IL-10 production in macrophages is regulated by a TLR-driven CREB-mediated mechanism that is linked to genes involved in cell metabolism

IL-10 is produced by macrophages in diverse immune settings and is critical in limiting immune-mediated pathology. In helminth infections, macrophages are an important source of IL-10; however, the molecular mechanism underpinning production of IL-10 by these cells is poorly characterized. In this study, bone marrow–derived macrophages exposed to excretory/secretory products released by Schistosoma mansoni cercariae rapidly produce IL-10 as a result of MyD88-mediated activation of MEK/ERK/RSK and p38. The phosphorylation of these kinases was triggered by TLR2 and TLR4 and converged on activation of the transcription factor CREB. Following phosphorylation, CREB is recruited to a novel regulatory element in the Il10 promoter and is also responsible for regulating a network of genes involved in metabolic processes, such as glycolysis, the tricarboxylic acid cycle, and oxidative phosphorylation. Moreover, skin-resident tissue macrophages, which encounter S. mansoni excretory/secretory products during infection, are the first monocytes to produce IL-10 in vivo early postinfection with S. mansoni cercariae. The early and rapid release of IL-10 by these cells has the potential to condition the dermal microenvironment encountered by immune cells recruited to this infection site, and we propose a mechanism by which CREB regulates the production of IL-10 by macrophages in the skin, but also has a major effect on their metabolic state

Curriculum Adaptations to Teach for Creativity Using a Published Language Arts Curriculum

The purpose of this qualitative action research study was to examine a published language arts curriculum, determine how Anna Craft’s possibility thinking framework could be integrated into the curriculum, and then observe how students responded to the implementation of lessons integrating the elements of possibility thinking. The findings revealed that a teacher can use the possibility thinking elements to encourage creativity while still teaching the objectives of a published curriculum. Creativity development can be encouraged by using a variety of supports that build possibility thinking. The data demonstrated a connection between life experiences and the curriculum through possibility thinking. The data also indicated that visual bridges in connection with writing can encourage the imagination. Flexible story structure and independent learning featured narrative as a tool to encourage the possibility thinking elements through dance, creating stories, and puppet plays. In addition, problem-solving played a key role when connected with narrative and collaboration to support the encouragement of creativity through the possibility thinking elements. Where students were engaged in collaboration, narrative, and problem-solving activities in connection with literacy instruction, it led to an increase in possibility thinking amongst students

CD4+ T cell hyporesponsiveness after repeated exposure to Schistosoma mansoni larvae is dependent upon interleukin-10

The effect that multiple percutaneous exposures to Schistosoma larvae has on the development of early CD4+ lymphocyte reactivity is unclear, yet it is important in the context of humans living in areas where schistosomiasis is endemic. In a murine model of multiple infections, we show that exposure of mice to repeated doses (4×) of Schistosoma mansoni cercariae, compared to a single dose (1×), results in CD4+ T cell hyporesponsiveness within the skin-draining lymph nodes (sdLN), manifested as reduced CD4+ cell proliferation and cytokine production. FoxP3+ CD4+ regulatory T cells were present in similar numbers in the sdLN of 4× and 1× mice and thus are unlikely to have a role in effecting hyporesponsiveness. Moreover, anergy of the CD4+ cell population from 4× mice was slight, as proliferation was only partly circumvented through the in vitro addition of exogenous interleukin-2 (IL-2), and the in vivo blockade of the regulatory molecule PD1 had a minimal effect on restoring responsiveness. In contrast, IL-10 was observed to be critical in mediating hyporesponsiveness, as CD4+ cells from the sdLN of 4× mice deficient for IL-10 were readily able to proliferate, unlike those from 4× wild-type cohorts. CD4+ cells from the sdLN of 4× mice exhibited higher levels of apoptosis and cell death, but in the absence of IL-10, there was significantly less cell death. Combined, our data show that IL-10 is a key factor in the development of CD4+ T cell hyporesponsiveness after repeated parasite exposure involving CD4+ cell apoptosis

A New Archaeoastronomical Investigation of the Irish Axial-Stone Circles

This paper presents the preliminary results of a project undertaken in 1994 to investigate the astronomical potential of the axial-stone circles (ASCs) of seven or more stones in Counties Cork and Kerry, south-west Ireland. This group of sites is of particular interest in that the monuments in the group bear a striking resemblance to the recumbent stone circles (RSCs) of Aberdeenshire, eastern Scotland, which appear to exhibit a strong pattern of alignment in relation to prominent hilltop summits and the rising and setting position of the moon. The first indications from the Irish data are that similar patterns of alignment are not evident in the Irish ASCs. The Irish sites show no preference for orientation upon prominent hilltops and no clear astronomical trends

Do patients at risk of infective endocarditis need antibiotics before dental procedures?

