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https://www.readbyqxmd.com/read/28230213/knock-in-human-fgfr3-achondroplasia-mutation-as-a-mouse-model-for-human-skeletal-dysplasia
#1
Yi-Ching Lee, I-Wen Song, Ya-Ju Pai, Sheng-De Chen, Yuan-Tsong Chen
Achondroplasia (ACH), the most common genetic dwarfism in human, is caused by a gain-of function mutation in fibroblast growth factor receptor 3 (FGFR3). Currently, there is no effective treatment for ACH. The development of an appropriate human-relevant model is important for testing potential therapeutic interventions before human clinical trials. Here, we have generated an ACH mouse model in which the endogenous mouse Fgfr3 gene was replaced with human FGFR3(G380R) (FGFR3(ACH)) cDNA, the most common mutation in human ACH...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28229933/nuclear-lamins-and-progerin-are-dispensable-for-antioxidant-nrf2-response-to-arsenic-and-cadmium
#2
Kazunori Hashimoto, Rima Majumdar, Yoshiaki Tsuji
Lamins are important constituents of the nuclear inner membrane and provide a platform for transcription factors and chromatin. Progerin, a C-terminal truncated lamin A mutant, causes premature aging termed Hutchinson-Gilford Progeria Syndrome (HGPS). Oxidative stress appears to be involved in the pathogenesis of HGPS, although the mechanistic role of progerin remains elusive. Here we examined whether nuclear lamins are important for a cellular antioxidant mechanism, and whether progerin compromises it. We investigated the activation of nuclear factor-E2-related factor 2 (Nrf2) which regulates various antioxidant genes including heme oxygenase-1 (HMOX1), following exposure to sodium arsenite or cadmium chloride in lamin knockdown human cell lines and primary HGPS human fibroblasts...
February 14, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28228489/age-dependent-shift-in-macrophage-polarisation-causes-inflammation-mediated-degeneration-of-enteric-nervous-system
#3
Laren Becker, Linh Nguyen, Jaspreet Gill, Subhash Kulkarni, Pankaj Jay Pasricha, Aida Habtezion
OBJECTIVE: The enteric nervous system (ENS) undergoes neuronal loss and degenerative changes with age. The cause of this neurodegeneration is poorly understood. Muscularis macrophages residing in close proximity to enteric ganglia maintain neuromuscular function via direct crosstalk with enteric neurons and have been implicated in the pathogenesis of GI motility disorders like gastroparesis and postoperative ileus. The aim of this study was to assess whether ageing causes alterations in macrophage phenotype that contributes to age-related degeneration of the ENS...
February 21, 2017: Gut
https://www.readbyqxmd.com/read/28227784/an-analytics-based-clinical-decision-support-system-for-cvd-risk-assessment-and-management
#4
Shreya Anand, Ravindra B Patil, P Krishnamoorthy, Shreya Anand, Ravindra B Patil, P Krishnamoorthy, Shreya Anand, Ravindra B Patil, P Krishnamoorthy
Cardiovascular disease (CVD) is a major cause of disability and premature death throughout the world. Acute coronary events and other cardiovascular events frequently occur suddenly, and are often fatal before medical care can be given. Risk factor modification can reduce clinical events and premature death in people with established cardiovascular disease as well as in those who are at high cardiovascular risk due to one or more risk factors. In this work, India specific World Health Organization-International Society of Hypertension (WHO-ISH) guidelines has been implemented to stratify the subjects by their risk profile...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28226744/toward-a-severity-index-for-rop-an-unsupervised-approach
#5
Peng Tian, Esra Ataer-Cansizoglu, Jayashree Kalpathy-Cramer, Susan Ostmo, Karyn Jonas, R V Paul Chan, J Peter Campbell, Michael F Chiang, Deniz Erdogmus, Peng Tian, Esra Ataer-Cansizoglu, Jayashree Kalpathy-Cramer, Susan Ostmo, Karyn Jonas, R V Paul Chan, J Peter Campbell, Michael F Chiang, Deniz Erdogmus, Michael F Chiang, Esra Ataer-Cansizoglu, Peng Tian, Deniz Erdogmus, J Peter Campbell, Jayashree Kalpathy-Cramer, R V Paul Chan, Susan Ostmo, Karyn Jonas
Retinopathy of prematurity (ROP) is a disease affecting low birth-weight infants and is the major cause of childhood blindness. Although accurate diagnosis is important, there is a high variability among expert decisions mostly due to subjective thresholds. Existing work focused on automated diagnosis of ROP. In this study, we construct a continuous severity index as an alternative to discrete classification. We follow an unsupervised approach by performing nonlinear dimensionality reduction. Instead of extracting several statistics of image features, each image is represented by the probability distribution of its features...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28224405/complications-of-acromegaly-cardiovascular-respiratory-and-metabolic-comorbidities
#6
REVIEW
Rosario Pivonello, Renata S Auriemma, Ludovica F S Grasso, Claudia Pivonello, Chiara Simeoli, Roberta Patalano, Mariano Galdiero, Annamaria Colao
Acromegaly is associated with an enhanced mortality, with cardiovascular and respiratory complications representing not only the most frequent comorbidities but also two of the main causes of deaths, whereas a minor role is played by metabolic complications, and particularly diabetes mellitus. The most prevalent cardiovascular complications of acromegaly include a cardiomyopathy, characterized by cardiac hypertrophy and diastolic and systolic dysfunction together with arterial hypertension, cardiac rhythm disorders and valve diseases, as well as vascular endothelial dysfunction...
