Lesbian, gay, bisexual, and transgender (LGBT) individuals experience health and health care disparities and have specific health care needs. Medical education organizations have called for ...LGBT-sensitive training, but how and to what extent schools educate students to deliver comprehensive LGBT patient care is unknown.
To characterize LGBT-related medical curricula and associated curricular development practices and to determine deans' assessments of their institutions' LGBT-related curricular content.
Deans of medical education (or equivalent) at 176 allopathic or osteopathic medical schools in Canada and the United States were surveyed to complete a 13-question, Web-based questionnaire between May 2009 and March 2010.
Reported hours of LGBT-related curricular content.
Of 176 schools, 150 (85.2%) responded, and 132 (75.0%) fully completed the questionnaire. The median reported time dedicated to teaching LGBT-related content in the entire curriculum was 5 hours (interquartile range IQR, 3-8 hours). Of the 132 respondents, 9 (6.8%; 95% CI, 2.5%-11.1%) reported 0 hours taught during preclinical years and 44 (33.3%; 95% CI, 25.3%-41.4%) reported 0 hours during clinical years. Median US allopathic clinical hours were significantly different from US osteopathic clinical hours (2 hours IQR, 0-4 hours vs 0 hours IQR, 0-2 hours; P = .008). Although 128 of the schools (97.0%; 95% CI, 94.0%-99.9%) taught students to ask patients if they "have sex with men, women, or both" when obtaining a sexual history, the reported teaching frequency of 16 LGBT-specific topic areas in the required curriculum was lower: at least 8 topics at 83 schools (62.9%; 95% CI, 54.6%-71.1%) and all topics at 11 schools (8.3%; 95% CI, 3.6%-13.0%). The institutions' LGBT content was rated as "fair" at 58 schools (43.9%; 95% CI, 35.5%-52.4%). Suggested successful strategies to increase content included curricular material focusing on LGBT-related health and health disparities at 77 schools (58.3%, 95% CI, 49.9%-66.7%) and faculty willing and able to teach LGBT-related curricular content at 67 schools (50.8%, 95% CI, 42.2%-59.3%).
The median reported time dedicated to LGBT-related topics in 2009-2010 was small across US and Canadian medical schools, but the quantity, content covered, and perceived quality of instruction varied substantially.
Ollier disease (OD) and Maffucci Syndrome (MS) are rare disorders characterized by multiple enchondromas, commonly causing bone deformities, limb length discrepancies, and pathological fractures. MS ...is distinguished from OD by the development of vascular anomalies. Both disorders are cancer predisposition syndromes with malignancies developing in ~50% of the individuals with OD or MS. Somatic gain-of-function variants in IDH1 and IDH2 have been described in the enchondromas, vascular anomalies and chondrosarcomas of approximately 80% of the individuals with OD and MS. To date, however, no investigation of germline causative variants for these diseases has been comprehensively performed. To search for germline causative variants, we performed whole exome sequencing or whole genome sequencing of blood or saliva DNA in 94 unrelated probands (68 trios). We found that 7 had rare germline missense variants in HIF1A, 6 had rare germline missense variants in VHL, and 3 had IDH1 variants including 2 with mosaic IDH1-p.Arg132His variant. A burden analysis using 94 probands assigned as cases and 2,054 unrelated individuals presenting no OD- or MS-related features as controls, found that variants in HIF1A, VHL, and IDH1 were all significantly enriched in cases compared to controls. To further investigate the role of HIF-1 pathway in the pathogenesis of OD and MS, we performed RNA sequencing of fibroblasts from 4 probands with OD or MS at normoxia and at hypoxia. When cultured in hypoxic conditions, both proband and control cells showed altered expression of a subset of HIF-1 regulated genes. However, the set of differentially expressed genes in proband fibroblasts included a significantly reduced number of HIF-1 regulated genes compared to controls. Our findings suggest that germline or early post-zygotic variants identified in HIF1A, VHL, and IDH1 in probands with OD and MS underlie the development of the phenotypic abnormalities in a subset of individuals with OD and MS, but extensive functional studies are needed to further confirm it.
