An in-depth Comparison of the Pediatric and Adult Urinary N-glycomes.
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ABSTRACT:
SUBMITTER: Li H
PROVIDER: S-EPMC7664126 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:In this study, we performed an in-depth characterization of the male pediatric infant urinary proteome by parallel proteomic analysis of normal healthy adult (n=6) and infant (n=6) males and comparison to available published data. A total of 1584 protein groups were identified. Of these, 708 proteins were identified in samples from both cohorts. Although present in both cohorts, 136 of these common proteins were significantly enriched in urine from adults and 94 proteins were significantly enriched in urine from infants. Using Gene Ontology, we found that the infant-enriched or specific subproteome (743 proteins) had an overrepresentation of proteins that are involved in translation and transcription, cellular growth and metabolic processes. In contrast, the adult enriched or specific subproteome (364 proteins) showed an overexpression of proteins involved in immune response and cell adhesion. This study demonstrates that the non-diseased male urinary proteome is quantitatively affected by age, has age-specific subproteomes, and identifies a common subproteome with no age-dependent abundance variations. These findings highlight the importance of age-matching in urinary proteomics. This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge.
| S-EPMC3796057 | biostudies-literature
Project description:Children with chronic myeloid leukemia (CML) tend to present with higher white blood counts and larger spleens than adults with CML, suggesting that the biology of pediatric and adult CML may differ. To investigate whether pediatric and adult CML have unique molecular characteristics, we studied the transcriptomic signature of pediatric and adult CML CD34+ cells and healthy pediatric and adult CD34+ control cells. Using high-throughput RNA sequencing, we found 567 genes (207 up- and 360 downregulated) differentially expressed in pediatric CML CD34+ cells compared to pediatric healthy CD34+ cells. Directly comparing pediatric and adult CML CD34+ cells, 398 genes (258 up- and 140 downregulated), including many in the Rho pathway, were differentially expressed in pediatric CML CD34+ cells. Using RT-qPCR to verify differentially expressed genes, VAV2 and ARHGAP27 were significantly upregulated in adult CML CD34+ cells compared to pediatric CML CD34+ cells. NCF1, CYBB, and S100A8 were upregulated in adult CML CD34+ cells but not in pediatric CML CD34+ cells, compared to healthy controls. In contrast, DLC1 was significantly upregulated in pediatric CML CD34+ cells but not in adult CML CD34+ cells, compared to healthy controls. These results demonstrate unique molecular characteristics of pediatric CML, such as dysregulation of the Rho pathway, which may contribute to clinical differences between pediatric and adult patients.
| S-EPMC8699058 | biostudies-literature
Project description:The goals of this study are to test whether the differences in clinical presentation of pediatric CML are due to unique molecular characteristics that differ from adult CML. Methods: CD34+ hematopoietic stem/progenitor cells mRNA profiles of pediatric normal/CML and adult normal/CML were generated by deep sequencing as reverse paired-end (75 bp) runs on the HiSeq 4000 sequencer. Raw fastq files were trimmed with Trimmomatic/0.36 and reads were aligned to the mm10 reference genome with STAR/2.5.1b aligner. Gene level counts were determined with STAR –quantMode option using gene annotations from GENCODE (vM13). QC assessments such as unique alignment counts, unique/multiple ratio or exon/intron ratio was derived with ngsutilsj-0.3-2180ca6 using the bam-stats option. Differential gene expression and all other pathway analysis are conducted with R/3.4.3. Samples were imported, normalized with trimmed mean of Mvalues (TMM) from the EdgeR/3.20.9 package and further transformed with VOOM from the Limma/3.34.9 package, resulting in a log2 normalized count matrix. A linear model using the Limma/3.34.9 package was then used to obtain p-values, adjusted pvalues and log-fold changes (LogFC). qRT–PCR validation was performed using TaqMan assays. Results: Using an optimized data analysis workflow, we mapped about 30 million sequence reads per sample to the mouse genome (build mm9) and identified 16,014 transcripts in the retinas of WT and Nrl−/− mice with BWA workflow and 34,115 transcripts with TopHat workflow. RNA-seq data confirmed stable expression of 25 known housekeeping genes, and 12 of these were validated with qRT–PCR. RNA-seq data had a linear relationship with qRT–PCR for more than four orders of magnitude and a goodness of fit (R2) of 0.8798. Approximately 10% of the transcripts showed differential expression between the WT and Nrl−/− retina, with a fold change ≥1.5 and p value <0.05. Altered expression of 25 genes was confirmed with qRT–PCR, demonstrating the high degree of sensitivity of the RNA-seq method. Hierarchical clustering of differentially expressed genes uncovered several as yet uncharacterized genes that may contribute to retinal function. Data analysis with BWA and TopHat workflows revealed a significant overlap yet provided complementary insights in transcriptome profiling. Conclusions: Our study demonstrates that unique molecular characteristics of pediatric CML, such as dysregulated Rho pathway, which may contribute to the clinical differences at presentation between adult and pediatric patients.
