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It is unclear how the tryptophan (TRP) breakdown pathway relates to the activated inflammatory state of patients with major depressive disorder (MDD). We determined in two different cohorts of patients with MDD (n = 281) and healthy controls (HCs) (n = 206) collected for the EU-MOODINFLAME project: a.) the monocyte expression levels of 5 key pro-inflammatory cytokine/chemokine genes (ICCGs), 5 type I interferon stimulated genes (ISGs), and 4 kynurenine pathway (KP) enzyme genes (i.e. IDO-1, KMO, CCBL1/KAT II and CCBL2/KAT III) by standard q-PCR, b.) serum levels of TRP, 5-HTrp, 5-HIAA, KYN, KYNA, 3-HK, XA, PIC, and QUIN by LC-MS/MS and/or HPLC, and calculated various TRP/KP metabolism ratios. We then correlated outcomes to each other, and to the clinical characteristics of patients. Both cohorts of patients differed clinically; patients of the Munich cohort (n = 50) were less overweight, less medicated, were less in the current episode and showed a higher HAM-D 17 score as compared with patients of the Muenster cohort (n = 231). An increased expression of ICCGs was found in the circulating monocytes of patients of both cohorts; this was in particular evident in the Munich cohort. In contrast, ISGs monocyte expression levels tended to be reduced (both cohorts). TRP serum levels were linked to the pro-inflammatory (ICCGs) monocyte state of patients; a decrease in TRP serum levels was found in the Munich cohort; TRP levels correlated negatively to patient's HAM-D 17 score. Contrary to what expected, KYN serum levels were not increased in patients (both cohorts); and an increased KYN/TRP ratio was only found in the Munich patients (who showed the lowest TRP serum levels). IDO-1 monocyte expression levels were decreased in patients (both cohorts) and negatively associated to their pro-inflammatory (ICCGs) monocyte state. Thus, a depletion of TRP via an ICCGs-inflammatory IDO activation is not likely in MDD. Downstream from KYN, and regarding compounds influencing glutama

Hintergrund: Die Prävalenz einer höhergradigen Mikrotie in der westlichen Bevölkerung wird mit 0,76-2,35 Fälle pro 10.000 Geburten angegeben, davon sind ca. 20-30% syndromaler Genese. Bei zusätzlicher kongenitaler Gehörgangsatresie wird bei einseitigem Vorliegen oft an ein Goldenhar-Syndrom oder bei beidseitiger Fehlbildung an ein Franceschetti-Syndrom gedacht. Bei zusätzlichen Dysmorphiezeichen, insbesondere dem Vorliegen von Spaltbildungen des Gaumens und Skelettfehlbildungen, sollte eine humangenetische Untersuchung zur Ursachenklärung angestrebt werden.Material und Methoden: Wir berichten über einen bei Erstvorstellung 7,7 Jahre alten Jungen syrischer nicht konsanguiner Eltern, der uns bei klinischem Verdacht auf Franceschetti-Syndrom zur pädaudiologischen Diagnostik und Optimierung der technischen Versorgung der Schwerhörigkeit vorgestellt wurde. Die Schwangerschaft und Geburt seien in Syrien unauffällig verlaufen. Das 7. Kind der Eltern wies deutliche Dysmorphiezeichen auf: Ohrmuscheldysplasie III°, vollständige Gehörgangsatresie bds., Z.n. operativem Verschluss einer Gaumenspalte im 2. Lebensjahr, dreieckige Gesichtsform mit spitzem, ausgeprägtem Unterkiefer, langes breites, akzentuiertes Philtrum, schmales Oberlippenrot, kräftige Nase mit breitem Nasenrücken, Epicanthus links, nach außen abfallende Lidachsen, lange gebogene Wimpern, sehr bauschige Augenbrauen, Zahnfehlstellungen, multiple Exostosen v.a. am proximalen rechten Oberarm, linken Schulterblatt, distalen linken Unterarm, mehreren Rippen, distalen Femur, deutliche Mikrocephalgie (<1. P.), proportionierter Minderwuchs und Dystrophie, prämature Pubarche, nicht altersgerechte Sprachentwicklung bei sukzessivem Zweispracherwerb Arabisch/Deutsch, Intelligenzminderung. Anamnestisch wurde auch berichtet, dass die motorische Entwicklung verzögert war (Sitzen: 24 Monate, Laufen: 3 Jahre, erste Worte: mit 3 Jahren). Es bestand im Alter von ca. 2-3 Jahren eine Knochenleitungshörgeräteversorgung über Softband, d

