Selective regulation of IFN-γ and IL-4 co-producing unconventional T cells by purinergic signaling.

Unconventional T cells, including mucosal-associated invariant T (MAIT), natural killer T (NKT), and gamma-delta T (γδT) cells, comprise distinct T-bet+, IFN-γ+ and RORγt+, IL-17+ subsets which play differential roles in health and disease. NKT1 cells are susceptible to ARTC2-mediated P2X7 receptor (P2RX7) activation, but the effects on other unconventional T-cell types are unknown. Here, we show that MAIT, γδT, and NKT cells express P2RX7 and are sensitive to P2RX7-mediated cell death.

mTOR signalling controls the formation of smooth muscle cell-derived luminal myofibroblasts during vasculitis.

The accumulation of myofibroblasts within the intimal layer of inflamed blood vessels is a potentially catastrophic complication of vasculitis, which can lead to arterial stenosis and ischaemia. In this study, we have investigated how these luminal myofibroblasts develop during Kawasaki disease (KD), a paediatric vasculitis typically involving the coronary arteries. By performing lineage tracing studies in a murine model of KD, we reveal that luminal myofibroblasts develop independently of adventitial fibroblasts and endothelial cells, and instead derive from smooth muscle cells (SMCs).

The mechanisms underlying conditioning of phantom percepts differ between those with hallucinations and synesthesia.

There are many different kinds of 'phantom' percepts but it is unknown whether they are united by common mechanisms. For example, synaesthesia (e.g.

Expedited organ donation in Victoria, Australia: donor characteristics and donation outcomes.

Deceased organ donation work-up typically takes 24 hours or more. Clinicians may thus discount the possibility of donation when the potential donor is physiologically unstable or family requirements do not allow this length of time. This may lead to loss of transplantable organs.

Point-of-care detection of fibrosis in liver transplant surgery using near-infrared spectroscopy and machine learning.

Introduction: Visual assessment and imaging of the donor liver are inaccurate in predicting fibrosis and remain surrogates for histopathology. We demonstrate that 3-s scans using a handheld near-infrared-spectroscopy (NIRS) instrument can identify and quantify fibrosis in fresh human liver samples.

Methods: We undertook NIRS scans on 107 samples from 27 patients, 88 from 23 patients with liver disease, and 19 from four organ donors.

Towards a point-of-care multimodal spectroscopy instrument for the evaluation of human cardiac tissue.

To demonstrate that point-of-care multimodal spectroscopy using Near-Infrared (NIR) and Raman Spectroscopy (RS) can be used to diagnose human heart tissue. We generated 105 spectroscopic scans, which comprised 4 NIR and 3 RS scans per sample to generate a "multimodal spectroscopic scan" (MSS) for each heart, done across 15 patients, 5 each from the dilated cardiomyopathy (DCM), Ischaemic Heart Disease (IHD) and Normal pathologies. Each of the MSS scans was undertaken in 3 s.

Early immune pressure initiated by tissue-resident memory T cells sculpts tumor evolution in non-small cell lung cancer.

Tissue-resident memory T (T) cells provide immune defense against local infection and can inhibit cancer progression. However, it is unclear to what extent chronic inflammation impacts T activation and whether T cells existing in tissues before tumor onset influence cancer evolution in humans. We performed deep profiling of healthy lungs and lung cancers in never-smokers (NSs) and ever-smokers (ESs), finding evidence of enhanced immunosurveillance by cells with a T-like phenotype in ES lungs.

Mechanistic Target of Rapamycin Inhibition Prevents Coronary Artery Remodeling in a Murine Model of Kawasaki Disease.

Objective: Remodeling of the coronary arteries is a common feature in severe cases of Kawasaki disease (KD). This pathology is driven by the dysregulated proliferation of vascular fibroblasts, which can lead to coronary artery aneurysms, stenosis, and myocardial ischemia. We undertook this study to investigate whether inhibiting fibroblast proliferation might be an effective therapeutic strategy to prevent coronary artery remodeling in KD.

Intimal macrophages develop from circulating monocytes during vasculitis.

Objective: Vasculitis is characterised by inflammation of the blood vessels. While all layers of the vessel can be affected, inflammation within the intimal layer can trigger thrombosis and arterial occlusion and is therefore of particular clinical concern. Given this pathological role, we have examined how intimal inflammation develops by exploring which (and how) macrophages come to populate this normally immune-privileged site during vasculitis.

A prediction model to determine the untapped lung donor pool outside of the DonateLife network in Victoria.

Lung transplantation is limited by a lack of suitable lung donors. In Australia, the national donation organisation (DonateLife) has taken a major role in optimising organ donor identification. However, the potential outside the DonateLife network hospitals remains uncertain.

Benefits of a Standardized Enteral Feeding Protocol on the Nutrition and Health Outcomes of Very Low Birth Weight Preterm Infants.

