Increased Incidence of Colon Tumors in AOM-Treated Apc1638N/+ Mice Reveals Higher Frequency of Tumor Associated Neutrophils in Colon Than Small Intestine

Colorectal cancer (CRC) is one of the most common cancers and a major cause of mortality. Mice with truncating Apc germline mutations have been used as a standard model of CRC, but most of the Apc-mutated lines develop multiple tumors in the proximal small intestine and rarely in the colon precluding detailed analysis of colon tumor microenvironment. Our aim was to develop a model with higher resemblance to human CRC and to characterize tumor infiltrating immune cells in spontaneously developing colon tumors compared to small intestinal tumors. Therefore, the Apc1638N/+ line was treated repeatedly with azoxymethane (AOM) and 90% colon tumor incidence and 4 to 5 colon tumors per mouse were achieved. Of note, AOM treatment specifically increased the tumor burden in the colon, but not in the small intestine. Histological grading and WNT-signaling activity did not differ significantly between small intestinal and colon tumors with some lesions progressing to invasive adenocarcinoma in both locations. However, characterization of the intratumoral myeloid cell compartment revealed a massive infiltration of colon tumors with neutrophils − 6-fold higher than in small intestinal tumors. Moreover, CCL17-expressing macrophages and dendritic cells accumulated in the tumors indicating the establishment of a tumor-promoting immunosuppressive environment. Thus, Apc1638N/+ mice treated with AOM are a suitable and straightforward model to study the influence of immune cells and chemokines on colon carcinogenesis

Enteric Virome Sensing-Its Role in Intestinal Homeostasis and Immunity

Pattern recognition receptors (PRRs) sensing commensal microorganisms in the intestine induce tightly controlled tonic signaling in the intestinal mucosa, which is required to maintain intestinal barrier integrity and immune homeostasis. At the same time, PRR signaling pathways rapidly trigger the innate immune defense against invasive pathogens in the intestine. Intestinal epithelial cells and mononuclear phagocytes in the intestine and the gut-associated lymphoid tissues are critically involved in sensing components of the microbiome and regulating immune responses in the intestine to sustain immune tolerance against harmless antigens and to prevent inflammation. These processes have been mostly investigated in the context of the bacterial components of the microbiome so far. The impact of viruses residing in the intestine and the virus sensors, which are activated by these enteric viruses, on intestinal homeostasis and inflammation is just beginning to be unraveled. In this review, we will summarize recent findings indicating an important role of the enteric virome for intestinal homeostasis as well as pathology when the immune system fails to control the enteric virome. We will provide an overview of the virus sensors and signaling pathways, operative in the intestine and the mononuclear phagocyte subsets, which can sense viruses and shape the intestinal immune response. We will discuss how these might interact with resident enteric viruses directly or in context with the bacterial microbiome to affect intestinal homeostasis

Comparison of iron-reduced and iron-supplemented semisynthetic diets in T cell transfer colitis

Clinical observations in inflammatory bowel disease patients and experimental studies in rodents suggest that iron in the intestinal lumen derived from iron-rich food or oral iron supplementation could exacerbate inflammation and that iron depletion from the diet could be protective. To test the hypothesis that dietary iron reduction is protective against colitis development, the impact of iron reduction in the diet below 10 mg/kg on the course of CD4+ CD62L+ T cell transfer colitis was investigated in adult C57BL/6 mice. Weight loss as well as clinical and histological signs of inflammation were comparable between mice pretreated with semisynthetic diets with either < 10mg/kg iron content or supplemented with 180 mg/kg iron in the form of ferrous sulfate or hemin. Accumulation and activation of Ly6C(high) monocytes, changes in dendritic cell subset composition and induction of proinflammatory Th1/Th17 cells in the inflamed colon were not affected by the iron content of the diets. Thus, dietary iron reduction did not protect adult mice against severe intestinal inflammation in T cell transfer induced colitis

Percepções de enfermeiros acerca da população LGBT+ e os seus entrelaces com a Atenção Primária à Saúde

Objetivo: este estudo busca investigar as demandas de saúde da população Lésbica, Gay, Bissexual e Trans (LGBT+), a partir das percepções de enfermeiros atuantes na Atenção Primária em Saúde. Método: estudo qualitativo, de cunho descritivo, realizado por meio de entrevistas semiestruturadas com 31 enfermeiros atuantes na Atenção Primária à Saúde, de um município da região central do estado do Rio Grande do Sul, Brasil. Resultados: para os enfermeiros, os problemas de saúde mais enfrentados pelo público LGBT+ estaria vinculado à saúde mental, violência ou ainda, às Infecções Sexualmente Transmissíveis (IST). Foi possível ainda, destacar a perpetuação de discursos cis-heteronormativos e que fortalecem o estigma de anormalidade associado a este público, já que para alguns profissionais a procura pela APS ocorreria por questões pontuais, como por exemplo, realização de testes rápidos. Conclusão: os achados deste estudo reiteram a necessidade de discussões nos meios acadêmicos e nos serviços de saúde, a fim de efetuar mudanças que possam melhorar a qualidade de vida desta população

