BET bromodomain protein inhibition is a therapeutic option for medulloblastoma

Medulloblastoma is the most common malignant brain tumor of childhood, and represents a significant clinical challenge in pediatric oncology, since overall survival currently remains under 70%. Patients with tumors overexpressing MYC or harboring a MYC oncogene amplification have an extremely poor prognosis. Pharmacologically inhibiting MYC expression may, thus, have clinical utility given its pathogenetic role in medulloblastoma. Recent studies using the selective small molecule BET inhibitor, JQ1, have identified BET bromodomain proteins, especially BRD4, as epigenetic regulatory factors for MYC and its targets. Targeting MYC expression by BET inhibition resulted in antitumoral effects in various cancers. Our aim here was to evaluate the efficacy of JQ1 against preclinical models for high-risk MYC-driven medulloblastoma. Treatment of medulloblastoma cell lines with JQ1 significantly reduced cell proliferation and preferentially induced apoptosis in cells expressing high levels of MYC. JQ1 treatment of medulloblastoma cell lines downregulated MYC expression and resulted in a transcriptional deregulation of MYC targets, and also significantly altered expression of genes involved in cell cycle progression and p53 signalling. JQ1 treatment prolonged the survival of mice harboring medulloblastoma xenografts and reduced the tumor burden in these mice. Our preclinical data provide evidence to pursue testing BET inhibitors, such as JQ1, as molecular targeted therapeutic options for patients with high-risk medulloblastomas overexpressing MYC or harboring MYC amplifications

Complementary and alternative medicine for management of premature ejaculation: a systematic review and meta-analysis

Introduction: Premature ejaculation (PE) is defined as ejaculation within one minute (lifelong PE) or three minutes (acquired PE); inability to delay ejaculation; and negative personal consequences. Management includes behavioral and pharmacological approaches. Aim: To systematically review effectiveness, safety, and robustness of evidence for complementary and alternative medicine (CAM) in managing PE. Methods: Nine databases including MEDLINE were searched to September 2015. Randomized controlled trials (RCTs) evaluating CAM for PE were included. Outcome measures: Studies were included if they reported intra-vaginal ejaculatory latency time (IELT) and/or another validated premature ejaculation measure. Adverse effects were summarized. Results: Ten RCTs were included. Two assessed acupuncture, five Chinese herbal medicine, one Ayurvedic herbal medicine, and two topical “severance secret” (SS) cream. Risk of bias was unclear in all studies due to unclear allocation concealment or blinding, and only five studies reported stopwatch-measured IELT. Acupuncture slightly increased IELT over placebo in one study (mean difference [MD]=0.55 min, p=0.001). In another study, Ayurvedic herbal medicine slightly increased IELT over placebo (MD=0.80 min, p=0.001). Topical SS cream improved IELT over placebo in two studies (MD=8.60 min, p<0.001), though inclusion criteria were broad (IELT <3 min). Three studies comparing Chinese herbal medicine against selective serotonin reuptake inhibitors (SSRIs) favored SSRIs (MD=1.01 min, p=0.02). However, combination treatment with Chinese medicine plus SSRIs improved IELT over SSRIs alone (two studies, MD=1.92 min, p<0.00001) and over Chinese medicine alone (two studies, MD=2.52 min, p<0.00001). Adverse effects were not consistently assessed, but where reported were generally mild. Conclusions: There is preliminary evidence for effectiveness of acupuncture, Chinese herbal medicine, Ayurvedic herbal medicine and topical SS cream in improving IELT and other outcomes. However, results are based on clinically heterogeneous studies of unclear quality. There is little data on adverse effects or potential for drug interactions. Further well-conducted RCTs would be valuable

Evaluation von 3D Human Pose Estimation Frameworks auf digitalem Bildmaterial für den Einsatz in der Forensik

In this thesis a 3D Human Pose Estimation Framework, specifically MMPose using RTM-m Pose and MotionBERT, will be tested. For each created rig anthropometric measurements corresponding to the body parts will be calculated and the rigs compared using the RMSD to review the accuracy and performance regarding various 3D-HPE challenges

Reflections on the Socratic Method

I have noticed the Socratic method is a term often used in academic circles in a variety of syntactical contexts. I began to wonder how the nature of the Socratic method has changed over time. Would Socrates approve of the various meanings associated with his name today? I conducted a detailed analysis of the historical text Alcibiades, seeking contemporary relevance. There is evidence that Socrates did not actually have a method, as it may appear. An analysis of the text shows that Socrates’ genius lies in his openness to adapt to the changing landscape of dialogue. In doing so, he and his student, Alcibiades, participate in the process of askesis, or self-cultivation. As Socrates demonstrates, engaging in askesis is equally important for the teacher and students

Science Notes - IAS Excellence in Science Teaching Award Nominations

The Iowa Academy of Science is currently accepting nominations for its Excellence in Science Teaching Awards. Each year, Iowa teachers are chosen to receive the award in six categories: biology, chemistry, earth science, physics, elementary science and junior high science

Editor\u27s Corner - Last Thoughts

It hardly seems possible that I have been the editorial assistant for the Iowa Science Teachers Journal for six years now. What seems even more impossible is the fact that I am leaving the Journal

Science News - National Middle Level Science Teachers Association

Efforts are currently underway to establish a national professional organization for teachers of middle school science. The National Middle Level Science Teachers Association (NMLSTA) is currently inviting educators across the nation to become members

Science Notes - American Agri-Women Sponsor Science Fair Project Competition

The American Agri-Women, a coalition of farm, ranch and agri-business women, is sponsoring a competition for students interested in industrial agriculture. Ag in the Classroom has been designed to encourage junior and senior high school students to choose and complete a science fair project based on the production or use of an industrial crop

Science Notes - Plans Underway for 1987 NEWMAST Workshops

The National Science Teachers Association, the National Council of Teachers of Mathematics and the National Aeronautics and Space Administration are again jointly sponsoring the NEWMAST Honors Workshops Program