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Friederike Lollies,1 Marisa Schnatschmidt,1 Angelika A Schlarb,1 Jon Genuneit2 1Faculty for Psychology and Sports Science, Bielefeld University, Bielefeld, North Rhine Westphalia, 33015, Germany; 2Pediatric Epidemiology, Department of Pediatrics, Medical Faculty, Leipzig University, Leipzig, Saxony, 04103, GermanyCorrespondence: Friederike LolliesFaculty for Psychology and Sports, Bielefeld University, POP 10 01 31, Bielefeld, 33015, GermanyTel +49 151 431 70887Email Friederike.lollies@uni-Bielefeld.dePurpose: Problems in infant and young child sleep can represent a serious challenge to parental behavior of mother and father. However, most research about the effect of infant and young child sleep on parenting has focused on mothers. Therefore, the present study aimed to explore the perception and consequences of infant and young child sleep problems of both parents.Participants and Methods: Participants were recruited via random sampling at, eg, kindergartens in North Rhine Westphalia. The sample includes data of heterosexual German-speaking couples with children without any medical or psychopathological problems. For this study, parents were asked to complete the test battery with regard to their youngest child. As sampling was via the kindergarten, the range of child age was 4– 68 months. A survey assessed data of parents (N=196, 46% female). The test battery contained the following questionnaires: Children Sleep Habits Questionnaire (CSHQ), Pittsburgh Sleep Quality Index (PSQI), Self-Report Measure for the Assessment of Emotion Regulation Skills (SEK-27), and a German version of the Infant Sleep Vignettes Interpretation Scale (ISVIS). For the outcome variables of parental sleep as well as for parental emotional competence, the statistical tests of ANOVA were used, and for parental sleep-related cognitions with the grouping variables of infant and young child sleep as well as parental gender, a MANOVA was used. According to the analysis of group differences, the age of the child was also included additional to the grouping variable of parental gender and children’s sleep.Results: Mothers and fathers in this sample were equally aware of their children’s sleep problems and reported similar sleep quality and emotion regulation themselves (all p > 0.05). Mothers as well as fathers of children with sleep problems had lower parental sleep quality (F(1, 183) = 110.01, p < 0.001) and emotion regulation (F(1, 184) = 143.16, p < 0.001) compared to parents of children without sleep problems. In children under 26 months of age, the child’s age seemed to have less negative impact on the father’s sleep quality (F(1, 183) = 5.01, p < 0.001) and emotion regulation (F(1, 184) = 0.72, p < 0.05) than on the outcomes of the mother. With regard to sleep-related cognition, there were statistically significant effects of parental gender (F(2, 185) = 44.39, p < 0.001) and interaction effects of parental gender × child sleep problems observed (F(2, 185) = 31.91, p < 0.001).Conclusion: The conclusion from this survey refers to the role of the father. According to the results, an association between paternal emotional competence, sleep quality as well as their sleep-related cognitions and infants and toddlers sleep behavior could be assumed in addition to and independent of the results of mothers. We would highlight the urgent need of inclusion of fathers in infant and developmental sleep research. In the context of sleep intervention, both parents should be provided with ongoing support to improve their sleep quality and competence in emotion regulation.Keywords: infant and young child sleep, parental sleep, parental emotion regulation, parental cognitions

Sleep and emotions are closely associated; however, the methodological challenges in the examination of sleep and the processes of emotion regulation in children and adolescents have not been investigated so far. Additionally, there is the demand to identify the levels of emotion regulating processes in which problematic or restricted sleep causes effect. Experimental sleep deprivation as well as prevalent sleep problems have been found to have negative influence on mental health and regulating functions. This review focuses first on the methodological protocols of the included studies. Subsequently, the results are summarized in the context of a multilevel model of emotion regulation. Thereafter, suggestions for future directions are given. Sleep problems and sleep deprivation are associated with a decrease of functional emotion regulating behavior and impaired emotion generation, and prolonged sleep enhances better mood and affect states, positive emotion expression, and faster sensory processing in response to emotional stimuli. This literature review highlights the limitations in current research, focusing on types of measurements, task characteristics, and data analysis. At the conclusion, suggestions are given for the future research direction in the field of sleep and emotion regulation in children and adolescents.

Additional file 1: Table 1. Descriptive statistics for outcomes at baseline across age groups, sexes, and sample attrition (drop-out after T1 vs. non-dropout). Table 2. Spearman correlations among the sleep variables for T1 (pre-intervention, N=59). Table 3. Spearman correlations among the sleep variables for T2 (post-intervention, n=36). Table 4. Spearman correlations among the sleep variables for T3 (three months after the intervention, n=25). Table 5. Spearman correlations among the sleep variables for T4 (six months after the intervention, n=18). Table 6. Spearman correlations among the sleep variables for T5 (twelve months after the intervention, n=14).

