The decision-making levels of urine tetrasaccharide for the diagnosis of Pompe disease in the Turkish population

2020 ◽  
Vol 33 (3) ◽  
pp. 391-395 ◽  
Author(s):  
Erhan Canbay ◽  
Melisa Vural ◽  
Sema Kalkan Uçar ◽  
Ebru Demirel Sezer ◽  
Hatice Karasoy ◽  
...  
Keyword(s):  
Decision Making ◽  
Pompe Disease ◽  
High Performance ◽  
Late Onset ◽  
Turkish Population ◽  
Reference Intervals ◽  
Healthy Controls ◽  
Age Group ◽  
Healthy Individuals ◽  
First Year Of Life

AbstractBackgroundRecently, urinary excretion of the tetrasaccharide 6-α-D-glucopyranosyl-maltotriose (Glc4) has been proposed as a marker for the diagnosis and monitoring of Pompe disease (PD). We aimed to determine the reference intervals and reliable decision-making levels of urine tetrasaccharide concentrations for the diagnosis of infantile- and late-onset Pompe patients in the Turkish population.MethodsIn this study, nine patients with PD (five of them with late-onset PD [LOPD]) and 226 healthy individuals (aged 0–64 years) were included. Urine Glc4 concentrations were determined using the ultra-high-performance liquid chromatography (UHPLC) tandem mass spectrometry (MS/MS) method.ResultsOur data showed that the urine tetrasaccharide levels decreased with age in healthy individuals (p < 0.001, r = −0.256). It was higher especially during the first year of life compared to that in the elder subjects. The tetrasaccharide level of Pompe patients was higher compared to that of healthy controls of the same age: 99 ± 68 mmol/mol creatinine for infantile onset vs. 4.0 ± 3.0 mmol/mol creatinine for healthy controls of the same age group and 12.1 ± 17.4 mmol/mol creatinine for late onset vs. 1.7±1.2 mmol/mol creatinine for healthy controls of the same age group.ConclusionsThe results of this study showed that the reference intervals of tetrasaccharide in urine changed over time; therefore, it is critically important to define age-based decision levels for the diagnosis of LOPD.

scholarly journals Experience with the Urinary Tetrasaccharide Metabolite for Pompe Disease in the Diagnostic Laboratory

Metabolites ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 446
Author(s):  
Jennifer T. Saville ◽  
Maria Fuller
Keyword(s):  
Pompe Disease ◽  
Late Onset ◽  
Reference Interval ◽  
Laboratory Diagnosis ◽  
Reference Intervals ◽  
Confirmatory Test ◽  
Diagnostic Laboratory ◽  
Age Related ◽  
Initial Drop ◽  
Monitoring Treatment

Following clinical indications, the laboratory diagnosis of the inherited metabolic myopathy, Pompe disease (PD), typically begins with demonstrating a reduction in acid alpha-glucosidase (GAA), the enzyme required for lysosomal glycogen degradation. Although simple in concept, a major challenge is defining reference intervals, as even carriers can have reduced GAA, and pseudodeficiencies complicate interpretation. Here, we developed a mass spectrometric assay for quantification of a urinary glycogen metabolite (tetrasaccharide) and reported on its utility as a confirmatory test for PD in a diagnostic laboratory. Using two age-related reference intervals, eight returned tetrasaccharide concentrations above the calculated reference interval but did not have PD, highlighting non-specificity. However, retrospective analysis revealed elevated tetrasaccharide in seven infantile-onset (IOPD) cases and sixteen late-onset (LOPD) cases, and normal concentrations in one heterozygote. Prospective tetrasaccharide analysis in nine individuals with reduced GAA confirmed IOPD in one, LOPD in six and identified two heterozygotes. Using this metabolite as a biomarker of therapeutic response was not overly informative; although most patients showed an initial drop following therapy initiation, tetrasaccharide concentrations fluctuated considerably and remained above reference intervals in all patients. While useful as a confirmation of PD, its utility as a biomarker for monitoring treatment warrants further investigation.

scholarly journals Metagenomic evidence for a polymicrobial signature of sepsis

2021 ◽  
Vol 7 (9) ◽  
Author(s):  
Cedric Chih Shen Tan ◽  
Mislav Acman ◽  
Lucy van Dorp ◽  
Francois Balloux
Keyword(s):  
Microbial Communities ◽  
High Performance ◽  
Operating Characteristic ◽  
Metagenomic Data ◽  
Healthy Controls ◽  
Clinical Testing ◽  
Healthy Individuals ◽  
Significant Progress ◽  
Boosted Tree ◽  
Host Component

