Peripheral blood mononuclear cells from pregnant and postpartum women were cultured in vitro with erythropoietin. Burst-forming unit (BFU-E)derived erythroid colonies composed of immature erythroblasts with low hemoglobin contents were observed by day 8 of culture. By day 12 of culture, numerous BFU-E-derived erythroid colonies with high hemoglobin contents were present. The Y/(y + f) globin synthetic ratio was approximately 12% in the early cultures and 6% in the late cultures, indicating that the proportion of fetal hemoglobin synthesis decreases during erythroid cell maturation. These studies also reveal that the capacity for fetal hemoglobin production by peripheral blood BFU-E in vitro is not altered during pregnancy.The major hemoglobin in humans during intrauterine life is fetal hemoglobin, a2Y2. Adult hemoglobin, a232, is first detected at around the 10th week of gestation and accounts for approximately 10% of all hemoglobins present until about the 30th week of gestation, when increasing amounts of adult hemoglobin are produced (1). By the time the infant is 6 months old, most of the hemoglobin present is adult hemoglobin (2). The mechanisms for the switching of hemoglobins during fetal development are presently not clear (3). These orderly ontogenetic changes provide an excellent model for studying gene regulation and expression. In addition, elucidation of the mechanisms for hemoglobin switching can provide a potentially useful approach to the therapy of patients with genetic disorders involving the j globin chain.Immature erythroid stem cells, burst-forming units that respond to erythropoietin (BFU-E), are present in adult human peripheral blood and can proliferate and differentiate into large colonies of erythroblasts in vitro (4, 5). These erythroblasts, derived from normal adult individuals, synthesize a substantial amount of fetal hemoglobin (6-8). Because HbF is increased in maternal peripheral blood during pregnancy (9-11), the present investigation was undertaken to determine if peripheral blood BFU-E in pregnant women have an increased capacity for HbF production in culture and to study the pattern of HbF synthesis during erythroid cell maturation in vitro. Evidence is presented that the capacity for HbF production by peripheral blood BFU-E in vitro is not altered during pregnancy. These studies also reveal that the proportion of HbF synthesis decreases during erythroid cell maturation. A preliminary report of these studies has been published elsewhere (12). METHODSSubjects. Forty-four pregnant and postpartum (3-7 months) women were studied. All women were healthy and had no known diseases or complications. Appropriate consent was obtained. [50][51][52][53][54][55][56][57][58][59][60] Ci/mmol; 1 Ci = 3.7 X 1010 becquerels), obtained from New England Nuclear, was added to each plasma clot on either day 6 or day 7, and either day 11 or day 12 of culture. Twenty-four hours later, 10 plasma clots thus labeled were pooled and washed twice with phosphate-buffered saline. Three milligrams o...

A rapid spectrophotometric assay capable of detecting the hemoglobin content of 1000 mature erythrocytes has been utilized to quantitate the total hemoglobin synthesized by the progeny of circulating human erythroid progenitors in both the plasma clot and methylcellulose culture systems. The pronounced variation in the effect of different erythropoietin preparations on the hemoglobin content of cultured human peripheral blood bursts, previously described in a subjective manner, has been objectively quantitated. Further experiments demonstrated that both lymphocyte conditioned media and dexamethasone substantially increased the total hemoglobin synthesized by the progeny of cultured erythroid progenitors. The elevated amount of hemoglobin present in erythroid cultures containing either lymphocyte conditioned media and/or dexamethasone was due to both increased colony numbers and colony size. Assay of the total hemoglobin content per erythroid culture is an accurate, sensitive, measure of erythropoiesis in vitro and should be a valuable adjunct to the enumeration of BFU-E-derived erythroid colonies.

Introduction Cognitive load refers to the amount of working memory that is being used in a task, like memorizing the anatomical landmarks on distinct boney specimens. Critically, cognitive load may be compromised when the load imposed by the environment and the content to be learned together exceeds a student’s capacity. Previous research shows that stereoscopic materials delivered in virtual reality (VR) can be more mentally taxing compared to desktop (i.e., two dimensional) delivery but may be similar to that encountered in real life. There is no data on the cognitive load of autostereoscopic displays. Given the increased reliance upon digital media for teaching in learning in anatomy classrooms, it is prudent to better understand the cognitive load imposed on learners across a variety of modalities employed. Methods Cognitive load will be compared across three different learning modalities: immersive virtual reality (VR, displayed on the Oculus Quest 2TM), autostereoscopic (displayed on the AlioscopyTM screen), and an identical printed, physical model. During a four‐minute learning phase, undergraduate students, with no prior formal anatomy education, will learn 10 anatomical landmarks on a displayed bony model (calcaneus, zygomatic bone, or hemipelvis) in each of the three modalities. A Stroop test will be administered as a secondary task throughout the learning phase to evaluate cognitive load. Stroop test reaction time, and accuracy of the participants' responses to the Stroop test will be recorded. After the learning phase, an untimed, recognition‐based test will be administered wherein participants will be asked to recall the ten landmarks learned with the aid of a 3D‐printed bone identical to the one used in the learning phase. Performance will be evaluated based on landmarks correctly identified and the results will be correlated with cognitive load measured in each learning modality. Results We hypothesize that the cognitive load will be highest for VR when compared to the cognitive load on the AlioscopyTM and physical model modalities which would manifest as lower reaction times and/or accuracy on the Stroop test. Further, we hypothesize that cognitive load will inversely correlate with the recognition test performance. Conclusion The results of this study will allow educators and students to make informed decisions when deciding which learning modalities should be used for anatomy education or any other education that requires nominative learning on complex objects. Understanding which modalities minimize cognitive load and improve learning will help improve outcomes and allow for more efficient anatomical education.