Epidemiology and predictors of spinal injury in adult major trauma patients: European cohort study

This is a European cohort study on predictors of spinal injury in adult (≥16 years) major trauma patients, using prospectively collected data of the Trauma Audit and Research Network from 1988 to 2009. Predictors for spinal fractures/dislocations or spinal cord injury were determined using univariate and multivariate logistic regression analysis. 250,584 patients were analysed. 24,000 patients (9.6%) sustained spinal fractures/dislocations alone and 4,489 (1.8%) sustained spinal cord injury with or without fractures/dislocations. Spinal injury patients had a median age of 44.5 years (IQR = 28.8–64.0) and Injury Severity Score of 9 (IQR = 4–17). 64.9% were male. 45% of patients suffered associated injuries to other body regions. Age <45 years (≥45 years OR 0.83–0.94), Glasgow Coma Score (GCS) 3–8 (OR 1.10, 95% CI 1.02–1.19), falls >2 m (OR 4.17, 95% CI 3.98–4.37), sports injuries (OR 2.79, 95% CI 2.41–3.23) and road traffic collisions (RTCs) (OR 1.91, 95% CI 1.83–2.00) were predictors for spinal fractures/dislocations. Age <45 years (≥45 years OR 0.78–0.90), male gender (female OR 0.78, 95% CI 0.72–0.85), GCS <15 (OR 1.36–1.93), associated chest injury (OR 1.10, 95% CI 1.01–1.20), sports injuries (OR 3.98, 95% CI 3.04–5.21), falls >2 m (OR 3.60, 95% CI 3.21–4.04), RTCs (OR 2.20, 95% CI 1.96–2.46) and shooting (OR 1.91, 95% CI 1.21–3.00) were predictors for spinal cord injury. Multilevel injury was found in 10.4% of fractures/dislocations and in 1.3% of cord injury patients. As spinal trauma occurred in >10% of major trauma patients, aggressive evaluation of the spine is warranted, especially, in males, patients <45 years, with a GCS <15, concomitant chest injury and/or dangerous injury mechanisms (falls >2 m, sports injuries, RTCs and shooting). Diagnostic imaging of the whole spine and a diligent search for associated injuries are substantial

Expression of the T Cell Receptor αβ on a CD123+ BDCA2+ HLA-DR+ Subpopulation in Head and Neck Squamous Cell Carcinoma

Human Plasmacytoid Dendritic Cells (PDCs) infiltrating solid tumor tissues and draining lymph nodes of Head and Neck Squamous Cell Carcinoma (HNSCC) show an impaired immune response. In addition to an attenuated secretion of IFN-α little is known about other HNSCC-induced functional alterations in PDCs. Particular objectives in this project were to gain new insights regarding tumor-induced phenotypical and functional alterations in the PDC population. We showed by FACS analysis and RT-PCR that HNSCC orchestrates an as yet unknown subpopulation exhibiting functional autonomy in-vitro and in-vivo besides bearing phenotypical resemblance to PDCs and T cells. A subset, positive for the PDC markers CD123, BDCA-2, HLA-DR and the T cell receptor αβ (TCR-αβ) was significantly induced subsequent to stimulation with HNSCC in-vitro (p = 0.009) and also present in metastatic lymph nodes in-vivo. This subgroup could be functionally distinguished due to an enhanced production of IL-2 (p = 0.02), IL-6 (p = 0.0007) and TGF-β (not significant). Furthermore, after exposure to HNSCC cells, mRNA levels revealed a D-J-beta rearrangement of the TCR-beta chain besides a strong enhancement of the CD3ε chain in the PDC population. Our data indicate an interface between the PDC and T cell lineage. These findings will improve our understanding of phenotypical and functional intricacies concerning the very heterogeneous PDC population in-vivo

Feminist Economics, Setting out the Parameters

___Introduction___ Feminist economics has developed its position over the past decade, towards a firmer embeddedness in economic science and a source of inspiration for activists, policy makers, and social science researchers in a wide variety of fields of research. This development has come about in a relatively short period of time, as is reflected, for example, in the follow-up book of the feminist economic primer Beyond Economic Man (Ferber/Nelson 1993), published ten years later: Feminist Economics Today (Ferber/Nelson, 2003) The strengthened position of feminist economics also shows in the 10-year anniversary of the prize-winning journal Feminist Economics, the flourishing of the International Association for Feminist Economics (IAFFE), as well as the more regular demand for feminist economic policy advise by institutions like the UN, OECD and governments in developed and developing countries, and in well-established training courses in feminist economics, such as at the Institute of Social Studies and University of Utah . It is impossible to give a fair overview of the state of the art of feminist economics in the number of pages available, even when limited to issues pertaining to development and macroeconomics . As a consequence, this is a very sketchy and subjective overview of what I perceive to be recent developments in feminist economics that have relevance for feminist development analysis and policy. The next section recognizes three trends in feminist economics, in particular the engagement of feminist economists with heterodox schools of economics. The following sections will briefly review developments in methodology and methods in feminist economics. These will be followed by three sections on topics that have recently become key themes or areas of research in feminist economics, in particular in the area of development economics: unpaid labour and the care economy; the two-way relationship between gender and trade; and gender, efficiency and growth. Each of these topics will be introduced, with references to the main literature, and some links to policy recommendations. The paper will end with a conclusion