Hintergrund: Das neuartige SARS-CoV-2-Virus breitete sich seit Dezember 2019 weltweit aus und die damit einhergehende Infektion (COVID-19) wurde zur Pandemie erklärt. Um das Infektionsgeschehen zu unterbrechen, wurden in Deutschland zahlreiche Maßnahmen getroffen, die das öffentliche und soziale Leben weitreichend einschränkten. Hierzu zählte auch die Schließung von Kindergärten und Schulen im März bis Mai 2020 (sog. Lockdown). Hiervon waren auch Kinder mit einer Sprachentwicklungsstörung (SES) betroffen.Material und Methoden: Von August bis November 2020 wurden Eltern von Kindern mit einer SES zum Therapieverlauf ihres Kindes während des Lockdowns befragt. In einem Fragebogen wurden allgemeine Informationen erfragt (Alter, Geschlecht, Vorerkrankungen, Anzahl der Geschwister, gesprochene Sprachen) sowie Angaben zum Therapieverlauf vor und während der Pandemie gemacht.Ergebnisse: 37 der eingeschlossenen Kinder erhielten vor der Pandemie eine logopädische Therapie. Bei 17 Kindern wurde die Therapie während des Lockdowns pausiert, während 20 Kinder weiterhin Logopädie erhielten. Hiervor erhielten die meisten Patienten (70%) Logopädie mit erhöhten Hygienemaßnahmen. Ein Patient (5%) setzte die Therapie telemedizinisch fort. Die restlichen fünf Patienten (25%) erhielten Logopädie ohne Veränderung oder besondere Hygienemaßnahmen. Die multivariate logistische Regression zeigte, dass Kinder, welche zu Hause eine andere Sprache als Deutsch sprechen, eine höhere relative Chance hatten, dass ihre Therapie während des Lockdowns pausiert wurde (Odds Ratio 5,11; 95%-Konfidenzintervall 1,09; 32,54). Das Alter, das Geschlecht oder das Vorliegen anderer Erkrankungen hatten keinen statistisch signifikanten Einfluss auf das Pausieren der Logopädie.Diskussion: SARS-CoV-2 wird vor allem durch Aerosole beim Husten und Sprechen übertragen, so dass eine logopädische Behandlung am Patienten durchaus als gefährdend eingestuft werden muss. Da Kinder mit einer SES ab dem Kindergartenalter beson

It is unclear how the tryptophan (TRP) breakdown pathway relates to the activated inflammatory state of patients with major depressive disorder (MDD). We determined in two different cohorts of patients with MDD (n = 281) and healthy controls (HCs) (n = 206) collected for the EU-MOODINFLAME project: a.) the monocyte expression levels of 5 key pro-inflammatory cytokine/chemokine genes (ICCGs), 5 type I interferon stimulated genes (ISGs), and 4 kynurenine pathway (KP) enzyme genes (i.e. IDO-1, KMO, CCBL1/KAT II and CCBL2/KAT III) by standard q-PCR, b.) serum levels of TRP, 5-HTrp, 5-HIAA, KYN, KYNA, 3-HK, XA, PIC, and QUIN by LC-MS/MS and/or HPLC, and calculated various TRP/KP metabolism ratios. We then correlated outcomes to each other, and to the clinical characteristics of patients. Both cohorts of patients differed clinically; patients of the Munich cohort (n = 50) were less overweight, less medicated, were less in the current episode and showed a higher HAM-D 17 score as compared with patients of the Muenster cohort (n = 231). An increased expression of ICCGs was found in the circulating monocytes of patients of both cohorts; this was in particular evident in the Munich cohort. In contrast, ISGs monocyte expression levels tended to be reduced (both cohorts). TRP serum levels were linked to the pro-inflammatory (ICCGs) monocyte state of patients; a decrease in TRP serum levels was found in the Munich cohort; TRP levels correlated negatively to patient's HAM-D 17 score. Contrary to what expected, KYN serum levels were not increased in patients (both cohorts); and an increased KYN/TRP ratio was only found in the Munich patients (who showed the lowest TRP serum levels). IDO-1 monocyte expression levels were decreased in patients (both cohorts) and negatively associated to their pro-inflammatory (ICCGs) monocyte state. Thus, a depletion of TRP via an ICCGs-inflammatory IDO activation is not likely in MDD. Downstream from KYN, and regarding compounds influencing glut