2021-12-31 | GSE163690 | GEO
Project description:To compare the clinicopathological characteristics and survival outcomes of children and adult diagnosed with medullary thyroid carcinoma (MTC). MTC patients were extracted from the Surveillance, Epidemiology and End Results (SEER) database from 1998 to 2016, followed by stratification into pediatric (<?20 years) or adult (??20 years) groups. In total, 2,197 patients (110 pediatric and 2087 adult) with MTC were identified. Pediatric patients were more likely to have localized stage (70.0% vs. 51.6%), negative regional nodes (48.2% vs. 30.8%) and receive total/subtotal thyroidectomy surgery (97.3% vs. 85.3%). Moreover, CSS and OS rates were significantly higher in pediatric patients (both P?<?0.001). Multivariable Cox regression analysis revealed that adult patients were significantly correlated with worse CSS and OS rates [(CSS: HR 11.60, 95% CI 1.62-83.02, P?=?0.015); (OS: HR 5.63, 95% CI 2.08-15.25, P?=?0.001)]. Further stratified analysis indicated that pediatric group might have significant better CSS and OS for patients with more advanced stage. Patients in the pediatric group were more likely to have earlier stage. Moreover, the prognosis of pediatric MTC patients was significantly better than that in adult patients.
| S-EPMC7413344 | biostudies-literature
Project description:BackgroundDifferences in the functioning of the immune system and the anatomical proportions of the neck between children and adults lead to different manifestations of deep neck infections. Magnetic resonance imaging (MRI) may serve as an alternative to computed tomography (CT) as the primary imaging modality.ObjectiveTo study characteristic MRI findings and the diagnostic accuracy of MRI in pediatric deep neck infections.Materials and methodsWe retrospectively studied a cohort of pediatric patients who underwent a neck 3-tesla MRI study over a five-year period. Inclusion criteria were: 1) emergency MRI findings indicating an infection, 2) infection as the final clinical diagnosis, 3) diagnostic image quality verified by the radiologist reading the study and 4) age under 18 years. Patient record data, including surgery reports, were compared with the MRI findings.ResultsData of 45 children were included and analysed. Compared to adults, children had a higher incidence of retropharyngeal infection and lymphadenitis, and a lower incidence of peritonsillar/parapharyngeal infection. MRI showed evidence of an abscess in 34 children. Of these 34 patients, 24 underwent surgery, which confirmed an abscess in 21 but no abscess in three patients. In addition, three patients underwent surgery without MRI evidence of abscess, and an abscess was found in one of these cases. The measures of diagnostic accuracy among the children were sensitivity 0.96, specificity 0.77, positive predictive value 0.89, negative predictive value 0.91 and accuracy 0.89. Compared with adults, children had lower C-reactive protein, but a similar proportion of them had an abscess, and abscess size and rate of surgery were similar.ConclusionDespite the differences in the infection foci, emergency MRI in children had equal diagnostic accuracy to that in adults.
