Childersbrock2495

The orphan small nucleolar RNA (snoRNA) ACA11 is overexpressed as a result of the t(4;14) chromosomal translocation in multiple myeloma (MM), increases reactive oxygen species, and drives cell proliferation. Like other snoRNAs, ACA11 is predominantly localized to a sub-nuclear organelle, the nucleolus. We hypothesized that increased ACA11 expression would increase ribosome biogenesis and protein synthesis. We found that ACA11 overexpression in MM cells increased nucleolar area and number as well as silver-binding nucleolar organizing regions (AgNORs). Supporting these data, samples from t(4;14)-positive patients had higher AgNORs scores than t(4;14)-negative samples. ACA11 also upregulated ribosome production, pre-47S rRNA synthesis, and protein synthesis in a ROS-dependent manner. Lastly, ACA11 overexpression enhanced the response to proteasome inhibitor in MM cells, while no effect was found in response to high doses of melphalan. Together, these data demonstrate that ACA11 stimulates ribosome biogenesis and influences responses to chemotherapy. ACA11 may be a useful target to individualize the treatment for t(4;14)-positive myeloma patients.In recent years, increasing efforts have been focused on testing strategies of improving victimized children's narrative productivity, given that, for many youth, finding out what has happened to them is crucial to intervening and promoting their well-being. Implicit encouragement strategies, such as back channeling by conversational partners, have shown some preliminary promise, but their precise effects on productivity and accuracy have not been adequately examined. In this study, 98 youth, ages 8-14, completed a laboratory-based stressful activity, and a week later, a surprise memory test regarding what happened in the lab activity. Interviewers varied their use of implicit encouragement. Open-ended recall questions asked youth about both factual details and detail about their feelings and thoughts during the laboratory activity. Implicit encouragement increased the amount of both types of details and had no effect on errors. read more In fact, few youth provided any incorrect information in their recall reports. Neither age nor stress was related to youth's productivity or accuracy, directly or in conjunction with implicit encouragement. Results highlight the value of interviewers using encouraging behaviors when questioning children and adolescents to elicit a range of information about prior stressful experiences.Tendons link muscle to bone and transfer forces necessary for normal movement. Tendon injuries can be debilitating and their intrinsic healing potential is limited. These challenges have motivated the development of model systems to study the factors that regulate tendon formation and tendon injury. Recent advances in understanding of embryonic and postnatal tendon formation have inspired approaches that aimed to mimic key aspects of tendon development. Model systems have also been developed to explore factors that regulate tendon injury and healing. We highlight current model systems that explore developmentally inspired cellular, mechanical, and biochemical factors in tendon formation and tenogenic stem cell differentiation. Next, we discuss in vivo, in vitro, ex vivo, and computational models of tendon injury that examine how mechanical loading and biochemical factors contribute to tendon pathologies and healing. These tendon development and injury models show promise for identifying the factors guiding tendon formation and tendon pathologies, and will ultimately improve regenerative tissue engineering strategies and clinical outcomes.Self-mutilation is often associated with psychiatric disorders. We describe here a 22-year-old male Indian with decreased sleep, aggressive behaviour, self-muttering, disorganised behaviour, frequent spitting, biting and self-mutilation; he bit off his right ring finger and left thumb (Van Gogh syndrome). Self-harm behaviour was frequently evidenced by family members resulting in various injuries. The patient was diagnosed with paranoid schizophrenia and was treated with anti-psychotics which resulted in a decrease in his behavioural disturbances along with treatment for his self-mutilation injuries. Here we discuss Van Gogh syndrome's presentation of self-mutilation in paranoid schizophrenia and its implications. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.Purpose Treatment with intravitreal injections of anti-vascular endothelial growth factor agents has been associated with an increased risk of arterial thromboembolic events. The aim of the present pilot study was to assess the effect of a single intravitreal injection of aflibercept on coagulation. Methods Treatment-naïve patients with age-related macular degeneration (n = 47), who were scheduled to undergo treatment with intravitreal injections of aflibercept, were enrolled. None of the included patients received any anticoagulation therapy or had a history of a recent arterial thromboembolic event. Blood samples were collected before the first intravitreal injection, and at 7 and 30 days after aflibercept administration. We evaluated coagulation parameters, such as platelet count and plasma fibrinogen and D-dimer levels; functional clotting parameters, such as prothrombin time, international normalized ratio, and activated partial thromboplastin time; and anticoagulant parameters, such as the levels of Proteins S and C. Results The levels of all of the evaluated biomarkers were within the normal range at baseline and at both the time points throughout the study. No statistically significant changes were observed in any of the measured parameters at 1 week and 1 month after aflibercept administration. Conclusion A single intravitreal injection of aflibercept in treatment-naïve patients with exudative age-related macular degeneration has no statistically significant effect on blood coagulation parameters for up to 1 month after aflibercept administration. Our results also provide an explorative statistical data, and further studies are required to evaluate any significant clinical effects of aflibercept on blood coagulation parameters. ClinicalTrialsgov ID NCT03509623. © The Author(s), 2020.