High emergency organ allocation rule in lung transplantation: a simulation study.

The scarcity of suitable organ donors leads to protracted waiting times and mortality in patients awaiting lung transplantation. This study aims to assess the short- and long-term effects of a high emergency organ allocation policy on the outcome of lung transplantation. We developed a simulation model of lung transplantation waiting queues under two allocation strategies, based either on waiting time only or on additional criteria to prioritise the sickest patients.

Lung Microbiota Is Related to Smoking Status and to Development of Acute Respiratory Distress Syndrome in Critically Ill Trauma Patients.

Rationale: Cigarette smoking is associated with increased risk of acute respiratory distress syndrome (ARDS) in patients after severe trauma; however, the mechanisms underlying this association are unknown.

Objectives: To determine whether cigarette smoking contributes to ARDS development after trauma by altering community composition of the lung microbiota.

Methods: We studied the lung microbiota of mechanically ventilated patients admitted to the ICU after severe blunt trauma.

Mortality Benefit of Recombinant Human Interleukin-1 Receptor Antagonist for Sepsis Varies by Initial Interleukin-1 Receptor Antagonist Plasma Concentration.

Objective: Plasma interleukin-1 beta may influence sepsis mortality, yet recombinant human interleukin-1 receptor antagonist did not reduce mortality in randomized trials. We tested for heterogeneity in the treatment effect of recombinant human interleukin-1 receptor antagonist by baseline plasma interleukin-1 beta or interleukin-1 receptor antagonist concentration.

Design: Retrospective subgroup analysis of randomized controlled trial.

Evidence of depression-associated circadian rhythm disruption and regret in prostate cancer patients after surgery.

Purpose: The purpose of this study is to investigate the association between prostate cancer (PCa) patients' regret that their surgery harmed them, and their scores on the two key symptoms of major depressive disorder (depressed mood, anhedonia) and a symptom of melancholic depression (disruption to circadian rhythm).

Methods: Forty PCa patients who had received surgery for their PCa completed a postal survey including background information, regret about surgery that 'did them a lot of harm' and three items drawn from the Zung Self-Rating Depression Scale measuring depressed mood, anhedonia and circadian rhythm disruption.

Results: There were significant correlations between all three symptoms of depression (depressed mood, anhedonia, disruption to circadian rhythm) and between patients' regret that surgery did them a lot of harm and their circadian rhythm disruption, but not between depressed mood or anhedonia and regret about surgery doing harm.

Mitigating Mitochondrial Genome Erosion Without Recombination.

Mitochondria are ATP-producing organelles of bacterial ancestry that played a key role in the origin and early evolution of complex eukaryotic cells. Most modern eukaryotes transmit mitochondrial genes uniparentally, often without recombination among genetically divergent organelles. While this asymmetric inheritance maintains the efficacy of purifying selection at the level of the cell, the absence of recombination could also make the genome susceptible to Muller's ratchet.

A pilot clinical trial of recombinant human angiotensin-converting enzyme 2 in acute respiratory distress syndrome.

Background: Renin-angiotensin system (RAS) signaling and angiotensin-converting enzyme 2 (ACE2) have been implicated in the pathogenesis of acute respiratory distress syndrome (ARDS). We postulated that repleting ACE2 using GSK2586881, a recombinant form of human angiotensin-converting enzyme 2 (rhACE2), could attenuate acute lung injury.

Methods: We conducted a two-part phase II trial comprising an open-label intrapatient dose escalation and a randomized, double-blind, placebo-controlled phase in ten intensive care units in North America.

Quantitative Evidence for Revising the Definition of Primary Graft Dysfunction after Lung Transplant.

Rationale: Primary graft dysfunction (PGD) is a form of acute lung injury that occurs after lung transplantation. The definition of PGD was standardized in 2005. Since that time, clinical practice has evolved, and this definition is increasingly used as a primary endpoint for clinical trials; therefore, validation is warranted.

Comparative Effectiveness of Enoxaparin vs Dalteparin for Thromboprophylaxis After Traumatic Injury.

Background: Enoxaparin 30 mg twice daily and dalteparin 5,000 units once daily are two common low-molecular-weight heparin (LMWH) thromboprophylaxis regimens used in the trauma population. Pharmacodynamic studies suggest that enoxaparin provides more potent anticoagulation than does dalteparin.

Methods: In 2009, our institution switched its formulary LMWH from enoxaparin to dalteparin followed by a switch back to enoxaparin in 2013.

Human lung tumor FOXP3+ Tregs upregulate four "Treg-locking" transcription factors.

Experimental data indicate that FOXP3+ Tregs can markedly curtail host antitumor immune responses, but the properties of human intratumoral Tregs are still largely unknown, in part due to significant methodologic problems. We studied the phenotypic, functional, epigenetic, and transcriptional features of Tregs in 92 patients with non-small-cell lung cancer, comparing the features of Tregs within tumors versus corresponding blood, lung, and lymph node samples. Intratumoral Treg numbers and suppressive function were significantly increased compared with all other sites but did not display a distinctive phenotype by flow cytometry.

An invasive social insect overcomes genetic load at the sex locus.

Some invasive hymenopteran social insects found new populations with very few reproductive individuals. This is despite the high cost of founder effects for such insects, which generally require heterozygosity at a single locus-the complementary sex determiner, csd-to develop as females. Individuals that are homozygous at csd develop as either infertile or subfertile diploid males or not at all.

Exposure to Ambient Particulate Matter Is Associated With Accelerated Functional Decline in Idiopathic Pulmonary Fibrosis.

