Central precocious puberty in a 3 year-old girl with Phenylketonuria: a rare association?

Background Central precocious puberty (CPP) and phenylketonuria (PKU) are two rare conditions, the latter being the rarer. To date, only one case featuring both these conditions has been reported, and hyperphenylalaninemia was assumed triggering CPP. Case presentation We present a 3.2 years old girl referred with a 12 months history of breast and pubic hair development, and vaginal discharge. Hyperphenylalaninemia had been identified by newborn screening and PKU subsequently confirmed by plasma amino acid and genetic analysis. Early dietary control of plasma phenylalanine had been excellent afterwards, resulting in phenylalanine concentrations consistently within the recommended range. Clinical scenario, hormonal assessment and imaging were in keeping with true idiopathic central precocious puberty. Treatment with long lasting gonadotropin-releasing hormone analogue led to regression of secondary sexual characteristics. Conclusion We describe for the first time CPP in a girl affected with PKU but with persistently well controlled blood phenylalanine concentrations. This finding is in contrast to a previous report which suggested persistently high phenylalaninemia levels as potential trigger for CPP in PKU patients. Our report, together with the lack of evidence in published cohort studies of children with PKU, strongly suggests this rare association is coincidental and independent of the presence of severe hyperphenylalaninemia.</p

Lipid changes within the epidermis of living skin equivalents observed across a time-course by MALDI-MS imaging and profiling

© 2015 Mitchell et al. Abstract Background: Mass spectrometry imaging (MSI) is a powerful tool for the study of intact tissue sections. Here, its application to the study of the distribution of lipids in sections of reconstructed living skin equivalents during their development and maturation is described. Methods: Living skin equivalent (LSE) samples were obtained at 14 days development, re-suspended in maintenance medium and incubated for 24 h after delivery. The medium was then changed, the LSE re-incubated and samples taken at 4, 6 and 24 h time points. Mass spectra and mass spectral images were recorded from 12 μm sections of the LSE taken at each time point for comparison using matrix assisted laser desorption ionisation mass spectrometry. Results: A large number of lipid species were identified in the LSE via accurate mass-measurement MS and MSMS experiments carried out directly on the tissue sections. MS images acquired at a spatial resolution of 50 μm × 50 μm showed the distribution of identified lipids within the developing LSE and changes in their distribution with time. In particular development of an epidermal layer was observable as a compaction of the distribution of phosphatidylcholine species. Conclusions: MSI can be used to study changes in lipid composition in LSE. Determination of the changes in lipid distribution during the maturation of the LSE will assist in the identification of treatment responses in future investigations

A new mutation in the promoter region of the PAX8 gene causes true congenital hypothyroidism with thyroid hypoplasia in a girl with Down's syndrome

&lt;b&gt;Background:&lt;/b&gt; Thyroid dysfunction is common in newborn infants with Down's syndrome (DS), but defects causing classic thyroid dysgenesis (TD) with permanent congenital hypothyroidism (CH) have not been described.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Objective:&lt;/b&gt; We studied a girl with DS and CH who had a mutation in the promoter sequence of the PAX8 gene.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results:&lt;/b&gt; A female infant was found to have trisomy 21 and CH, with a venous thyrotropin (TSH) of &gt;150 mU/L and a free thyroxine (fT4) of 15.1 pmol/L (day 12). Thyroid peroxidase antibodies and thyroglobulin antibodies were elevated. Scintigraphy showed normal uptake, but ultrasound identified a small gland with heterogenous echotexture and cystic changes. Sequence analysis of the PAX8 gene revealed a new heterozygous maternally inherited mutation (−3C&gt;T) close to the transcription initiation site. Electromobility shift assay studies of the wild type and the mutant PAX8 sequence incubated with nuclear extracts from PCCL3 cells exhibited that the sequence at position −3 is not involved in specific protein binding. However, the mutant PAX8 promoter showed a significantly reduced transcriptional activation of a luciferase reporter gene in vitro tested in HEK, PCCL3, as well as in HeLa cells, indicating that this mutation is very likely to lead to reduced PAX8 expression.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions:&lt;/b&gt; The persistent CH in this patient with DS is likely to be attributable to the diminished PAX8 expression due to a new heterozygous mutation in the PAX8 promoter sequence. Our case shows that true CH may occur in DS, as in the general population. Furthermore, it is possible that the trisomy 21 itself may have resulted in a more severe phenotypic expression of the PAX8 mutation in the child than the mother

Trends in Scottish newborn screening programme for congenital hypothyroidism 1980-2014: strategies for reducing age at notification after initial and repeat sampling