Our understanding of the host component of sepsis has made significant progress. However, detailed study of the microorganisms causing sepsis, either as single pathogens or microbial assemblages, has received far less attention. Metagenomic data offer opportunities to characterize the microbial communities found in septic and healthy individuals. In this study we apply gradient-boosted tree classifiers and a novel computational decontamination technique built upon SHapley Additive exPlanations (SHAP) to identify microbial hallmarks which discriminate blood metagenomic samples of septic patients from that of healthy individuals. Classifiers had high performance when using the read assignments to microbial genera [area under the receiver operating characteristic (AUROC=0.995)], including after removal of species ‘culture-confirmed’ as the cause of sepsis through clinical testing (AUROC=0.915). Models trained on single genera were inferior to those employing a polymicrobial model and we identified multiple co-occurring bacterial genera absent from healthy controls. While prevailing diagnostic paradigms seek to identify single pathogens, our results point to the involvement of a polymicrobial community in sepsis. We demonstrate the importance of the microbial component in characterising sepsis, which may offer new biological insights into the aetiology of sepsis, and ultimately support the development of clinical diagnostic or even prognostic tools.

scholarly journals Appetite-Regulating Hormone Ghrelin Predicts Decision-Making in Healthy Controls but Not Individuals With Low-Weight Eating Disorders

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A623-A624
Author(s):  
Naila Shiraliyeva ◽  
Madeline Rogers Stull ◽  
Danielle L Kahn ◽  
Lauren Breithaupt ◽  
Meghan Slattery ◽  
...  
Keyword(s):  
Decision Making ◽  
Delay Discounting ◽  
Energy Homeostasis ◽  
Area Under The Curve ◽  
Healthy Controls ◽  
Impulsive Behavior ◽  
Healthy Individuals ◽  
Preclinical Research ◽  
Low Weight

Abstract Background: Ghrelin is an orexigenic hormone known to regulate appetite, glucose homeostasis, and other food-related functions. The potential role of ghrelin beyond energy homeostasis is not well understood. Ghrelin receptors are evident in the mesolimbic reward pathway, and preclinical research has shown that ghrelin administration increases impulsive behavior and choices in rats. However, little is known about whether and how ghrelin is associated with food-independent behavior and decision-making in humans. We investigated the relationship between ghrelin levels and monetary decision-making using a well-established behavioral paradigm in healthy individuals and individuals with a low-weight eating disorder (LWED), as patients with LWEDs have been shown to have high ghrelin levels and resistance to the effects of this hormone. We hypothesized that higher ghrelin levels would predict more impulsive choices of immediate rewards in healthy individuals, while this relationship would be less pronounced in individuals with LWEDs. Methods: Sixty-four female participants with a LWED and 34 healthy controls (HC), aged 10-22 years, presented after a 10-hour fast to undergo a standardized mixed meal followed by a delay discounting task. During this task, participants decided between smaller immediate and larger delayed monetary rewards. Based on their choices, the delay discounting parameter k was calculated as a marker of choice preferences with higher values indicating a stronger preference for the immediate smaller reward. Blood was drawn prior to and 30, 60, and 120 min after the meal for analysis of ghrelin, and area under the curve was calculated as a cumulative measurement of ghrelin levels. Results: As per study design, BMI was lower in the LWED group (17.3±1.5 kg/m2) compared to the HC group (mean±SD: 21.4±2.5 kg/m2; t[96]=11.33, p&lt;0.0001, d=-1.99). Groups did not differ by age (LWED: 18.3±3.2 years, HC: 18.0±3.1 years; t[96]=-0.36, p=0.720, d=-0.10). Ghrelin levels were higher in the LWED compared to HC group (t[96]=-2.67, p=0.009, d=0.57). K was numerically lower in the LWED compared to the HC group, but the difference was not significant (t[96]=1.37, p=0.175, d=-0.30). Importantly, in HC higher ghrelin levels were associated with higher k values (r=0.37, p=0.032). This relationship was not observed in the LWED group (r=-0.13, p=0.304). Conclusions: In HC, higher levels of ghrelin predicted a stronger preference for smaller immediate rewards, which is consistent with increased impulsive choices shown in animal research. We did not observe this relationship in our LWED sample. Our results indicate that beyond energy homeostasis, ghrelin might play a broader role in reward-related behavior and decision-making, such as monetary choices. Future studies are required to further explore the role of ghrelin in human behavior in both clinical and non-clinical populations.

scholarly journals A Comparison of Gait Patterns between Late-Onset Pompe Disease and Age-Matched Healthy Individuals: Does Late-Onset Pompe Disease have a Typical Gait Pattern?

