Using Multiphoton Intravital Microscopy to Study Neutrophil Transmigration and Blood-Brain Barrier Permeability in a Mouse Model of Herpes Simplex Virus Encephalitis.

Multiphoton intravital microscopy (MP-IVM) is an imaging technique used for the observation of living organisms at a microscopic resolution. The tissue of interest is exposed through a window allowing imaging of cells in real time. Using MP-IVM, the temporospatial kinetics of leukocyte transendothelial migration can be visualized and quantitated using reporter mice and cell-specific fluorophore-conjugated monoclonal antibodies to track the leukocytes within and outside of vascular beds.

Astrocyte- and Neuron-Derived CXCL1 Drives Neutrophil Transmigration and Blood-Brain Barrier Permeability in Viral Encephalitis.

Herpes simplex virus (HSV)-1 encephalitis has significant morbidity partly because of an over-exuberant immune response characterized by leukocyte infiltration into the brain and increased blood-brain barrier (BBB) permeability. Determining the role of specific leukocyte subsets and the factors that mediate their recruitment into the brain is critical to developing targeted immune therapies. In a murine model, we find that the chemokines CXCL1 and CCL2 are induced in the brain following HSV-1 infection.

Impact of mRNA chemistry and manufacturing process on innate immune activation.

Messenger RNA (mRNA) represents an attractive therapeutic modality for potentially a wide range of clinical indications but requires uridine chemistry modification and/or tuning of the production process to prevent activation of cellular innate immune sensors and a concomitant reduction in protein expression. To decipher the relative contributions of these factors on immune activation, here, we compared, in multiple cell and in vivo models, mRNA that encodes human erythropoietin incorporating either canonical uridine or 1-methyl-pseudouridine (1mΨ), synthesized by either a standard process shown to have double-stranded RNA (dsRNA) impurities or a modified process that yields a highly purified mRNA preparation. Our data demonstrate that the lowest stimulation of immune endpoints was with 1mΨ made by the modified process, while mRNA containing canonical uridine was immunostimulatory regardless of process.

CXCL10 stabilizes T cell-brain endothelial cell adhesion leading to the induction of cerebral malaria.

Malaria remains one of the world's most significant human infectious diseases and cerebral malaria (CM) is its most deadly complication. CM pathogenesis remains incompletely understood, hindering the development of therapeutics to prevent this lethal complication. Elevated levels of the chemokine CXCL10 are a biomarker for CM, and CXCL10 and its receptor CXCR3 are required for experimental CM (ECM) in mice, but their role has remained unclear.

Splenic differentiation and emergence of CCR5CXCL9CXCL10 monocyte-derived dendritic cells in the brain during cerebral malaria.

Dendritic cells have an important role in immune surveillance. After being exposed to microbial components, they migrate to secondary lymphoid organs and activate T lymphocytes. Here we show that during mouse malaria, splenic inflammatory monocytes differentiate into monocyte-derived dendritic cells (MO-DCs), which are CD11bF4/80CD11cMHCIIDC-SIGNLy6c and express high levels of CCR5, CXCL9 and CXCL10 (CCR5CXCL9/10 MO-DCs).

Millennial generation student nurses' perceptions of the impact of multiple technologies on learning.

Aim: To determine how millennial nursing students perceive the effects of instructional technology on their attentiveness, knowledge, critical thinking, and satisfaction. BACKGROUND Millennial learners develop critical thinking through experimentation, active participation, and multitasking with rapid shifts between technological devices. They desire immediate feedback.

Critical care issues in management of high-grade lymphoma.

Lymphoma presents itself from slow growing and asymptomatic to aggressive and destructive. Suspicion of aggressive lymphoma warrants prompt diagnostic evaluation because the tumor can be extremely fast growing and can cause significant sequelae including but not limited to tissue damage, immune suppression, organ failure, compromised circulation, and death. The standard evaluation includes laboratory assay, infectious disease panel, radiographic imaging with computed tomography, bone marrow biopsy, and tissue diagnosis.

