Insomnia treatment in the third trimester of pregnancy reduces postpartum depression symptoms: A randomized clinical trial

Mental health is an important medical issue in perinatal care, and there is increasing evidence that insomnia during pregnancy is associated with postpartum depression (PPD). Therefore, the present study evaluated the effect of insomnia treatment during the third trimester of pregnancy on PPD symptoms. Fifty-four pregnant women with insomnia were randomly assigned to trazodone, diphenhydramine, or placebo treatment. Sleep quality was measured by actigraphy at baseline, and after 2 and 6 weeks of treatment. In addition, depression was assessed 2 and 6 weeks after delivery. Trazodone and diphenhydramine improved sleep profile compared to placebo after 6 weeks of treatment. Further, depressive symptoms were reduced 2 and 6 weeks after delivery in trazodone and diphenhydramine groups compared to placebo. No differences in depressive symptoms were observed between the trazodone and diphenhydramine groups. These findings indicate that insomnia treatment with trazodone or diphenhydramine during the third trimester of pregnancy may prevent PPD.     

Mast cells are an essential hematopoietic component for polyp development

It is generally agreed that most colon cancers develop from adenomatous polyps, and it is this fact on which screening strategies are based. Although there is overwhelming evidence to link intrinsic genetic lesions with the formation of these preneoplastic lesions, recent data suggest that the tumor stromal environment also plays an essential role in this disease. In particular, it has been suggested that CD34(+) immature myeloid precursor cells are required for tumor development and invasion. Here we have used mice conditional for the stabilization of beta-catenin or defective for the adenomatous polyposis coli (APC) gene to reinvestigated the identity and importance of tumor-infiltrating hematopoietic cells in polyposis. We show that, from the onset, polyps are infiltrated with proinflammatory mast cells (MC) and their precursors. Depletion of MC either pharmacologically or through the generation of chimeric mice with genetic lesions in MC development leads to a profound remission of existing polyps. Our data suggest that MC are an essential hematopoietic component for preneoplastic polyp development and are a novel target for therapeutic intervention.     

Practical recommendations to conduct a neuroimaging meta‐analysis for neuropsychiatric disorders

Over the past decades, neuroimaging has become widely used to investigate structural and functional brain abnormality in neuropsychiatric disorders. The results of individual neuroimaging studies, however, are frequently inconsistent due to small and heterogeneous samples, analytical flexibility, and publication bias toward positive findings. To consolidate the emergent findings toward clinically useful insight, meta‐analyses have been developed to integrate the results of studies and identify areas that are consistently involved in pathophysiology of particular neuropsychiatric disorders. However, it should be considered that the results of meta‐analyses could also be divergent due to heterogeneity in search strategy, selection criteria, imaging modalities, behavioral tasks, number of experiments, data organization methods, and statistical analysis with different multiple comparison thresholds. Following an introduction to the problem and the concepts of quantitative summaries of neuroimaging findings, we propose practical recommendations for clinicians and researchers for conducting transparent and methodologically sound neuroimaging meta‐analyses. This should help to consolidate the search for convergent regional brain abnormality in neuropsychiatric disorders.     

Validation of the Farsi version of the revised Adolescent Sleep Hygiene Scale (ASHSr): a cross-sectional study

Background

Restoring sleep is associated with a broad variety of favorable cognitive, emotional, social and behavioral benefits during the day. This holds particularly true for adolescents, as maturational, social, cognitive, emotional and behavioral changes might unfavorably impact on adolescents’ sleep. Among adolescents, poor sleep hygiene practices are a potentially modifiable risk factor that can be addressed via appropriate interventions. Accordingly, having reliable and valid self-report measures to assess sleep hygiene practices is essential to gauge individual responses to behavioral interventions and evaluate sleep hygiene recommendations. The aim of the present study therefore was to translate and to test the psychometric properties (internal consistency, test-retest reliability, factorial and concurrent validity) of the Farsi/Persian version of the revised version of the Adolescent Sleep Hygiene Scale (ASHSr).

Method

A total of 1013 adolescents (mean age: M?=?15.4 years; SD?=?1.2; range: 12–19 years; 42.9% females) completed the ASHSr and the Pittsburgh Sleep Quality Index (PSQI) in their classroom during an official school lesson. Further, 20% completed the ASHSr 6 weeks later to evaluate the test-retest reliability. Cronbach’s alpha coefficients were calculated to examine internal consistency, confirmatory factor analysis (CFA) was used to test factorial validity, whereas concurrent validity and test-retest reliability were examined via correlation analyses.