The ontogeny of human haematopoietic stem cells (HSCs) is poorly defined owing to the inability to identify HSCs as they emerge and mature at different haematopoietic sites
. Here we created a ...single-cell transcriptome map of human haematopoietic tissues from the first trimester to birth and found that the HSC signature RUNX1
HOXA9
MLLT3
MECOM
HLF
SPINK2
distinguishes HSCs from progenitors throughout gestation. In addition to the aorta-gonad-mesonephros region, nascent HSCs populated the placenta and yolk sac before colonizing the liver at 6 weeks. A comparison of HSCs at different maturation stages revealed the establishment of HSC transcription factor machinery after the emergence of HSCs, whereas their surface phenotype evolved throughout development. The HSC transition to the liver marked a molecular shift evidenced by suppression of surface antigens reflecting nascent HSC identity, and acquisition of the HSC maturity markers CD133 (encoded by PROM1) and HLA-DR. HSC origin was tracked to ALDH1A1
KCNK17
haemogenic endothelial cells, which arose from an IL33
ALDH1A1
arterial endothelial subset termed pre-haemogenic endothelial cells. Using spatial transcriptomics and immunofluorescence, we visualized this process in ventrally located intra-aortic haematopoietic clusters. The in vivo map of human HSC ontogeny validated the generation of aorta-gonad-mesonephros-like definitive haematopoietic stem and progenitor cells from human pluripotent stem cells, and serves as a guide to improve their maturation to functional HSCs.
Prostate cancer is the most common cancer affecting men often resulting in aggressive tumors with poor prognosis. Even with new treatment strategies, drug resistance often occurs in advanced prostate ...cancers. The use of lysosomotropic agents offers a new treatment possibility since they disrupt lysosomal membranes and can trigger a series of events leading to cell death. In addition, combining lysosomotropic agents with targeted inhibitors can induce increased cell death in different cancer types, but prostate cancer cells have not been investigated.
We treated prostate cancer cells with lysosomotropic agents and determine their cytotoxicity, lysosome membrane permeabilization (LMP), reactive oxygen species (ROS) levels, and mitochondrial dysfunction. In addition, we treated cells with lysosomotropic agent in combination with tyrosine kinase inhibitor, lapatinib, and determined cell death, and the role of ROS in this cell death.
Herein, we found that siramesine was the most effective lysosomotropic agent at inducing LMP, increasing ROS, and inducing cell death in three different prostate cancer cell lines. Siramesine was also effective at increasing cell death in combination with the tyrosine kinase inhibitor, lapatinib. This increase in cell death was mediated by lysosome membrane permeabilization, an increased in ROS levels, loss of mitochondrial membrane potential and increase in mitochondrial ROS levels. The combination of siramesine and lapatinib induced apoptosis, cleavage of PARP and decreased expression of Bcl-2 family member Mcl-1. Furthermore, lipid peroxidation occurred with siramesine treatment alone or in combination with lapatinib. Treating cells with the lipid peroxidation inhibitor alpha-tocopherol resulted in reduced siramesine induced cell death alone or in combination with lapatinib. The combination of siramesine and lapatinib failed to increase cell death responses in normal prostate epithelial cells.
This suggests that lysomotropic agents such as siramesine in combination with tyrosine kinase inhibitors induces cell death mediated by ROS and could be an effective treatment strategy in advanced prostate cancer.
Arabidopsis seed size is regulated by the IKU pathway that includes IKU2 (a leucine-rich repeat kinase) and MINI3 (a WRKY transcription factor). We report the cloning of the IKU1 (At2g35230) gene. ...iku1 mutants cause reduced endosperm growth and the production of small seeds. IKU1 encodes a protein containing a VQ motif, which is a motif specific to plants. IKU1 is expressed in the early endosperm and its progenitor, the central cell. Restoration of IKU1 function in the endosperm is sufficient to rescue seed size. A genomic construct carrying mutations in the VQ motif failed to complement the iku1 mutation, suggesting an essential role for the VQ motif. IKU1 interacts with MINI3 in the yeast two-hybrid system, consistent with an IKU1 function in the IKU-MINI pathway. Our data support the proposition that endosperm development is an important determinant of seed size.
