Regulatory T Cells Facilitate Thymic Recovery After HSCT by Directly Enhancing Immigration of Donor Derived Thymic Progenitors

BACKGROUND & AIMS: An increasing number of physicians use repeated measurements of stool calprotectin to monitor intestinal inflammation in patients with inflammatory bowel diseases (IBDs). A lateral flow-based rapid test allows patients to measure their own stool calprotectin values at home. The test comes with a software application (IBDoc; Buhlmann Laboratories AG, Schonenbuch, Switzerland) that turns a smartphone camera into a results reader. We compared results from this method with those from the hospital-based reader (Quantum Blue; Buhlmann Laboratories AG) and enzyme-linked immunosorbent assay (ELISA) analysis. METHODS: In a single-center comparison study, we asked 101 participants (10 years of age or older) in the Netherlands to perform the IBDoc measurement on stool samples collected at home, from June 2015 to October 2016. Participants then sent the residual extraction fluid and a fresh specimen from the same bowel movement to our pediatric and adult IBD center at the University Medical Center Groningen, where the level of calprotectin was measured by the Quantum Blue reader and ELISA analysis, respectively. The primary outcome was the agreement of results between IBDoc and the Quantum Blue and ELISA analyses, determined by Bland-Altman plot analysis. RESULTS: We received 152 IBDoc results, 138 samples of residual extraction fluid for Quantum Blue analysis, and 170 fresh stool samples for ELISA analysis. Spearman's rank correlation coefficient was 0.94 for results obtained by IBDoc vs Quantum Blue and 0.85 for results obtained by IBDoc vs ELISA. At the low range of calprotectin level (= 100 mu g/g), and 71% of IBDoc-ELISA results were in agreement. At the high range of calprotectin level (>= 500 mu g/g), 81% of IBDoc-Quantum Blue results were within the predefined limits of agreement (+/- 200 mu g/g) and 64% of IBDoc-ELISA results were in agreement. CONCLUSIONS: Measurements of fecal levels of calprotectin made with home-based lateral flow method were in agreement with measurements made by Quantum Blue and ELISA, as long as concentrations wer

Гераклиты – карбонатные образования газовых источников и грязевых вулканов миоцена

Морфологические признаки, минералогия, геохимия и состав газовой фракции гераклитов подтвердили их генетическую общность с современными карбонатными образованиями метановых источников и грязевых вулканов Черного моря. Присутствие в гераклитах битумов, метана и этана может служить индикатором наличия нефти и газа на Гераклейском полуострове и прилегающему к нему шельфе.Морфологічні ознаки, мінералогія, геох!мія i склад газової фракцїї гераклитів підтвердили їх генетичну спільність із сучасними карбонатними утвореннями метанових джерел i грязьових вулканів Чорного моря. Присутність у гераклітах бітумів, метану i етану може слугувати як індикатор наявності нафти й газу на Гераклейськом niвocтpoвi i прилеглому до нього шельфі.Morphological attributes, mineralogy, geochemistry and structure of gas fraction Geraklit have confirmed their proximity to modern carbonate formations of methane sources and mud volcanoes in the Black sea. Presence of bitumen, methane and ethane in Geraklites serves as indicator of occurence of oil fields and gas on the Geraklejskij peninsula and adjoining to them a shelf

