207 research outputs found
Autism spectrum disorders in children and adolescents with Moebius sequence
Moebius sequence is a rare congenital disorder usually defined as a combination of facial weakness with impairment of ocular abduction. A strong association of Moebius sequence with autism spectrum disorders (ASDs) has been suggested in earlier studies with heterogenous age groups. The primary caregivers of all children and adolescents with Moebius sequence aged 6â17Â years known to the German Moebius foundation were anonymously asked to complete two screening measures of ASD [Behavior and Communication Questionnaire (VSK); Marburger Aspergerâs Syndrome Rating Scale (MBAS)]. For those who reached the cut-off for ASD, well standardized diagnostic instruments (Autism Diagnostic Interview-Revised, Autism Diagnostic Observation Schedule, WISC-III, and Kinder-DIPS) should be administered. Minimal diagnostic criteria for Moebius sequence were congenital facial weakness (uni- or bilateral) and impairment of ocular abduction (uni- or bilateral). Familiar cases should be excluded. The primary caregivers of 35/46 children and adolescents (18 males, 17 females, mean age 11.5Â years) sent back completed questionnaires, but only 27 subjects met inclusion criteria. According to the primary caregivers, none of these subjects showed mental retardation. Two probands (both males 9 and 16Â years old) reached the cut-off of the MBAS whereas the results of the VSK did not indicate ASDs in any of the patients. The 9Â year old boy could be examined personally and did not meet diagnostic criteria of ASD. ASDs might be not as frequent as reported in previous studies on patients with Moebius sequence, at least not in patients without mental retardation
Physiologically-Based Pharmacokinetic (PBPK) Modeling of Buprenorphine in Adults, Children and Preterm Neonates
Buprenorphine plays a crucial role in the therapeutic management of pain in adults,
adolescents and pediatric subpopulations. However, only few pharmacokinetic studies of
buprenorphine in children, particularly neonates, are available as conducting clinical trials in
this population is especially challenging. Physiologically-based pharmacokinetic (PBPK) modeling
allows the prediction of drug exposure in pediatrics based on age-related physiological differences.
The aim of this study was to predict the pharmacokinetics of buprenorphine in pediatrics with PBPK
modeling. Moreover, the drug-drug interaction (DDI) potential of buprenorphine with CYP3A4
and P-glycoprotein perpetrator drugs should be elucidated. A PBPK model of buprenorphine
and norbuprenorphine in adults has been developed and scaled to children and preterm neonates,
accounting for age-related changes. One-hundred-percent of the predicted AUClast values in adults
(geometric mean fold error (GMFE): 1.22), 90% of individual AUClast predictions in children (GMFE:
1.54) and 75% in preterm neonates (GMFE: 1.57) met the 2-fold acceptance criterion. Moreover,
the adult model was used to simulate DDI scenarios with clarithromycin, itraconazole and rifampicin.
We demonstrate the applicability of scaling adult PBPK models to pediatrics for the prediction
of individual plasma profiles. The novel PBPK models could be helpful to further investigate
buprenorphine pharmacokinetics in various populations, particularly pediatric subgroups
External Model Performance Evaluation of Twelve Infliximab Population Pharmacokinetic Models in Patients with Inflammatory Bowel Disease
Infliximab is approved for treatment of various chronic inflammatory diseases including
inflammatory bowel disease (IBD). However, high variability in infliximab trough levels has been
associated with diverse response rates. Model-informed precision dosing (MIPD) with population
pharmacokinetic models could help to individualize infliximab dosing regimens and improve therapy.