To compare nutrition and health outcomes before and after implementing a standardized enteral feeding protocol on nutrition and health outcomes in very low birth weight preterm infants. A retrospective chart review was performed evaluating preterm infants, born less than 34 weeks gestation and weighing less than 1500 g, before and after the implementation of a standardized enteral feeding protocol. Outcomes included weaning of parenteral nutrition, initiation and advancement of enteral feeds, initiation of human-milk fortifier (HMF), change in weight -score and neonatal morbidities.

Lung-resident memory B cells established after pulmonary influenza infection display distinct transcriptional and phenotypic profiles.

Recent studies have established that memory B cells, largely thought to be circulatory in the blood, can take up long-term residency in inflamed tissues, analogous to widely described tissue-resident T cells. The dynamics of recruitment and retention of memory B cells to tissues and their immunological purpose remains unclear. Here, we characterized tissue-resident memory B cells (B) that are stably maintained in the lungs of mice after pulmonary influenza infection.

A diverse fibroblastic stromal cell landscape in the spleen directs tissue homeostasis and immunity.

The spleen is a compartmentalized organ that serves as a blood filter and safeguard of systemic immune surveillance. Labyrinthine networks of fibroblastic stromal cells construct complex niches within the white pulp and red pulp that are important for tissue homeostasis and immune activation. However, the identity and roles of the global splenic fibroblastic stromal cells in homeostasis and immune responses are poorly defined.

Successful Implementation of an Increased Viral Risk Donor Waiting List for Preconsented Kidney Transplant Candidates in Victoria, Australia.

Unlabelled: Increased viral risk donors (IVRDs) with increased risk behaviors for blood-borne virus infection and negative nucleic acid testing have a low absolute risk of "window period" infection. Utilization and allocation of IVRD organs differ between jurisdictions.

Methods: We examined the characteristics and utilization of deceased donor IVRD kidneys and recipient outcomes within a 2-y period (July 31, 2018-July 31, 2020) postimplementation of a new opt-in allocation pathway for preconsented recipients in Victoria, Australia.

An Audit of Lung Donor Pool: Optimal Current Donation Strategies and the Potential of Novel Time-Extended Donation After Circulatory Death Donation.

Background: In Australia, increased organ donation and subsequent lung transplantation (LTx) rates have followed enhanced donor identification, referral and management, as well as the introduction of a donation after circulatory death (DCD) pathway. However, the number of patients waiting for LTx still continues to exceed the number of lung donors and the search for further suitable donors is critical.

Methods: All 2014-2018 Victorian DonateLife hospital deaths after intensive care unit (ICU) admission were analysed retrospectively to quantify unrecognised lung donors using current criteria, as well as novel time-extended (90 mins-24 hrs post-withdrawal) DCD lung donors.

Adaptive immunity to human coronaviruses is widespread but low in magnitude.

Objectives: Endemic human coronaviruses (hCoVs) circulate worldwide but cause minimal mortality. Although seroconversion to hCoV is near ubiquitous during childhood, little is known about hCoV-specific T-cell memory in adults.

Methods: We quantified CD4 T-cell and antibody responses to hCoV spike antigens in 42 SARS-CoV-2-uninfected individuals.

Improving the predictability of time to death in controlled donation after circulatory death lung donors.

Although the use of donation after circulatory death (DCD) donors has increased lung transplant activity, 25-40% of intended DCD donors do not convert to actual donation because of no progression to asystole in the required time frame after withdrawal of cardiorespiratory support (WCRS). No studies have specifically focussed on DCD lung donor progression. This retrospective study reviewed intended DCD lung donors to make a prediction model of the likelihood of progression to death using logistic regression and classification and regression tree (CART).

A Retrospective Review of Declined Lung Donors: Estimating the Potential of Ex Vivo Lung Perfusion.

Background: Even in the extended-criteria era, the reasons for declining lung donors are not always clear. Furthermore, it has not been determined how many actual declined lungs would be retrieved by ex vivo lung perfusion (EVLP) beyond that already achieved in centers with an existing high utilization rate.

Methods: This retrospective study reviewed all lung donor referrals between 2014 and 2018, including detailed formal referrals and preliminary notifications.

Common Criteria for Ex Vivo Lung Perfusion Have No Significant Impact on Posttransplant Outcomes.

Background: Although it is intense in health care resources, by facilitating assessment and reconditioning, ex vivo lung perfusion (EVLP) has the potential to expand the donor pool and improve lung transplant outcomes. However, inclusion criteria used in EVLP trials have not been validated.

Methods: This retrospective study from 2014 to 2018 reviewed our local state-based donation organization donor records as well as subsequent recipient outcomes to explore the relation between EVLP indications used in clinical trials and recipient outcomes.

Conflicts of interest in the context of end of life care for potential organ donors in Australia.

End-of-life (EOL) care has become an integral part of intensive care medicine and includes the exploration of possibilities for deceased organ and tissue donation. Donation physicians are specialist doctors with expertise in EOL processes encompassing organ and tissue donation, who contribute significantly to improvements in organ and tissue donation services in many countries around the world. Donation physicians are usually also intensive care physicians, and thus they may be faced with the dual obligation of caring for dying patients and their families in the intensive care unit (ICU), whilst at the same time ensuring organ and tissue donation is considered according to best practice.