Proportion of various types of thyroid disorders among newborns with congenital hypothyroidism and normally located gland: A regional cohort study

Objective To determine the proportion of the various types of thyroid disorders among newborns detected by the neonatal TSH screening programme, with a normally located thyroid gland.Patients and methods Of the 882 575 infants screened in our centre between 1981 and 2002, 85 infants with a normally located gland had persistent elevation of serum TSH values (an incidence of 1/10 383). Six of these 85 patients were lost to follow-up and were therefore excluded from the study. During follow-up, patients were classified as having permanent or transient hypothyroidism.Results Among the 79 patients included in the study, transient (n = 30, 38% of cases) and permanent (n = 49, 62% of cases) congenital hypothyroidism (CH) was demonstrated during the follow-up at the age of 0.7 +/- 0.6 years and 2.6 +/- 1.8 years (P < 0.0001), respectively. The proportion of premature births was significantly higher in the group with transient CH (57%) than in the group with permanent CH (2%) (P < 0.0001). A history of iatrogenic iodine overload was identified during the neonatal period in 69% of transient cases. Among permanent CH cases (n = 49), patients were classified as having a goitre (n = 27, 55% of cases), a normal sized and shaped thyroid gland (n = 14, 29% of cases) or a hypoplastic gland (n = 8, 16% of cases). The latter patients demonstrated global thyroid hypoplasia (n = 3), a right hemithyroid (n = 2), hypoplasia of the left lobe (n = 2), or asymmetry in the location of the two lobes (n = 1). Patients with a normal sized and shaped thyroid gland showed a significantly less severe form of hypothyroidism than those with a goitre or a hypoplastic thyroid gland (P < 0.0002). Among permanent CH cases, those with a goitre (n = 27) had an iodine organification defect (n = 10), Pendred syndrome (n = 1), a defect of thyroglobulin synthesis (n = 8), or a defect of sodium iodine symporter (n = 1), and in seven patients no aetiology could be determined. Among permanent cases with a normal sized and shaped thyroid gland (n = 14), a specific aetiology was found in only one patient (pseudohypoparathyroidism) and two patients had Down's syndrome. Among those with a globally hypoplastic gland, a TSH receptor gene mutation was found in two patients.Conclusions A precise description of the phenotype can enhance our understanding of various forms of neonatal hypothyroidism as well as their prevalence and management. It also helps to identify cases of congenital hypothyroidism of unknown aetiology, which will need to be investigated in collaboration with molecular biologists

Sorting of chromosomes by magnetic separation

Chromosomes were isolated from Chinese hamster x human hybrid cell lines containing four and nine human chromosomes. Human genomic DNA was biotinylated by nick translation and used to label the human chromosomes by in situ hybridization in suspension. Streptavidin was covalently coupled to the surface of magnetic beads and these were incubated with the hybridized chromosomes. The human chromosomes were bound to the magnetic beads through the strong biotin-streptavidin complex and then rapidly separated from nonlabeled Chinese hamster chromosomes by a simple permanent magnet. The hybridization was visualized by additional binding of avidin-FITC (fluorescein) to the unoccupied biotinylated human DNA bound to the human chromosomes. After magnetic separation, up to 98% of the individual chromosomes attached to magnetic beads were classified as human chromosomes by fluorescence microscopy

Characterization of Prion Disease Associated with a Two-Octapeptide Repeat Insertion

Genetic prion disease accounts for 10–15% of prion disease. While insertion of four or more octapeptide repeats are clearly pathogenic, smaller repeat insertions have an unclear pathogenicity. The goal of this case series was to provide an insight into the characteristics of the 2-octapeptide repeat genetic variant and to provide insight into the risk for Creutzfeldt–Jakob disease in asymptomatic carriers. 2-octapeptide repeat insertion prion disease cases were collected from the National Prion Disease Pathology Surveillance Center (US), the National Prion Clinic (UK), and the National Creutzfeldt–Jakob Disease Registry (Australia). Three largescale population genetic databases were queried for the 2-octapeptide repeat insertion allele. Eight cases of 2-octapeptide repeat insertion were identified. The cases were indistinguishable from the sporadic Creutzfeldt–Jakob cases of the same molecular subtype. Western blot characterization of the prion protein in the absence of enzymatic digestion with proteinase K revealed that 2-octapeptide repeat insertion and sporadic Creutzfeldt–Jakob disease have distinct prion protein profiles. Interrogation of large-scale population datasets suggested the variant is of very low penetrance. The 2-octapeptide repeat insertion is at most a low-risk genetic variant. Predictive genetic testing for asymptomatic blood relatives is not likely to be justified given the low risk

