scholarly journals Urine metabolic phenotyping in children with nocturnal enuresis and comorbid neurobehavioral disorders

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mei-Ching Yu ◽  
Ta-Min Wang ◽  
Yee-Hsuan Chiou ◽  
Meng-Kung Yu ◽  
Chiao-Fan Lin ◽  
...  
Keyword(s):  
Nocturnal Enuresis ◽  
Urinary Metabolites ◽  
Resonance Spectroscopy ◽  
School Aged Children ◽  
Hyperactivity Disorder ◽  
Metabolic Marker ◽  
Neurobehavioral Disorders ◽  
Potential Link ◽  
Healthy Control

AbstractNocturnal enuresis (NE) is a common problem among 10% school-aged children. The etiologies underlying childhood NE is complex and not fully understood nowadays. Nevertheless, increasing evidence suggests a potential link between neurobehavioral disorders and enuresis in children. In this study, we aimed to explore novel metabolomic insights into the pathophysiology of NE and also, its association with pediatric psychiatric problems. Urine collected from 41 bedwetting children and 27 healthy control children was analyzed by using 1H-nuclear magnetic resonance spectroscopy from August 2017 to December 2018. At regular follow-up, there were 14 children with refractory NE having a diagnosis of attention deficient hyperactivity disorder (ADHD) or anxiety. Eventually, we identified eight significantly differential urinary metabolites and particularly increased urinary excretion of betaine, creatine and guanidinoacetate linked to glycine, serine and threonine metabolism were associated with a comorbidity of neurobehavioral disorders in refractory bedwetting children. Notably, based on physiological functions of betaine acting as a renal osmolyte and methyl group donor, we speculated its potential role in modulation of renal and/or central circadian clock systems, becoming a useful urinary metabolic marker in diagnosis of treatment-resistant NE in children affected by these two disorders.

Attention-deficit/hyperactivity disorder (ADHD) as a risk factor for persistent nocturnal enuresis in children: A two-year follow-up study

2005 ◽  
Vol 94 (11) ◽  
pp. 1619-1625 ◽  
Author(s):  
Dieter Baeyens ◽  
Herbert Roeyers ◽  
Isolde Demeyere ◽  
Sylvie Verté ◽  
Piet Hoebeke ◽  
...  
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Risk Factor ◽  
Attention Deficit ◽  
Nocturnal Enuresis ◽  
Hyperactivity Disorder ◽  
Follow Up Study

scholarly journals Urinary myo-inositol is associated with the clinical outcome in focal segmental glomerulosclerosis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jung Nam An ◽  
Jin Seong Hyeon ◽  
Youngae Jung ◽  
Young Wook Choi ◽  
Jin Hyuk Kim ◽  
...  
Keyword(s):  
Focal Segmental Glomerulosclerosis ◽  
Urinary Metabolites ◽  
Urine Samples ◽  
Resonance Spectroscopy ◽  
Important Indicator ◽  
Clinical Prognosis ◽  
Segmental Glomerulosclerosis ◽  
Healthy Control ◽  
Validation Set

Abstract Focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) have similar initial histological findings; however, their prognoses are distinct. Therefore, it is of great importance to discriminate FSGS from MCD in the early phase of disease and predict clinical prognosis. A discovery set of 184 urine samples (61 healthy control, 80 MCD, and 43 FSGS) and a validation set of 61 urine samples (12 healthy control, 26 MCD, and 23 FSGS) were collected at the time of kidney biopsy. Metabolic profiles were examined using nuclear magnetic resonance spectroscopy. Of 70 urinary metabolites, myo-inositol was significantly higher in FSGS patients than in control patients (discovery set, 2.34-fold, P < 0.001; validation set, 2.35-fold, P = 0.008) and MCD patients (discovery set, 2.48-fold, P = 0.002; validation set, 1.69-fold, P = 0.042). Myo-inositol showed an inverse relationship with the initial estimated glomerular filtration rate (eGFR) and was associated with the plasma level of soluble urokinase-type plasminogen activator receptor in FSGS patients. Myo-inositol treatment ameliorated the decreased expression of ZO-1 and synaptopodin in an in vitro FSGS model, and as myo-inositol increased, myo-inositol oxygenase tissue expression decreased proportionally to eGFR. Furthermore, urinary myo-inositol exhibited an increase in the power to discriminate FSGS patients, and its addition could better predict the response to initial treatment. In conclusion, urinary myo-inositol may be an important indicator in the diagnosis and treatment of FSGS patients.

