Department of Radio-diagnosis...
April 2018: Journal of Pediatric Neurosciences
Tessa van Dijk, Sacha Ferdinandusse, Jos P N Ruiter, Mariëlle Alders, Inge B Mathijssen, Jillian S Parboosingh, A Micheil Innes, Hanne Meijers-Heijboer, Bwee Tien Poll-The, Francois P Bernier, Ronald J A Wanders, Ryan E Lamont, Frank Baas
Pontocerebellar hypoplasia (PCH) is a heterogeneous neurodegenerative disorder with a prenatal onset. Using whole-exome sequencing, we identified variants in the gene Coenzyme A (CoA) synthase (COASY) gene, an enzyme essential in CoA synthesis, in four individuals from two families with PCH, prenatal onset microcephaly, and arthrogryposis. In family 1, compound heterozygous variants were identified in COASY: c.[1549_1550delAG]; [1486-3 C>G]. In family 2, all three affected siblings were homozygous for the c...
August 8, 2018: European Journal of Human Genetics: EJHG
Kay L Richards, Carol J Milligan, Robert J Richardson, Nikola Jancovski, Morten Grunnet, Laura H Jacobson, Eivind A B Undheim, Mehdi Mobli, Chun Yuen Chow, Volker Herzig, Agota Csoti, Gyorgy Panyi, Christopher A Reid, Glenn F King, Steven Petrou
Dravet syndrome is a catastrophic, pharmacoresistant epileptic encephalopathy. Disease onset occurs in the first year of life, followed by developmental delay with cognitive and behavioral dysfunction and substantially elevated risk of premature death. The majority of affected individuals harbor a loss-of-function mutation in one allele of SCN1A , which encodes the voltage-gated sodium channel NaV 1.1. Brain NaV 1.1 is primarily localized to fast-spiking inhibitory interneurons; thus the mechanism of epileptogenesis in Dravet syndrome is hypothesized to be reduced inhibitory neurotransmission leading to brain hyperexcitability...
August 3, 2018: Proceedings of the National Academy of Sciences of the United States of America
Shouyi Wang, Panpan Fan, Dezhi Xiong, Pu Yang, Junwen Zheng, Dongchi Zhao
Data regarding neonatal brain volumes represent a basis for monitoring early brain development, and large sample of neonatal brain volume data has not been well described. This study was focused on neonatal brain volumes at different postmenstrual ages (PMA) and postnatal age (PNA).A cohort of 415 neonates with PMA 30 to 43 weeks were recruited for the determination of brain volumes. Intracranial cavity (ICC), total brain tissue (TBT), and cerebrospinal fluid (CSF) were evaluated on the basis of T1-weighted sagittal plane magnetic resonance images...
August 2018: Medicine (Baltimore)
Christopher D Smyser, Muriah D Wheelock, David D Limbrick, Jeffrey J Neil
Brain injury sustained during the neonatal period may disrupt development of critical structural and functional connectivity networks leading to subsequent neurodevelopmental impairment in affected children. These networks can be characterized using structural (via diffusion MRI) and functional (via resting state-functional MRI) neuroimaging techniques. Advances in neuroimaging have led to expanded application of these approaches to study term- and prematurely-born infants, providing improved understanding of cerebral development and the deleterious effects of early brain injury...
July 27, 2018: NeuroImage
Kevin T Sheets, Juli R Bagó, Ivory L Paulk, Shawn D Hingtgen
Glioblastoma (GBM), the most common and aggressive primary brain cancer, carries a life expectancy of 12-15 months. The short life expectancy is due in part to the inability of the current treatment, consisting of surgical resection followed by radiation and chemotherapy, to eliminate invasive tumor foci. Treatment of these foci may be improved with tumoricidal human mesenchymal stem cells (MSCs). MSCs exhibit potent tumor tropism and can be engineered to express therapeutic proteins that kill tumor cells. Advancements in preclinical models indicate that surgical resection induces premature MSC loss and reduces therapeutic efficacy...
July 16, 2018: Journal of Visualized Experiments: JoVE
Dorit Schleinitz, Anna Seidel, Ruth Stassart, Jürgen Klammt, Petra G Hirrlinger, Ulrike Winkler, Susanne Köhler, John T Heiker, Ria Schönauer, Joanna Bialek, Knut Krohn, Katrin Hoffmann, Peter Kovacs, Johannes Hirrlinger
Microcephaly is a devastating condition defined by a small head and small brain compared to the age- and sex-matched population. Mutations in a number of different genes causative for microcephaly have been identified, e.g., MCPH1, WDR62 , and ASPM . Recently, mutations in the gene encoding the enzyme asparagine synthetase ( ASNS ) were associated to microcephaly and so far 24 different mutations in ASNS causing microcephaly have been described. In a family with two affected girls, we identified novel compound heterozygous variants in ASNS (c...