Games in Higher Education

International audienceThis entry presents an overview of how and why Learning Games are used in higher education.Learning Games can be defined as games that are designed to captivate the learners’ attention and facilitate their learning process. They have explicit educational purposes and can be used for teaching at all levels of education. All types of games can be used for learning: board games, card games, role-playing games, First Person Shooter games, simulation games, management games, puzzle games, treasure hunts…The main characteristic of Learning Games for higher education is the fact that they are designed to teach specific complex skills taught at university or during professional training programs. Unfortunately, it is not infrequent to observe strong opposition on the part of this target audience to this mode of learning, that these adult students associate with children.The use of Learning Games in primary school seems natural to teachers and is encouraged by specialists in didactics and neuroscience. This learning technique is much less frequently used in middle school and is almost completely absent from higher education. Yet teachers at all these levels are faced with the same problems, such as lack of motivation and investment, for which games are known to be an effective solution. This entry presents an overview of the games that can be used for higher education and the reasons why some teachers and students still show resistance to this type of learning. The numerous advantages of games for higher education will then be presented, citing games presently used in universities, in graduate schools and for professional training. Finally, thisDraft : Marfisi-Schottman I. (2019) Games in Higher Education. In: Tatnall A. (eds) Encyclopedia of Education and Information Technologies. Springer, Chamentry presents the current research questions that need to be addressed concerning the design of games for higher education and the acceptance of these games by teachers

Low levels of IgM antibodies recognizing oxidation-specific epitopes are associated with human non-alcoholic fatty liver disease

Background: Lipid oxidation of membrane phospholipids is accompanied by the formation of oxidation-specific epitopes (OSE). These epitopes are recognized by specific antibodies and represent danger-associated molecular patterns that are generated during chronic inflammatory processes. In a murine model for hepatic inflammation during non-alcoholic fatty liver disease (NAFLD), increased antibody levels targeting OSE were found to be protective. Here, our aim was to determine an association between OSE-specific antibody titers and NAFLD in humans. Methods: IgM and IgG levels with specificity for various OSE were assessed in the plasma of patients with NAFLD (n = 71) and healthy controls (n = 68). Antibody titers were comprehensively analyzed in patients with NAFLD after classification by histological evaluation of liver biopsies. Statistical analysis was performed to determine significant correlations and odds ratios. To study the specificity for NAFLD, plasma antibody titers were measured in patients with hepatitis C (n = 40) and inflammatory bowel disease (n = 62). Results: IgM titers against OSE were lower in patients with NAFLD compared to controls. Further biopsy-based classification of patients with NAFLD did not show any difference in IgM levels. Plasma IgM titers towards the P1 mimotope demonstrated an inverse correlation with markers for obesity, systemic inflammation, and liver damage. In contrast, hepatitis C and increased disease activity during inflammatory bowel disease was not associated with reduced IgM titers. Conclusions: Our data highlight the importance of immune recognition of OSE by IgM antibodies in the pathophysiology of NAFLD

Features of Muon Arrival Time Distributions of High Energy EAS at Large Distances From the Shower Axis

In view of the current efforts to extend the KASCADE experiment (KASCADE-Grande) for observations of Extensive Air Showers (EAS) of primary energies up to 1 EeV, the features of muon arrival time distributions and their correlations with other observable EAS quantities have been scrutinised on basis of high-energy EAS, simulated with the Monte Carlo code CORSIKA and using in general the QGSJET model as generator. Methodically various correlations of adequately defined arrival time parameters with other EAS parameters have been investigated by invoking non-parametric methods for the analysis of multivariate distributions, studying the classification and misclassification probabilities of various observable sets. It turns out that adding the arrival time information and the multiplicity of muons spanning the observed time distributions has distinct effects improving the mass discrimination. A further outcome of the studies is the feature that for the considered ranges of primary energies and of distances from the shower axis the discrimination power of global arrival time distributions referring to the arrival time of the shower core is only marginally enhanced as compared to local distributions referring to the arrival of the locally first muon.Comment: 24 pages, Journal Physics G accepte

The cholesterol derivative 27-hydroxycholesterol reduces steatohepatitis in mice.