Gesunder Schlaf spielt eine übergeordnete Rolle für die frühe emotionale Entwicklung. Frühere Forschungsbefunde weisen darauf hin, dass der angemessene Umgang mit eigenen Emotionen und damit einhergehend prosozialen Verhalten mit einer guten Schlafqualität assoziiert scheint. Die Ergebnisse der Studien, welche dieser Dissertation zu Grunde liegen, leisten einen Beitrag zur bestehenden Forschung bezüglich des Zusammenhangs zwischen kindlichen Schlafproblemen und Emotionsregulation im intra- wie auch interpersonellen Kontext. So zeigen die Ergebnisse der Literaturübersicht, dass alle Dimensionen der Emotionsregulation gemäß Thompson (1994) durch schlechte Schlafqualität, Schlafprobleme oder auch durch experimentelle Schlafmanipulation im Kindes- und Jugendalter negativ beeinträchtigt scheinen. Darüber hinaus deuten die Ergebnisse der Interventionsstudie darauf hin, dass sich die Kompetenz der Emotionsregulation im Kindesalter nach der Behandlung von Schlafproblemen verbessern kann und dieser Effekt auch nach drei Monaten noch vorhanden zu sein scheint. Dieses Ergebnis zeigt, dass eine Veränderung des Schlafkonstrukts zu einer Veränderung der Emotionsregulation führen kann. Dies bedeutet, dass im Falle von früh auftretenden Störungen bezüglich der Emotionsregulation der Schlaf des betroffenen Kindes unbedingt exploriert werden sollte. Zukunftsweisende Ergebnisse gehen auch aus der Umfrage-Studie hervor. Es zeigt sich, dass neben der elterlichen Schlafqualität auch die mütterliche und väterliche Emotionsregulation negativ von kindlichen Schlafproblemen beeinflusst scheint. Außerdem liegen Hinweise dafür vor, dass Mütter und Väter eine unterschiedliche Auffassung zum Umgang mit nächtlichen Schlafproblemen von Kindern haben. Um die Effektivität von Interventionen zu steigern, müssen zukünftige Interventionen beide Elternteile einbeziehen und einen zusätzlichen Fokus auf den elterlichen Schlaf, die Emotionsregulation und die Eltern-Kind-Interaktion legen.

Background: Pediatric sleep problems are strongly linked to future emotional problems. However, research regarding the effect of internet-based cognitive behavior therapy for insomnia (iCBT-I) in early childhood on the outcome of emotion dysregulation is missing. Participants: 200 children (47% female) aged 7 to 63 months (M = 23.13) suffering from behavioral insomnia participated in the Mini-KiSS 6-week online treatment. Methods: A prepost- follow-up design was implemented. Sleep disorders were stated according to ICSD-3 and DSM-5 criteria and emotional dysregulation was assessed with an emotion dysregulation profile for children. Difference scores were calculated, a repeated-measures ANOVA, and stepwise multiple linear regression was performed. Results: After iCBT-I Mini-KiSS for young children, emotion dysregulation significantly declined immediately after the intervention (p = 0.000) and in the follow-up measurement after three months (p = 0.002). Age was associated with the change in emotion dysregulation at follow-up measurement (p = 0.017). Gender or the type of sleep disturbance did not have statistically significant impact on change in emotion dysregulation at any measurement (p ≥ 0.05). Clinically significant improvement of emotional dysregulation was achieved in 14.5% of the children from pre- to post-measurement, and 25.3% improved at follow-up. Conclusions: The findings show that treatment of pediatric insomnia reduce emotion dysregulation of infants and toddlers. Therefore, early sleep intervention might prevent mental disorder in young children. In future, an extended longitudinal design is needed to examine the preventing power of early-improved sleep on later psychopathological disorders. Beyond, future studies should examine underlying mechanisms in more detail.

