Attention deficit-hyperactivity disorder (ADHD) is the most prevalent neuropsychiatric condition in childhood. ADHD is a multifactorial trait with a strong genetic component. One neurodevelopmental ...hypothesis is that ADHD is associated with a lag in brain maturation. Sphingolipids are essential for brain development and neuronal functioning, but their role in ADHD pathogenesis is unexplored. We hypothesized that serum sphingolipid levels distinguish ADHD patients from unaffected subjects.
We characterized serum sphingolipid profiles of ADHD patients and two control groups: non-affected relatives and non-affected subjects without a family history of ADHD. Sphingolipids were measured by LC-MS/MS in 77 participants (28 ADHD patients, 28 related controls, and 21 unrelated controls). ADHD diagnosis was based on the Diagnostic and Statistical Manual of Mental Disorders (DSM IV-TR). Diagnostic criteria were assessed by two independent observers. Groups were compared by parametrical statistics.
Serum sphingomyelins C16:0, C18:0, C18:1, C24:1, ceramide C24:0, and deoxy-ceramide C24:1 were significantly decreased in ADHD patients at 20-30% relative reductions. In our sample, decreased serum sphingomyelin levels distinguished ADHD patients with 79% sensitivity and 78% specificity.
Our results showed lower levels of all major serum sphingomyelins in ADHD. These findings may reflect brain maturation and affect neuro-functional pathways characteristic for ADHD.
Thyroid cancer is the most frequent endocrine malignancy, and its incidence is increasing. A current limitation of cytological evaluation of thyroid nodules is that 20–25% are reported as ...indeterminate. Therefore, an important challenge for clinicians is to determine whether an indeterminate nodule is malignant, and should undergo surgery, or benign, and should be recommended to follow-up. The emergence of precision medicine has offered a valuable solution for this problem, with four tests currently available for the molecular diagnosis of indeterminate cytologies. However, efforts to critically analyze the quality of the accumulated evidence are scarce. This systematic review and meta-analysis is aimed to contribute to a better knowledge about the four available molecular tests, their technical characteristics, clinical performance, and ultimately to help clinicians to make better decisions to provide the best care options possible. For this purpose, we address three critical topics: (i) the proper theoretical accuracy, considering the intended clinical use of the test (rule-in vs rule-out) and the impact on clinical decisions; (ii) the quality of the evidence reported for each test (iii) and how accurate and effective have the tests proved to be after their clinical use. Together with the upcoming evidence, this work provides significant and useful information for healthcare system decision-makers to consider the use of molecular testing as a public health need, avoiding unnecessary surgical risks and costs.
Behavioral variability may be an ADHD key feature. Currently used ex-Gaussian/Fast Fourier Transform analyses characterize general distribution and oscillatory/rhythmic components of performance but ...are unable to demonstrate slow cumulative changes over entire tasks. Objective: To explore how performance of ADHD children and unaffected sibs gradually evolves in relation to genetic variants linked to ADHD. Method: A total of 40 kids (20 ADHD-discordant sib pairs) between 8 and 13 years resolved a visual Go/NoGo with 10% NoGo probability. Variable number tandem repeats (VNTRs) at DRD4 and SLC6A3 were identified following standard protocols. Performance changes were assessed by linear/logistic mixed-effect models. Results: Models exploring SLC6A3 effects demonstrated less accentuated increments of response time (RT) (p = .046) and cumulative increments in the correct responses to “NoGo” (p = .00027) in 10R/10R participants. Models for DRD4 showed faster decline of correct responses to “Go” (p = .0078) in 2R/7R carriers. Conclusion: Dynamical analysis of attention/inhibition measures may unravel new correlates to DRD4 and SLC6A3 variants.
Background/Aims
Hemorrhagic complications during ECMO may affect a large proportion of the patients depending on the clinical setting. To guarantee optimal delivery of blood products to these ...patients, blood banks require updated information on the transfusion requirements. Few studies to date provide this information. This work assesses transfusion requirements in neonates and children during ECMO during the past 9 years.
Methods
We reviewed blood bank and hospital records of patients who underwent ECMO at our institution between May 2003 and May 2012. Data obtained included age, weight, diagnosis, type, length of ECMO, and daily transfusion requirements during ECMO. Descriptive and non-parametric inferential statistic analyses were performed. Our series included 98 patients.
Results
Mean time of patients on ECMO was 9.2 days, with the longest treatment spanning 22 days. Mean daily transfusion requirements were 39.5 ml/kg of RBC, 12.9 ml/kg of plasma, 34.3 ml/kg of platelets and 1.4 ml/kg of cryoprecipitate. Patients who underwent ECMO due to cardiac disease or congenital diaphragmatic hernia (CDH) required significantly higher transfusion volumes of plasma (p<0.05), platelets (p< 0.05) and cryoprecipitate (p<0.05) when compared to patients underwent ECMO due to respiratory disease. Concomitant with the aging of ECMO circuits, patients showed increased requirements of RBC, plasma, and CRYO around the seventh day of the ECMO run. This effect was not observed for platelets, which remained nearly consistent around 2.2 transfusions/day.
Conclusions
ECMO patients required significant transfusion support, which was particularly higher among patients who underwent ECMO due to cardiac disease or congenital diaphragmatic hernia.