scholarly journals Reduced adaptation of glutamatergic stress response is associated with pessimistic expectations in depression

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jessica A. Cooper ◽  
Makiah R. Nuutinen ◽  
Victoria M. Lawlor ◽  
Brittany A. M. DeVries ◽  
Elyssa M. Barrick ◽  
...  
Keyword(s):  
Acute Stress ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Resonance Spectroscopy ◽  
Stress Task ◽  
Healthy Control ◽  
Underlying Mechanisms ◽  
Induced Changes ◽  
Acute Stressor

AbstractStress is a significant risk factor for the development of major depressive disorder (MDD), yet the underlying mechanisms remain unclear. Preclinically, adaptive and maladaptive stress-induced changes in glutamatergic function have been observed in the medial prefrontal cortex (mPFC). Here, we examine stress-induced changes in human mPFC glutamate using magnetic resonance spectroscopy (MRS) in two healthy control samples and a third sample of unmedicated participants with MDD who completed the Maastricht acute stress task, and one sample of healthy control participants who completed a no-stress control manipulation. In healthy controls, we find that the magnitude of mPFC glutamate response to the acute stressor decreases as individual levels of perceived stress increase. This adaptative glutamate response is absent in individuals with MDD and is associated with pessimistic expectations during a 1-month follow-up period. Together, this work shows evidence for glutamatergic adaptation to stress that is significantly disrupted in MDD.

scholarly journals Neuroendocrine Neoplasms: Identification of Novel Metabolic Circuits of Potential Diagnostic Utility

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 374
Author(s):  
Beatriz Jiménez ◽  
Mei Ran Abellona U ◽  
Panagiotis Drymousis ◽  
Michael Kyriakides ◽  
Ashley K. Clift ◽  
...  
Keyword(s):  
1H Nmr ◽  
Cancer Metabolism ◽  
Proton Nuclear Magnetic Resonance ◽  
Neuroendocrine Neoplasms ◽  
Resonance Spectroscopy ◽  
Diagnostic Utility ◽  
Signalling Molecules ◽  
Prognostic Accuracy ◽  
Diagnostic Potential ◽  
Healthy Control

The incidence of neuroendocrine neoplasms (NEN) is increasing, but established biomarkers have poor diagnostic and prognostic accuracy. Here, we aim to define the systemic metabolic consequences of NEN and to establish the diagnostic utility of proton nuclear magnetic resonance spectroscopy (1H-NMR) for NEN in a prospective cohort of patients through a single-centre, prospective controlled observational study. Urine samples of 34 treatment-naïve NEN patients (median age: 59.3 years, range: 36–85): 18 had pancreatic (Pan) NEN, of which seven were functioning; 16 had small bowel (SB) NEN; 20 age- and sex-matched healthy control individuals were analysed using a 600 MHz Bruker 1H-NMR spectrometer. Orthogonal partial-least-squares-discriminant analysis models were able to discriminate both PanNEN and SBNEN patients from healthy control (Healthy vs. PanNEN: AUC = 0.90, Healthy vs. SBNEN: AUC = 0.90). Secondary metabolites of tryptophan, such as trigonelline and a niacin-related metabolite were also identified to be universally decreased in NEN patients, while upstream metabolites, such as kynurenine, were elevated in SBNEN. Hippurate, a gut-derived metabolite, was reduced in all patients, whereas other gut microbial co-metabolites, trimethylamine-N-oxide, 4-hydroxyphenylacetate and phenylacetylglutamine, were elevated in those with SBNEN. These findings suggest the existence of a new systems-based neuroendocrine circuit, regulated in part by cancer metabolism, neuroendocrine signalling molecules and gut microbial co-metabolism. Metabonomic profiling of NEN has diagnostic potential and could be used for discovering biomarkers for these tumours. These preliminary data require confirmation in a larger cohort.

scholarly journals DNA Methylation in LIME1 and SPTBN2 Genes Is Associated with Attention Deficit in Children