Results

A first-order confirmatory factor analysis (CFA) corroborated the six-factor structure of the ASHSr, including a physiological, behavioral arousal, cognitive/emotional, daytime sleep, sleep environment, and sleep stability factor. A second-order CFA showed that a higher-order sleep hygiene construct explained sufficient variance in each factor. Cronbach’s alpha values ranged between .71 and .75, correlations for test-retest reliability between .82 and .87. Significant correlations were found between most ASHSr scales and the PSQI indices. However, the magnitude of these correlations was weak.

Conclusions

The Farsi/Persian version of the Adolescent Sleep Hygiene Scale can be used as a reliable and valid tool for evaluation of sleep hygiene practices among Farsi/Persian-speaking adolescents.

     

Transcriptomic and Immunophenotypic Characterization of Tumor Immune Microenvironment in Squamous Cell Carcinoma of the Oral Tongue

The tumor immune microenvironment of oral tongue squamous cell carcinoma may be accountable for differences in clinical behavior, particularly between different age groups. We performed RNA expression profiling and evaluated tumor infiltrating lymphocytes (TILs) and their T-cell subsets in order to assess the functional status of oral tongue squamous cell carcinoma tumor microenvironment and detect potentially clinically useful associations. Archival surgical pathology material from sixteen oral tongue squamous cell carcinoma patients was microscopically evaluated for TIL densities. RNA was extracted from macrodissected whole tumor sections and normal controls and RNA expression profiling was performed by the NanoString PanCancer IO 360 Gene Expression Panel. Immunostains for CD4, CD8 and FOXP3 were evaluated manually and by digital image analysis. Oral tongue squamous cell carcinomas had increased TIL densities, numerically dominated by CD4 + T cells, followed by CD8 + and FOXP3 + T cells. RNA expression profiling of tumors versus normal controls showed tumor signature upregulation in inhibitory immune signaling (CTLA4, TIGIT and PD-L2), followed by inhibitory tumor mechanisms (IDO1, TGF-β, B7-H3 and PD-L1). Patients older than 44 years showed a tumor microenvironment with increased Tregs and CTLA4 expression. Immunohistochemically assessed CD8% correlated well with molecular signatures related to CD8 + cytotoxic T-cell functions. FOXP3% correlated significantly with CTLA4 upregulation. CTLA4 molecular signature could be predicted by FOXP3% assessed by immunohistochemistry (R² = 0.619, p = 0.026). Oral tongue squamous cell carcinoma hosts a complex inhibitory immune microenvironment, partially reflected in immunohistochemically quantified CD8 + and FOXP3 + T-cell subsets. Immunohistochemistry can be a useful screening tool for detecting tumors with upregulated expression of the targetable molecule CTLA4.Electronic supplementary materialThe online version of this article (10.1007/s12105-020-01229-w) contains supplementary material, which is available to authorized users.     

Somatic activation of beta-catenin bypasses pre-TCR signaling and TCR selection in thymocyte development

Mutation or ablation of T cell factor 1 and lymphocyte enhancer factor 1 indicated involvement of the Wnt pathway in thymocyte development. The central effector of the Wnt pathway is beta-catenin, which undergoes stabilization upon binding of Wnt ligands to frizzled receptors. We report here that conditional stabilization of beta-catenin in immature thymocytes resulted in the generation of single positive T cells that lacked the alpha beta TCR and developed in the absence of pre-TCR signaling and TCR selection. Although active beta-catenin induced differentiation in the absence of TCRs, its action was associated with reduced proliferation and survival when compared to developmental changes induced by the pre-TCR or the alpha beta TCR.     

Lines of Murine Oligodendroglial Precursor Cells Immortalized by an Activated neu Tyrosine Kinase Show Distinct Degrees of Interaction with Axons In Vitro and In Vivo

Replication-defective retroviruses expressing the t- neu oncogene, or a hybrid protein with the neu tyrosine kinase linked to the external region of the human epidermal growth factor receptor ( egfr-neu ), were used to establish lines of murine oligodendroglial precursor cells. Differentiation of the t- neu lines into myelin-associated glycoprotein (MAG)-positive oligodendrocytes was induced by dibutyryl cAMP, and the egfr-neu line showed limited differentiation in vitro upon withdrawal of epidermal growth factor. Cerebellar granule cell neurons expressed mitogens for the cell lines. Upon transplantation into demyelinated lesions, t- neu line cells engaged with the demyelinated axons whereas the egfr-neu line cells differentiated further and ensheathed the axons. These cell lines thus interact with neurons in vitro and in vivo and can be used as tools to define the molecules involved in different stages of neuron-glia interaction.