This study aimed to (1) characterise sleep disturbances and emotional/behavioural difficulties among healthy German children and adolescents aged 3 to 13 years, (2) examine the association between ...parent-reported sleep problems and emotional/behavioural difficulties, (3) point out possible relations between specific kinds of sleep disturbances and different behavioural difficulties.
Data were collected between 2011 and 2015 within the LIFE Child study in Germany. The sample included 1101 3- to 13-year-old children and adolescents. Information on sleep disturbances-assessed via the Children's Sleep Habits Questionnaire (CSHQ), emotional/behavioural difficulties-assessed via the Strengths and Difficulties Questionnaire (SDQ), and socioeconomic status was provided by participants' parents. Multiple regressions were applied to analyse the associations between general and specific sleep disturbances (independent variables) and emotional/behavioural difficulties (dependent variables).
The total CSHQ score was positively associated with the total SDQ score and all SDQ subscales (emotional problems, conduct problems, hyperactivity/inattention, peer relationship problems). Most of the CSHQ subscales were related to SDQ subscale scores, except for a few non-significant relations with hyperactivity/inattention and conduct problems. The CSHQ total score, daytime sleepiness, sleep duration and parasomnias showed the strongest associations with the SDQ total score.
This study confirms an association between children's and adolescents' sleep habits and psychological health. We were able to demonstrate the association between sleep problems and emotional/behavioural difficulties in a large sample of healthy participants. In particular, we observed a significant relation between parasomnias and hyperactive/inattentive behaviour as well as a significant association between emotional problems and sleep problems, especially daytime sleepiness, sleep anxiety and parasomnias.
For many drugs, mechanisms of action with regard to desired effects and/or unwanted side effects are only incompletely understood. To investigate possible pleiotropic effects and respective molecular ...mechanisms, we describe here a catalogue of commonly used drugs and their impact on the blood transcriptome.
From a population-based cohort in Germany (LIFE-Adult), we collected genome-wide gene-expression data in whole blood using in Illumina HT12v4 micro-arrays (n = 3,378; 19,974 gene expression probes per individual). Expression profiles were correlated with the intake of active substances as assessed by participants' medication. This resulted in a catalogue of fourteen substances that were identified as associated with differential gene expression for a total of 534 genes. As an independent replication cohort, an observational study of patients with suspected or confirmed stable coronary artery disease (CAD) or myocardial infarction (LIFE-Heart, n = 3,008, 19,966 gene expression probes per individual) was employed. Notably, we were able to replicate differential gene expression for three active substances affecting 80 genes in peripheral blood mononuclear cells (carvedilol: 25; prednisolone: 17; timolol: 38). Additionally, using gene ontology enrichment analysis, we demonstrated for timolol a significant enrichment in 23 pathways, 19 of them including either GPER1 or PDE4B. In the case of carvedilol, we showed that, beside genes with well-established association with hypertension (GPER1, PDE4B and TNFAIP3), the drug also affects genes that are only indirectly linked to hypertension due to their effects on artery walls or their role in lipid biosynthesis.
Our developed catalogue of blood gene expressions profiles affected by medication can be used to support both, drug repurposing and the identification of possible off-target effects.
Summary
The disease burden of chronic‐relapsing and therapy‐refractory superficial dermatophytosis dramatically increased in India within the past 5‐6 years. In order to evaluate the prevalence of ...this trend, 201 skin scrapings were collected from patients from all parts of India and were tested for dermatophytes using both fungal culture and a PCR‐ELISA directly performed with native skin scrapings. Fungal culture material was identified by genomic Sanger sequencing of the internal transcribed spacer (ITS) region and the translation elongation factor (TEF)‐1α gene. In total, 149 (74.13%) out of the 201 samples showed a dermatophyte‐positive culture result. Out of this, 138 (92.62%) samples were identified as Trichophyton (T.) mentagrophytes and 11 (7.38%) as Trichophyton rubrum. The PCR‐ELISA revealed similar results: 162 out of 201 (80.56%) samples were dermatophyte‐positive showing 151 (93.21%) T mentagrophytes‐ and 11 (6.79%) T rubrum‐positive samples. In this study, we show for the first time a dramatic Indian‐wide switch from T rubrum to T mentagrophytes. Additionally, sequencing revealed a solely occurring T mentagrophytes “Indian ITS genotype” that might be disseminated Indian‐wide due to the widespread abuse of topical clobetasol and other steroid molecules mixed with antifungal and antibacterial agents.
