Associations of sleep with psychological problems and well-being in adolescence: causality or common genetic predispositions?

Background: Whereas short and problematic sleep are associated with psychological problems in adolescence, causality remains to be elucidated. This study therefore utilized the discordant monozygotic cotwin design and cross-lagged models to investigate how short and problematic sleep affect psychological functioning. Methods: Adolescent twins (N = 12,803, 13–20 years, 42% male) completed questionnaires on sleep and psychological functioning repeatedly over a two-year interval. Monozygotic twin pairs were classified as concordant or discordant for sleep duration and trouble sleeping. Resulting subgroups were compared regarding internalizing problems, externalizing problems, and subjective well-being. Results: Cross-sectional analyses indicated associations of worse psychological functioning with both short sleep and problematic sleep, and cross-lagged models indicate bidirectional associations. Longitudinal analyses showed that an increase in sleep problems experienced selectively by one individual of an identical twin pair was accompanied by an increase of 52% in internalizing problem scores and 25% in externalizing problem scores. These changes were significantly different from the within-subject changes in cotwins with unchanged sleep quality (respectively, 3% increase and 5% decrease). Psychological functioning did, however, not worsen with decreasing sleep duration. Conclusions: The findings suggest that sleep quality, rather than sleep duration, should be the primary target for prevention and intervention, with possible effect on psychological functioning in adolescents

Megakaryocyte lineage development is controlled by modulation of protein acetylation

Treatment with lysine deacetylase inhibitors (KDACi) for haematological malignancies, is accompanied by haematological side effects including thrombocytopenia, suggesting that modulation of protein acetylation affects normal myeloid development, and specifically megakaryocyte development. In the current study, utilising ex-vivo differentiation of human CD34+ haematopoietic progenitor cells, we investigated the effects of two functionally distinct KDACi, valproic acid (VPA), and nicotinamide (NAM), on megakaryocyte differentiation, and lineage choice decisions. Treatment with VPA increased the number of megakaryocyte/erythroid progenitors (MEP), accompanied by inhibition of megakaryocyte differentiation, whereas treatment with NAM accelerated megakaryocyte development, and stimulated polyploidisation. Treatment with bot

Neoadjuvant chemoradiotherapy plus surgery versus active surveillance for oesophageal cancer: A stepped-wedge cluster randomised trial

Background: Neoadjuvant chemoradiotherapy (nCRT) plus surgery is a standard treatment for locally advanced oesophageal cancer. With this treatment, 29% of patients have a pathologically complete response in the resection specimen. This provides the rationale for investigating an active surveillance approach. The aim of this study is to assess the (cost-)effectiveness of active surveillance vs. standard oesophagectomy after nCRT for oesophageal cancer. Methods: This is a phase-III multi-centre, stepped-wedge cluster randomised controlled trial. A total of 300 patients with clinically complete response (cCR, i.e. no local or disseminated disease proven by histology) after nCRT will be randomised to show non-inferiority of active surveillance to standard oesophagectomy (non-inferiority margin 15%, intra-correlation coefficient 0.02, power 80%, 2-sided α 0.05, 12% drop-out). Patients will undergo a first clinical response evaluation (CRE-I) 4-6 weeks after nCRT, consisting of endoscopy with bite-on-bite biopsies of the primary tumour site and other suspected lesions. Clinically complete responders will undergo a second CRE (CRE-II), 6-8 weeks after CRE-I. CRE-II will include 18F-FDG-PET-CT, followed by endoscopy with bite-on-bite biopsies and ultra-endosonography plus fine needle aspiration of suspected lymph nodes and/or PET- positive lesions. Patients with cCR at CRE-II will be assigned to oesophagectomy (first phase) or active surveillance (second phase of the study). The duration of the first phase is determined randomly over the 12 centres, i.e., stepped-wedge cluster design. Patients in the active surveillance arm will undergo diagnostic evaluations similar to CRE-II at 6/9/12/16/20/24/30/36/48 and 60 months after nCRT. In this arm, oesophagectomy will be offered only to patients in whom locoregional regrowth is highly suspected or proven, without distant dissemination. The main study parameter is overall survival; secondary endpoints include percentage of patients who do not undergo surgery, quality of life, clinical irresectability (cT4b) rate, radical resection rate, postoperative complications, progression-free survival, distant dissemination rate, and cost-effectiveness. We hypothesise that active surveillance leads to non-inferior survival, improved quality of life and a reduction in costs, compared to standard oesophagectomy. Discussion: If active surveillance and surgery as needed after nCRT leads to non-inferior survival compared to standard oesophagectomy, this organ-sparing approach can be implemented as a standard of care

Red Blood Cells : Chasing Interactions

Human red blood cells (RBC) are highly differentiated cells that have lost all organelles and most intracellular machineries during their maturation process. RBC are fundamental for the nearly all basic physiologic dynamics and they are key cells in the body's respiratory system by being responsible for the oxygen transport to all cells and tissues, and delivery of carbon dioxide to the lungs. With their flexible structure RBC are capable to deform in order to travel through all blood vessels including very small capillaries. Throughout their in average 120 days lifespan, human RBC travel in the bloodstream and come in contact with a broad range of different cell types. In fact, RBC are able to interact and communicate with endothelial cells (ECs), platelets, macrophages, and bacteria. Additionally, they are involved in the maintenance of thrombosis and hemostasis and play an important role in the immune response against pathogens. To clarify the mechanisms of interaction of RBC and these other cells both in health and disease as well as to highlight the role of important key players, we focused our interest on RBC membrane components such as ion channels, proteins, and phospholipids