T-cell prolymphocytic leukemia (T-PLL) is an aggressive malignancy with a median survival of the patients of less than two years. Besides characteristic chromosomal translocations, frequent mutations affect the ATM gene, JAK/STAT pathway members, and epigenetic regulators. We here performed a targeted mutation analysis for 40 genes selected from a RNA sequencing of 10 T-PLL in a collection of 28 T-PLL, and an exome analysis of five further cases. Nonsynonymous mutations were identified in 30 of the 40 genes, 18 being recurrently mutated. We identified recurrently mutated genes previously unknown to be mutated in T-PLL, which are SAMHD1, HERC1, HERC2, PRDM2, PARP10, PTPRC, and FOXP1. SAMHD1 regulates cellular deoxynucleotide levels and acts as a potential tumor suppressor in other leukemias. We observed destructive mutations in 18% of cases as well as deletions in two further cases. Taken together, we identified additional genes involved in JAK/STAT signaling (PTPRC), epigenetic regulation (PRDM2), or DNA damage repair (SAMHD1, PARP10, HERC1, and HERC2) as being recurrently mutated in T-PLL. Thus, our study considerably extends the picture of pathways involved in molecular pathogenesis of T-PLL and identifies the tumor suppressor gene SAMHD1 with ~20% of T-PLL affected by destructive lesions likely as major player in T-PLL pathogenesis.

Classical Hodgkin lymphoma (cHL) and anaplastic large cell lymphoma (ALCL) feature high expression of activator protein-1 (AP-1) transcription factors, which regulate various physiological processes but also promote lymphomagenesis. The AP-1 factor basic leucine zipper transcription factor, ATF-like 3 (BATF3), is highly transcribed in cHL and ALCL; however, its functional importance in lymphomagenesis is unknown. Here we show that proto-typical CD30+ lymphomas, namely cHL (21/30) and primary mediastinal B-cell lymphoma (8/9), but also CD30+ diffuse large B-cell lymphoma (15/20) frequently express BATF3 protein. Mass spectrometry and co-immunoprecipitation established interactions of BATF3 with JUN and JUNB in cHL and ALCL lines. BATF3 knockdown using short hairpin RNAs was toxic for cHL and ALCL lines, reducing their proliferation and survival. We identified MYC as a critical BATF3 target and confirmed binding of BATF3 to the MYC promoter. JAK/STAT signaling regulated BATF3 expression, as chemical JAK2 inhibition reduced and interleukin 13 stimulation induced BATF3 expression in cHL lines. Chromatin immunoprecipitation substantiated a direct regulation of BATF3 by STAT proteins in cHL and ALCL lines. In conclusion, we identified STAT-mediated BATF3 expression that is essential for lymphoma cell survival and promoted MYC activity in cHL and ALCL, hence we recognized a new oncogenic axis in these lymphomas.

Neurodermatitis (better called atopic dermatitis or atopic eczema, AE) is a chronic inflammatory skin disorder, which often appears already in early childhood and may be associated with a reduced quality of life for affected children. Research in adult patients has shown that AE often is associated with sleep problems. There is, however, little published information regarding this point in childhood. The main target of this paper is to provide an overview of the current evidence for the relation between sleep and AE in early childhood. A systematic literature research was conducted to identify relevant studies. The seven studies detected for this age group show that similar to adults, children with AE have increased sleep problems. They experience reduced sleep efficiency and sleep duration with an increased sleep fragmentation and prolonged sleep onset latency. Moreover, the severity of the disease directly influences the sleep quality. In general, there are few studies, which address the described relations in childhood. Therefore, more systematic research is required in this area. It is important to diagnose and treat chronic skin diseases such as AE early in childhood also to prevent sleep problems and related adverse effects on children's psychological well-being and on future development of children.

Schlafstorungen im Kindesalter sind weitverbreitet. Grunde hierfur werden viel untersucht und diskutiert. Es scheint, dass das Verhalten der Eltern einen besonderen Einfluss auf den Schlaf des Kindes hat. In diesem Review werden Ergebnisse von Studien vorgestellt, welche sich mit genau diesem Zusammenhang beschaftigen. Mit Blick auf die Instrumente wurden die Daten der Familien vornehmlich mittels Selbsteinschatzung durch die Eltern erhoben. Das Alter der Kinder variierte zwischen null bis funf Jahren. Aus den Ergebnissen der ausgewahlten 10 Publikationen geht hervor, dass Eltern durch die Anwendung von aktivem Beruhigen den Schlaf der Kinder deutlich beeintrachtigen konnen und die Qualitat des Schlafes gefahrden. Es wird angenommen, dass durch zu schnelles aktives Eingreifen der Eltern bei Einschlafproblemen oder nachtlichem Erwachen dem Kind die Moglichkeit genommen wird, eigene Beruhigungsstrategien zu entwickeln. Im Gegensatz haben autonomiefordernde Strategien, emotionale Verfugbarkeit und Abendrituale beim Zubettgehen das Potenzial, Schlafproblemen des Kindes entgegenzuwirken und zu einer verbesserten Schlafqualitat beizutragen. Schlafbezogene Erziehungsstrategien stellen einen Teil eines komplexen Systems dar, in dem noch weitere Faktoren Einfluss auf den kindlichen Schlaf haben.