What you need to know: - Patients with prosthetic heart valves, previous infective endocarditis, and some types of congenital heart disease are at highest risk of infective endocarditis - Invasive dental procedures cause bacteraemia, which can be complicated by infective endocarditis in those at increased risk of the disease - Antibiotic prophylaxis reduces the incidence of bacteraemia, but high level studies confirming that this reduces the incidence of infective endocarditis are lacking - Warn high risk patients undergoing high risk dental interventions of the risk of infective endocarditis. Offer these patients antibiotic prophylaxis, and discuss with them the risks and benefits of this option - Where patients are at moderate risk, encourage preventative measures, such as maintaining good oral hygiene and infection control, and discourage tattooing or piercin

Modified Single Prolonged Stress Reduces Cocaine Self-Administration During Acquisition Regardless of Rearing Environment

Until recently, there were few rodent models available to study the interaction of post-traumatic stress disorder (PTSD) and drug taking. Like PTSD, single prolonged stress (SPS) produces hypothalamic-pituitary-adrenal (HPA) axis dysfunction and alters psychostimulant self-administration. Other stressors, such as isolation stress, also alter psychostimulant self-administration. However, it is currently unknown if isolation housing combined with SPS can alter the acquisition or maintenance of cocaine self-administration. The current study applied modified SPS (modSPS; two hours restraint immediately followed by cold swim stress) to rats raised in an isolation condition (Iso), enrichment condition (Enr), or standard condition (Std) to measure changes in cocaine self-administration and HPA markers. Regardless of rearing condition, rats exposed to modSPS had greater corticosterone (CORT) release and reduced cocaine self-administration during initial acquisition compared to non-stressed controls. In addition, during initial acquisition, rats that received both Iso rearing and modSPS showed a more rapid increase in cocaine self-administration across sessions compared to Enr and Std rats exposed to modSPS. Following initial acquisition, a dose response analysis showed that Iso rats were overall most sensitive to changes in cocaine unit dose; however, modSPS had no effect on the cocaine dose response curve. Further, there was no effect of either modSPS or differential rearing on expression of glucocorticoid receptor (GR) in hypothalamus, medial prefrontal cortex, amygdala, or nucleus accumbens. By using modSPS in combination with Iso housing, this study identified unique contributions of each stressor to acquisition of cocaine self-administration

Nurses\u27 Alumnae Association Bulletin, April 1961

Alumnae Meetings 1960 Social Committee Clara Melville Scholarship Fund Bulletin Committee Private Duty Nurse\u27s Section Report of the School of Nursing and Nursing Service Staff Nurses Association Student Activities Personal Items of Interest Expansion of Jefferson Artificial Kidney Unit Medical Work in the Congo Marriages New Arrivals Necrology Annual Giving Fun

Radiotherapy for Soft Tissue Sarcoma of the Proximal Lower Extremity

Soft-tissue sarcoma (STS) is a histopathologically diverse group of tumors accounting for approximately 10,000 new malignancies in the US each year. The proximal lower extremity is the most common site for STS, accounting for approximately one-third of all cases. Coordinated multimodality management in the form of surgery and radiation is often critical to local control, limb preservation, and functional outcome. Based on a review of currently available Medline literature and professional experience, this paper provides an overview of the treatment of STS of the lower extremity with a particular focus on the modern role of radiotherapy

Nurses\u27 Alumnae Association Bulletin, April 1962

Staff Nurses Association Alumnae Meetings 1961 Social Committee Clara Melville Scholarship Fund Ways and Means Report Cook Book Report Bulletin Committee Private Duty Nurse\u27s Section Hospital Report and Nursing Service Federal Nursing Service Practice of Nursing Report of Student Council Activities Medical Work in Ghan