Deregulated JAK/STAT signalling in lymphomagenesis, and its implications for the development of new targeted therapies

Gene expression profiling has implicated several intracellular signalling cascades, including the JAK/STAT pathway, in the pathogenesis of particular subtypes of lymphoma. In marked contrast to the situation in patients with either acute lymphoblastic leukaemia or a myeloproliferative neoplasm, JAK2 coding sequence mutations are rare in lymphoma patients with an activated JAK/STAT “signature”. This is instead the consequence of mutational events that result in the increased expression of non-mutated JAK2; positively or negatively affect the activity of other components of the JAK/STAT pathway; or establish an autocrine signalling loop that drives JAK-mediated cytokine-independent proliferation. Here, we detail these genetic lesions, their functional consequences, and impact on patient outcome. In light of the approval of a JAK1/JAK2 inhibitor for the treatment of myelofibrosis, and preliminary studies evaluating the efficacy of other JAK inhibitors, the therapeutic potential of compounds that target JAK/STAT signalling in the treatment of patients with lymphoma is also discussed

Focusing on optic tectum circuitry through the lens of genetics

The visual pathway is tasked with processing incoming signals from the retina and converting this information into adaptive behavior. Recent studies of the larval zebrafish tectum have begun to clarify how the 'micro-circuitry' of this highly organized midbrain structure filters visual input, which arrives in the superficial layers and directs motor output through efferent projections from its deep layers. The new emphasis has been on the specific function of neuronal cell types, which can now be reproducibly labeled, imaged and manipulated using genetic and optical techniques. Here, we discuss recent advances and emerging experimental approaches for studying tectal circuits as models for visual processing and sensorimotor transformation by the vertebrate brain

Reengineering Introductory Psychology for the Virtual Classroom: Qualitative Report on Initial Course Design and Preliminary Student Feedback

For students of any academic background or vocational preference, introductory psychology is also one of the most popular social science courses. For many students in the community college setting, the introductory psychology course may be the only formal exposure to non- pseudoscience theory a student will receive. The Virginia Community College System (VCCS) has transfer agreements with many of the four-year institutions in Virginia, and there is a reengineering effort underway that, among many other things, will help ensure consistency with regards to students’ exposure to essential course and learning objectives. One component of reengineering is to create default template-style course shells for high enrollment/high non- productive grade courses including Principles of Psychology, and this paper reports on the background, design, and initial delivery of the Online version of PSY200

Dietary Acid Load and Bone Turnover During Long-Duration Spaceflight and Bed Rest

Background Bed rest studies document that a lower dietary acid load is associated with lower bone resorption. Objective We tested the effect of dietary acid load on bone metabolism during spaceflight. Design Controlled 4-d diets with a high or low animal proteinto-potassium (APro:K) ratio (High and Low diets, respectively) were given to 17 astronauts before and during spaceflight. Each astronaut had 1 High and 1 Low diet session before flight and 2 High and 2 Low sessions during flight, in addition to a 4-d session around flight day 30 (FD30), when crew members were to consume their typical in-flight intake. At the end of each session, blood and urine samples were collected. Calcium, total protein, energy, and sodium were maintained in each crew member's preflight and in-flight controlled diets. Results Relative to preflight values, N-telopeptide (NTX) and urinary calcium were higher during flight, and bone-specific alkaline phosphatase (BSAP) was higher toward the end of flight. The High and Low diets did not affect NTX, BSAP, or urinary calcium. Dietary sulfur and age were significantly associated with changes in NTX. Dietary sodium and flight day were significantly associated with urinary calcium during flight. The net endogenous acid production (NEAP) estimated from the typical dietary intake at FD30 was associated with loss of bone mineral content in the lumbar spine after the mission. The results were compared with data from a 70-d bed rest study, in which control (but not exercising) subjects APro:K was associated with higher NTX during bed rest. Conclusions Long-term lowering of NEAP by increasing vegetable and fruit intake may protect against changes in loss of bone mineral content during spaceflight when adequate calcium is consumed, particularly if resistive exercise is not being performed. This trial was registered at clinicaltrials.gov as NCT01713634

Dr. Mary Edwards Walker: years ahead of her time.

