TEMPORAL CHANGES IN INNATE AND ADAPTIVE IMMUNITY DURING SEPSIS AS DETERMINED BY ELISPOT.

Background: The inability to evaluate host immunity in a rapid quantitative manner in patients with sepsis has severely hampered development of novel immune therapies. The enzyme-linked immunospot (ELISpot) assay is a functional bioassay that measures the number of cytokine-secreting cells and the relative amount of cytokine produced at the single-cell level. A key advantage of ELISpot is its excellent dynamic range enabling a more precise quantifiable assessment of host immunity.

A Whole Blood Enzyme-Linked Immunospot Assay for Functional Immune Endotyping of Septic Patients.

Sepsis initiates simultaneous pro- and anti-inflammatory processes, the pattern and intensity of which vary over time. The inability to evaluate the immune status of patients with sepsis in a rapid and quantifiable manner has undoubtedly been a major reason for the failure of many therapeutic trials. Although there has been considerable effort to immunophenotype septic patients, these methods have often not accurately assessed the functional state of host immunity, lack dynamic range, and are more reflective of molecular processes rather than host immunity.

Severe immunosuppression and not a cytokine storm characterizes COVID-19 infections.

COVID-19-associated morbidity and mortality have been attributed to a pathologic host response. Two divergent hypotheses have been proposed: hyperinflammatory cytokine storm; and failure of host protective immunity that results in unrestrained viral dissemination and organ injury. A key explanation for the inability to address this controversy has been the lack of diagnostic tools to evaluate immune function in COVID-19 infections.

Development of Stable Boron Nitride Nanotube and Hexagonal Boron Nitride Dispersions for Electrophoretic Deposition.

Boron nitride nanotubes (BNNTs) represent a relatively new class of materials that provides alternative electrical and thermal properties to the carbon analogue. The high chemical and thermal stability and large band gap combined with high electrical resistance make BNNTs desirable in several thin-film applications. In this study, stable BNNT and hexagonal boron nitride (hBN) particle dispersions have been developed using environmentally friendly advanced oxidation processing (AOP) that can be further modified for electrophoretic deposition (EPD) to produce thin films.

Theoretical insight on the origin of anelasticity in zinc oxide nanowires.

Anelasticity of nanowires has recently attracted attention as an interesting property for high efficiency mechanical damping materials. While the mechanism of anelasticity has so far been analysed using continuum mechanical models based on defect diffusion, the mechanisms behind anelasticity have not yet been determined on an atomic level. Such information is needed in order to be able to design and synthesise new nanomaterials having desired mechanical properties.

IL-10 Has Differential Effects on the Innate and Adaptive Immune Systems of Septic Patients.

Sepsis, a disease of divergent pro- and anti-inflammatory-mediated pathways, has a high prevalence of morbidity and mortality, yet an understanding of potential unifying mediators between these pathways that may improve clinical outcomes is largely unclear. IL-10 has classically been designated an immunosuppressive cytokine, although recent data suggest that under certain conditions IL-10 can be immune stimulatory. We sought to further investigate the effect of IL-10 on innate and adaptive immunity in an in vitro human observational cohort study in patients with sepsis via modulation of IL-10 on IFN-γ production by T cells and TNF-α production and HLA-DR expression by monocytes.

Adsorption of toxic gases on silicene/Ag(111).

Silicene is a two-dimensional nanomaterial, composed of Si atoms arranged into a buckled honeycomb network. It has become of great interest in recent years due to its remarkable properties such as its natural compatibility with current silicon-based technology. Due to its extreme thinness on the nanoscale, and large lateral dimensions, it has potential applications in gas sensing, gas storage and components in modern electronic devices.

Tuning the work function of the silicene/4 × 4 Ag(111) surface.

Silicene, the silicon analog of graphene, is an atomically thin two-dimensional material with promising applications in gas sensing, storage and as components in modern electronic devices. Silicene epitaxially grown on the Ag(111) surface can expand the utility of the silver surface by enabling the tuning of its work function through the functionalisation of silicene. Here we examine the electronic and structural properties and the thermodynamic stability of functionalised silicene/4 × 4 Ag(111) using density functional theory calculations coupled with ab initio molecular dynamics (AIMD) simulations.

Acceptability of financial incentives for maintenance of weight loss in mid-older adults: a mixed methods study.

Background: Health insurers worldwide implement financial incentive schemes to encourage health-related behaviours, including to facilitate weight loss. The maintenance of weight loss is a public health challenge, and as non-communicable diseases become more prevalent with increasing age, mid-older adults could benefit from programs which motivate weight loss maintenance. However, little is understood about their perceptions of using financial incentives to maintain weight loss.

How ionic species structure influences phase structure and transitions from protic ionic liquids to liquid crystals to crystals.

The phase behaviour of n-alkylammonium (C6 to C16) nitrates and formates has been characterised using synchrotron small angle and wide angle X-ray scattering (SAXS/WAXS), differential scanning calorimetry (DSC), cross polarised optical microscopy (CPOM) and Fourier transform infrared spectroscopy (FTIR). The protic salts may exist as crystalline, liquid crystalline or ionic liquid materials depending on the alkyl chain length and temperature. n-Alkylammonium nitrates with n ≥ 6 form thermotropic liquid crystalline (LC) lamellar phases, whereas n ≥ 8 was required for the formate series to form this LC phase.