Introduction Traditional anatomy learning relies on models and cadaveric specimens that are time and resource intensive to produce, which compromises their accessibility. To mitigate this, the use of three‐dimensional visualization technology (3DVT) to learn anatomy has substantially increased. Still, learning in an immersive virtual reality (VR) environment may pose new challenges, including increased self‐reported levels of cognitive load and cybersickness likely due to its immersive nature that isolates the learner from their surroundings. Autostereoscopy is a novel and potential solution, as it provides a headset‐free stereoscopic view of a three‐dimensional (3D) model. There is, however, a paucity of information about the use and educational efficacy of autostereoscopic 3DVT. The purpose of this study is to examine the strengths and limitations of implementing a non‐immersive autostereoscopic (AlioscopyTM) screen for learning anatomy. Methods A large‐scale study on the efficacy of VR, autostereoscopy, and 3D printed physical models for learning anatomy is currently underway. We suspect that cognitive load and cybersickness may compete with learning capacity. Based on the literature, we hypothesize the AlioscopyTM screen to represent a sort of middle‐of‐the‐road option, with moderate cognitive load and cybersickness levels (VR>AlioscopyTM>physical), that supports large‐group learning (as opposed to single‐user immersive VR) yet retains the accessibility associated with digital assets (as compared to physical specimens). As such, it is prudent to consider the feasibility of implementing an AlioscopyTM screen for anatomical teaching and summarize the strengths and limitations of the technology. Results According to the company’s website, 3D images on the 42” AlioscopyTM display we are using can be viewed from 2.5m to 9.0m away, with optimal results at 4.0m, by a theoretical maximum of “20 to 50 people spread over an area of 90°”. We suspect a practical limit of 14 people per display (2 people for each of the 7 viewing zones) and a comfortable limit of 7 (1 per zone). This allows viewers to comfortably situate themselves in a “sweet spot” where each of their eyes receives a clear, distinct image, which is required for the stereoscopic effect. The stereo‐3D effect is prominent, with objects allowed to both protrude from and recess into the display considerably. Display content was created using a plugin (provided by AlioscopyTM) for the videogame engine Unity, allowing existing Unity content to function on the modality easily. Conclusion The AlioscopyTMscreen represents a novel approach to promoting material accessibility and viewing 3D stereoscopic images in a group setting. The nature of this set up may both decrease the inherent issues most immersive 3DVT impose and offer an opportunity for collaborative learning not available with the use of single‐user headsets.

Introduction: E3 (ubiquitin) ligases play a major role in the ubiquitin-proteasome system (UPS), responsible for the ubiquitination and degradation of various proteins. The UPS has many roles, including regulation of the cell cycle. To mediate these functions, there are many different types of E3s, each with different substrates. A major E3 system involved in oncogenesis is the Mdm2/MdmX system, which acts as a heterodimer to degrade the tumour suppressor, p53, responsible for inducing cell cycle arrest and/or apoptosis in cancer cells, as needed. Upon overexpression/hyperactivation through mutation, the Mdm2/MdmX system can promote carcinogenesis through increasing degradation of p53, preventing necessary cell cycle arrest/apoptosis in cancer cells. Methods: A literature review was conducted to synthesize and analyze research on Mdm2/MdmX E3 overexpression/ hyperactivation, and the treatment options available for cancers in which overexpression/hyperactivation plays a role. Results: There are many types of mutations that may be present in cancer cells, however mutations leading to the inactivation of p53 are some of the most common. Inactivation of p53 can be achieved by direct gene mutation, or overexpression/hyperactivation of Mdm2/Mdmx. Current drugs target the expression of MdmX/Mdm2 or their binding interactions with p53. Inhibition of these interactions triggers apoptosis in cancer cells due to increased p53 activity. Therapies that have been developed to target the Mdm2/MdmX system include small molecule inhibitors such as Nutlins and MI compounds, as well as peptide drugs. Discussion: Although direct mutations of p53 are commonly found in cancer, mutated p53 is not a viable drug target, so instead many treatment options specifically target a dysregulated Mdm2/MdmX system. Future studies should investigate novel drug targets, minimization of side effects, and treatment in the presence of mutations to other DNA repair systems. Conclusion: This literature review aids in establishing an interdisciplinary perspective on the types of oncogenic mutations in the Mdm2/MdmX pathway, combining biochemical and mechanistic research with clinical applications and pharmacology, as well as identifying future drug targets involved in this system.