Aberrant innate immune signaling has been identified as a potential key driver of the complex pathophysiology of myelodysplastic neoplasms (MDS). This study of a large, clinically and genetically ...well-characterized cohort of treatment-naïve MDS patients confirms intrinsic activation of inflammatory pathways in general mediated by caspase-1, interleukin (IL)-1β and IL-18 in low-risk (LR)-MDS bone marrow and reveals a previously unrecognized heterogeneity of inflammation between genetically defined LR-MDS subgroups. Principal component analysis resolved two LR-MDS phenotypes with low (cluster 1) and high (cluster 2) levels of IL1B gene expression, respectively. Cluster 1 contained 14/17 SF3B1-mutated cases, while cluster 2 contained 8/8 del(5q) cases. Targeted gene expression analysis of sorted cell populations showed that the majority of the inflammasome-related genes, including IL1B, were primarily expressed in the monocyte compartment, consistent with a dominant role in determining the inflammatory bone marrow environment. However, the highest levels of IL18 expression were found in hematopoietic stem and progenitor cells (HSPCs). The colony forming activity of healthy donor HSPCs exposed to monocytes from LR-MDS was increased by the IL-1β-neutralizing antibody canakinumab. This work reveals distinct inflammatory profiles in LR-MDS that are of likely relevance to the personalization of emerging anti-inflammatory therapies.
Background For many drugs, mechanisms of action with regard to desired effects and/or unwanted side effects are only incompletely understood. To investigate possible pleiotropic effects and ...respective molecular mechanisms, we describe here a catalogue of commonly used drugs and their impact on the blood transcriptome. Methods and results From a population-based cohort in Germany (LIFE-Adult), we collected genome-wide gene-expression data in whole blood using in Illumina HT12v4 micro-arrays (n = 3,378; 19,974 gene expression probes per individual). Expression profiles were correlated with the intake of active substances as assessed by participants’ medication. This resulted in a catalogue of fourteen substances that were identified as associated with differential gene expression for a total of 534 genes. As an independent replication cohort, an observational study of patients with suspected or confirmed stable coronary artery disease (CAD) or myocardial infarction (LIFE-Heart, n = 3,008, 19,966 gene expression probes per individual) was employed. Notably, we were able to replicate differential gene expression for three active substances affecting 80 genes in peripheral blood mononuclear cells (carvedilol: 25; prednisolone: 17; timolol: 38). Additionally, using gene ontology enrichment analysis, we demonstrated for timolol a significant enrichment in 23 pathways, 19 of them including either GPER1 or PDE4B. In the case of carvedilol, we showed that, beside genes with well-established association with hypertension (GPER1, PDE4B and TNFAIP3), the drug also affects genes that are only indirectly linked to hypertension due to their effects on artery walls or their role in lipid biosynthesis. Conclusions Our developed catalogue of blood gene expressions profiles affected by medication can be used to support both, drug repurposing and the identification of possible off-target effects.
In recent decades, the use of psychosocial and psychiatric care systems has increased worldwide. A recent article proposed the concept of psychiatrization as an explanatory framework, describing ...multiple processes responsible for the spread of psychiatric concepts and forms of treatment. This article aims to explore the potentials of the Open Dialogue (OD) approach for engaging in less psychiatrizing forms of psychosocial support. While OD may not be an all-encompassing solution to de-psychiatrization, this paper refers to previous research showing that OD has the potential to 1) limit the use of neuroleptics, 2), reduce the incidences of mental health problems and 3) decrease the use of psychiatric services. It substantiates these potentials to de-psychiatrize psychosocial support by exploring the OD's internal logic, its use of language, its processes of meaning-making, its notion of professionalism, its promotion of dialogue and how OD is set up structurally. The conclusion touches upon the dangers of co-optation, formalization and universalization of the OD approach and stresses the need for more societal, layperson competencies in dealing with psychosocial crises.
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