Phenomenon: Lesbian, gay, bisexual, and transgender (LGBT) individuals face significant barriers in accessing appropriate and comprehensive medical care. Medical students' level of preparedness and ...comfort caring for LGBT patients is unknown. Approach: An online questionnaire (2009-2010) was distributed to students (n = 9,522) at 176 allopathic and osteopathic medical schools in Canada and the United States, followed by focus groups (2010) with students (n = 35) at five medical schools. The objective of this study was to characterize LGBT-related medical curricula, to determine medical students' assessments of their institutions' LGBT-related curricular content, and to evaluate their comfort and preparedness in caring for LGBT patients. Findings: Of 9,522 survey respondents, 4,262 from 170 schools were included in the final analysis. Most medical students (2,866/4,262; 67.3%) evaluated their LGBT-related curriculum as "fair" or worse. Students most often felt prepared addressing human immunodeficiency virus (HIV; 3,254/4,147; 78.5%) and non-HIV sexually transmitted infections (2,851/4,136; 68.9%). They felt least prepared discussing sex reassignment surgery (1,061/4,070; 26.1%) and gender transitioning (1,141/4,068; 28.0%). Medical education helped 62.6% (2,669/4,262) of students feel "more prepared" and 46.3% (1,972/4,262) of students feel "more comfortable" to care for LGBT patients. Four focus group sessions with 29 students were transcribed and analyzed. Qualitative analysis suggested students have significant concerns in addressing certain aspects of LGBT health, specifically with transgender patients. Insights: Medical students thought LGBT-specific curricula could be improved, consistent with the findings from a survey of deans of medical education. They felt comfortable, but not fully prepared, to care for LGBT patients. Increasing curricular coverage of LGBT-related topics is indicated with emphasis on exposing students to LGBT patients in clinical settings.
Forest loss in hotspots around the world impacts not only local climate where loss occurs, but also influences climate and vegetation in remote parts of the globe through ecoclimate teleconnections. ...The magnitude and mechanism of remote impacts likely depends on the location and distribution of forest loss hotspots, but the nature of these dependencies has not been investigated. We use global climate model simulations to estimate the distribution of ecologically-relevant climate changes resulting from forest loss in two hotspot regions: western North America (wNA), which is experiencing accelerated dieoff, and the Amazon basin, which is subject to high rates of deforestation. The remote climatic and ecological net effects of simultaneous forest loss in both regions differed from the combined effects of loss from the two regions simulated separately, as evident in three impacted areas. Eastern South American Gross Primary Productivity (GPP) increased due to changes in seasonal rainfall associated with Amazon forest loss and changes in temperature related to wNA forest loss. Eurasia's GPP declined with wNA forest loss due to cooling temperatures increasing soil ice volume. Southeastern North American productivity increased with simultaneous forest loss, but declined with only wNA forest loss due to changes in VPD. Our results illustrate the need for a new generation of local-to-global scale analyses to identify potential ecoclimate teleconnections, their underlying mechanisms, and most importantly, their synergistic interactions, to predict the responses to increasing forest loss under future land use change and climate change.
Competitive and cooperative interactions between organisms, including bacteria, can significantly impact the composition of a community and the fitness of its members, as well as the fitness of their ...hosts when communities are living on or within other organisms. Understanding the underlying mechanisms is critical to the development of strategies to control microbiological communities that impact animal and plant health and also for understanding the evolution of social behaviors, which has been challenging for evolutionary biologists. Contact-dependent growth inhibition (CDI) is a phenomenon defined by the delivery of a protein toxin to the cytoplasm of neighboring bacteria upon cell–cell contact, resulting in growth inhibition or death unless a specific immunity protein is present. CDI was first described based on observations of interbacterial killing and has been assumed to function primarily as a means of eliminating competitor cells. However, recent molecular evidence indicates that multiple levels of specificity restrict CDI toxin delivery and activity to the same bacterial strain, and that CDI system proteins can mediate cooperative behaviors among ‘self’ cells, a phenomenon called contact-dependent signaling (CDS). Here we review these recent findings and discuss potential biological and evolutionary implications of CDI system-mediated interbacterial competition and cooperation.