Background: Recently, we reported signs of inflammation (raised IL-8, reduced miR-146a) and signs of vascular repair (raised HGF) in the serum of Ecuadorian patients with type 2 diabetes (T2D). In contrast, we found that the circulating monocytes lacked up-regulation of classical inflammatory genes (IL-1B, IL-6, and TNF) and there was even significant down-regulation of PTGS2. Notably, genes and a microRNA involved in adhesion, cell differentiation and morphology (CD9, DHRS3, PTPN7 and miR-34c-5p) were up-regulated in the T2D monocytes, suggesting a role of the anti-inflammatory cells in adhesion, vascular repair and invasion. Aim: To determine the gene expression of the vascular repair factor HGF in the circulating monocytes of patients with T2D and to investigate the relationship between HGF and the expression of the other previously tested monocyte genes and the contribution to the raised serum level of HGF. In addition, we tested the level of 6 microRNAs, which were previously found abnormal in the circulating monocytes, in the serum of the patients. Methods: A gene and microRNA expression study in monocytes and serum of 64 Ecuadorian patients with T2D (37-85 years) and 44 non-diabetic controls (32-87 years). Results: The gene expression of HGF was significantly raised in the monocytes of the patients with T2D and associated with the expression of genes involved in adhesion, cell differentiation and morphology. HGF gene expression did not correlate with the serum level of HGF. The monocyte expression of pro-inflammatory cytokine genes was also not associated with the serum levels of these cytokines. The level of miR-574-3p was significantly decreased in the serum of the patients with T2D, and correlated in expression with the decreased well-established inflammation-regulating miR-146a. The level of the microRNAs in serum did not correlate with their expression level in monocytes. Conclusion: In circulating monocytes of Ecuadorian T2D patients, the microRNA and g

Background: There is an ongoing search for biomarkers in psychiatry, for example, as diagnostic tools or predictors of treatment response. The neurotrophic factor S100 calcium binding protein B (S100B) has been discussed as a possible predictor of antidepressant response in patients with major depression, but also as a possible biomarker of an acute depressive state. The aim of the present study was to study the association of serum S100B levels with antidepressant treatment response and depression severity in melancholically depressed inpatients. Methods: After a wash-out period of 1 week, 40 inpatients with melancholic depression were treated with either venlafaxine or imipramine. S100B levels and Hamilton Depression Rating Scale (HAM-D) scores were assessed at baseline, after 7 weeks of treatment, and after 6 months. Results: Patients with high S100B levels at baseline showed a markedly better treatment response defined as relative reduction in HAM-D scores than those with low baseline S100B levels after 7 weeks (P=.002) and 6 months (P=.003). In linear regression models, S100B was a significant predictor for treatment response at both time points. It is of interest to note that nonresponders were detected with a predictive value of 85% and a false negative rate of 7.5%. S100B levels were not associated with depression severity and did not change with clinical improvement. Conclusions: Low S100B levels predict nonresponse to venlafaxine and imipramine with high precision. Future studies have to show which treatments are effective in patients with low levels of S100B so that this biomarker will help to reduce patients' burden of nonresponding to frequently used antidepressants.

There is increasing evidence that inflammatory macrophages in adipose tissue are involved in insulin resistance of type 2 diabetes (T2D). Due to a relative paucity of data on circulating monocytes in T2D, it is unclear whether the inflammatory changes of adipose tissue macrophages are reflected in these easily accessible cells. Objective To study the expression pattern of microRNAs and mRNAs related to inflammation in T2D monocytes. Design A microRNA finding study on monocytes of T2D patients and controls using array profiling was followed by a quantitative Real Time PCR (qPCR) study on monocytes of an Ecuadorian validation cohort testing the top over/under-expressed microRNAs. In addition, monocytes of the validation cohort were tested for 24 inflammation-related mRNAs and 2 microRNAs previously found deregulated in (auto)-inflammatory monocytes. Results In the finding study, 142 significantly differentially expressed microRNAs were identified, 15 having the strongest power to discriminate T2D patients from controls (sensitivity 66%, specificity 90%). However, differences in expression of these microRNAs between patients and controls were small. On the basis of >1.4 or <0.6-fold change expression 5 microRNAs were selected for further validation. One microRNA (miR-34c-5p) was validated as significantly over-expressed in T2D monocytes. In addition, we found over expression of 3 mRNAs (CD9, DHRS3 and PTPN7) in the validation cohort. These mRNAs are important for cell morphology, adhesion, shape change, and cell differentiation. Classical inflammatory genes (e.g. TNFAIP3) were only over-expressed in monocytes of patients with normal serum lipids. Remarkably, in dyslipidemia, there was a reduction in the expression of inflammatory genes (e.g. ATF3, DUSP2 and PTGS2). Conclusions The expression profile of microRNAs/mRNAs in monocytes of T2D patients indicates an altered adhesion, differentiation, and shape change potential. Monocyte inflammatory activation was only found