Managing patients with indolent lymphoma treated with bendamustine: a nursing perspective.

Indolent lymphoma is one of the most frequently occurring subtypes of non-Hodgkin lymphoma (NHL). Indolent NHL has a long natural history, and patients will likely receive multiple therapies during the course of their disease. Treatment options are rapidly evolving and, because oncology nurses play a major role in managing patients undergoing treatment for indolent NHL, they need to be aware of the potential adverse effects associated with new therapies that may affect patients in their care.

Local expression of interleukin-2 by B16 melanoma cells results in decreased tumour growth and long-term tumour dormancy.

The tumour microenvironment is complex containing not only neoplastic cells but also a variety of host cells. The heterogeneous infiltrating immune cells include subsets of cells with opposing functions, whose activities are mediated either directly or through the cytokines they produce. Systemic delivery of cytokines such as interleukin-2 ( IL-2) has been used clinically to enhance anti-tumour responses, but these molecules are generally thought to have evolved to act locally in a paracrine fashion.

CXCR3 chemokine receptor-ligand interactions in the lymph node optimize CD4+ T helper 1 cell differentiation.

Differentiation of naive CD4(+) T cells into T helper (Th) cells is a defining event in adaptive immunity. The cytokines and transcription factors that control Th cell differentiation are understood, but it is not known how this process is orchestrated within lymph nodes (LNs). Here we have shown that the CXCR3 chemokine receptor was required for optimal generation of interferon-γ (IFN-γ)-secreting Th1 cells in vivo.

IL-12 suppresses vascular endothelial growth factor receptor 3 expression on tumor vessels by two distinct IFN-gamma-dependent mechanisms.

IL-12 has been shown to be effective in enhancing antitumor responses. However, how IL-12 exerts its antiangiogenic effect is largely unknown. In this study, we elucidate this mechanism using B16 transfected to express IL-12 (B16/IL-12), a system that provides constant, local production of IL-12 within the tumor microenvironment.

Social support, depression, functional status, and gender differences in older adults undergoing first-time coronary artery bypass graft surgery.

Background: Older adults have more difficulty with coronary artery bypass graft (CABG) surgery than younger adults, partly because of depression and social isolation. During hospitalization, older adult patients undergoing CABG name nurses as their primary source of social support.

Methods: A secondary analysis was used to investigate the relationships among social support, depression, functional status, and postoperative length of stay.

Omental immune aggregates and tumor metastasis within the peritoneal cavity.

The omentum, an important peritoneal tissue, is studded with a high number of immune aggregates, or "milky spots," the number, function, and phenotype of which is largely unknown. We have analyzed the immune composition on the normal omentum and also have shown that both free immune cells and tumor cells in the peritoneal fluid bind preferentially to these immune aggregates. This binding may be mediated by the network of collagen I fibers, which overlay these areas.

A survey of mothers' comfort discussing contraception with infant providers at well-child visits.

Objective: To determine whether mothers feel comfortable with their infants' providers discussing contraception with them at their infants' well-child checks.

Methods: A cross-sectional survey was conducted using a convenience sample of 114 mothers presenting at a community family medicine residency program for well-child visits among infants up to 17 months old.

Results: Almost all mothers (87%) felt comfortable talking with their infants' providers about contraception and were likely to accept the advice of their infants' providers to see their own doctors regarding contraception (83%) or to use a prescription from their infants' providers for contraception (75%).

Radiation-induced IFN-gamma production within the tumor microenvironment influences antitumor immunity.

Alterations to the tumor microenvironment following localized irradiation may influence the effectiveness of subsequent immunotherapy. The objective of this study was to determine how IFN-gamma influences the inflammatory response within this dynamic environment following radiotherapy. B16/OVA melanoma cells were implanted into C57BL/6 (wild-type (WT)) and IFN-gamma-deficient (IFN-gamma-/-) mice.