Schroedercollier6392

Three-dimensional (3D) spheroid models are rapidly gaining favor for drug discovery applications due to their improved morphological characteristics, cellular complexity, long lifespan in culture, and higher physiological relevance relative to two-dimensional (2D) cell culture models. High-content imaging (HCI) of 3D spheroid models has the potential to provide valuable information to help researchers untangle disease pathophysiology and assess novel therapies more effectively. The transition from 2D monolayer models to dense 3D spheroids in HCI applications is not trivial, however, and requires 3D-optimized protocols, instrumentation, and resources. Here, we discuss considerations for moving from 2D to 3D models and present a framework for HCI and analysis of 3D spheroid models in a drug discovery setting. We combined scaffold-free, multicellular spheroid models with scalable, automation-compatible plate technology enabling image-based applications ranging from high-throughput screening to more complex, lower-throughput microphysiological systems of organ networks. We used this framework in three case studies investigation of lipid droplet accumulation in a human liver nonalcoholic steatohepatitis (NASH) model, real-time immune cell interactions in a multicellular 3D lung cancer model, and a high-throughput screening application using a 3D co-culture model of gastric carcinoma to assess dose-dependent drug efficacy and specificity. The results of these proof-of-concept studies demonstrate the potential for high-resolution image-based analysis of 3D spheroid models for drug discovery applications, and confirm that cell-level and temporal-spatial analyses that fully exploit multicellular features of spheroid models are not only possible but soon will be routine practice in drug discovery workflows.The Dark Triad (i.e., narcissism, psychopathy, Machiavellianism) has garnered intense attention over the past 15 years. We examined the structure of these traits' measure-the Dark Triad Dirty Dozen (DTDD)-in a sample of 11,488 participants from three W.E.I.R.D. (i.e., North America, Oceania, Western Europe) and five non-W.E.I.R.D. (i.e., Asia, Middle East, non-Western Europe, South America, sub-Saharan Africa) world regions. The results confirmed the measurement invariance of the DTDD across participants' sex in all world regions, with men scoring higher than women on all traits (except for psychopathy in Asia, where the difference was not significant). We found evidence for metric (and partial scalar) measurement invariance within and between W.E.I.R.D. and non-W.E.I.R.D. world regions. The results generally support the structure of the DTDD.Objectives Prosthetic joint infections (PJI) are treated with prolonged periods of intravenous (IV) antibiotics combined with one or more appropriate surgical procedures. In Belgium, patients receive their IV treatments as inpatients, whereas in other parts of the world similar IV antibiotics can be given as outpatient parenteral antibiotic therapy (OPAT), without jeopardising patient outcomes. The purpose of this paper was to analyse the financial feasibility of OPAT for PJI in Belgium. Methods Patients with PJI treated with a two-stage revision between January 2013 and June 2016 were selected for analysis of in-hospital costs. An OPAT cost simulation was made for comparable lengths of stay, for the different antimicrobial regimens used. A cost minimization analysis comparing the non-OPAT costs and the OPAT cost simulation was performed, with a sensitivity analysis accounting for cost uncertainties. Results Based on the financial data of 12 two-stage revisions and 4 different antibiotic regimens, the average simulated cost difference for OPAT was €2.402 surplus for the patient, €-25.950 for health care and €-23.548 in total. Conclusion Projected cost savings for OPAT-treatment of PJI are substantial. However, OPAT within the current Belgian system was significantly more expensive for the patients. This can be attributed to the Belgian health insurance system; its current reimbursement regulations prevent OPAT from truly making a breakthrough in Belgium.Experiments on isolated mammalian gut are essential components of the physiology curriculum worldwide. Over the years, these routine experiments have been largely replaced by simulation modules, to reduce the euthanization of animals for understanding established facts and mechanisms in gut physiology. However, a medical undergraduate needs hands-on training to handle a living tissue to have a better understanding of physiology. The present sourcebook update describes the use of avian gut, which is usually discarded in abattoirs, as an effective replacement of mammalian gut to understand basic gut smooth muscle physiology. The avian gut can be used to study the effect of various drugs and ions as used in mammalian gut experiments. The experiment protocol described in the update can be performed by students of basic sciences and medical students using minimal laboratory set up and at low cost, producing results comparable to mammalian gut experiments. Ethical permissions may not be necessary; however, the disposal of tissue waste has to follow proper guidelines.As literature indicates, historic racism and implicit bias throughout academia have been profound metrics leading to a lack of diversity, as related to people from underrepresented groups according to race and ethnicity, among biomedical sciences graduate students in U.S. universities. Recognizing such challenges, a team of biomedical scientists and inclusivity educators developed and implemented a pilot training program within an academic health sciences center as an initial step to educate faculty and staff regarding their roles in the promotion of an inclusive academic environment, receptive to all students, including underrepresented students. The 3-h workshop included didactic modules, videos, teaching modules, and active attendee participation. Faculty and staff were presented common terminology and ways to promote the development of an inclusive and diverse academic workforce. CVT-313 Compared with pre-workshop, post-workshop survey results indicated a statistically significant improvement in attendee knowledge of correctly identifying definitions of "implicit bias," "status leveling," "color-blind racial attitudes," "tokenism," and "failure to differentiate.