| S-EPMC9107440 | biostudies-literature
Project description:We aimed to investigate the characteristic presentation of Miller Fisher syndrome (MFS) in pediatrics and compare it with that in adults. We performed a retrospective review of medical records, laboratory findings, and disease course of pediatric MFS. The data were compared with those of adult MFS, and literature review was done. Unpaired and paired comparisons between groups were made using Wilcoxon rank-sum and signed-rank tests, respectively. Median age for pediatric MFS was 9.8 ± 6.5 years. There were 5 (45.5%) male and 6 (54.5%) female patients. All patients had preceding infection. Two patients (22.2%) had tested positive for anti-GQ1b antibody. Ten patients (90.1%) were treated with intravenous immunoglobulin, and 2 (18.2%) also received intravenous methylprednisolone. Within one month, 8 (72.7%) patients showed recovery, and all 11 (100%) recovered fully within 3 months. Further, the pediatric group had higher frequency of unilateral involvement of ophthalmoplegia, ataxia, and autonomic symptoms but lower antiganglioside antibody positivity and manifestations of areflexia than the adult group. Neuro-ophthalmic manifestations and disease course of pediatric MFS were similar to those of adult MFS as stated in the literature. However, the presence of autonomic symptoms was higher and anti-GQ1b antibody positivity was lower in pediatric MFS than in adult MFS.
| S-EPMC7761853 | biostudies-literature
Project description:The conjunctival microcirculation in 14 pediatric and eight adult sickle cell anemia (SCA) patients was studied using computer-assisted intravital microscopy. The bulbar conjunctiva in SCA patients in both age groups exhibited a blanched/avascular appearance characterized by decreased vascularity. SCA patients from both age groups had many of the same abnormal morphometric [vessel diameter, vessel distribution, morphometry (shape), tortuosity, arteriole:venule (A:V) ratio, and hemosiderin deposits] and dynamic [vessel sludging/sludged flow, boxcar blood (trickled) flow, and abnormal flow velocity] abnormalities. A severity index (SI) was computed to quantify the degree of vasculopathy for comparison between groups. The severity of vasculopathy differed significantly between the pediatric and adult patients (SI: 4.2 ± 1.8 vs. 6.6 ± 2.4; P = 0.028), indicative of a lesser degree of overall severity in the pediatric patients. Specific abnormalities that were less prominent in the pediatric patients included abnormal vessel morphometry and tortuosity. Sludged flow, abnormal vessel distribution, abnormal A:V ratio, and boxcar flow appeared in high prevalence in both age groups. The results indicate that SCA microvascular abnormalities develop in childhood and the severity of vasculopathy likely progresses with age. Intervention and effective treatment/management modalities should target pediatric patients to ameliorate, slow down, or prevent progressive microvascular deterioration.