2015 ◽  
Vol 2 (s1) ◽  
pp. S31-S31
Author(s):  
Edward Silk ◽  
Richard K. Jones ◽  
Christian Hendriksz ◽  
Reena Sharma ◽  
Ana Jovanovic ◽  
...  
Keyword(s):  
Pompe Disease ◽  
Late Onset ◽  
Gait Pattern ◽  
Healthy Individuals ◽  
Gait Patterns

scholarly journals Metagenomic evidence for a polymicrobial signature of sepsis

2020 ◽  
Author(s):  
Cedric Chih Shen Tan ◽  
Mislav Acman ◽  
Lucy van Dorp ◽  
Francois Balloux
Keyword(s):  
Microbial Communities ◽  
High Performance ◽  
Metagenomic Data ◽  
Healthy Controls ◽  
Clinical Testing ◽  
Healthy Individuals ◽  
Significant Progress ◽  
Clinical Diagnostic ◽  
Boosted Tree ◽  
Host Component

AbstractOur understanding of the host component of sepsis has made significant progress. However, detailed study of the microorganisms causing sepsis, either as single pathogens or microbial assemblages, has received far less attention. Metagenomic data offer opportunities to characterise the microbial communities found in septic and healthy individuals. In this study we apply gradient-boosted tree classifiers and a novel computational decontamination technique built upon SHapley Additive exPlanations (SHAP) to identify microbial hallmarks which discriminate blood metagenomic samples of septic patients from that of healthy individuals. Classifiers had high performance when using the read assignments to microbial genera (AUROC = 0.995), including after removal of species ‘confirmed’ as the cause of sepsis through clinical testing (AUROC = 0.915). Models trained on single genera were inferior to those employing a polymicrobial model and we identified multiple co-occurring bacterial genera absent from healthy controls.ImportanceWhile prevailing diagnostic paradigms seek to identify single pathogens, our results point to the involvement of a polymicrobial community in sepsis. We demonstrate the importance of the microbial component in characterising sepsis, which may offer new biological insights into the aetiology of sepsis and allow the development of clinical diagnostic or even prognostic tools.

scholarly journals Magnetization Transfer Ratio in Lower Limbs of Late Onset Pompe Patients Correlates With Intramuscular Fat Fraction and Muscle Function Tests

2021 ◽  
Vol 12 ◽  
Author(s):  
Claudia Nuñez-Peralta ◽  
Paula Montesinos ◽  
Alicia Alonso-Jiménez ◽  
Jorge Alonso-Pérez ◽  
David Reyes-Leiva ◽  
...  
Keyword(s):  
Pompe Disease ◽  
Muscle Function ◽  
Late Onset ◽  
Magnetization Transfer ◽  
Intramuscular Fat ◽  
Fatty Tissue ◽  
Healthy Controls ◽  
Function Tests ◽  
Fat Fraction ◽  
Spearman Test

