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- Prahalad, P., et al.
(author)
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Hemoglobin A1c trajectories in the first 18 months after diabetes diagnosis in the SWEET diabetes registry
- 2022
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In: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 23:2, s. 228-236
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Journal article (peer-reviewed)abstract
- Aim: A majority of youth with type 1 diabetes do not meet recommended hemoglobin A1c (HbA1c) targets. The SWEET diabetes registry is a multi-national registry of youth with diabetes. We used data from this registry to identify characteristics associated with glycemic control. Methods: Patients in the SWEET diabetes registry with at least one HbA1c value within 10 days of diagnosis and three follow up measurements in the first 18 months of diagnosis were included (similar to 10% of the SWEET diabetes registry). Locally weighted scatterplot smoothing was used to generate curves of HbA1c. Wilcoxon, Kruskal-Wallis, chi 2-tests were used to calculate differences between groups. Results: The mean HbA1c of youth in the SWEET diabetes registry is highest at diagnosis and lowest between months 4 and 5 post-diabetes diagnosis. HbA1c continues to increase steadily through the first 18 months of diagnosis. There are no differences in HbA1c trajectories based on sex or use of diabetes technology. Youth in North America/Australia/New Zealand had the highest HbA1c throughout the first 18 months of diagnosis. The trajectory of youth from countries with nationalized health insurance was lower than those countries without nationalized health insurance. Youth from countries with the highest gross domestic product (GDP) had the highest HbA1c throughout the first 18 months of diagnosis. Conclusions: In this subset of patients, the trajectory of youth from countries with nationalized health insurance was lower than those countries without nationalized health insurance. High GDP and high use of technology did not seem to protect from a higher trajectory.
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- Ombrello, MJ, et al.
(author)
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Genetic architecture distinguishes systemic juvenile idiopathic arthritis from other forms of juvenile idiopathic arthritis: clinical and therapeutic implications
- 2017
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In: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 76:5, s. 906-913
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Journal article (peer-reviewed)abstract
- Juvenile idiopathic arthritis (JIA) is a heterogeneous group of conditions unified by the presence of chronic childhood arthritis without an identifiable cause. Systemic JIA (sJIA) is a rare form of JIA characterised by systemic inflammation. sJIA is distinguished from other forms of JIA by unique clinical features and treatment responses that are similar to autoinflammatory diseases. However, approximately half of children with sJIA develop destructive, long-standing arthritis that appears similar to other forms of JIA. Using genomic approaches, we sought to gain novel insights into the pathophysiology of sJIA and its relationship with other forms of JIA.MethodsWe performed a genome-wide association study of 770 children with sJIA collected in nine countries by the International Childhood Arthritis Genetics Consortium. Single nucleotide polymorphisms were tested for association with sJIA. Weighted genetic risk scores were used to compare the genetic architecture of sJIA with other JIA subtypes.ResultsThe major histocompatibility complex locus and a locus on chromosome 1 each showed association with sJIA exceeding the threshold for genome-wide significance, while 23 other novel loci were suggestive of association with sJIA. Using a combination of genetic and statistical approaches, we found no evidence of shared genetic architecture between sJIA and other common JIA subtypes.ConclusionsThe lack of shared genetic risk factors between sJIA and other JIA subtypes supports the hypothesis that sJIA is a unique disease process and argues for a different classification framework. Research to improve sJIA therapy should target its unique genetics and specific pathophysiological pathways.
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- Prahalad, P, et al.
(author)
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ISPAD Annual Conference 2018 Highlights
- 2019
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In: PEDIATRIC DIABETES. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 20:4, s. 375-379
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Journal article (other academic/artistic)
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- Rani, Komal, et al.
(author)
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A novel approach to correlate the salivary exosomes and their protein cargo in the progression of cognitive impairment into Alzheimer’s disease
- 2021
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In: Journal of Neuroscience Methods. - : Elsevier. - 0165-0270 .- 1872-678X. ; 347
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Journal article (peer-reviewed)abstract
- BackgroundCognition is the ability of a person to think, remember, and interconnect ideas from various dimensions to strive for solutions. Cognitive defects accompany all forms of dementia and the decline in cognition is a most feared aspect. Mild cognitive impairment is considered as a transitional phase and the progressive loss in cognition can finally lead to Alzheimer’s disease.New MethodIn this study, we demonstrated a novel method based on nanoparticle tracking analysis (NTA) technique to directly correlate salivary exosomes concentration with the progression of cognitive impairment (CI) in Alzheimer’s disease (AD).This could open up the possibility for an early and cost-effective screening of Alzheimer's disease.ResultsUsing our novel method, the total salivary exosomes concentration was measured by NTA technique, followed by validation of key exosomal cargo proteins through an automated western blot analyzer. We observed significant differences in salivary exosomes concentration among the groups of cognitively impaired and Alzheimer’s disease patients (p = 0.0023) compared to the healthy control cohort. The method was validated through CD63 (exosomes surface marker) fluorescent antibody based quantification, which yielded a similar outcome (p = 0.0286). We further corroborated our findings with the expression level of oligomeric amyloid-beta, phosphorylated-tau protein from salivary exosomes. The Aβ oligomer/fibril abundance (p = 0.0291), phospho-tau (p = 0.0325) and Aβ protein abundance (p = 0.0198) was significantly higher in Alzheimer’s and cognitively impaired patients in comparison to the healthy controls.Comparison with Existing Method(s)There are few molecular biomarkers available to differentiate between various stages of cognitive impairment. Moreover, the current methodologies utilizing the few biomarkers available are either invasive or expensive; also, for a patient with mild cognitive complains, it is impractical to use these as a screening tool.ConclusionOur initial results indicate that the salivary exosomes concentration based on the nano-tracking technique has the potential to be used as a cost-effective screening method for early disease detection.
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- Rastogi, Simran, et al.
(author)
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The Evolving Landscape of Exosomes in Neurodegenerative Diseases : Exosomes Characteristics and a Promising Role in Early Diagnosis
- 2021
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In: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 22:1
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Research review (peer-reviewed)abstract
- Neurodegenerative diseases (ND) remains to be one of the biggest burdens on healthcare systems and serves as a leading cause of disability and death. Alzheimer’s disease (AD) is among the most common of such disorders, followed by Parkinson’s disease (PD). The basic molecular details of disease initiation and pathology are still under research. Only recently, the role of exosomes has been linked to the initiation and progression of these neurodegenerative diseases. Exosomes are small bilipid layer enclosed extracellular vesicles, which were once considered as a cellular waste and functionless. These nano-vesicles of 30–150 nm in diameter carry specific proteins, lipids, functional mRNAs, and high amounts of non-coding RNAs (miRNAs, lncRNAs, and circRNAs). As the exosomes content is known to vary as per their originating and recipient cells, these vesicles can be utilized as a diagnostic biomarker for early disease detection. Here we review exosomes, their biogenesis, composition, and role in neurodegenerative diseases. We have also provided details for their characterization through an array of available techniques. Their updated role in neurodegenerative disease pathology is also discussed. Finally, we have shed light on a novel field of salivary exosomes as a potential candidate for early diagnosis in neurodegenerative diseases and compared the biomarkers of salivary exosomes with other blood/cerebrospinal fluid (CSF) based exosomes within these neurological ailments
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