Search results for "onset."
showing 10 items of 478 documents
Investigating fibrosis and inflammation in an ex vivo NASH murine model.
2020
Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease, characterized by excess fat accumulation (steatosis). Nonalcoholic steatohepatitis (NASH) develops in 15–20% of NAFLD patients and frequently progresses to liver fibrosis and cirrhosis. We aimed to develop an ex vivo model of inflammation and fibrosis in steatotic murine precision-cut liver slices (PCLS). NASH was induced in C57Bl/6 mice on an amylin and choline-deficient l-amino acid-defined (CDAA) diet. PCLS were prepared from steatohepatitic (sPCLS) and control (cPCLS) livers and cultured for 48 h with LPS, TGFβ1, or elafibranor. Additionally, C57Bl/6 mice were placed on CDAA diet for 12 wk to receive elafibranor…
PI3K inhibition reduces murine and human liver fibrogenesis in precisioncut liver slices
2019
Background: Liver fibrosis results from continuous inflammation and injury. Despite its high prevalence worldwide, no approved antifibrotic therapies exist. Omipalisib is a selective inhibitor of the PI3K/mTOR pathway that controls nutrient metabolism, growth and proliferation. It has shown antifibrotic properties in vitro. While clinical trials for idiopathic pulmonary fibrosis have been initiated, an in-depth preclinical evaluation is lacking. We evaluated omipalisib's effects on fibrogenesis using the ex vivo model of murine and human precision-cut tissue slices (PCTS).Methods: Murine and human liver and jejunum PCTS were incubated with omipalisib up to 10 mu M for 48 h. PI3K pathway act…
Bi-allelic JAM2 Variants Lead to Early-Onset Recessive Primary Familial Brain Calcification
2020
International audience; Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder characterized by a combination of neurological, psychiatric, and cognitive decline associated with calcium deposition on brain imaging. To date, mutations in five genes have been linked to PFBC. However, more than 50% of individuals affected by PFBC have no molecular diagnosis. We report four unrelated families presenting with initial learning difficulties and seizures and later psychiatric symptoms, cerebellar ataxia, extrapyramidal signs, and extensive calcifications on brain imaging. Through a combination of homozygosity mapping and exome sequencing, we mapped this phenotype to chromo…
Autosomal-Recessive Mutations in AP3B2, Adaptor-Related Protein Complex 3 Beta 2 Subunit, Cause an Early-Onset Epileptic Encephalopathy with Optic At…
2016
International audience; Early-onset epileptic encephalopathy (EOEE) represents a heterogeneous group of severe disorders characterized by seizures, interictal epileptiform activity with a disorganized electroencephalography background, developmental regression or retardation, and onset before 1 year of age. Among a cohort of 57 individuals with epileptic encephalopathy, we ascertained two unrelated affected individuals with EOEE associated with developmental impairment and autosomal-recessive variants in AP3B2 by means of whole-exome sequencing. The targeted sequencing of AP3B2 in 86 unrelated individuals with EOEE led to the identification of an additional family. We gathered five addition…
Skeletal alterations, developmental delay and new mutations in juvenile-onset Pompe disease.
2018
Abstract Pompe disease is an autosomal recessive disorder caused by a deficiency of acid α-glucosidase. In addition to the severe infantile form with cardiac involvement, late-onset variants can affect older children, adolescents (aged >1 year old) or adults. Patients with juvenile (a subgroup of late-onset type) Pompe disease typically do not have cardiac alterations e.g. hypertrophic cardiomyopathy, and the diagnosis is often difficult because it can clinically resemble myriad other neuromuscular disorders. A high level of clinical suspicion is necessary for a timely and accurate diagnosis. We describe 3 interesting cases of patients with juvenile-onset Pompe disease who presented some un…
Mediterranean diet and knee osteoarthritis outcomes: A longitudinal cohort study.
2018
Objectives: Mediterranean diet has several beneficial effects on health, but data regarding the association between Mediterranean diet and knee osteoarthritis (OA) are limited mainly to cross-sectional studies. We investigated whether higher Mediterranean diet adherence is prospectively associated with lower risk of radiographic OA (ROA), radiographic symptomatic knee OA (SxOA) and pain worsening in North American people at high risk or having knee OA. Methods: Adherence to the Mediterranean diet was evaluated using a validated Mediterranean diet score (aMED), categorized in five categories (Q1 to Q5, higher values reflecting higher adherence to Mediterranean diet). Knee OA outcomes include…
Formin 2 links neuropsychiatric phenotypes at young age to an increased risk for dementia
2017
Age-associated memory decline is due to variable combinations of genetic and environmental risk factors. How these risk factors interact to drive disease onset is currently unknown. Here we begin to elucidate the mechanisms by which post-traumatic stress disorder (PTSD) at a young age contributes to an increased risk to develop dementia at old age. We show that the actin nucleator Formin 2 (Fmn2) is deregulated in PTSD and in Alzheimer's disease (AD) patients. Young mice lacking the Fmn2 gene exhibit PTSD-like phenotypes and corresponding impairments of synaptic plasticity, while the consolidation of new memories is unaffected. However, Fmn2 mutant mice develop accelerated age-associated me…
miRNomic Signature in Very Low Birth-Weight Neonates Discriminates Late-Onset Gram-Positive Sepsis from Controls
2021
Background and Objectives. Neonatal sepsis is a serious condition with a high rate of mortality and morbidity. Currently, the gold standard for sepsis diagnosis is a positive blood culture, which takes 48–72 h to yield results. We hypothesized that identifying differentially expressed miRNA pattern in neonates with late-onset Gram-positive sepsis would help with an earlier diagnosis and therapy. Methods. This is a prospective observational study in newborn infants with late-onset Gram positive bacterial sepsis and non-septic controls. Complementary to blood culture, an aliquot of 0.5 mL of blood was used to determine small non-coding RNA expression profiling using the GeneChip miRNA 4.0 Arr…
Ebola Virus Disease Complicated by Late-Onset Encephalitis and Polyarthritis, Sierra Leone
2016
To the Editor: Ebola virus (EBOV) disease is usually an acute illness, but increasing evidence exists of persistent infections and post-Ebola syndromes. We report a case of EBOV encephalitis.
Usefulness of current candidate genetic markers to identify childhood cancer patients at risk for platinum-induced ototoxicity: Results of the Europe…
2020
Background Irreversible sensorineural hearing loss is a common side effect of platinum treatment with the potential to significantly impair the neurocognitive, social and educational development of childhood cancer survivors. Genetic association studies suggest a genetic predisposition for cisplatin-induced ototoxicity. Among other candidate genes, thiopurine methyltransferase (TPMT) is considered a critical gene for susceptibility to cisplatin-induced hearing loss in the FDA drug label and a pharmacogenetic guideline. The aim of this cross-sectional cohort study was to confirm the genetic associations in a large pan-European population and to evaluate the diagnostic accuracy of the genetic…