<p>BACKGROUND & AIMS: Non-alcoholic steatohepatitis is characterized by hepatic steatosis with inflammation. Although steatosis is benign and reversible, inflammation can increase liver damage. Hepatic inflammation has been associated with accumulation of cholesterol in lysosomes of Kupffer cells. 27-Hydroxycholesterol (27HC), a derivative of cholesterol formed by CYP27A1, can mobilize cholesterol from the lysosomes to the cytoplasm. We investigated whether 27HC can change the intracellular distribution cholesterol and reduce hepatic inflammation in mice. METHODS: We transplanted bone marrow from irradiated wild-type or Cyp27a1(-/-) mice to mice that do not express the low density lipoprotein receptor (Ldlr(-/-)), which are hyperlipidemic; 9 weeks later, mice were fed either regular chow or a high-fat, high-cholesterol (HFC) diet for 3 months. In a separate experiment, Ldlr(-/-) mice were given subcutaneous injections of 27HC and placed on regular chow or HFC diets for 3 weeks. Blood and liver tissues samples were collected and analyzed for intracellular cholesterol distribution and inflammation. RESULTS: In Ldlr(-/-) mice that received bone marrow transplants from Cyp27a1(-/-) mice, lysosomes of Kupfer cells had a greater accumulation of cholesterol than those of mice that received bone marrow from wild-type mice, after the HFC diet. Liver histology and gene expression analyses showed increased inflammation and liver damage in mice given bone marrow transplants from Cyp27a1(-/-) mice and placed on the HFC diet. Administration of 27HC to Ldlr(-/-) mice, following the HFC diet, reduced the accumulation of lysosomal cholesterol and hepatic inflammation, compared with mice that were not given 27HC. CONCLUSIONS: Accumulation of cholesterol in lysosomes of Kupfer cells promotes hepatic inflammation in mice. The cholesterol derivative 27HC reduces accumulation of cholesterol in lysosomes and might be used to treat non-alcoholic steatohepatitis.</p>

Does It Pay To Be a Woman? Labour Demand Effects of Maternity-Related Job Protection and Replacement Incomes

In countries with strong employment protection laws it is often considered to be unwise to hire a woman in childbearing age because she might get pregnant. However, such labour demand e ects of job protection measures related to maternity leave are often rather anecdotal. To provide analytical evidence, this paper studies the impact of changes in maternity-related job protection in Germany on employment opportunities for women in childbearing age without children for whom the observed e ects should be largely demand-related. Exogenous, discrete policy changes in the German labour market of the 1980s and 1990s constitute the setting for a difference-in-differences analysis of the transition into employment as well as wages. The data for this study are taken from the German Socio-Economic Panel and from the German Microcensus. Doubling the job-protected leave period from 6 months to 12 months between 1986 and 1988 led to an approximately 6% lower probability of being hired for women in childbearing age without a university degree.In addition, I nd a 5-10% increase in wages for women in childbearing age associated with the latter reform. Since this effect disappears when controlling for having a child in the future, this may indicate an increased need to signal commitment by increased effort after the reform

Orthogonalities and functional equations

In this survey we show how various notions of orthogonality appear in the theory of functional equations. After introducing some orthogonality relations, we give examples of functional equations postulated for orthogonal vectors only. We show their solutions as well as some applications. Then we discuss the problem of stability of some of them considering various aspects of the problem. In the sequel, we mention the orthogonality equation and the problem of preserving orthogonality. Last, but not least, in addition to presenting results, we state some open problems concerning these topics. Taking into account the big amount of results concerning functional equations postulated for orthogonal vectors which have appeared in the literature during the last decades, we restrict ourselves to the most classical equations