Emerging research has linked psychological well-being with many physiological markers as well as morbidity and mortality. In this analysis, the relationship between components of eudaimonic ...well-being and serum sphingolipids levels was investigated using data from a large national survey of middle-aged American adults (Midlife in the United States). Health behaviors (i.e., diet, exercise, and sleep) were also examined as potential mediators of these relationships. Serum levels of total ceramides-the main molecular class of sphingolipids previously associated with several disease conditions-were inversely linked with environmental mastery. In addition, significant correlations were found between specific ceramide, dihydroceramide, and hexosylceramides species with environmental mastery, purpose in life, and self-acceptance. Using hierarchical regression and mediation analyses, health behaviors appeared to mediate these associations. However, the link between ceramides and environmental mastery was partially independent of health behaviors, suggesting the role of additional mediating factors. These findings point to sphingolipid metabolism as a novel pathway of health benefits associated with psychological well-being. In particular, having a sense of environmental mastery may promote restorative behaviors and benefit health via improved blood sphingolipid profiles.
Abstract only
Background
ADHD is the most prevalent neurodevelopmental disorder in children and has been associated with a lag in neuronal maturation. Sphingolipids are essential for myelination, ...neuronal function and development. We hypothesized that serum sphingolipid profiles are different in ADHD.
Objective
To characterize the serum sphingolipid profile in ADHD patients and two independent control groups: non‐affected relatives and non‐affected subjects without family history of ADHD.
Method
Sphingolipid profiles were determined by mass spectrometry in 77 participants (28 ADHD, 28 related controls and 21 unrelated controls). Diagnosis was based on the criteria of Diagnostic and Statistical Manual of Mental Disorders (DSM IV‐TR). Groups were compared by parametrical statistics.
Results
All major sphingomyelins (C16:0, C18:0, C18:1 and C24:1), ceramide C24:0 and deoxyceramide C24:1 were significantly decreased in ADHD at relative reductions between 20‐30%. In our sample, decreased serum sphingomyelin levels distinguished ADHD patients with 79% sensitivity, 78% specificity and an estimated negative predictive value of 97%.
Conclusion
Serum sphingomyelin and select ceramides are decreased in ADHD patients. Longitudinal studies are required to evaluate if these findings reflect an ADHD specific pathomechanisms. Low serum sphingomyelins levels are a potential biomarker for ADHD.
Grant support: None
Objective: Epidemiological studies suggest that long-chain polyunsaturated fatty acids (LC-PUFAs) may be suitable as endophenotypes for ADHD. To be appropriated vulnerability traits, endophenotypes ...should be altered in unaffected relatives of index cases. Serum profiles of LC-PUFAs in unaffected relatives of ADHD patients remain understudied. The main objective of this study was to compare serum LC-PUFAs in ADHD patients, unaffected relatives of index cases, and general-population unaffected participants. Method: LC-PUFA profiles of 72 participants (27 ADHD patients, 27 unaffected relatives, and 18 general-population participants) were obtained by gas chromatography–mass spectrometry (GC-MS). Groups were compared by parametrical statistics. Results: Unaffected females from the general population presented lower Docosapentaenoic acid (DPA; p = .0012) and a-linolenic acid (ALA; p = .0091) levels compared with ADHD females and unaffected relatives. In addition, docosahexaenoic acid (DHA)/ALA and DHA/DPA ratios, addressing desaturase activity, were significantly lower in ADHD patients and unaffected relatives of ADHD patients in the female-subgroup (p = .022 and .04, respectively). Conclusion: DHA/ALA, DHA/DPA, serum DPA, and serum ALA may be suitable as endophenotypes for ADHD women.
Background:
Although most thyroid nodules with indeterminate cytology are benign, in most of the world, surgery remains as the most frequent diagnostic approach. We have previously reported a 10-gene ...thyroid genetic classifier, which accurately predicts benign thyroid nodules. The assay is a prototype diagnostic kit suitable for reference laboratory testing and could potentially avoid unnecessary diagnostic surgery in patients with indeterminate thyroid cytology.
Methods:
Classifier performance was tested in two independent, ethnically diverse, prospective multicenter trials (TGCT-1/Chile and TGCT-2/USA). A total of 4061 fine-needle aspirations were collected from 15 institutions, of which 897 (22%) were called indeterminate. The clinical site was blind to the classifier score and the clinical laboratory blind to the pathology report. A matched surgical pathology and valid classifier score was available for 270 samples.
Results:
Cohorts showed significant differences, including (i) clinical site patient source (academic, 43% and 97% for TGCT-1 and -2, respectively); (ii) ethnic diversity, with a greater proportion of the Hispanic population (40% vs. 3%) for TGCT-1 and a greater proportion of African American (11% vs. 0%) and Asian (10% vs. 1%) populations for TGCT-2; and (iii) tumor size (mean of 1.7 and 2.5 cm for TGCT-1 and -2, respectively). Overall, there were no differences in the histopathological profile between cohorts. Forty-one of 155 and 45 of 115 nodules were malignant (cancer prevalence of 26% and 39% for TGCT-1 and -2, respectively). The classifier predicted 37 of 41 and 41 of 45 malignant nodules, yielding a sensitivity of 90% 95% confidence interval; CI 77–97 and 91% 95% CI 79–98 for TGCT-1 and -2, respectively. One hundred one of 114 and 61 of 70 nodules were correctly predicted as benign, yielding a specificity of 89% 95% CI 82–94 and 87% 95% CI 77–94, respectively. The negative predictive values for TGCT-1 and TGCT-2 were 96% and 94%, respectively, whereas the positive predictive values were 74% and 82%, respectively. The overall accuracy for both cohorts was 89%.
Conclusions:
Clinical validation of the classifier demonstrates equivalent performance in two independent and ethnically diverse cohorts, accurately predicting benign thyroid nodules that can undergo surveillance as an alternative to diagnostic surgery.
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