2018: Frontiers in Genetics
Justin Cohen, Luca D'Agostino, Ferit Tuzer, Claudio Torres
Developments in medicine have led to a significant increase in the average human lifespan. This increase in aging is most readily apparent in the case of HIV where antiretroviral therapy has shifted infection from a terminal to a chronic but manageable disease. Despite this advance, patients suffer from co-morbidities best described as an accelerated aging phenotype. A potential contributor is cellular senescence, an aging-associated growth arrest, which has already been linked to other HIV co-morbidities such as lipodystrophies and osteoporosis in response to antiretroviral drugs...
July 25, 2018: Mechanisms of Ageing and Development
Petra Loid, Riikka Mäkitie, Alice Costantini, Heli Viljakainen, Minna Pekkinen, Outi Mäkitie
The genetic background of severe early-onset obesity is still incompletely understood. Deletions at 2p25.3 associate with early-onset obesity and variable intellectual disability. Myelin-transcriptor-factor-1-like (MYT1L) gene in this locus has been proposed a candidate gene for obesity. We report on a 13-year-old boy presenting with overweight already at 1 year of age (body mass index [BMI] Z-score +2.3) and obesity at 2 years of age (BMI Z-score +3.8). The patient had hyperphagia and delayed neurological, cognitive and motor development...
July 28, 2018: American Journal of Medical Genetics. Part A
Tessa Martherus, André Oberthuer, Janneke Dekker, Stuart B Hooper, Erin V McGillick, Angela Kribs, Arjan B Te Pas
Most very preterm infants have difficulty aerating their lungs and require respiratory support at birth. Currently in clinical practice, non-invasive ventilation in the form of continuous positive airway pressure (CPAP) and positive pressure ventilation (PPV) is applied via facemask. As most very preterm infants breathe weakly and unnoticed at birth, PPV is often administered. PPV is, however, frequently ineffective due to pressure settings, mask leak and airway obstruction. Meanwhile, high positive inspiratory pressures and spontaneous breathing coinciding with inflations can generate high tidal volumes...
July 26, 2018: Archives of Disease in Childhood. Fetal and Neonatal Edition
M Avellanet, A Mena, E Aisa-Pardo
INTRODUCTION: Cerebral palsy describes a group of developmental and posture disorders, which cause a limitation of activity due to non-progressive damage occurring in the developing brain. A population register facilitates the identification of cerebral palsy cases within a specific geographic population. Its usefulness is recognized in the world literature but in Spain, published databases focus on the treatment or complications of cerebral palsy. AIMS: To propose a population register that can be useful in different areas of our environment and to evaluate its validity through its application in two differentiated and geographically delimited health areas...
September 1, 2018: Revista de Neurologia
Narendra K Arora, M K C Nair, Sheffali Gulati, Vaishali Deshmukh, Archisman Mohapatra, Devendra Mishra, Vikram Patel, Ravindra M Pandey, Bhagabati C Das, Gauri Divan, G V S Murthy, Thakur D Sharma, Savita Sapra, Satinder Aneja, Monica Juneja, Sunanda K Reddy, Praveen Suman, Sharmila B Mukherjee, Rajib Dasgupta, Poma Tudu, Manoja K Das, Vinod K Bhutani, Maureen S Durkin, Jennifer Pinto-Martin, Donald H Silberberg, Rajesh Sagar, Faruqueuddin Ahmed, Nandita Babu, Sandeep Bavdekar, Vijay Chandra, Zia Chaudhuri, Tanuj Dada, Rashna Dass, M Gourie-Devi, S Remadevi, Jagdish C Gupta, Kumud K Handa, Veena Kalra, Sunil Karande, Ramesh Konanki, Madhuri Kulkarni, Rashmi Kumar, Arti Maria, Muneer A Masoodi, Manju Mehta, Santosh Kumar Mohanty, Harikumaran Nair, Poonam Natarajan, A K Niswade, Atul Prasad, Sanjay K Rai, Paul S S Russell, Rohit Saxena, Shobha Sharma, Arun K Singh, Gautam B Singh, Leena Sumaraj, Saradha Suresh, Alok Thakar, Sujatha Parthasarathy, Bhadresh Vyas, Ansuman Panigrahi, Munish K Saroch, Rajan Shukla, K V Raghava Rao, Maria P Silveira, Samiksha Singh, Vivek Vajaratkar
BACKGROUND: Neurodevelopmental disorders (NDDs) compromise the development and attainment of full social and economic potential at individual, family, community, and country levels. Paucity of data on NDDs slows down policy and programmatic action in most developing countries despite perceived high burden. METHODS AND FINDINGS: We assessed 3,964 children (with almost equal number of boys and girls distributed in 2-<6 and 6-9 year age categories) identified from five geographically diverse populations in India using cluster sampling technique (probability proportionate to population size)...