Objectives: To determine ages at first capillary sampling and notification and age at notification after second sampling in Scottish newborns referred with elevated thyroid-stimulating hormone (TSH). Subjects and methods: Referrals between 1980 and 2014 inclusive were grouped into seven 5-year blocks and analysed according to agreed standards. Results: Of 2 116 132 newborn infants screened, 919 were referred with capillary TSH elevation ≥8 mU/L of whom 624 had definite (606) or probable (18) congenital hypothyroidism. Median age at first sampling fell from 7 to 5 days between 1980 and 2014 (standard 4–7 days), with 22, 8 and 3 infants sampled &gt;7 days during 2000–2004, 2005–2009 and 2010–2014. Median age at notification was consistently ≤14 days, range falling during 2000–2004, 2005–2009 and 2010–2014 from 6 to 78, 7–52 and 7–32 days with 12 (14.6%), 6 (5.6%) and 5 (4.3%) infants notified &gt;14 days. However 18/123 (14.6%) of infants undergoing second sampling from 2000 onwards breached the ≤26-day standard for notification. By 2010–2014, the 91 infants with confirmed congenital hypothyroidism had shown favourable median age at first sample (5 days) with start of treatment (10.5 days) approaching age at notification. Conclusion: Most standards for newborn thyroid screening are being met by the Scottish programme, but there is a need to reduce age range at notification, particularly following second sampling. Strategies to improve screening performance include carrying out initial capillary sampling as close to 96 hours as possible; introducing 6-day laboratory reporting and use of electronic transmission for communicating repeat requests

Symmetric R-spaces: A submanifold geometry and transformation theory

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Mindin\u27 my bus\u27ness

https://digitalcommons.library.umaine.edu/mmb-vp/2117/thumbnail.jp

Making the case for mobile cognition: EEG and sports performance

In the high stakes world of International sport even the smallest change in performance can make the difference between success and failure, leading sports professionals to become increasingly interested in the potential benefits of neuroimaging. Here we describe evidence from EEG studies that either identify neural signals associated with expertise in sport, or employ neurofeedback to improve performance. Evidence for the validity of neurofeedback as a technique for enhancing sports performance remains limited. By contrast, progress in characterizing the neural correlates of sporting behavior is clear: frequency domain studies link expert performance to changes in alpha rhythms, whilst time-domain studies link expertise in response evaluation and motor output with modulations of P300 effects and readiness potentials. Despite early promise, however, findings have had relatively little impact for sports professionals, at least in part because there has been a mismatch between lab tasks and real sporting activity. After selectively reviewing existing findings and outlining limitations, we highlight developments in mobile EEG technology that offer new opportunities for sports neuroscience

Measured parental height in Turner syndrome—a valuable but underused diagnostic tool

Early diagnosis of Turner syndrome (TS) is necessary to facilitate appropriate management, including growth promotion. Not all girls with TS have overt short stature, and comparison with parental height (Ht) is needed for appropriate evaluation. We examined both the prevalence and diagnostic sensitivity of measured parental Ht in a dedicated TS clinic between 1989 and 2013. Lower end of parental target range (LTR) was calculated as mid-parental Ht (correction factor 12.5 cm minus 8.5 cm) and converted to standard deviation scores (SDS) using UK 1990 data, then compared with patient Ht SDS at first accurate measurement aged &gt; 1 year. Information was available in 172 girls of whom 142 (82.6%) were short at first measurement. However, both parents had been measured in only 94 girls (54.6%). In 92 of these girls age at measurement was 6.93 ± 3.9 years, Ht SDS vs LTR SDS − 2.63 ± 0.94 vs − 1.77 ± 0.81 (p &lt; 0.001), Ht SDS &lt; LTR in 78/92 (85%). Eleven of the remaining 14 girls were &lt; 5 years, while karyotype was 45,X/46,XX in 2 and 45,X/47,XXX in 3. Conclusion: This study confirms the sensitivity of evaluating height status against parental height but shows that the latter is not being consistently measured

Prediction of Anthropometric Foot Characteristics in Children

BACKGROUND: The establishment of growth reference values is needed in pediatric practice where pathologic conditions can have a detrimental effect on the growth and development of the pediatric foot. This study aims to use multiple regression to evaluate the effects of multiple predictor variables (height, age, body mass, and gender) on anthropometric characteristics of the peripubescent foot. METHODS: Two hundred children aged 9 to 12 years were recruited, and three anthropometric measurements of the pediatric foot were recorded (foot length, forefoot width, and navicular height). RESULTS: Multiple regression analysis was conducted, and coefficients for gender, height, and body mass all had significant relationships for the prediction of forefoot width and foot length (P or = 0.7). The coefficients for gender and body mass were not significant for the prediction of navicular height (P > or = .05), whereas height was (P < or = .05).CONCLUSIONS: Normative growth reference values and prognostic regression equations are presented for the peripubescent foot