Search

Metabolites, lipids, and other small molecules are key constituents of tissues supporting cellular programs in health and disease. Here, we present METASPACE, a community-populated knowledge base of spatial metabolomes from imaging mass spectrometry data. METASPACE is enabled by a high-performance engine for metabolite annotation in a confidence-controlled way that makes results comparable between experiments and laboratories. By sharing their results publicly, engine users continuously populate a knowledge base of annotated spatial metabolomes in tissues currently including over 3000 datasets from human cancer cohorts, whole-body sections of animal models, and various organs. The spatial metabolomes can be visualized, explored and shared using a web app as well as accessed programmatically for large-scale analysis. By using novel computational methods inspired by natural language processing, we illustrate that METASPACE provides molecular coverage beyond the capacity of any individual laboratory and opens avenues towards comprehensive metabolite atlases on the levels of tissues and organs.

Many pre-health students pursue extracurricular shadowing opportunities to gain clinical experience. The Virginia Tech School of Neuroscience introduced a formal course that provides a clinical experience superior to that received by many medical students. This course is composed of weekly 75-minute seminars that cover diseases affecting the nervous system, their diagnosis and treatment, complemented by weekly half-day intensive clinical experiences with unprecedented access to a team of neurosurgeons (in hospital operating rooms, Intensive Care Units, emergency room, angiographic suites, and wards). In the operating rooms, students routinely "scrub-in" for complex surgeries. On hospital rounds, students experience direct patient care and receive in-depth exposure to modern nervous system imaging. Students participate in two 24-hour "on-call" experiences with team providers. After call, students participate in cognitive and psychological studies to assess physiological and psychological effects of call-related sleep deprivation. Students prepare weekly essays on challenging socioeconomic and ethical questions, exploring subjects such as the cost of medicine and inequalities in access to health care. Towards the end of the course, students meet with the admission dean of the Virginia Tech Carilion medical school; they prepare a personal statement for medical school/graduate school applications, and attend a half-day block of mock medical school/graduate school interviews delivered by experienced clinicians. In lieu of a final exam, each student presents to the entire neurosurgery department, an in-depth clinical analysis of a case in which they participated. We provide details on implementation, challenges and outcomes based on experiences from three semesters with a total enrollment of approximately 60 students.

© 2018 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists Minimally invasive approaches to hysterectomy have been shown to be safe, effective and have recovery advantages over open hysterectomy, yet in Australia 36% of hysterectomies are still conducted by open surgery. In 2006, a survey of Australian gynaecological specialists found the main impediment to increasing laparoscopic hysterectomy to be a lack of surgical skills training opportunities. We resurveyed specialists to explore contemporary factors influencing surgeons’ approaches to hysterectomy; 258 (estimated ~19%) provided analysable responses. Despite >50% of surveyed specialists wishing to practise laparoscopic hysterectomy in the future, lack of surgical skills, arising from the lack of training opportunities, remains the main impediment.

© 2017 Objective: To explore factors influencing how well-informed women felt about hysterectomy, influences on their decision making, and on them receiving a less-invasive alternative to open surgery. Methods: Online questionnaire, conducted in 2015–2016, of women who had received a hysterectomy in Australia, in the preceding two years. Results: Questionnaires were completed by 2319/6000 women (39% response). Most women (n = 2225; 96%) felt well-informed about hysterectomy. Women were more aware of the open abdominal approach (n = 1798; 77%), than of less-invasive vaginal (n = 1552; 67%), laparoscopic (n = 1540; 66%), laparoscopic-assisted (n = 1303; 56%), and robotic approaches (n = 289; 12%). Most women (n = 1435; 62%) reported their gynaecologist was the most influential information source. Women who received information about hysterectomy from a GP (OR = 1.47; 95% CI 1.15-1.90), or from a gynaecologist (OR = 1.3; 95% CI 1.06-1.58), were more likely to feel better informed (p < 0.01). Conclusion: This study is important because it helps clinicians, researchers and health policy makers to understand why many women still receive an open abdominal approach despite many learned societies recommending to avoid it if possible. Practice implications: Additional information, or education about avoiding open abdominal approach where possible may lead to a greater number of women receiving less-invasive types of hysterectomy in the future.

© The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. 1,4-Dihydroxy-2-naphthoic acid (1,4-DHNA) is a bacterial-derivedmetabolite that binds the aryl hydrocarbon receptor (AhR) and exhibits anti-inflammatory activity in the gut. The structure-dependent AhR activity of hydroxyl/carboxy-substituted naphthoic acids (NAs)was determined in young adultmouse colonic (YAMC) cells and human Caco2 colon cancer cells using CYP1A1/CYP1B1mRNAs asAh-responsive genes. Compounds used in this study include 1,4-, 3,5-, and 3,7-DHNA, 1,4- dimethoxy-2-naphthoic acid (1,4-DMNA), 1- and 4-hydroxy-2-naphthoic acid (1-HNA, 4-HNA), 1- and 2-naphthoic acid (1-NA, 2- NA), and 1- and 2-naphthol (1-NOH, 2-NOH). 1,4-DHNAwas themost potent compoundamong hydroxyl/carboxy naphthalene derivatives, and the fold induction response for CYP1A1 and CYP1B1was similar to that observed for 2,3,7,8-tetrachlorodibenzop- dioxin (TCDD) in YAMC and Caco2 cells. 1- and 4-HNAwere less potent than 1,4-DHNA but inducedmaximal (TCDD-like) response for CYP1B1 (both cell lines) and CYP1A1 (Caco2 cells).With the exception of 1- and 2-NA, all compounds significantly induced Cyp1b1 inYAMCcells and these responseswere not observed in AhR-deficient YAMC cells generated using CRISPR/ Cas9 technology. In addition,we also observed that 1- and 2-NOH(and 1,4-DHNA)wereweakAhR agonists, and 1- and 2-NOH also exhibited partialAhR antagonist activity. Structure-activity relationship studies for CYP1A1 but not CYP1B1were similar in both cell lines, and CYP1A1 induction required one or both 1,4-dihydroxy substituents and activitywas significantly enhanced by the 2-carboxyl group.We also used computational analysis to showthat 1,4-DHNAand TCDDshare similar interactions within the AhR binding pocket and differ primarily due to the negatively charged group of 1,4-DHNA.