Objectives: Magnetization transfer (MT) imaging exploits the interaction between bulk water protons and protons contained in macromolecules to induce signal changes through a special radiofrequency pulse. MT detects muscle damage in patients with neuromuscular conditions, such as limb-girdle muscular dystrophies or Charcot-Marie-Tooth disease, which are characterized by progressive fiber loss and replacement by fatty tissue. In Pompe disease, in which there is, in addition, an accumulation of glycogen inside the muscle fibers, MT has not been tested yet. Our aim is to estimate MT ratio (MTR) in the skeletal muscle of these patients and correlate it with intramuscular fat fraction (FF) and results of muscle function tests.Methods: We obtained two-point axial Dixon and Dixon-MT sequences of the right thigh on a 1.5 Teslas MRI scanner in 60 individuals, including 29 late onset Pompe disease patients, 2 patients with McArdle disease, and 29 age and sex matched healthy controls. FF and MTR were estimated. Muscle function using several muscle function tests, including quantification of muscle strength, timed test quality of life scales, conventional spirometry obtaining forced vital capacity while sitting and in the supine position, were assessed in all patients.Results: MTR was significantly lower in Pompe patients compared with controls (45.5 ± 8.5 vs. 51.7 ± 2.3, Student T-test, p &lt; 0.05). There was a negative correlation between the MTR and FF muscles studied (correlation coefficient: −0.65, Spearman test: p &lt; 0.05). MTR correlated with most of the muscle function test results. We analyzed if there was any difference in MTR values between Pompe patients and healthy controls in those muscles that did not have an increase in fat, a measure that could be related to the presence of glycogen in skeletal muscles, but we did not identify significant differences except in the adductor magnus muscle (48.4 ± 3.6 in Pompe vs. 51 ± 1.3 in healthy controls, Student T-test = 0.023).Conclusions: MTR is a sensitive tool to identify muscle loss in patients with Pompe disease and shows a good correlation with muscle function tests. Therefore, the MT technique can be useful in monitoring muscle degeneration in Pompe disease in clinical trials or natural history studies.

Differences in Reward and Persistency characterise Behavior in Chronic Pain for the Iowa Gambling Task in a Web-based Lab-in-the-field study (Preprint)

2020 ◽  
Author(s):  
Lili Zhang ◽  
Himanshu Vashisht ◽  
Alekhya Nethra ◽  
Brian Slattery ◽  
Tomas Ward
Keyword(s):  
Decision Making ◽  
Social Media ◽  
Chronic Pain ◽  
Iowa Gambling Task ◽  
Learning Curves ◽  
Self Report ◽  
Healthy Controls ◽  
Gambling Task ◽  
Convenience Sample ◽  
Pain Experiences

BACKGROUND Chronic pain is a significant world-wide health problem. It has been reported that people with chronic pain experience decision-making impairments, but these findings have been based on conventional lab experiments to date. In such experiments researchers have extensive control of conditions and can more precisely eliminate potential confounds. In contrast, there is much less known regarding how chronic pain impacts decision-making captured via lab-in-the-field experiments. Although such settings can introduce more experimental uncertainty, it is believed that collecting data in more ecologically valid contexts can better characterize the real-world impact of chronic pain. OBJECTIVE We aim to quantify decision-making differences between chronic pain individuals and healthy controls in a lab-in-the-field environment through taking advantage of internet technologies and social media. METHODS A cross-sectional design with independent groups was employed. A convenience sample of 45 participants were recruited through social media - 20 participants who self-reported living with chronic pain, and 25 people with no pain or who were living with pain for less than 6 months acting as controls. All participants completed a self-report questionnaire assessing their pain experiences and a neuropsychological task measuring their decision-making, i.e. the Iowa Gambling Task (IGT) in their web browser at a time and location of their choice without supervision. RESULTS Standard behavioral analysis revealed no differences in learning strategies between the two groups although qualitative differences could be observed in learning curves. However, computational modelling revealed that individuals with chronic pain were quicker to update their behavior relative to healthy controls, which reflected their increased learning rate (95% HDI from 0.66 to 0.99) when fitted with the VPP model. This result was further validated and extended on the ORL model because higher differences (95% HDI from 0.16 to 0.47) between the reward and punishment learning rates were observed when fitted on this model, indicating that chronic pain individuals were more sensitive to rewards. It was also found that they were less persistent in their choices during the IGT compared to controls, a fact reflected by their decreased outcome perseverance (95% HDI from -4.38 to -0.21) when fitted using the ORL model. Moreover, correlation analysis revealed that the estimated parameters had predictive value for the self-reported pain experiences, suggesting that the altered cognitive parameters could be potential candidates for inclusion in chronic pain assessments. CONCLUSIONS We found that individuals with chronic pain were more driven by rewards and less consistent when making decisions in our lab-in-the-field experiment. In this case study, it was demonstrated that compared to standard statistical summaries of behavioral performance, computational approaches offered superior ability to resolve, understand and explain the differences in decision- making behavior in the context of chronic pain outside the lab.

Late onset Pompe Disease in India – Beyond the Caucasian phenotype

2021 ◽  
Author(s):  
Ratna Dua Puri ◽  
Nitika Setia ◽  
Vinu N ◽  
Sujatha Jagadeesh ◽  
Sheela Nampoothiri ◽  
...  
Keyword(s):  
Pompe Disease ◽  
Late Onset
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