Brain structure in bipolar disorder : A longitudinal neuroimaging study in twins

In this longitudinal twin study, the goal was to ascertain the extent to which BD shows abnormalities in subcortical and cortical brain regions at baseline and over time. Baseline assessments in this study revealed that BD was associated with smaller volumes of the thalamus, putamen and nucleus accumbens. These associations were strongly influenced by genes influencing both BD and smaller volumes of these regions, indicating that BD may share some genetic background with structural abnormalities in brain regions involved in emotion processing. Furthermore, at baseline, BD was associated with subtle deficits in cortical surface area, cortical thickness and cortical volume. Here, unique environmental factors primarily drove the associations between BD and cortical measures, particularly those involving cortical thinning. In contrast, although brain structure deficits may arise during development, these appear to remain relatively stable over time in adulthood, as structural brain changes in cortical and subcortical brain regions were not different among BD patients, co-twins and healthy controls. This suggests that BD is not a disease that shows progressive structural brain atrophy and may be specifically associated with subtle brain abnormalities that arise earlier in life, perhaps even during neurodevelopment. This finding contrasts with results obtained in schizophrenia, where significant progressive brain atrophy during adulthood, particularly in fronto-temporal regions, has been observed and linked to the genetic liability for the disease. Therefore, schizophrenia and BD may show different neuroanatomical trajectories, with the former showing more severe abnormalities than the latter. However, more longitudinal studies with larger cohorts than the one described here are necessary to confirm the absence of structural brain change over time in BD, especially since findings of structural brain changes in prefrontal cortical and subcortical structures conflict considerably between studies. In addition, many factors may affect brain measures and could contribute to inconsistencies across studies, such as lithium use, age, familial load, mood status, number of episodes, number of hospitalizations and variability in imaging methodology. Finally, to account more comprehensively for the genetic and environmental contributions to structural brain abnormalities in BD, cross-sectionally and longitudinally, (prospective) longitudinal studies with larger cohorts (such as those included by the ENIGMA consortium) are required. More insight into which specific genetic and/or environmental influences contribute to the development of BD and associated brain anomalies, particularly in brain networks subserving emotion processing, could serve as a guide in the developing intervention strategies directed at reducing disease burden or even preventing disease onset

Genetic and environmental influences on circulating NK and T cells and their relation to bipolar disorder

BACKGROUND: In previous studies we found mild deficiencies of circulating T cells in patients with bipolar disorder (BD) and children at risk for BD, correlating to a higher inflammatory state. The genetic and environmental influences on these T cell deficiencies in association with BD development are unknown. OBJECTIVES: The aim is to quantify genetic and environmental factors that contribute to the association between the liability to develop BD and T cell deficiencies. METHODS: Participants of a Dutch bipolar twin study (11 monozygotic BD twin pairs, 15 dizygotic BD twin pairs, 15 monozygotic and 12 dizygotic healthy twin pairs) were included. A detailed FACS analysis of frozen stored leukocytes was carried out to determine the percentages of T cells and various other leukocyte and lymphocyte subsets. A bivariate liability threshold twin model was used to determine genetic and environmental (common and unique) influences on the correlation between BD and the various subsets. RESULTS: Lower percentages of T cells and higher percentages of NK cells were associated with the familial liability to develop BD. Neither genetic nor shared or unique environmental factors could explain the associations. Lithium usage explained part of the association for T cells, smoking in part that for NK cells. CONCLUSIONS: Our results confirm that BD is the result of a complex interaction between various genetic and environmental risk factors, in which T and NK cells act as important intermediate immune players

Contribution of genes and unique environment to cross-sectional and longitudinal measures of subcortical volumes in bipolar disorder

The influence of genes and environment on the association between bipolar disorder (BD) and volumes of subcortical brain regions involved in emotion processing has rarely been studied. Furthermore, as far as we know, longitudinal twin studies of subcortical brain volume change in BD have not been carried out at all. In this study, we focused on the genetic and environmental contributions to cross-sectional and longitudinal measures of subcortical brain volumes in BD.A total of 99 twins from monozygotic and dizygotic pairs concordant or discordant for BD and 129 twins from monozygotic and dizygotic healthy control pairs underwent magnetic resonance imaging at baseline. Longitudinal assessment was carried out in 48 twins from monozygotic and dizygotic patient pairs and 52 twins from monozygotic and dizygotic control pairs. Subcortical volume measures were obtained with Freesurfer software and analyzed with structural equation modeling software OpenMx.At baseline, BD was phenotypically and genetically associated with smaller volumes of the thalamus, putamen and nucleus accumbens. BD was not associated with subcortical brain volume change over time in any of the examined regions. Heritability of subcortical volumes at baseline was high, whereas subcortical volume change had low heritability.Genes contributing to BD showed overlap with those associated with smaller volumes of the thalamus, putamen and nucleus accumbens at baseline. Further evaluation of genetic contributions to abnormalities in subcortical brain regions assumed to be involved in emotion processing is recommended