Introduction Cortisol release is often associated with physiological arousal or perceived stress. Findings in adults as well as in older children and adolescents show that cortisol is also connected to sleep. Furthermore, it is assumed that high-quality sleep is a predictor of regular cortisol release throughout the day. Objective This review summarizes the current literature on how sleep and cortisol levels are associated in early childhood. Methods In order to identify studies on sleep and cortisol in young children, a structured literature search was performed in the PsychINFO, PsycARTICLES, PSYNDEX, and Google Scholar databases. Results A total of 14 studies could be included this review. According to the results of the reviewed publications, daily cortisol release patterns develop within the first 6 months of life. In addition, young children display a cortisol awakening response (CAR) and cortisol levels are influenced by taking naps during the day as well as by the quality of nighttime sleep. Conclusion After reviewing the recent findings in the literature concerning children from birth up to the age of 5 years, it can be assumed that sleep patterns and sleep are associated with cortisol secretion in early childhood. This finding could be included in the creation and further development of interventional sleep training programs., Einleitung Die Ausschüttung von Cortisol wird oft mit physiologischer Erregung oder wahrgenommenem Stress in Verbindung gebracht. Außerdem zeigen Ergebnisse von Erwachsenen oder älteren Kindern und Jugendlichen, dass Cortisol ebenfalls mit Schlaf zusammenhängt. Es wurde gezeigt, dass eine gute Schlafqualität ein Prädiktor für regelmäßige Cortisolauschüttung über den Tag hinweg ist. Ziel der Arbeit In der vorliegenden Übersichtarbeit wird zusammengefasst, wie der Zusammenhang von Schlaf und Cortisol in der frühen Kindheit in der aktuellen wissenschaftlichen Literatur dargestellt wird. Methode Um die bestehenden Studien zu der Thematik von Schlaf und Cortisol im Kleinkindalter zu ermitteln, wurde eine strukturierte Literaturrecherche in den Datenbanken PsychINFO, PsycARTICLES, PSYNDEX und Google Scholar durchgeführt. Ergebnis Es konnten insgesamt 14 Studien berücksichtigt werden. Den Ergebnissen zufolge entwickeln Kinder innerhalb der ersten 6 Monate ihres Lebens regelmäßige Muster in der Cortisolausschüttung. Darüber hinaus zeigen auch junge Kinder eine „cortisol awakening response“ (CAR), und Cortisolspiegel werden durch Tagesschlaf wie auch durch die Qualität des nächtlichen Schlafs beeinflusst. Schlussfolgerung Nach der Sichtung der Studien zum Zusammenhang von Schlaf und Cortisol bei Kindern im Alter von 0 bis zu 5 Jahren kann angenommen werden, dass Schlafmuster und Schlaf mit der Cortisolausschüttung assoziiert sind. Diese Aussage kann bei der Neu- und Weiterentwicklung von Schlaftrainingsprogrammen berücksichtigt werden.

The generation and functions of human peripheral blood (PB) IgM(+)IgD(+)CD27(+) B lymphocytes with somatically mutated IgV genes are controversially discussed. We determined their differential gene expression to naive B cells and to IgM-only and IgG(+) memory B cells. This analysis revealed a high similarity of IgM(+)(IgD(+))CD27(+) and IgG(+) memory B cells but also pointed at distinct functional capacities of both subsets. In vitro analyses revealed a tendency of activated IgM(+)IgD(+)CD27(+) B cells to migrate to B-cell follicles and undergo germinal center (GC) B-cell differentiation, whereas activated IgG(+) memory B cells preferentially showed a plasma cell (PC) fate. This observation was supported by reverse regulation of B-cell lymphoma 6 and PR domain containing 1 and differential BTB and CNC homology 1, basic leucine zipper transcription factor 2 expression. Moreover, IgM(+)IgD(+)CD27(+) B lymphocytes preferentially responded to neutrophil-derived cytokines. Costimulation with catecholamines, carcinoembryonic antigen cell adhesion molecule 8 (CEACAM8), and IFN-γ caused differentiation of IgM(+)IgD(+)CD27(+) B cells into PCs, induced class switching to IgG2, and was reproducible in cocultures with neutrophils. In conclusion, this study substantiates memory B-cell characteristics of human IgM(+)IgD(+)CD27(+) B cells in that they share typical memory B-cell transcription patterns with IgG(+) post-GC B cells and show a faster and more vigorous restimulation potential, a hallmark of immune memory. Moreover, this work reveals a functional plasticity of human IgM memory B cells by showing their propensity to undergo secondary GC reactions upon reactivation, but also by their special role in early inflammation via interaction with immunomodulatory neutrophils.