February 21, 2017: Pituitary
https://www.readbyqxmd.com/read/28224101/vein-of-galen-malformation-in-a-neonate-a-case-report-and-review-of-endovascular-management
#7
Surasak Puvabanditsin, Rajeev Mehta, Kristy Palomares, Natalie Gengel, Christina Ferrucci Da Silva, Sudipta Roychowdhury, Gaurav Gupta, Arun Kashyap, David Sorrentino
Vein of Galen malformation (VOGM) is a rare congenital vascular malformation caused by the maldevelopment of its embryonic precursor, the median prosencephalic vein of Markowski. VOGM results in neonatal morbidity and mortality, and premature delivery does not improve the outcome. We report a term female neonate in whom a vein of Galen malformation was diagnosed prenatally at 37 wk of gestation during a growth ultrasound and confirmed by fetal magnetic resonance imaging. Signs of cardiac decompensation were evident in the fetus...
February 8, 2017: World Journal of Clinical Pediatrics
https://www.readbyqxmd.com/read/28222900/genetic-analysis-of-the-sod1-and-c9orf72-genes-in-hungarian-patients-with-amyotrophic-lateral-sclerosis
#8
Kornélia Tripolszki, Bernadett Csányi, Dóra Nagy, Antonia Ratti, Cinzia Tiloca, Vincenzo Silani, Éva Kereszty, Nóra Török, László Vécsei, József I Engelhardt, Péter Klivényi, Nikoletta Nagy, Márta Széll
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the death of motor neurons. To date, more than 20 genes have been implicated in ALS, and of these, the 2 most frequently mutated are the superoxide dismutase 1 (SOD1) gene and the chromosome 9 open reading frame 72 (C9ORF72) gene. In this study, we aimed to investigate the contribution of these 2 Mendelian genes to the development of the disease in Hungarian ALS patients (n = 66). Direct sequencing of the SOD1 gene revealed a novel (p...
January 29, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28222322/reversal-of-dabigatran-associated-major-bleeding-with-activated-prothrombin-concentrate-a-prospective-cohort-study
#9
Sam Schulman, B Ritchie, S Nahirniak, P L Gross, M Carrier, A Majeed, H-G Hwang, M Zondag
The reversal of dabigatran-associated major bleeding can now be achieved with the antidote idarucizumab. We evaluated activated prothrombin complex concentrate (aPCC) as an alternative for this purpose. Patients treated with dabigatran and suffering a major bleed were treated as per existing hospital protocol with aPCC. They were subsequently recruited for a 30-day follow-up. Effectiveness was evaluated by the treating physician, using an Assessment Guide. Safety outcomes were arterial or venous thromboembolism or death...
February 16, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28221857/listeria-monocytogenes-isolates-carrying-virulence-attenuating-mutations-in-internalin-a-are-commonly-isolated-from-ready-to-eat-food-processing-plant-and-retail-environments
#10
A VAN Stelten, A R Roberts, C S Manuel, K K Nightingale
Listeria monocytogenes is a human foodborne pathogen that may cause an invasive disease known as listeriosis in susceptible individuals. Internalin A (InlA; encoded by inlA) is a virulence factor that facilitates crossing of host cell barriers by L. monocytogenes . At least 19 single nucleotide polymorphisms (SNPs) in inlA that result in a premature stop codon (PMSC) have been described worldwide. SNPs leading to a PMSC in inlA have been shown to be causally associated with attenuated virulence. L. monocytogenes pathogens carrying virulence-attenuating (VA) mutations in inlA have been commonly isolated from ready-to-eat (RTE) foods but rarely have been associated with human disease...