Informing the development of Australia's national eating disorders research and translation strategy : a rapid review methodology

Background Eating disorders (EDs) are highly complex mental illnesses associated with significant medical complications. There are currently knowledge gaps in research relating to the epidemiology, aetiology, treatment, burden, and outcomes of eating disorders. To clearly identify and begin addressing the major deficits in the scientific, medical, and clinical understanding of these mental illnesses, the Australian Government Department of Health in 2019 funded the InsideOut Institute (IOI) to develop the Australian Eating Disorder Research and Translation Strategy, the primary aim of which was to identify priorities and targets for building research capacity and outputs. A series of rapid reviews (RR) were conducted to map the current state of knowledge, identify evidence gaps, and inform development of the national research strategy. Published peer-reviewed literature on DSM-5 listed EDs, across eight knowledge domains was reviewed: (1) population, prevalence, disease burden, Quality of Life in Western developed countries; (2) risk factors; (3) co-occurring conditions and medical complications; (4) screening and diagnosis; (5) prevention and early intervention; (6) psychotherapies and relapse prevention; (7) models of care; (8) pharmacotherapies, alternative and adjunctive therapies; and (9) outcomes (including mortality). While RRs are systematic in nature, they are distinct from systematic reviews in their aim to gather evidence in a timely manner to support decision-making on urgent or high-priority health concerns at the national level. Results Three medical science databases were searched as the primary source of literature for the RRs: Science Direct, PubMed and OVID (Medline). The search was completed on 31st May 2021 (spanning January 2009-May 2021). At writing, a total of 1,320 articles met eligibility criteria and were included in the final review. Conclusions For each RR, the evidence has been organised to review the knowledge area and identify gaps for further research and investment. The series of RRs (published separately within the current series) are designed to support the development of research and translation practice in the field of EDs. They highlight areas for investment and investigation, and provide researchers, service planners and providers, and research funders rapid access to quality current evidence, which has been synthesised and organised to assist decision-making

Global perspectives on observing ocean boundary current systems

© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Todd, R. E., Chavez, F. P., Clayton, S., Cravatte, S., Goes, M., Greco, M., Ling, X., Sprintall, J., Zilberman, N., V., Archer, M., Aristegui, J., Balmaseda, M., Bane, J. M., Baringer, M. O., Barth, J. A., Beal, L. M., Brandt, P., Calil, P. H. R., Campos, E., Centurioni, L. R., Chidichimo, M. P., Cirano, M., Cronin, M. F., Curchitser, E. N., Davis, R. E., Dengler, M., deYoung, B., Dong, S., Escribano, R., Fassbender, A. J., Fawcett, S. E., Feng, M., Goni, G. J., Gray, A. R., Gutierrez, D., Hebert, D., Hummels, R., Ito, S., Krug, M., Lacan, F., Laurindo, L., Lazar, A., Lee, C. M., Lengaigne, M., Levine, N. M., Middleton, J., Montes, I., Muglia, M., Nagai, T., Palevsky, H., I., Palter, J. B., Phillips, H. E., Piola, A., Plueddemann, A. J., Qiu, B., Rodrigues, R. R., Roughan, M., Rudnick, D. L., Rykaczewski, R. R., Saraceno, M., Seim, H., Sen Gupta, A., Shannon, L., Sloyan, B. M., Sutton, A. J., Thompson, L., van der Plas, A. K., Volkov, D., Wilkin, J., Zhang, D., & Zhang, L. Global perspectives on observing ocean boundary current systems. Frontiers in Marine Science, 6, (2010); 423, doi: 10.3389/fmars.2019.00423.Ocean boundary current systems are key components of the climate system, are home to highly productive ecosystems, and have numerous societal impacts. Establishment of a global network of boundary current observing systems is a critical part of ongoing development of the Global Ocean Observing System. The characteristics of boundary current systems are reviewed, focusing on scientific and societal motivations for sustained observing. Techniques currently used to observe boundary current systems are reviewed, followed by a census of the current state of boundary current observing systems globally. The next steps in the development of boundary current observing systems are considered, leading to several specific recommendations.RT was supported by The Andrew W. Mellon Foundation Endowed Fund for Innovative Research at WHOI. FC was supported by the David and Lucile Packard Foundation. MGo was funded by NSF and NOAA/AOML. XL was funded by China’s National Key Research and Development Projects (2016YFA0601803), the National Natural Science Foundation of China (41490641, 41521091, and U1606402), and the Qingdao National Laboratory for Marine Science and Technology (2017ASKJ01). JS was supported by NOAA’s Global Ocean Monitoring and Observing Program (Award NA15OAR4320071). DZ was partially funded by the Joint Institute for the Study of the Atmosphere and Ocean (JISAO) under NOAA Cooperative Agreement NA15OAR4320063. BS was supported by IMOS and CSIRO’s Decadal Climate Forecasting Project. We gratefully acknowledge the wide range of funding sources from many nations that have enabled the observations and analyses reviewed here