| S-EPMC2964448 | biostudies-literature
Project description:ImportanceMortality from pediatric out-of-hospital cardiac arrest (OHCA) is high and has not improved in decades, unlike adult mortality. The low frequency of pediatric OHCA and weight-based medication and equipment needs may lead to lower quality of pediatric resuscitation compared with adults.ObjectiveTo compare the quality of pediatric and adult resuscitation from OHCA in a controlled simulation environment and to evaluate whether teamwork, knowledge, experience, and cognitive load are associated with resuscitation performance.Design, setting, and participantsThis cross-sectional in-situ simulation study was conducted between September 2020 and August 2021 in the metropolitan area of Portland, Oregon, and included engine companies from fire-based emergency services (EMS) agencies.ExposuresParticipating EMS crews completed 4 simulation scenarios presented in random order: (1) adult female with ventricular fibrillation; (2) adult female with pulseless electrical activity; (3) school-aged child with ventricular fibrillation; and (4) infant with pulseless electrical activity. All patients were pulseless on EMS arrival. Data were captured by the research team in real time during the scenarios.Main outcomes and measuresThe primary outcome was defect-free care, which included correct cardiopulmonary resuscitation depth, rate, and compression to ventilation ratio, time to bag-mask ventilation, and time to defibrillation, if applicable. Outcomes were determined by direct observation by an experienced physician. Secondary outcomes included additional time-based interventions and the use of correct medication doses and equipment size. We measured teamwork using the clinical teamwork scale, cognitive load with the National Aeronautics and Space Administration task load index (NASA-TLX), and knowledge using advanced life support resuscitation tests.ResultsAmong the 215 clinicians (39 crews) who participated in 156 simulations, 200 (93%) were male, and the mean (SD) age was 38.7 (0.6) years. No pediatric shockable scenario was defect free and only 5 pediatric nonshockable scenarios (12.8%) were defect free, while 11 (28.2%) adult shockable scenarios and 27 adult nonshockable scenarios (69.2%) were defect free. The mental demand subscale of the NASA-TLX was higher in the pediatric compared with the adult scenarios (mean [SD] pediatric score, 59.1 [20.7]; mean [SD] adult score, 51.4 [21.1]; P = .01). Teamwork scores were not associated with defect-free care.Conclusions and relevanceIn this simulation study of OHCA, resuscitation quality was significantly lower for pediatric than adult resuscitation. Mental demand may have been a contributor.
| S-EPMC10193176 | biostudies-literature
Project description:The Investigators will conduct a longitudinal, mixed-methods cohort study to assess primary and secondary psychosocial outcomes among 705 MyCode pediatric participants and their parents, and health behaviors of parents whose children receive an adult- or pediatric-onset genomic result. Data will be gathered via quantitative surveys using validated measures of distress, family functioning, quality of life, body image, perceived cancer/heart disease risk, genetic counseling satisfaction, genomics knowledge, and adjustment to genetic information; qualitative interviews with adolescents and parents; and electronic health records review of parents’ cascade testing uptake and initiation of risk reduction behaviors. The investigators will also conduct empirical and theoretical legal research to examine the loss of chance doctrine and its applicability to genomic research.
| 2296574 | ecrin-mdr-crc
Project description:Introduction and hypothesisThis study's aims were to detect and quantify bacterial DNA in the urine of randomized trial participants about to undergo treatment for urinary urgency incontinence (UUI) without clinical evidence of urinary tract infection (UTI) and to determine if the presence of bacterial DNA in baseline urine relates to either baseline urinary symptoms or UTI risk after urinary tract instrumentation.MethodsWomen without clinical evidence of baseline UTI were randomized to cystoscopic onabotulinum toxin A injection and oral placebo medication versus cystoscopic placebo injection and active oral medication. Bacterial DNA in participants' catheterized urine was measured by quantitative polymerase chain reaction (qPCR).ResultsBacterial DNA was detected in the urine of 38.7 % of participants (60 out of 155). In these 60 qPCR-positive participants, baseline daily UUI episodes were greater than in the 95 qPCR-negative participants (5.71 [±2.60] vs 4.72 [±2.86], p = 0.004). Neither symptom severity by questionnaire nor treatment outcome was associated with qPCR status or with qPCR level in qPCR-positive subjects. In contrast, the presence of urinary bacterial DNA was associated with UTI risk: only 10 % of the qPCR-positive women developed a UTI post-treatment, while 24 % of the qPCR-negative women did so. The median qPCR level for qPCR-positive samples did not differ significantly by UTI status (UTI 2.58 × 10(5) vs no UTI 1.35 × 10(5) copies/mL, p = 0.6).ConclusionsThese results may indicate a urinary bacterial contribution to both baseline UUI and the risk of post-treatment UTI.
| S-EPMC4128900 | biostudies-literature