Women phsycians in the United States were virtually nonexistent in the early to mid-1800s. Traditional medical schools still did not accept women, and few secretarian or eclectic medical schools were beginning to open their doors to female students. In 1849 at Geneva College, Elizabeth Blackwell became the first woman to achieve a medical degree in the United States.1 At the time of the Civil War, the few women who had managed to obtain medical degrees mainly served as nurses in the war, because society was not yet ready to accept the female physician.2 Dr. Mary Edwards Walker would help change the role of women physicians, becoming not only a valuable surgeon for the Union Army, but also a catalyst for the introduction and advancement of women in medicine

Dietary and Urinary Sulfur can Predict Changes in Bone Metabolism During Space Flight

Mitigating space flight-induced bone loss is critical for space exploration, and diet can play a major role in this effort. Previous ground-based studies provide evidence that dietary composition can influence bone resorption during bed rest. In this study we examined the role of dietary intake patterns as one factor that can influence bone mineral loss in astronauts during space flight. Crew members were asked to consume, for 4 days at a time, prescribed menus with either a low (0.3-0.6 g/mEq) or high (1.0-1.3 g/mEq) ratio of animal protein to potassium (APro:K). Menus were developed for each crewmember, and were designed to meet both crew preferences and study constraints. Intakes of energy, total protein, calcium, and sodium were held relatively constant between the two diets. The order of the menus was randomized, and crews completed each set (low and high) once before and twice during space flight, for a total of 6 controlled diet sessions. One inflight session and three postflight sessions (R+30, R+180, R+365) monitored typical dietary intake. As of this writing, data are available from 14 crew members. The final three subjects' inflight samples are awaiting return from the International Space Station via Space-X. On the last day of each of the 4-d controlled diet sessions, 24-h urine samples were collected, along with a fasting blood sample on the morning of the 5th day. Preliminary analyses show that urinary excretion of sulfate (normalized to lean body mass) is a significant predictor of urinary n-telopeptide (NTX). Dietary sulfate (normalized to lean body mass) is also a significant predictor of urinary NTX. The results from this study, will be important to better understand diet and bone interrelationships during space flight as well as on Earth. This study was funded by the Human Health Countermeasures Element of the NASA Human Research Program

Positron emission tomography in detection of metastatic leiomyosarcoma in a postoperative patient: a case report

In leiomyosarcoma (LMS) abnormal vaginal bleeding is the most common reported symptom in patients (56%), followed by pelvic mass (54%), and pain (22%). LMS is often hard to diagnosis on a uterine biopsy because it does not originate in the endometrium and may not invade into the cavity. Non-specific symptoms as well as difficulty in diagnosis being made by biopsy, means that many LMS tumors are often mistaken for fibroids preoperatively. To our knowledge this is the only reported case of FDG-PET being used in the postoperative evaluation of a patient with LMS and a suspicious lung mass. Our case shows there may be a place for PET scans in the post-op surveillance of LMS. This method would be ideally suited, considering the metastatic spread pattern of LMS

Revealing Gender Bias: An Experiential Exercise

Stereotyping and biases continue to be a problem in many facets of society. Understanding how biases may affect recruitment and retention of employees has become a priority issue for companies, not only from an image perspective but also from a firm performance perspective, since both research and industry experience have shown that diverse teams generate better results. The need to address these issues, particularly with students who will become leaders in organizations, remains a priority in business education. In this article, we present an experiential activity that management instructors can use to help students understand and appreciate the reality and power of unconscious bias. The focus of this activity is on uncovering gender bias, yet the basic framework of the activity can easily be adapted to focus on other types of unconscious bias and stereotyping