HEARTBiT: A Transcriptomic Signature for Excluding Acute Cellular Rejection in Adult Heart Allograft Patients.

Background: Nine mRNA transcripts associated with acute cellular rejection (ACR) in previous microarray studies were ported to the clinically amenable NanoString nCounter platform. Here we report the diagnostic performance of the resulting blood test to exclude ACR in heart allograft recipients: HEARTBiT.

Methods: Blood samples for transcriptomic profiling were collected during routine post-transplantation monitoring in 8 Canadian transplant centres participating in the Biomarkers in Transplantation initiative, a large (n = 1622) prospective observational study conducted between 2009 and 2014.

Incidence and etiology of postoperative neurological symptoms after peripheral nerve block: a retrospective cohort study.

Background: Nerve injury from peripheral nerve block (PNB) is an uncommon but potentially serious complication. We present a retrospective cohort study to evaluate the incidence and etiology of new postoperative neurological symptoms after surgery and regional anesthesia.

Methods: We performed a retrospective cohort study of all PNBs performed on elective orthopedic and plastic surgical patients over 6 years (2011-2017).

Ensembling Electrical and Proteogenomics Biomarkers for Improved Prediction of Cardiac-Related 3-Month Hospitalizations: A Pilot Study.

Background: Many risk models for predicting mortality, hospitalizations, or both in patients with heart failure have been developed but do not have sufficient discriminatory ability. The purpose of this study was to identify predictive biomarkers of hospitalizations in heart failure patients using omics-based technologies applied to blood and electrical monitoring of the heart.

Methods: Blood samples were collected from 58 heart failure patients during enrollment into this study.

Association of Serum MiR-142-3p and MiR-101-3p Levels with Acute Cellular Rejection after Heart Transplantation.

Background: Identifying non-invasive and reliable blood-derived biomarkers for early detection of acute cellular rejection in heart transplant recipients is of great importance in clinical practice. MicroRNAs are small molecules found to be stable in serum and their expression patterns reflect both physiological and underlying pathological conditions in human.

Methods: We compared a group of heart transplant recipients with histologically-verified acute cellular rejection (ACR, n = 26) with a control group of heart transplant recipients without allograft rejection (NR, n = 37) by assessing the levels of a select set of microRNAs in serum specimens.

Obstructive sleep apnea, pain, and opioids: is the riddle solved?

Purpose Of Review: Perioperative opioid-based pain management of patients suffering from obstructive sleep apnea (OSA) may present challenges because of concerns over severe ventilatory compromise. The interaction between intermittent hypoxia, sleep fragmentation, pain, and opioid responses in OSA, is complex and warrants a special focus of perioperative outcomes research.

Recent Findings: Life-threatening opioid-related respiratory events are rare.

Proteomic biomarkers of recovered heart function.

Aims: Chronic heart failure is a costly epidemic that affects up to 2% of people in developed countries. The purpose of this study was to discover novel blood proteomic biomarker signatures of recovered heart function that could lead to more effective heart failure patient management by both primary care and specialty physicians.

Methods And Results: The discovery cohort included 41 heart transplant patients and 20 healthy individuals.

Computational biomarker pipeline from discovery to clinical implementation: plasma proteomic biomarkers for cardiac transplantation.

Recent technical advances in the field of quantitative proteomics have stimulated a large number of biomarker discovery studies of various diseases, providing avenues for new treatments and diagnostics. However, inherent challenges have limited the successful translation of candidate biomarkers into clinical use, thus highlighting the need for a robust analytical methodology to transition from biomarker discovery to clinical implementation. We have developed an end-to-end computational proteomic pipeline for biomarkers studies.

Nitazoxanide stimulates autophagy and inhibits mTORC1 signaling and intracellular proliferation of Mycobacterium tuberculosis.

Tuberculosis, caused by Mycobacterium tuberculosis infection, is a major cause of morbidity and mortality in the world today. M. tuberculosis hijacks the phagosome-lysosome trafficking pathway to escape clearance from infected macrophages.

Regulation of mTORC1 signaling by pH.

Background: Acidification of the cytoplasm and the extracellular environment is associated with many physiological and pathological conditions, such as intense exercise, hypoxia and tumourigenesis. Acidification affects important cellular functions including protein synthesis, growth, and proliferation. Many of these vital functions are controlled by mTORC1, a master regulator protein kinase that is activated by various growth-stimulating signals and inactivated by starvation conditions.

Out-of-hospital cardiac arrests occurring in southern Ontario health care clinics: bystander cardiopulmonary resuscitation and automated external defibrillator use.

Objective: To determine the proportion of public-location out-of-hospital cardiac arrests (OHCAs) that occur in health care clinics and to describe bystander cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED) use during these episodes.

Design: Our study was a retrospective cohort study of 679 nontraumatic OHCAs recorded in the Resuscitation Outcomes Consortium Epistry-Cardiac Arrest database.

Setting: Out-of-hospital medical clinics and other public locations in Toronto, Ont, and the surrounding municipal regions of Hamilton, Durham, York, Peel, Simcoe, and Muskoka.

Global analysis of yeast endosomal transport identifies the vps55/68 sorting complex.

Endosomal transport is critical for cellular processes ranging from receptor down-regulation and retroviral budding to the immune response. A full understanding of endosome sorting requires a comprehensive picture of the multiprotein complexes that orchestrate vesicle formation and fusion. Here, we use unsupervised, large-scale phenotypic analysis and a novel computational approach for the global identification of endosomal transport factors.

Palmitoylation by the DHHC protein Pfa4 regulates the ER exit of Chs3.

The yeast chitin synthase Chs3 provides a well-studied paradigm for polytopic membrane protein trafficking. In this study, high-throughput analysis of the yeast deletion collection identifies a requirement for Pfa4, which is an uncharacterized protein with protein acyl transferase (PAT) homology, in Chs3 transport. PATs, which are the enzymatic mediators of protein palmitoylation, have only recently been discovered, and few substrates have been identified.