October 2016: Journal of Food Protection
https://www.readbyqxmd.com/read/28215668/potential-of-surfactant-coated-nanoparticles-to-improve-brain-delivery-of-arylsulfatase-a
#11
Tilman Schuster, Astrid Mühlstein, Claudia Yaghootfam, Olga Maksimenko, Elena Shipulo, Svetlana Gelperina, Jörg Kreuter, Volkmar Gieselmann, Ulrich Matzner
The lysosomal storage disorder (LSD) metachromatic leukodystrophy (MLD) is caused by a deficiency of the soluble, lysosomal hydrolase arylsulfatase A (ASA). The disease is characterized by accumulation of 3-O-sulfogalactosylceramide (sulfatide), progressive demyelination of the nervous system and premature death. Enzyme replacement therapy (ERT), based on regular intravenous injections of recombinant functional enzyme, is in clinical use for several LSDs. For MLD and other LSDs with central nervous system (CNS) involvement, however, ERT is limited by the blood-brain barrier (BBB) restricting transport of therapeutic enzymes from the blood to the brain...
February 16, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28215172/the-phosphodiesterase-5-inhibitors-pde-5i-for-erectile-dysfunction-ed-a-therapeutic-challenge-for-psychiatrists
#12
Chong Siew Koon, Hatta Sidi, Jaya Kumar, Srijit Das, Ong Wan Xi, Muhammad Hizri Hatta, Cesar Alfonso
Erectile function (EF) is a prerequisite for satisfactory sexual intercourse (SI) and central to male sexual functioning. Satisfactory SI eventually leads to orgasm - a biopsychophysiological state of euphoria - leading to a sense of bliss, enjoyment and positive mental well being. For a psychiatrist, treating ED is self-propelled to harmonize these pleasurable experiences alongside with encouragement of physical wellness and sensuality. Hence, the role of PDE-5i is pivotal in the context of treating ED constitutes a therapeutic challenge...
February 15, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28214925/missed-opportunities-in-neonatal-deaths-in-rwanda-applying-the-three-delays-model-in-a-cross-sectional-analysis-of-neonatal-death
#13
Efua Wilmot, Marcel Yotebieng, Alison Norris, Fidele Ngabo
Objective Administered in a timely manner, current evidence-based interventions could reduce neonatal deaths from infections, intrapartum injuries and complications due to prematurity. The three delays model (delay in seeking care, in arriving at a health facility, and in receiving adequate care), which has been applied to understanding maternal deaths, may be useful for understanding neonatal deaths. We assess the main causes of neonatal deaths in Rwanda and their associated delays. Methods Using a cross-sectional study design, we evaluated data from 2012 from 40 facilities in which babies were delivered...
February 18, 2017: Maternal and Child Health Journal
https://www.readbyqxmd.com/read/28214061/open-physeal-fracture-of-the-distal-phalanx-of-the-hallux-case-study-diagnosis-and-management
#14
Brandon Morris, Scott Mullen, Paul Schroeppel, Bryan Vopat
Open physeal fractures of the distal phalanx of the hallux are the lesser described counterpart to the same fracture of the finger, known by its eponym as a "Seymour fracture". Displaced Salter-Harris phalangeal fractures present with a concomitant nailbed or soft tissue injury. Often these fractures occur in the summer months when open-toe footwear can be worn, however, they may occur indoors as well. Frequently, the injury results from direct axial load of the toe, or "stubbing", which causes the fracture and associated soft tissue injury...
February 6, 2017: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28214002/relation-between-ventricular-premature-complexes-and-incident-heart-failure
#15
Vratika Agarwal, Eric Vittinghoff, Isaac R Whitman, Thomas A Dewland, Jonathan W Dukes, Gregory M Marcus
Ventricular premature complexes (VPCs) may represent a reversible cause of heart failure (HF); however, the type of patients most prone remains unknown. This study leverages a large population-based database to examine interactions that might prove clinically useful in risk-stratifying patients with VPCs. We used the California Healthcare Cost and Utilization Project to identify patients with VPCs and incident systolic HF from January 1, 2005, to December 31, 2009. We calculated hazard ratios for predictors of incident systolic HF using multivariable Cox proportional hazard models...