There is increasing evidence that inflammatory macrophages in adipose tissue are involved in insulin resistance of type 2 diabetes (T2D). Due to a relative paucity of data on circulating monocytes in T2D, it is unclear whether the inflammatory changes of adipose tissue macrophages are reflected in these easily accessible cells. Objective To study the expression pattern of microRNAs and mRNAs related to inflammation in T2D monocytes. Design A microRNA finding study on monocytes of T2D patients and controls using array profiling was followed by a quantitative Real Time PCR (qPCR) study on monocytes of an Ecuadorian validation cohort testing the top over/under-expressed microRNAs. In addition, monocytes of the validation cohort were tested for 24 inflammation-related mRNAs and 2 microRNAs previously found deregulated in (auto)-inflammatory monocytes. Results In the finding study, 142 significantly differentially expressed microRNAs were identified, 15 having the strongest power to discriminate T2D patients from controls (sensitivity 66%, specificity 90%). However, differences in expression of these microRNAs between patients and controls were small. On the basis of >1.4 or <0.6-fold change expression 5 microRNAs were selected for further validation. One microRNA (miR-34c-5p) was validated as significantly over-expressed in T2D monocytes. In addition, we found over expression of 3 mRNAs (CD9, DHRS3 and PTPN7) in the validation cohort. These mRNAs are important for cell morphology, adhesion, shape change, and cell differentiation. Classical inflammatory genes (e.g. TNFAIP3) were only over-expressed in monocytes of patients with normal serum lipids. Remarkably, in dyslipidemia, there was a reduction in the expression of inflammatory genes (e.g. ATF3, DUSP2 and PTGS2). Conclusions The expression profile of microRNAs/mRNAs in monocytes of T2D patients indicates an altered adhesion, differentiation, and shape change potential. Monocyte inflammatory activation was only

Background: There is increasing evidence that chronic inflammation is an important determinant in insulin resistance and in the pathogenesis of type 2 diabetes (T2D). MicroRNAs constitute a newly discovered system of cell regulation and in particular two microRNAs (miR-146a and miR-155) have been described as regulators and biomarkers of inflammation. Aim: To determine a putative association between the levels of miR-146a and miR-155 in serum of T2D patients, clinical parameters and serological indicators of inflammation. Methods: We performed quantitative Real Time PCR (qPCR) of microRNAs from serum (56 Ecuadorian T2D ambulatory patients and 40 non-diabetic controls). In addition, we evaluated T2D-related serum cytokines. chemokines and growth factors using a commercially available multi-analyte cytometric bead array system. We correlated outcomes to clinical parameters, including BMI, HbA1c and lipid state. Results: The Ecuadorian non-diabetic controls appeared as overweight (BMI>25: patients 85%, controls 82.5%) and as dyslipidemic (hypercholesterolemia: patients 60.7%, controls 67.5%) as the patients. The serum levels of miR-146a were significantly reduced in T2D patients as compared to these non-diabetic, but obese/dyslipidemic control group (mean patients 0.61, mean controls set at 1; p=0.042), those of miR-155 were normal. The serum levels of both microRNAs correlated to each other (r=0.478; p<0.001) and to leptin levels. The microRNAs did not correlate to BMI, glycemia and dyslipidemia. From the tested cytokines, chemokines and growth factors, we found IL-8 and HGF significantly raised in T2D patients versus non-diabetic controls (p=0.011 and 0.023 respectively). Conclusions: This study shows decreased serum anti-inflammatory miR-146a, increased pro-inflammatory IL- 8 and increased HGF (a vascular/insular repair factor) as discriminating markers of failure of glucose control occurring on the background of obesity and dyslipidemia.