How the aryl hydrocarbon receptor (AhR) regulates dendritic-cell (DC) differentiation is unknown. We show that activation of AhR by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) caused enhanced differentiation from immature DCs (IDCs) to mature DCs (MDCs) in the bone-marrow-derived DCs (BMDC) from B6 wild-type mice but not in the BMDCs from AhR-null mice as indicated by the expression of CD11c and class II major histocompatibility complex (MHC). Enhanced maturation of BMDCs was associated with elevated levels of CD86 and an increased AhR-dependent nuclear accumulation of nuclear factor-kappa-light-chain enhancer of activated B cell (NF-κB) member RelB in BMDCs. The expression of interleukin (IL) 10 and chemokine DC-CK1 was suppressed, whereas that of CXCL2, CXCL3 and IL-22 was significantly increased in AhR-activated BMDCs. Furthermore, TCDD induced expression of the regulatory enzymes indoleamine 2,3-dioxygenase (IDO1) and indoleamine 2,3-dioxygenase-like 1 (IDO2). Increased expression of IDO2 was associated with coexpression of the cell-surface marker CCR6. Interestingly, mRNA expression of the chemokine receptor CCR6 was drastically decreased in AhR-null IDCs and MDCs. Overall, these data demonstrate that AhR modifies the maturation of BMDCs associated with the induction of the regulatory enzyme IDO and altered expression of cytokine, chemokines and DC-specific surface markers and receptors.

Background The purpose of the present study was to investigate activation of inflammatory markers in human macrophages derived from the U937 cell line after exposure to particulate matter (PM) collected on dairy farms in California and to identify the most potent components of the PM. Methods PM from different dairies were collected and tested to induce an inflammatory response determined by the expression of various pro-inflammatory genes, such as Interleukin (IL)-8, in U937 derived macrophages. Gel shift and luciferase reporter assays were performed to examine the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Toll-like-receptor 4 (TLR4). Results Macrophage exposure to PM derived from dairy farms significantly activated expression of pro-inflammatory genes, including IL-8, cyclooxygenase 2 and Tumor necrosis factor-alpha, which are hallmarks of inflammation. Acute phase proteins, such as serum amyloid A and IL-6, were also significantly upregulated in macrophages treated with PM from dairies. Coarse PM fractions demonstrated more pro-inflammatory activity on an equal-dose basis than fine PM. Urban PM collected from the same region as the dairy farms was associated with a lower concentration of endotoxin and produced significantly less IL-8 expression compared to PM collected on the dairy farms. Conclusion The present study provides evidence that the endotoxin components of the particles collected on dairies play a major role in mediating an inflammatory response through activation of TLR4 and NF-κB signaling.

Tubular organs are required for transport of liquids or gases. The Drosophila tracheal system and the human lungs need to undergo liquid to air transition to enable oxygen transport in the postembryonic or neonatal development respectively. In humans, a failure of airway liquid-clearance can lead to severe clinical syndromes, such as neonatal respiratory distress syndrome or transient tachypnea of newborn. However, the underlying molecular mechanisms are poorly understood. Previously, we identified the transmembrane J-domain protein Wurst as a key regulator of airway clearance in Drosophila. Wurst is involved in endocytosis and recruits clathrin and the associated Heat shock cognate protein 70 to the apical membrane. In wurst mutant embryos airways are oversized and airway liquidclearance is impaired. Here we show that wurst expression in tracheal cells, but not in the respiratory openings, is sufficient to rescue airway clearance and air-filling. We found that only tracheal specific RNAi knock-down of wurst is essential for airway liquid-clearance in post embryonic stages resulting in severe growth arrest and early lethality. In the tracheal wurst knock-down, clathrin accumulated at the apical cell membrane. Cell culture assays identified Wurst co-localization with endocytic markers and co-clustering at the plasma membrane. In summary, our data characterize Wurst as a key regulator of airway liquid-clearance and physiology. Wurst is conserved and a single ortholog was identified in humans, termed DNAJC22. Thus, investigating the molecular function of Wurst/DNAJC22 in airway liquid-clearance will contribute to a better understanding of clinical relevant lung syndromes.