January 25, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28213294/a-low-cost-simplified-and-scaleable-pneumotachograph-and-face-mask-for-neonatal-mouse-respiratory-measurements
#16
Jenny J Sun, Roshan Nanu, Russell S Ray
INTRODUCTION: Neonatal respiratory disorders are a leading cause of perinatal mortality due to complications resulting from premature births and prenatal exposure to drugs of abuse, but optimal treatments for these symptoms are still unclear due to a variety of confounds and risk factors. Mouse models present an opportunity to study the underlying mechanisms and efficacy of potential treatments of these conditions with controlled variables. However, measuring respiration in newborn mice is difficult and commercial components are expensive and often require modification, creating a barrier and limiting our understanding of the short and long-term effects of birth complications on respiratory function...
February 15, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28212984/hiv-1-vpr-disrupts-mitochondria-axonal-transport-and-accelerates-neuronal-aging
#17
Ying Wang, Maryline Santerre, Italo Tempera, Kayla Martin, Ruma Mukerjee, Bassel E Sawaya
Disruption of mitochondria axonal transport, essential for the maintenance of synaptic and neuronal integrity and function, has been identified in neurodegenerative diseases. Whether HIV-1 viral proteins affect mitochondria axonal transport is unknown, albeit HIV-associated neurocognitive disorders occur in around half of the patients living with HIV. Therefore, we sought to examine the effect of HIV-1 viral protein R (Vpr) on mitochondria axonal transport. Using mice primary neuronal cultures, we demonstrated that 4-day Vpr treatment reduced the ratio of moving mitochondria associated with (i) less energy (ATP) supply, (ii) reduction in Miro-1 and (iii) increase of α-synuclein which led to loss of microtubule stability as demonstrated by inconsecutive distribution of acetylated α-tubulin along the axons...
February 14, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28211974/whole-exome-sequencing-identified-1-base-pair-novel-deletion-in-bcl2-associated-athanogene-3-bag3-gene-associated-with-severe-dilated-cardiomyopathy-dcm-requiring-heart-transplant-in-multiple-family-members
#18
Muhammad Arshad Rafiq, Ayeshah Chaudhry, Melanie Care, Danna A Spears, Chantal F Morel, Robert M Hamilton
Dilated cardiomyopathy (DCM) is characterized by dilation and impaired contraction of the left ventricle or both ventricles. Among hereditary DCM, the genetic causes are heterogeneous, and include mutations encoding cytoskeletal, nucleoskeletal, mitochondrial, and calcium-handling proteins. We report three severely affected males, in a four-generation pedigree, with DCM phenotype who underwent cardiac transplant. Cardiomegaly with marked biventricular dilation and fibrosis were noticeable histopathological findings...
March 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28211648/cognitive-development-in-preterm-infants-multi-faceted-deficits-reflect-vulnerability-of-rigorous-neurodevelopmental-pathways
#19
Jessie R Maxwell, Tracylyn R Yellowhair, Akosua Y Oppong, Jenny E Camacho, Jean R Lowe, Lauren L Jantzie, Robin K Ohls
Prematurity remains the major cause of neonatal morbidity and mortality, with 15 million preterm births occurring worldwide in 2010. Infants born less than 37 weeks gestation are at high risk of abnormal neurodevelopmental outcomes, given that the central nervous system is extremely sensitive to an abnormal intra- and extra-uterine environment. Children born preterm have multiple neurodevelopmental sequelae involving dynamic and complex cognitive deficits. Former preterm infants have difficulty with each domain of cognition, including executive function, language, learning and memory, complex attention, perceptual-motor function and social cognition when compared to children born at term...
February 17, 2017: Minerva Pediatrica
https://www.readbyqxmd.com/read/28211317/primary-human-cytomegalovirus-hcmv-infection-in-pregnancy
#20
Horst Buxmann, Klaus Hamprecht, Matthias Meyer-Wittkopf, Klaus Friese
BACKGROUND: In 0.5-4% of pregnancies, the prospective mother sustains a primary infection with human cytomegalovirus (HCMV). An HCMV infection of the fetus in the first or second trimester can cause complex post-encephalitic impairment of the infant brain, leading to motor and mental retardation, cerebral palsy, epilepsy, retinal defects, and progressive hearing loss. METHODS: This review is based on pertinent publications from January 2000 to October 2016 that were retrieved by a selective search in PubMed employing the terms "cytomegalovirus and pregnancy" and "congenital cytomegalovirus...
January 27, 2017: Deutsches Ärzteblatt International
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