Red Blood Cells: Chasing Interactions

Human red blood cells (RBC) are highly differentiated cells that have lost all organelles and most intracellular machineries during their maturation process. RBC are fundamental for the nearly all basic physiologic dynamics and they are key cells in the body's respiratory system by being responsible for the oxygen transport to all cells and tissues, and delivery of carbon dioxide to the lungs. With their flexible structure RBC are capable to deform in order to travel through all blood vessels including very small capillaries. Throughout their in average 120 days lifespan, human RBC travel in the bloodstream and come in contact with a broad range of different cell types. In fact, RBC are able to interact and communicate with endothelial cells (ECs), platelets, macrophages, and bacteria. Additionally, they are involved in the maintenance of thrombosis and hemostasis and play an important role in the immune response against pathogens. To clarify the mechanisms of interaction of RBC and these other cells both in health and disease as well as to highlight the role of important key players, we focused our interest on RBC membrane components such as ion channels, proteins, and phospholipids

Red Blood Cells : Chasing Interactions

Human red blood cells (RBC) are highly differentiated cells that have lost all organelles and most intracellular machineries during their maturation process. RBC are fundamental for the nearly all basic physiologic dynamics and they are key cells in the body's respiratory system by being responsible for the oxygen transport to all cells and tissues, and delivery of carbon dioxide to the lungs. With their flexible structure RBC are capable to deform in order to travel through all blood vessels including very small capillaries. Throughout their in average 120 days lifespan, human RBC travel in the bloodstream and come in contact with a broad range of different cell types. In fact, RBC are able to interact and communicate with endothelial cells (ECs), platelets, macrophages, and bacteria. Additionally, they are involved in the maintenance of thrombosis and hemostasis and play an important role in the immune response against pathogens. To clarify the mechanisms of interaction of RBC and these other cells both in health and disease as well as to highlight the role of important key players, we focused our interest on RBC membrane components such as ion channels, proteins, and phospholipids

Epigenetic drug screen identifies the histone deacetylase inhibitor NSC3852 as a potential novel drug for the treatment of pediatric acute myeloid leukemia

BACKGROUND: Acute myeloid leukemia (AML) is a heterogeneous disease regarding morphology, immunophenotyping, genetic abnormalities, and clinical behavior. The overall survival rate of pediatric AML is 60% to 70%, and has not significantly improved over the past two decades. Children with Down syndrome (DS) are at risk of developing acute megakaryoblastic leukemia (AMKL), which can be preceded by a transient myeloproliferative disorder during the neonatal period. Intensification of current treatment protocols is not feasible due to already high treatment-related morbidity and mortality. Instead, more targeted therapies with less severe side effects are highly needed. PROCEDURE: To identify potential novel therapeutic targets for myeloid disorders in children, including DS-AMKL and non-DS-AML, we performed an unbiased compound screen of 80 small molecules targeting epigenetic regulators in three pediatric AML cell lines that are representative for different subtypes of pediatric AML. Three candidate compounds were validated and further evaluated in normal myeloid precursor cells during neutrophil differentiation and in (pre-)leukemic pediatric patient cells. RESULTS: Candidate drugs LMK235, NSC3852, and bromosporine were effective in all tested pediatric AML cell lines with antiproliferative, proapoptotic, and differentiation effects. Out of these three compounds, the pan-histone deacetylase inhibitor NSC3852 specifically induced growth arrest and apoptosis in pediatric AML cells, without disrupting normal neutrophil differentiation. CONCLUSION: NSC3852 is a potential candidate drug for further preclinical testing in pediatric AML and DS-AMKL

The development, validity, and reliability of the auditory vocal hallucination rating scale questionnaire (AVHRS-Q)

PURPOSE: The Auditory Vocal Hallucination Rating Scale Questionnaire (AVHRS-Q) is a short self-report measure assessing several characteristics of auditory vocal hallucinations (AVH) that was derived from a validated clinical interview (the auditory vocal hallucination rating scale; AVHRS). This study investigated the internal reliability, convergent validity, and divergent validity of the AVHRS-Q using two clinical samples. METHODS: In sample I, 32 psychiatric patients with AVH were recruited from an academic hospital service and assessed with the AVHRS and the AVHRS-Q. Data for sample II were retrospectively retrieved from a pseudonymised Routine Outcome Monitoring (ROM) database collected in the context of mental healthcare at the same academic hospital service. Data from 82 psychiatric patients with AVH were retrieved, who completed the AVHRS-Q, and measures of psychological distress (the Outcome Questionnaire; OQ-45, and the Symptom Checklist; SCL-90) and quality of life (the Manchester Short Assessment of Quality of Life; MANSA). RESULTS: The AVHRS-Q showed good internal consistency in both samples. Severity scores of the AVHRS-Q were strongly correlated to the severity scores of the AVHRS (r = 0.90, p < 0.01). The AVHRS-Q and AVHRS did not differ in the identification of mild and severe voice-hearers [X2 (1, N = 32) = 15.71]. AVHRS-Q severity scores had moderate correlations with measures of psychological distress (OQ-45, r = 0.43, p < 0.01; SCL-90, r = 0.50, p < 0.05) and quality of life (MANSA, r = - 0.22, p < 0.01). CONCLUSIONS: The AVHRS-Q demonstrated good reliability, convergent validity, and divergent validity, suggesting it can be applied in both clinical and research settings for a quick and reliable assessment of AVH