Children ◽  
2021 ◽  
Vol 8 (2) ◽  
pp. 92
Author(s):  
Sung-Chou Li ◽  
Ho-Chang Kuo ◽  
Lien-Hung Huang ◽  
Wen-Jiun Chou ◽  
Sheng-Yu Lee ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Attention Deficit ◽  
Performance Test ◽  
Neurodevelopmental Disorder ◽  
Continuous Performance Test ◽  
Attention Deficits ◽  
Clinical Settings ◽  
Hyperactivity Disorder ◽  
Cpg Sites ◽  
Healthy Control

DNA methylation levels are associated with neurodevelopment. Attention-deficit/hyperactivity disorder (ADHD), characterized by attention deficits, is a common neurodevelopmental disorder. We used methylation microarray and pyrosequencing to detect peripheral blood DNA methylation markers of ADHD. DNA methylation profiling data from the microarray assays identified potential differentially methylated CpG sites between 12 ADHD patients and 9 controls. Five candidate CpG sites (cg00446123, cg20513976, cg07922513, cg17096979, and cg02506324) in four genes (LIME1, KCNAB2, CAPN9, and SPTBN2) were further examined with pyrosequencing. The attention of patients were tested using the Conners’ Continuous Performance Test (CPT). In total, 126 ADHD patients with a mean age of 9.2 years (78.6% males) and 72 healthy control subjects with a mean age of 9.3 years (62.5% males) were recruited. When all participants were categorized by their CPT performance, the DNA methylation levels in LIME1 (cg00446123 and cg20513976) were found to be significantly higher and those in SPTBN2 (cg02506324) were significantly lower in children with worse CPT performance. Therefore, DNA methylation of two CpG sites in LIME1 and one CpG site in SPTBN2 is associated with attention deficits in children. DNA methylation biomarkers may assist in identifying attention deficits of children in clinical settings.

scholarly journals DNA methylation and lipid metabolism: an EWAS of 226 metabolic measures

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Monica del C. Gomez-Alonso ◽  
Anja Kretschmer ◽  
Rory Wilson ◽  
Liliane Pfeiffer ◽  
Ville Karhunen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Lipid Metabolism ◽  
Population Based ◽  
Total Serum ◽  
Resonance Spectroscopy ◽  
Metabolic Disturbances ◽  
Cpg Sites ◽  
Gene Transcripts

Abstract Background The discovery of robust and trans-ethnically replicated DNA methylation markers of metabolic phenotypes, has hinted at a potential role of epigenetic mechanisms in lipid metabolism. However, DNA methylation and the lipid compositions and lipid concentrations of lipoprotein sizes have been scarcely studied. Here, we present an epigenome-wide association study (EWAS) (N = 5414 total) of mostly lipid-related metabolic measures, including a fine profiling of lipoproteins. As lipoproteins are the main players in the different stages of lipid metabolism, examination of epigenetic markers of detailed lipoprotein features might improve the diagnosis, prognosis, and treatment of metabolic disturbances. Results We conducted an EWAS of leukocyte DNA methylation and 226 metabolic measurements determined by nuclear magnetic resonance spectroscopy in the population-based KORA F4 study (N = 1662) and replicated the results in the LOLIPOP, NFBC1966, and YFS cohorts (N = 3752). Follow-up analyses in the discovery cohort included investigations into gene transcripts, metabolic-measure ratios for pathway analysis, and disease endpoints. We identified 161 associations (p value < 4.7 × 10−10), covering 16 CpG sites at 11 loci and 57 metabolic measures. Identified metabolic measures were primarily medium and small lipoproteins, and fatty acids. For apolipoprotein B-containing lipoproteins, the associations mainly involved triglyceride composition and concentrations of cholesterol esters, triglycerides, free cholesterol, and phospholipids. All associations for HDL lipoproteins involved triglyceride measures only. Associated metabolic measure ratios, proxies of enzymatic activity, highlight amino acid, glucose, and lipid pathways as being potentially epigenetically implicated. Five CpG sites in four genes were associated with differential expression of transcripts in blood or adipose tissue. CpG sites in ABCG1 and PHGDH showed associations with metabolic measures, gene transcription, and metabolic measure ratios and were additionally linked to obesity or previous myocardial infarction, extending previously reported observations. Conclusion Our study provides evidence of a link between DNA methylation and the lipid compositions and lipid concentrations of different lipoprotein size subclasses, thus offering in-depth insights into well-known associations of DNA methylation with total serum lipids. The results support detailed profiling of lipid metabolism to improve the molecular understanding of dyslipidemia and related disease mechanisms.