The aim of this study was to evaluate the predictive performance of published infliximab population
pharmacokinetic models for IBD patients with an external data set. The data set consisted of 105 IBD
patients with 336 infliximab concentrations. Literature review identified 12 published models eligible
for external evaluation. Model performance was evaluated with goodness-of-fit plots, prediction- and
variability-corrected visual predictive checks (pvcVPCs) and quantitative measures. For anti-drug
antibody (ADA)-negative patients, model accuracy decreased for predictions > 6 months, while
bias did not increase. In general, predictions for patients developing ADA were less accurate for
all models investigated. Two models with the highest classification accuracy identified necessary
dose escalations (for trough concentrations < 5 ”g/mL) in 88% of cases. In summary, population
pharmacokinetic modeling can be used to individualize infliximab dosing and thereby help to
prevent infliximab trough concentrations dropping below the target trough concentration. However,
predictions of infliximab concentrations for patients developing ADA remain challenging
The UNE Flu Crew: An Interprofessional Influenza Prevention Team
Research poster stemming from IPEC mini-grant funded student project The UNE Flu Crew: An Interdisciplinary Approach to the Assessment of Knowledge, Beliefs and Perceptions surrounding Influenza Immunizations and the Promotion of Preventing Infection. Osteopathic medicine and public health students collaborated to assess the knowledge and perceptions regarding the influenza vaccine among the University of New Englandâs student and faculty populations. The project also provided a peer-to-peer education model where members of the Flu Crew designed a teaching curriculum and provided community outreach to the UNE Biddeford campus and local community schools.https://dune.une.edu/minigrant_flucrew/1001/thumbnail.jp
Dynamic clonal progression in xenografts of acute lymphoblastic leukemia with intrachromosomal amplification of chromosome 21
Intrachromosomal amplification of chromosome 21 is a heterogeneous chromosomal rearrangement occurring in 2% of childhood precursor B-cell acute lymphoblastic leukemia. There are no cell lines with iAMP21 and these abnormalities are too complex to faithfully engineer in animal models. As a resource for future functional and pre-clinical studies, we have created xenografts from intrachromosomal amplification of chromosome 21 leukemia patient blasts and characterised them by in-vivo and ex-vivo luminescent imaging, FLOW immunophenotyping, and histological and ultrastructural analysis of bone marrow and the central nervous system. Investigation of up to three generations of xenografts revealed phenotypic evolution, branching genomic architecture and, compared with other B-cell acute lymphoblastic leukemia genetic subtypes, greater clonal diversity of leukemia initiating cells. In support of intrachromosomal amplification of chromosome 21 as a primary genetic abnormality, it was always retained through generations of xenografts, although we also observed the first example of structural evolution of this rearrangement. Clonal segregation in xenografts revealed convergent evolution of different secondary genomic abnormalities implicating several known tumour suppressor genes and a region, containing the B-cell adaptor, PIK3AP1, and nuclear receptor co-repressor, LCOR, in the progression of B-ALL. Tracking of mutations in patients and derived xenografts provided evidence for co-operation between abnormalities activating the RAS pathway in B-ALL and for their aggressive clonal expansion in the xeno-environment. Bi-allelic loss of the CDKN2A/B locus was recurrently maintained or emergent in xenografts and also strongly selected as RNA sequencing demonstrated a complete absence of reads for genes associated with the deletions
Prediction of DrugâDrugâGene Interaction Scenarios of (E)-Clomiphene and Its Metabolites Using Physiologically Based Pharmacokinetic Modeling
Clomiphene, a selective estrogen receptor modulator (SERM), has been used for the
treatment of anovulation for more than 50 years. However, since (E)-clomiphene ((E)-Clom) and its
metabolites are eliminated primarily via Cytochrome P450 (CYP) 2D6 and CYP3A4, exposure can be
affected by CYP2D6 polymorphisms and concomitant use with CYP inhibitors. Thus, clomiphene
therapy may be susceptible to drugâgene interactions (DGIs), drugâdrug interactions (DDIs) and
drugâdrugâgene interactions (DDGIs). Physiologically based pharmacokinetic (PBPK) modeling is a
tool to quantify such DGI and DD(G)I scenarios. This study aimed to develop a whole-body PBPK
model of (E)-Clom including three important metabolites to describe and predict DGI and DD(G)I
effects. Model performance was evaluated both graphically and by calculating quantitative measures.
Here, 90% of predicted Cmax and 80% of AUClast values were within two-fold of the corresponding
observed value for DGIs and DD(G)Is with clarithromycin and paroxetine. The model also revealed
quantitative contributions of different CYP enzymes to the involved metabolic pathways of (E)-Clom
and its metabolites. The developed PBPK model can be employed to assess the exposure of (E)-Clom
and its active metabolites in as-yet unexplored DD(G)I scenarios in future studies
Worse glycemic control, higher rates of diabetic ketoacidosis, and more hospitalizations in children, adolescents, and young adults with type 1 diabetes and anxiety disorders