July 2018: PLoS Medicine
Natalie Suff, Rajvinder Karda, Juan Antinao Diaz, Joanne Ng, Julien Baruteau, Dany Perocheau, Mark Tangney, Peter W Taylor, Donald Peebles, Suzanne M K Buckley, Simon N Waddington
Preterm birth is a serious global health problem, being the leading cause of death in infants under five years of age. At least 40% of cases are associated with infection. It is thought that the most common way for pathogens to access the uterine cavity is by ascending from the vagina. Bioluminescent pathogens have revolutionized the understanding of infectious diseases. We hypothesized that bioluminescent E. coli can be used to track and monitor ascending vaginal infection in pregnant mice. Two different strains of bioluminescent E...
July 20, 2018: American Journal of Pathology
Zhi-Zhi Liu, Jian Zhu, Chang-Ling Wang, Xin Wang, Ying-Ying Han, Ling-Yan Liu, Hong A Xu
Axons are directed to their correct targets by guidance cues during neurodevelopment. Many axon guidance cues have been discovered; however, much less known is about how the growth cones transduce the extracellular guidance cues to intracellular responses. Collapsin response mediator proteins (CRMPs) are a family of intracellular proteins that have been found to mediate growth cone behavior in vitro ; however, their roles in vivo in axon development are much less explored. In zebrafish embryos, we find that CRMP2 and CRMP4 are expressed in the retinal ganglion cell layer when retinal axons are crossing the midline...
2018: Neural Plasticity
Niels Hadrup, Katrin Loeschner, Karen Mandrup, Gitte Ravn-Haren, Henrik L Frandsen, Erik H Larsen, Henrik R Lam, Alicja Mortensen
Selenium (Se) nanoparticles have been proposed as food supplements. However, the particle formulation may exert unexpected toxicity. The aim was therefore to compare toxicity of low doses of Se nanoparticles and the dissolved, ionized Se species selenite. Female rats were dosed orally for 28 d with either: 0.05, 0.5, or 4 mg Se/kg body weight (bw)/day as 20 nm Se nanoparticles or 0.05 or 0.5 mg Se/kg bw/day as sodium selenite. Male rats were dosed 4 mg Se/kg bw/day as Se nanoparticles. Body weight and clinical appearance were recorded throughout the experiment...
July 23, 2018: Drug and Chemical Toxicology
Laura D Crocker, Sarah M Jurick, Kelsey R Thomas, Amber V Keller, Mark Sanderson-Cimino, Briana Boyd, Carie Rodgers, Elizabeth W Twamley, Amy J Jak
Although trauma-focused treatment, including Cognitive Processing Therapy (CPT), effectively reduces PTSD symptoms, treatment dropout, nonresponse, and relapse are substantial. Executive functioning (EF) is essential to engage the cognitive skills involved in CPT (e.g., inhibiting/evaluating distorted thoughts, flexibly generating alternative thoughts). It was hypothesized that worse baseline EF would be associated with reduced CPT completion and responsivity. Seventy-four Iraq/Afghanistan-era Veterans with PTSD and history of mild-to-moderate traumatic brain injury were randomized to either standard CPT or modified CPT that included cognitive rehabilitation strategies (SMART-CPT)...
September 2018: Behaviour Research and Therapy
Ana I Rojo, Marta Pajares, Angel J García-Yagüe, Izaskun Buendia, Fred Van Leuven, Masayuki Yamamoto, Manuela G López, Antonio Cuadrado
Chronic neuroinflammation is a hallmark of the onset and progression of brain proteinopathies such as Alzheimer disease (AD) and it is suspected to participate in the neurodegenerative process. Transcription factor NRF2, a master regulator of redox homeostasis, controls acute inflammation but its relevance in low-grade chronic inflammation of AD is inconclusive due to lack of good mouse models. We have addressed this question in a transgenic mouse that combines amyloidopathy and tauopathy with either wild type (AT-NRF2-WT) or NRF2-deficiency (AT-NRF2-KO)...
July 11, 2018: Redox Biology
Alexa S Hendricks, Hossam A Shaltout, Brian M Westwood, Mark C Chappell, Debra I Diz
Antenatal betamethasone (BM) therapy for women in jeopardy of premature delivery accelerates the lung development in preterm infants and reduces infant mortality rates, but may induce early programming events with chronic cardiovascular consequences. In a sheep model of fetal programming, in utero BM-exposed (BMX) offspring as adults exhibit elevated mean arterial pressure (MAP), decreased baroreflex sensitivity (BRS) for control of heart rate and insulin resistance accompanied by dysregulation of the brain renin-angiotensin system (RAS)...
July 19, 2018: Clinical Science (1979-)
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