Attention deficit and hyperactivity disorder and nocturnal enuresis co-occurrence in the pediatric population: a systematic review and meta-analysis

2021 ◽  
Author(s):  
Ana Cecília de Sena Oliveira ◽  
Bruno da Silva Athanasio ◽  
Flávia Cristina de Carvalho Mrad ◽  
Monica Maria de Almeida Vasconcelos ◽  
Maicon Rodrigues Albuquerque ◽  
...  
Keyword(s):  
Systematic Review ◽  
Attention Deficit ◽  
Nocturnal Enuresis ◽  
Pediatric Population ◽  
Meta Analysis ◽  
Hyperactivity Disorder

scholarly journals Robust diagnostic classification via Q-learning

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Victor Ardulov ◽  
Victor R. Martinez ◽  
Krishna Somandepalli ◽  
Shuting Zheng ◽  
Emma Salzman ◽  
...  
Keyword(s):  
Autism Spectrum ◽  
Decision Function ◽  
Diagnostic Classification ◽  
Decision Making Process ◽  
Domain Experts ◽  
Q Learning ◽  
School Aged Children ◽  
Hyperactivity Disorder ◽  
Clinical Diagnoses ◽  
Learning Frameworks

AbstractMachine learning (ML) models have demonstrated the power of utilizing clinical instruments to provide tools for domain experts in gaining additional insights toward complex clinical diagnoses. In this context these tools desire two additional properties: interpretability, being able to audit and understand the decision function, and robustness, being able to assign the correct label in spite of missing or noisy inputs. This work formulates diagnostic classification as a decision-making process and utilizes Q-learning to build classifiers that meet the aforementioned desired criteria. As an exemplary task, we simulate the process of differentiating Autism Spectrum Disorder from Attention Deficit-Hyperactivity Disorder in verbal school aged children. This application highlights how reinforcement learning frameworks can be utilized to train more robust classifiers by jointly learning to maximize diagnostic accuracy while minimizing the amount of information required.

scholarly journals NIMG-53. GLUTAMATE/GABA RATIO ON MRS IS ELEVATED IN PATIENTS WITH LOWER GRADE GLIOMAS AND SEIZURES

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii159-ii160
Author(s):  
Roberta Rudà ◽  
Riccardo Pascuzzo ◽  
Francesca Mo ◽  
Alessia Pellerino ◽  
Peter B Barker ◽  
...  
Keyword(s):  
Tumor Location ◽  
Resonance Spectroscopy ◽  
Lower Grade ◽  
Lack Of Information ◽  
Baseline Evaluation ◽  
Grade Ii ◽  
Grade Iii

Abstract BACKGROUND There is lack of information on the role of excitatory and inhibitory neurotransmitters in the development of seizures in patients with lower grade gliomas. Increase of glutamate and downregulation of GABA have been suggested in preclinical models and human surgical samples to be associated with brain tumor-related epilepsy. MATERIAL AND METHODS We prospectively investigated with the use of magnetic resonance spectroscopy (MRS) the differences in the ratio of metabolites (glutamate/GABA, glutamate/creatine and GABA/creatine) in the peritumoral areas between patients with or without seizures in a series of lower grade gliomas. Tumors were classified according to WHO Classification of 2016 as follows:11 grade II IDH mutated and 1p/19q codeleted; 3 grade III IDH mutated and 1p/19q codeleted; 6 grade II IDH mutated and 1p/19q intact; 1 grade III IDH mutated and 1p/19q intact; 1 grade II IDH wild-type. Patients received surgery alone or followed by temozolomide chemotherapy according to the presence of risk factors. RESULTS At baseline evaluation, maximum glutamate/GABA values were significantly higher (p=0.023) in the peritumoral area of patients with seizures (1.008 ± 0.368) with respect to those without seizures (0.691 ± 0.170). No other metabolites ratio showed significant differences between the two groups. Similar results were obtained when analyzing the metabolites ratio in the examinations during the follow-up. In the cohort of patients with seizures (n.14) variations of metabolite ratios were not associated with tumor location, 1p/19q codeletion, use of AEDs, concomitant chemotherapy or seizure characteristics (type, duration, frequency). CONCLUSIONS The study is ongoing with the aim of analyzing further the correlations between ratio of metabolites and status of the tumor (stable vs progressive).

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