Frontline Science: Defects in immune function in patients with sepsis are associated with PD-1 or PD-L1 expression and can be restored by antibodies targeting PD-1 or PD-L1.

Sepsis is a heterogeneous syndrome comprising a highly diverse and dynamic mixture of hyperinflammatory and compensatory anti-inflammatory immune responses. This immune phenotypic diversity highlights the importance of proper patient selection for treatment with the immunomodulatory drugs that are entering clinical trials. To better understand the serial changes in immunity of critically ill patients and to evaluate the potential efficacy of blocking key inhibitory pathways in sepsis, we undertook a broad phenotypic and functional analysis of innate and acquired immunity in the same aliquot of blood from septic, critically ill nonseptic, and healthy donors.

TLR3 agonist improves survival to secondary pneumonia in a double injury model.

Background: Toll-like receptors (TLR) can initiate various immune responses and are therefore activated under diverse infectious states. Previous studies have focused on TLR3 primarily as an antiviral pathway. However, recent research has demonstrated its efficacy in bacterial infection.

Immunosuppression in patients who die of sepsis and multiple organ failure.

Context: Severe sepsis is typically characterized by initial cytokine-mediated hyperinflammation. Whether this hyperinflammatory phase is followed by immunosuppression is controversial. Animal studies suggest that multiple immune defects occur in sepsis, but data from humans remain conflicting.

Increased susceptibility to Candida infection following cecal ligation and puncture.

Secondary infection following septic insult represents a significant cause of morbidity and mortality in hospitalized patients. Sepsis induced immunosuppression is a major factor in the host's susceptibility to nosocomial infections and Candida albicans accounts for a growing number of these. Given the importance of improving our understanding of the immune response to sepsis and the increasing rates of C.

IL-15 prevents apoptosis, reverses innate and adaptive immune dysfunction, and improves survival in sepsis.

IL-15 is a pluripotent antiapoptotic cytokine that signals to cells of both the innate and adaptive immune system and is regarded as a highly promising immunomodulatory agent in cancer therapy. Sepsis is a lethal condition in which apoptosis-induced depletion of immune cells and subsequent immunosuppression are thought to contribute to morbidity and mortality. This study tested the ability of IL-15 to block apoptosis, prevent immunosuppression, and improve survival in sepsis.

Bim siRNA decreases lymphocyte apoptosis and improves survival in sepsis.

To assess the degree of lymphocyte apoptosis and survival in mice treated with small interfering RNA (siRNA) targeted to Bim, a proapoptotic molecule from the Bcl-2 family, within a clinically relevant model of sepsis. C57BL/6 mice were treated with a single dose of Bim siRNA complexed in cationic liposomes via tail vein injection. Approximately 24 h later, mice were subjected to either cecal ligation and puncture (CLP) or sham surgery.

Splenic CD4+ T cells have a distinct transcriptional response six hours after the onset of sepsis.

Background: In animal and human autopsy studies of sepsis, CD4+ splenocytes either undergo apoptosis or are polarized to the Th2 effector subtype. In mice, these changes occur within 24 hours of the onset of sepsis. Preventing the loss of CD4+ T cells and the Th2-polarization of CD4+ T cells provides a significant survival advantage in mouse models of sepsis.

Antibiotics improve survival and alter the inflammatory profile in a murine model of sepsis from Pseudomonas aeruginosa pneumonia.

Differing antibiotic regimens can influence both survival and the inflammatory state in sepsis. We investigated whether the addition and/or type of antimicrobial agent could effect mortality in a murine model of Pseudomonas aeruginosa pneumonia-induced sepsis and if antibiotics altered systemic levels of cytokines. FVB/N mice were subjected to intratracheal injection of pathogenic bacteria and were given gentamicin, imipenem, or 0.

Adoptive transfer of apoptotic splenocytes worsens survival, whereas adoptive transfer of necrotic splenocytes improves survival in sepsis.

In sepsis, both necrotic and apoptotic cell death can occur. Apoptotic cells induce anergy that could impair the host response, whereas necrotic cells cause immune activation that might result in enhanced antimicrobial defenses. We determined whether adoptive transfer of apoptotic or necrotic cells impacted survival in a clinically relevant sepsis model.

Effects of age on mortality and antibiotic efficacy in cecal ligation and puncture.

The incidence and mortality of sepsis increase with age, consequently, 80% of the clinical mortality from sepsis occurs in patients over age 65. Despite this aged clinical population, most research models of sepsis use 6- to 16-week-old mice as patient surrogates. This age range of mice corresponds to human ages 10 to 17 years.

Depletion of dendritic cells, but not macrophages, in patients with sepsis.

Dendritic cells (DCs) are a group of APCs that have an extraordinary capacity to interact with T and B cells and modulate their responses to invading pathogens. Although a number of defects in the immune system have been identified in sepsis, few studies have examined the effect of sepsis on DCs, which is the purpose of this study. In addition, this study investigated the effect of sepsis on macrophages, which are reported to undergo apoptosis, and MHC II expression, which has been noted to be decreased in sepsis.