•Streamflow and carbon (C) estimates compared across plant parameterization schemes.•Comparisons conducted at a relatively wet and dry (two) western U.S. forested site.•The wet site had a three-fold ...difference in potential sequestered C across parameters.•The dry site’s streamflow estimates were sensitive to plant parameter schemes.•We cannot invalidate C allocation strategies using site/species-specific field data.
Increasingly sophisticated process-based ecosystem models account for the ability of plants to vary the proportion of net photosynthate that is allocated to individual organs – such as leaves, stems and roots. Because the governing mechanisms are still not well understood, models differ in the strategies used to represent carbon allocation processes. Allocation schemes may have important implications for ecosystem structure and biogeochemical cycling, thus there is a need to better understand how different carbon allocation strategies influence estimates of variables that are of interest to model users. At the same time, uncertainty in other ecophysiological parameters that are commonly used in carbon cycling models may influence these estimates and interact with different carbon allocation strategies. We use a coupled ecohydrologic model to understand how uncertainty in three relatively simple allocation strategies affects carbon (C) and streamflow estimates in two case study forested mountain watersheds in the western United States: a relatively wet site located in the western Oregon Cascades, and a drier site in California’s Sierra Nevada. Ecophysiological parameters controlling productivity rates, morphology, and nutrient requirements for growth are varied as well. The influence of specific ecophysiological parameters and allocation strategies on C sequestration and streamflow estimates differed between sites. At the wetter site, uncertainty in C cycling processes resulted in a three-fold difference in potential sequestered carbon, but had a negligible effect on annual and low monthly streamflow estimates. Conversely, at the drier site, C pool estimates showed limited sensitivity to ecophysiological parameter uncertainty, but considerable difference in annual and low monthly streamflow estimates across ecophysiological assumptions. At both sites, stemwood C pool estimates exceeded literature-derived field values when branch mortality—a surrogate for density thinning—was not included in addition to background mortality. Despite using site- and species-specific information, we are unable to invalidate any of the allocation strategies considered. Our results suggest that uncertainty in parameterization of ecophysiological parameters and assumptions about carbon allocation can strongly influence model estimates of both streamflow and forest carbon sequestration potential, but that influence is likely to vary with site bioclimatic characteristics.
Studies have demonstrated students' resistance to active learning, despite evidence illustrating that their learning is improved relative to students in lectures. Specifically, while active learning ...and group work are effective at engaging students in their learning process, studies report that students' perceptions of active learning approaches are not always positive. What remains underexplored is whether students' perceptions of active learning improve with effective instructor facilitation and whether there exists differential perceptions between racially minoritized students and represented students. Here, we estimate students' perceptions of effective instructor facilitation as the mediator in the relationship between active learning and perceptions of learning and perceived utility for class activities (task value). Then, we examine differences by racial identification. We collected classroom observation data to empirically categorize courses as active learning or lecture-based and surveyed 4,257 college students across 25 STEM classrooms at a research-intensive university. We first examined the relationship between active learning on student perceptions and found a negative relationship between active learning and perceptions of learning and task value for both racially minoritized students and represented students. Next, we assessed whether students' perceptions of instructor effectiveness in facilitating group activities mediate these negative relationships. We found that, on average, students of all races were more likely to positively perceive instructor facilitation in active learning classes relative to lectures. In turn, the positive perceptions of instructor facilitation partially suppressed the negative relationship between active learning and perceptions of learning and task value. These results demonstrate that effective instructor facilitation can influence both students' self-assessment of learning and perceived utility of the learning activities, and underscores the importance of developing pedagogical competence among college instructors.
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