The aim of the study was to explore the metabolic characteristics and outcome parameters in youth with type 1 diabetes and anxiety disorders. HbA1c levels, rates of severe hypoglycemia, diabetic ketoacidosis (DKA), and hospital admission in children, adolescents, and young adults with type 1 diabetes and an anxiety disorder from 431 diabetes-care-centers participating in the nationwide German/Austrian/Swiss/Luxembourgian diabetes survey DPV were analyzed and compared with youth without anxiety disorders. Children, adolescents, and young adults with type 1 diabetes and anxiety disorders (n =â1325) had significantly higher HbA1c (8.5% vs. 8.2%), higher rates of DKA (4.2 vs. 2.5 per 100 patient-years), and higher hospital admission rates (63.6 vs. 40.0 per 100 patient-years) than youth without anxiety disorders (all pâ<â0.001). Rates of severe hypoglycemia did not differ. Individuals with anxiety disorders other than needle phobia (n =â771) had higher rates of DKA compared to those without anxiety disorders (4.2 vs. 2.5 per 100 patient-years, p = 0.003) whereas the rate of DKA in individuals with needle phobia (n =â555) was not significantly different compared to those without anxiety disorders. Children, adolescents, and young adults with anxiety disorders other than needle phobia had higher hospitalization rates (73.7 vs. 51.4 per 100 patient-years) and more inpatient days (13.2 vs. 10.1âdays) compared to those with needle phobia (all pâ<â0.001). Children, adolescents, and young adults with type 1 diabetes and anxiety disorders had worse glycemic control, higher rates of DKA, and more hospitalizations compared to those without anxiety disorders. Because of the considerable consequences, clinicians should screen for comorbid anxiety disorders in youth with type 1 diabetes
Sustainable Turf Management
Report completed by students enrolled in HORT 4061: Turfgrass Management, taught by Eric Watkins in fall 2014.This project was completed as part of a year-long partnership between the City of Rosemount and the University of Minnesotaâs Resilient Communities Project (http://www.rcp.umn.edu). The City of Rosemount is home to more than 30 parks, yet has only four staff working to maintain them. With limited time and expertise to determine and respond to the unique needs of each park and recreation facility in the city, the Public Works Department had mostly standardized their maintenance techniques. The goal of this project was to identify more effective and efficient long-term maintenance techniques for parks within the City of Rosemount in order to better preserve its natural public spaces and promote active living as the population grows. In collaboration with Jim Koslowski, Public Works Supervisor for the City of Rosemount, and Tom Schuster, Parks Supervisor for the City of Rosemount, four teams of students in HORT 4061: Turfgrass Management analyzed the soil, plant species, and drainage patterns at four different parksâthe Dakota County Technical College Ames Soccer Complex, Brockway Disc Golf Course, Innisfree Park, and Meadows Parkâand provided recommendations for how best to restore and maintain turf at these facilities. A combined final report from the project including links to brief YouTube videos on each of the parks is available.This project was supported by the Resilient Communities Project (RCP), a program at the University of Minnesota that convenes the wide-ranging expertise of U of M faculty and students to address strategic local projects that advance community resilience and sustainability. RCP is a program of the Center for Urban and Regional Affairs (CURA). More information at http://www.rcp.umn.edu
Measured energy content of frequently purchased restaurant meals : multi-country cross sectional study
Funding: This work was supported in part by the US Department of Agriculture under agreement no. 58-1950-4-003 with Tufts University and a Tufts University Provost award to SBR. The study had additional funding in Brazil from FAPESP grants 2013/18520-0 and 2013/14489-1 to VS; in China from the National Science Foundation of China grant No 91431102 to JRS and International Partnership Program of Chinese Academy of Sciences grant No GJHZ1660 to JRS; in Finland from internal funding by the University of Eastern Finland to JP; in Ghana from the University of Georgia Global Research Collaborative Grant Program to AKA. The views expressed are those of the authors. The sponsors had no role in the design, undertaking, or reporting of the study.Peer reviewedPublisher PD
Adjuvant therapy for children treated by enucleation at diagnosis of retinoblastoma
Introduction
Advanced localized retinoblastoma can be cured by enucleation, but extraocular spread of retinoblastoma cells is associated with a high mortality. Risk-stratified adjuvant treatment with chemotherapy and radiotherapy has been shown to reduce the risk for extraocular relapse in children with histopathological risk factors.
Methods
Data of 184 patients with retinoblastoma and primary enucleation were collected in a prospective, multicenter, observational study between 2013 and 2020. The clinical characteristics were evaluated as risk factors and progression-free and overall survival rates were compared.
Results
Seventy-one percent of 184 children with retinoblastoma treated with primary enucleation were diagnosed with low risk histopathological factors (pT1/pT2a) and received no adjuvant therapy. Children with intermediate risk (pT2b,pT3; 48 children, 26.0%) and high risk for metastasis (pT4; 5 children, 2.7%) received risk-stratified adjuvant treatment. None of the children with low risk or intermediate risk (pT1-pT3) relapsed, but two of five children with high-risk retinoblastoma (pT4) developed extraocular relapses and one deceased. The 2-year progression-free survival rate and 2-year overall survival rate was 100% for children with pT1-3 retinoblastoma. However, the 2-year progression-free survival rate and 2-year overall survival rate for children with pT4 was statistically notably reduced with 2 of 5 children developing progression and 1 death among the 5 children within 2 years after diagnosis.
Conclusion
Primary enucleation alone and with additional risk-stratified adjuvant chemotherapy treatment provides high cure rates in patients with pT1-3 retinoblastoma, but children with pT4 retinoblastoma remain at high risk to develop extraocular retinoblastoma. International prospective clinical trials are required to evaluate reduction of intensity of adjuvant chemotherapy in some risk groups (pT2, pT3) and intensification for pT4 retinoblastoma
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