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Here, we demonstrate the expected temperature dependence of the allosteric regulation of rabbit muscle pyruvate kinase by Ala to demonstrate that this effector reduces substrate (phosphoenolpyruvate) affinity at 35°C and at 10°C but is silent at intermediate temperatures. We then explore the use of hydrogen/deuterium exchange with mass spectrometry to evaluate the areas of the protein that are modified in the mechanism that gives rise to the silent coupling between Ala and phosphoenolpyruvate. Many of the peptide regions of the protein identified as changing in this silent system (Ala as the effector) were included in changes previously identified for allosteric inhibition by Phe.Aim Quantitative endogenous steroid profiling in blood appears as a complementary approach to the urinary module of the World Anti-Doping Agency's Athlete Biological Passport Steroidal Module for the detection of testosterone doping. To refine this approach further, a UHPLC-MS/MS method was developed for the simultaneous determination of 14 free and 14 conjugated steroids in serum. NSC-185 manufacturer Results The method was validated for quantitative purposes with satisfactory results in terms of selectivity, linearity range, trueness, precision and combined uncertainty ( less then 20 %). The validated method was then applied to serum samples from both healthy women and women diagnosed with mild hyperandrogenism. link2 Conclusion The UHPLC-MS/MS method showed promising capability in quantifying free and conjugated steroids in serum and determining variations of their concentration/distribution within serum samples from different populations.Purpose This was a companion study to a previous one (Biller & Johnson, 2019). The purpose was to develop a detailed descriptive profile of a minimally verbal child with a unique medical history and autism spectrum disorder (ASD). The present report describes his social-cognitive and speech sound production abilities in relation to his potentially burgeoning spoken language. Method This in-depth, descriptive, clinical single-case study focused on a 3-year-old boy who was diagnosed with a chromosomal abnormality and ASD. The size of his spoken vocabulary fell at the upper limit for classifying a child as minimally verbal. His demographic information was obtained, in addition to general information from his mother. Four social-cognitive and three speech sound production abilities were assessed, as well as his overall performance in both domains. The study included a parent interview and two child assessment sessions. Results The child exhibited low social-cognitive and speech sound production abilities for his age, with social-cognitive abilities higher than speech sound production abilities. Comparison with the previous study revealed substantial gaps in social cognition and speech sound production between this child and five other minimally verbal children with ASD. His higher abilities in these two domains co-occurred with his larger spoken vocabulary size. Conclusions Although the child's social-cognitive abilities were low for his age, with his speech sound production abilities even lower, both domains were perhaps high enough to support spoken vocabulary at the upper limit for minimally verbal children. Indeed, there appeared to be quantitative and qualitative differences between him and other minimally verbal children in the previous study. link3 The possibility was explored that there is a point or threshold along the developmental continua for social cognition and speech sound production that allows for expansion into useful language.Background IGF-I is used as a biomarker to detect Growth Hormone doping in athletes' blood samples. Objective Our aim was to develop and validate a fast, high-throughput and accurate quantification of intact IGF-I from volumetric absorptive microsampling (VAMS) dried blood using LC coupled to high resolution mass spectrometry (LC-HRMS). Methodology & results IGF-I was extracted from the VAMS, released from its binding proteins, concentrated using microelution SPE and analyzed by LC-HRMS. The method was successfully validated in accordance with the World Anti-Doping Agency's requirements. Subsequently, IGF-I measurements from capillary dried blood and serum were compared. Conclusion The combination of VAMS, microelution SPE and LC-HRMS is a promising strategy applicable to IGF-I quantification in athletes' samples.Constitutional thinness (CT) is a non-pathological state of underweight. The present study aimed to explore skeletal muscle energy storage in individuals with constitutional thinness and to further characterize muscle phenotype at baseline and in response to overfeeding. Thirty subjects with CT (15 females, 15 males) and 31 normal-weight control subjects (16 females, 15 males) participated in the study. Histological and enzymological analyses were performed on muscle biopsies before and after overfeeding. In skeletal muscle of CT participants compared to controls, it was observed a lower content in intramuscular triglycerides for type I (p less then 0.01, -17%) and type IIA (p less then 0.05, -14%) muscle fibers, a lower glycogen content for type I fibers (p less then 0.01, -6%) and type IIA fibers (p less then 0.05, -5%), a specific fiber type distribution, a marked muscle hypotrophy (p less then 0.001, -20%), a low capillary-to-fiber ratio (p less then 0.001, -19%), and a low citrate synthase activity (p less then 0.05, -18%). In response to overfeeding, CT participants increased their intramuscular triglycerides content in type I (p less then 0.01, +10%) and type IIA (p less then 0.01, +9%) muscle fibers. CT individuals seem to present an unusual muscle phenotype and different adaptations to overfeeding compared to normal-weight