Background: Idiopathic pulmonary fibrosis (IPF), a progressive disease with an unknown pathogenesis, may be due in part to an abnormal response to injurious stimuli by alveolar epithelial cells. Air pollution and particulate inhalation of matter evoke a wide variety of pulmonary and systemic inflammatory diseases. We therefore hypothesized that increased average ambient particulate matter (PM) concentrations would be associated with an accelerated rate of decline in FVC in IPF.

Structures and properties of phosphate-based bioactive glasses from computer simulation: a review.

Phosphate-based bioactive glasses (PBGs) dissolve harmlessly in the body with a dissolution rate which depends sensitively on composition. This makes them proposed vectors for e.g.

Shining Light on the Function of NPH3/RPT2-Like Proteins in Phototropin Signaling.

NRL proteins coordinate different aspects of phototropin signaling through signaling processes that are conserved in land plants and algae.

Clinical Risk Factors and Prognostic Model for Primary Graft Dysfunction after Lung Transplantation in Patients with Pulmonary Hypertension.

Rationale: Pulmonary hypertension from pulmonary arterial hypertension or parenchymal lung disease is associated with an increased risk for primary graft dysfunction after lung transplantation.

Objective: We evaluated the clinical determinants of severe primary graft dysfunction in pulmonary hypertension and developed and validated a prognostic model.

Methods: We conducted a retrospective cohort study of patients in the multicenter Lung Transplant Outcomes Group with pulmonary hypertension at transplant listing.

Antiseptics for burns.

Background: Burn wounds cause high levels of morbidity and mortality worldwide. People with burns are particularly vulnerable to infections; over 75% of all burn deaths (after initial resuscitation) result from infection. Antiseptics are topical agents that act to prevent growth of micro-organisms.

Functional characterization of a constitutively active kinase variant of phototropin 1.

Phototropins (phots) are plasma membrane-associated serine/threonine kinases that coordinate a range of processes linked to optimizing photosynthetic efficiency in plants. These photoreceptors contain two light-, oxygen-, or voltage-sensing (LOV) domains within their N terminus, with each binding one molecule of flavin mononucleotide as a UV/blue light-absorbing chromophore. Although phots contain two LOV domains, light-induced activation of the C-terminal kinase domain and subsequent receptor autophosphorylation is controlled primarily by the A'α-LOV2-Jα photosensory module.

Selective sweeps of mitochondrial DNA can drive the evolution of uniparental inheritance.

Although the uniparental (or maternal) inheritance of mitochondrial DNA (mtDNA) is widespread, the reasons for its evolution remain unclear. Two main hypotheses have been proposed: selection against individuals containing different mtDNAs (heteroplasmy) and selection against "selfish" mtDNA mutations. Recently, uniparental inheritance was shown to promote adaptive evolution in mtDNA, potentially providing a third hypothesis for its evolution.

SipA Activation of Caspase-3 Is a Decisive Mediator of Host Cell Survival at Early Stages of Salmonella enterica Serovar Typhimurium Infection.

invasion protein A (SipA) is a dual-function effector protein that plays roles in both actin polymerization and caspase-3 activation in intestinal epithelial cells. To date its function in other cell types has remained largely unknown despite its expression in multiple cell types and its extracellular secretion during infection. Here we show that in macrophages SipA induces increased caspase-3 activation early in infection.

Bone loss with antiepileptic drug therapy: a twin and sibling study.

Unlabelled: Changes in areal bone mineral density (aBMD) and other predictors of bone loss were evaluated in 48 same-sex twin/age-matched sibling pairs discordant for antiepileptic drug (AED) use. AED users had reduced BMD at the hip regions. Prolonged AED users had greater aBMD loss, predicting a higher risk of bone fragility.

Influential factors on treatment decision making among patients with colorectal cancer: A scoping review.

Purpose: In recent years, a greater emphasis has been placed on shared decision-making (SDM) techniques between providers and patients with the goal of helping patients make informed decisions about their care and subsequently to improve patient health outcomes. Previous research has shown variability in treatment decision-making among patients with colorectal cancer (CRC), and there is little comprehensive information available to help explain this variability. Thus, the purpose of this study was to evaluate the current state of the literature on factors that are influential in treatment decision-making among patients with CRC.

A metric of our own: Failure to rescue after trauma.

Background: Failure to rescue (FTR) is defined as death after an adverse event. The original metric was derived in elective surgical populations and reclassifies deaths not preceded by recorded adverse events as FTR cases under the assumption these deaths resulted from missed adverse events. This approach lacks face validity in trauma because patients often die without adverse events as a direct result of injury.

Fifty Years of Research in ARDS. Genomic Contributions and Opportunities.

Clinical factors alone poorly explain acute respiratory distress syndrome (ARDS) risk and ARDS outcome. In the search for individual factors that may influence ARDS risk, the past 20 years have witnessed the identification of numerous genes and genetic variants that are associated with ARDS. The field of ARDS genomics has cycled from candidate gene association studies to bias-free approaches that identify new candidates, and increasing effort is made to understand the functional consequences that may underlie significant associations.

Models of Lung Transplant Research: a consensus statement from the National Heart, Lung, and Blood Institute workshop.

Lung transplantation, a cure for a number of end-stage lung diseases, continues to have the worst long-term outcomes when compared with other solid organ transplants. Preclinical modeling of the most common and serious lung transplantation complications are essential to better understand and mitigate the pathophysiological processes that lead to these complications. Various animal and in vitro models of lung transplant complications now exist and each of these models has unique strengths.