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1.
Pediatr Infect Dis J ; 43(4): 345-349, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38190645

ABSTRACT

BACKGROUND: Multiplex polymerase chain reaction assays have the potential to reduce antibiotic use and shorten length of inpatient stay in children with suspected central nervous system infection by obtaining an early microbiological diagnosis. The clinical impact of the implementation of the BioFire FilmArray Meningitis/Encephalitis Panel on the management of childhood meningitis was evaluated at the John Radcliffe Hospital in Oxford and Children's Health Ireland at Temple Street in Dublin. METHODS: Children who had lumbar punctures performed as part of a septic screen were identified retrospectively through clinical discharge coding and microbiology databases from April 2017 to December 2018. Anonymized clinical and laboratory data were collected. Comparison of antibiotic use, length of stay and outcome at discharge was made with a historical cohort in Oxford (2012-2016), presenting before implementation of the FilmArray. RESULTS: The study included 460 children who had a lumbar puncture as part of an evaluation for suspected central nervous system infection. Twelve bacterial cases were identified on the FilmArray that were not detected by conventional bacterial culture. Bacterial culture identified one additional case of bacterial meningitis, caused by Escherichia coli , which had not been identified on the FilmArray. Duration of antibiotics was shorter in children when FilmArray was used than before its implementation; enterovirus meningitis (median: 4 vs. 5 days), human parechovirus meningitis (median: 4 vs. 4.5 days) and culture/FilmArray-negative cerebrospinal fluid (median: 4 vs. 6 days). CONCLUSIONS: The use of a FilmArray can identify additional bacterial cases of meningitis in children that had been negative by traditional culture methods. Children with viral meningitis and culture-negative meningitis received shorter courses of antibiotics and had shorter hospital stays when FilmArray was used. Large studies to evaluate the clinical impact and cost effectiveness of incorporating the FilmArray into routine testing are warranted.


Subject(s)
Central Nervous System Infections , Encephalitis , Meningitis, Bacterial , Meningitis, Viral , Meningitis , Child , Humans , Encephalitis/diagnosis , Retrospective Studies , Meningitis/microbiology , Cohort Studies , Bacteria/genetics , Multiplex Polymerase Chain Reaction/methods , Central Nervous System Infections/diagnosis , Anti-Bacterial Agents/therapeutic use , Meningitis, Viral/diagnosis
2.
Nat Commun ; 12(1): 3447, 2021 06 08.
Article in English | MEDLINE | ID: mdl-34103494

ABSTRACT

Congenital heart disease (CHD) is the most common class of human birth defects, with a prevalence of 0.9% of births. However, two-thirds of cases have an unknown cause, and many of these are thought to be caused by in utero exposure to environmental teratogens. Here we identify a potential teratogen causing CHD in mice: maternal iron deficiency (ID). We show that maternal ID in mice causes severe cardiovascular defects in the offspring. These defects likely arise from increased retinoic acid signalling in ID embryos. The defects can be prevented by iron administration in early pregnancy. It has also been proposed that teratogen exposure may potentiate the effects of genetic predisposition to CHD through gene-environment interaction. Here we show that maternal ID increases the severity of heart and craniofacial defects in a mouse model of Down syndrome. It will be important to understand if the effects of maternal ID seen here in mice may have clinical implications for women.


Subject(s)
Cardiovascular System/embryology , Embryo, Mammalian/pathology , Iron Deficiencies , Animals , Aorta, Thoracic/abnormalities , Biomarkers/metabolism , Cell Differentiation , Coronary Vessels/embryology , Coronary Vessels/pathology , Dietary Supplements , Edema/pathology , Embryo, Mammalian/abnormalities , Embryonic Development , Female , Gene Expression Profiling , Gene-Environment Interaction , Green Fluorescent Proteins/metabolism , Iron/metabolism , Lymphatic Vessels/embryology , Lymphatic Vessels/pathology , Mice, Inbred C57BL , Myocardium/pathology , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Penetrance , Phenotype , Pregnancy , Signal Transduction , Stem Cells/pathology , Transgenes , Tretinoin/metabolism
4.
Front Psychiatry ; 11: 281, 2020.
Article in English | MEDLINE | ID: mdl-32362843

ABSTRACT

Anorexia nervosa (AN) is a psychiatric illness characterized by extreme overvaluation of weight and disturbed eating. Despite having the highest mortality rate of any psychiatric illness, the etiology and neurobiology of AN are poorly understood. A growing body of research has begun to elucidate the role of reward processing, as well as cognitive and limbic networks, in the symptomology of AN. However, these advances have so far failed to contribute therapeutically, suggesting a new understanding may be necessary. A disturbance in the interoceptive system, involved in perceiving and interpreting the physiological condition of the body, has recently been proposed as a central mechanism of pathology in AN, through links to hunger and satiety, risk prediction errors, emotional awareness, and body dysmorphia. This review summarizes the existing literature in order to clarify possible underlying mechanisms and proposes a novel model of the neuro-circuitry of AN. Detailed neuroanatomical studies and new methods for studying interoception may allow further refinement of this model and the development of improved treatment.

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