CD8 T Cells Mediate Lethal Lung Pathology in the Absence of PD-L1 and Type I Interferon Signalling following LCMV Infection.

CD8 T cells are critical to the adaptive immune response against viral pathogens. However, overwhelming antigen exposure can result in their exhaustion, characterised by reduced effector function, failure to clear virus, and the upregulation of inhibitory receptors, including programmed cell death 1 (PD-1). However, exhausted T cell responses can be "re-invigorated" by inhibiting PD-1 or the primary ligand of PD-1: PD-L1.

Extracellular RNA Sensing Mediates Inflammation and Organ Injury in a Murine Model of Polytrauma.

Severe traumatic injury leads to marked systemic inflammation and multiorgan injury. Endogenous drivers such as extracellular nucleic acid may play a role in mediating innate immune response and the downstream pathogenesis. Here, we explored the role of plasma extracellular RNA (exRNA) and its sensing mechanism in inflammation and organ injury in a murine model of polytrauma.

Patterns of Practice and Improvements in Survival Among Patients With Stage 2/3 Rectal Cancer Treated With Trimodality Therapy.

Importance: This study quantifies the trends in trimodality therapy use and its association with pathologic stage and overall survival of patients with rectal cancer at the population level.

Objective: To describe changes between 2006 and 2016 in the sequence and use of chemotherapy/radiation therapy (C/RT), multiagent (MA) chemotherapy, and total neoadjuvant therapy (TNT) for patients with stage 2/3 rectal cancer and identify associations with pathologic stage and survival over time.

Design, Setting, And Participants: This retrospective cohort analysis included patient records from the National Cancer Database between 2006 and 2016.

TLR7 Mediates Acute Respiratory Distress Syndrome in Sepsis by Sensing Extracellular miR-146a.

TLR7 (Toll-like receptor 7), the sensor for single-stranded RNA, contributes to systemic inflammation and mortality in murine polymicrobial sepsis. Recent studies show that extracellular miR-146a-5p serves as a TLR7 ligand and plays an important role in regulating host innate immunity. However, the role of miR-146a-5p and TLR7 signaling in pulmonary inflammation, endothelial activation, and sepsis-associated acute respiratory distress syndrome remains unclear.

Role of extracellular microRNA-146a-5p in host innate immunity and bacterial sepsis.

Extracellular miRNAs (ex-miRNAs) mediate intercellular communication and play a role in diverse physiological and pathological processes. Using small RNA sequencing, we identify that miRNAs are the most abundant RNA species in the plasma and differentially expressed in murine and human sepsis, such as miR-146a-5p. Exogenous miR-146a-5p, but not its duplex precursor, induces a strong immunostimulatory response through a newly identified UU-containing motif and TLR7 activation, and an immunotolerance by rapid IRAK-1 protein degradation via TLR7→MyD88 signaling and proteasome activation, whereas its duplex precursor acts by targeting 3' UTR of gene Ago2 binding.

Hypobaria Exposure Worsens Cardiac Function and Endothelial Injury in AN Animal Model of Polytrauma: Implications for Aeromedical Evacuation.

Background: Aeromedical evacuation can expose traumatically injured patients to low pressure (hypobaria) and hypoxia. Here, we sought to assess the impact of hypobaria on inflammation, organ injury, and mortality in a mouse model of polytrauma.

Methods: Eight to 12-week-old male C57BL/6J mice were subjected to sham or polytrauma consisting of bowel ischemia by superior mesenteric artery occlusion, hindlimb muscle crush, and tibia fracture.

Extracellular miR-146a-5p Induces Cardiac Innate Immune Response and Cardiomyocyte Dysfunction.

Previous studies have demonstrated that transient myocardial ischemia leads to release of cellular nucleic acids such as RNA. Extracellular RNA reportedly plays a pivotal role in myocardial inflammation and ischemic injury in animals. RNA profiling has identified that numerous microRNA (miRNAs), such as ss-miR-146a-5p, are upregulated in plasma following myocardial ischemia, and certain uridine-rich miRNAs exhibit strong proinflammatory effects in immune cells via ssRNA-sensing mechanism.

Toll-like receptors 2 and 7 mediate coagulation activation and coagulopathy in murine sepsis.

Background: Sepsis is a life-threatening condition often manifested as marked inflammation and severe coagulopathy. Toll-like receptors (TLRs) play a pivotal role in inflammation, organ dysfunction and mortality in animal sepsis.

Objectives: To investigate the role of TLR signaling in mediating sepsis-induced coagulopathy (SIC) in a mouse model.

Measurement of forces applied using a Macintosh direct laryngoscope compared with a Glidescope video laryngoscope in patients with predictors of difficult laryngoscopy: A randomised controlled trial.

Background: In patients with predictive features associated with easy direct laryngoscopy, videolaryngoscoy with the GlideScope has been shown to require less force when compared with Macintosh direct laryngoscopy.

Objective: The aim of this study was to compare forces applied with Glidescope vs. Macintosh laryngoscopes in patients with predictive features associated with difficult direct laryngoscopy.

Sorafenib and radiation: a promising combination in colorectal cancer.

Purpose: To examine the combination of radiation and the multikinase inhibitor sorafenib in human colorectal cancer cell lines and xenografts.

Methods And Materials: HT29 and SW48 colorectal cancer cells were studied in vitro using MTT assays to establish the optimal timing of radiation and sorafenib. This optimal timing was then investigated in clonogenic survival assays.

Dosimetric impact of online correction via cone-beam CT-based image guidance for stereotactic lung radiotherapy.

Purpose: To evaluate the dosimetric impact of online cone-beam computed tomography (CBCT) guided correction in lung stereotactic body radiation therapy (SBRT).

Methods And Materials: Twenty planning and 162 CBCT images from 20 patients undergoing lung SBRT were analyzed. The precorrection CBCT (CBCT after patient setup, no couch correction) was registered to planning CT using soft tissue; couch shift was applied, with a second CBCT for verification (postcorrection CBCT).

Clinical manifestations of noncoronary atherosclerotic vascular disease after moderate dose irradiation.

Background: Accelerated atherosclerosis and carotid stenosis are well-established risks occurring after high radiation doses that are used to treat cancers of the head and neck. Noncoronary vascular disease has been observed and may relate to more moderate dose irradiation.

Methods: A search of patients treated for Hodgkin disease, non-Hodgkin lymphoma, or seminoma was performed to identify cases with noncoronary vascular complications after irradiation.

Human interleukin-1-induced murine osteoclastogenesis is dependent on RANKL, but independent of TNF-alpha.

Although interleukin-1 (IL-1) has been implicated in the pathogenesis of inflammatory osteolysis, the means by which it recruits osteoclasts and promotes bone destruction are largely unknown. Recently, a cytokine-driven, stromal cell-free mouse osteoclastogenesis model was established. A combination of macrophage colony stimulating factor (M-CSF) and receptor activator of NFkappaB ligand (RANKL) was proven to be sufficient in inducing differentiation of bone marrow hematopoietic precursor cells to bone-resorbing osteoclasts in the absence of stromal cells or osteoblasts.