participants, suggesting a specific energy metabolism and muscle adaptations. NCT02004821 Novelty ●Low intramuscular triglycerides and glycogen content in skeletal muscle of constitutionally thin individuals ●Low oxidative capacity, low capillary supply, and fiber hypotrophy in skeletal muscle of constitutionally thin participants ●Increase in intramuscular triglycerides in constitutional thinness in response to overfeeding.Purpose It is not clear if behavioral indices of listening effort are sensitive to changes in signal-to-noise ratio (SNR) for young children (7-12 years old) from multilingual backgrounds. The purpose of this study was to explore the effects of SNR on listening effort in multilingual school-aged children (native English, nonnative English) as measured with a single- and a dual-task paradigm with low-linguistic speech stimuli (digits). The study also aimed to explore age effects on digit triplet recognition and response times (RTs). Method Sixty children with normal hearing participated, 30 per language group. Participants completed single and dual tasks in three SNRs (quiet, -10 dB, and -15 dB). Speech stimuli for both tasks were digit triplets. Verbal RTs were the listening effort measure during the single-task paradigm. A visual monitoring task was the secondary task during the dual-task paradigm. Results Significant effects of SNR on RTs were evident during both single- and dual-task paradigms. As expected, language background did not affect the pattern of RTs. The data also demonstrate a maturation effect for triplet recognition during both tasks and for RTs during the dual-task only. Conclusions Both single- and dual-task paradigms were sensitive to changes in SNR for school-aged children between 7 and 12 years of age. Language background (English as native language vs. English as nonnative language) had no significant effect on triplet recognition or RTs, demonstrating practical utility of low-linguistic stimuli for testing children from multilingual backgrounds.A biomarker of doping indicates the biological response to the use of a prohibited substance or method. Uncovering novel biomarkers of doping is a key objective in order to improve antidoping outcomes such as the detection of doping and changing athlete behavior toward doping practices. While the antidoping field has been successful in validating novel metabolites of prohibited substances, there has been less success in developing new biomarkers of doping. Employing the most suitable study designs and analytical approaches is critical to successfully uncovering novel biomarkers of doping with a high potential for translation into routine analysis. Here we argue that the antidoping field is well positioned for biomarker discovery and outline considerations for the development of novel biomarkers of doping.Purpose This study aims to give an insight in clinical reasoning (diagnosis and intervention) of speech-language pathologists (SLPs) in the Netherlands for children with speech sound disorder (SSD). Method The study featured a mixed-method (qualitative and quantitative) design. Semistructured interviews containing nondirective, open-ended questions were conducted with 33 SLPs, which were analyzed using a constant comparative analysis. Other SLPs (137) filled out a questionnaire on the same topics. Multiple-choice questions were analyzed by descriptive frequencies, while open-ended questions were analyzed thematically. Results The results indicate that SLPs use a variety of assessments to diagnose SSD, complemented by observation and, often, case history. In total, 85 different diagnostic labels were reported. The choice of intervention is based on what is appealing to the child and what matches his or her age as well as on the specific diagnosis and severity. Interventions are used for multiple speech disorders, and according to SLPs, parents play a large role in diagnostics and intervention. Conclusion These results reveal the need for (a) a clear and consistent terminology of diagnoses in the field of pediatric SSD, (b) a fast and easy-to-administer comprehensive differential diagnostic instrument in combination with an instrument to assess participation in everyday life, and (c) a tool to conduct a case history online.Purpose The purpose of this study was to construct and validate a recorded word recognition test for monolingual Spanish-speaking children utilizing a picture board and a picture-pointing task. Design The Spanish Pediatric Picture Identification Test was developed and validated in this study. Test construction steps included (a) producing new digital recordings of word lists created by Comstock and Martin (1984) using a bilingual Spanish-English female, (b) obtaining list equivalency, (c) creating digitally illustrated pictures representing the word lists, (d) validating the pictures using monolingual Spanish-speaking and bilingual Spanish-English children, and (e) re-establishing list equivalency and obtaining performance-intensity functions using a picture-pointing task with monolingual Spanish-speaking children and bilingual Spanish-English adults. Results Normative data for three Spanish word recognition lists were established. Performance-intensity functions at sensation levels from 0 to 40 dB SL in 8-dB steps were obtained, establishing list equivalency for Lists 1, 2, and 3. Conclusions The Spanish Pediatric Picture Identification Test was developed and validated as a picture-pointing task for word recognition with monolingual Spanish-speaking children. The two validated channel recordings include an English translation for ease of testing by clinicians lacking Spanish language skills. Future validation will be conducted with bilingual Spanish-English children with normal hearing and with hearing loss.
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