In Vitro Induction of Human Regulatory T Cells Using Conditions of Low Tryptophan Plus Kynurenines.

Thymic regulatory T cells (tTregs) and induced regulatory T cells (iTregs) suppress murine acute graft-versus-host disease (GVHD). Previously, we demonstrated that the plasmacytoid dendritic cell indoleamine 2,3-dioxygenase (IDO) fosters the in vitro development of human iTregs via tryptophan depletion and kynurenine (Kyn) metabolites. We now show that stimulation of naïve CD4+ T cells in low tryptophan (low Trp) plus Kyn supports human iTreg generation. In vitro, low Trp + Kyn iTregs and tTregs potently suppress T effector cell proliferation equivalently but are phenotypically distinct. Compared with tTregs or T effector cells, bioenergetics profiling reveals that low Trp + Kyn iTregs have increased basal glycolysis and oxidative phosphorylation and use glutaminolysis as an energy source. Low Trp + Kyn iTreg viability was reliant on interleukin (IL)-2 in vitro. Although in vivo IL-2 administration increased low Trp + Kyn iTreg persistence on adoptive transfer into immunodeficient mice given peripheral blood mononuclear cells to induce GVHD, IL-2-supported iTregs did not improve recipient survival. We conclude that low Trp + Kyn create suppressive iTregs that have high metabolic needs that will need to be addressed before clinical translation.

The role of cocaine in fatal crashes: first results of the Québec drug study.

As part of a major undertaking to establish the contribution of drugs in road crashes in Quebec, the present study focuses on the role of cocaine. Coroner, forensic laboratory and police accident records from April 1999 to December 2000 were matched for 265 fatally injured drivers of passenger vehicles. Cocaine was found in 7.9% of urine samples and 6.0% of blood samples. In order to set up a control group, two roadside surveys were conducted in August 1999 and 2000. The survey sample was distributed proportionately to the number of fatal accidents per time of day and day of the week. During both daytime and nighttime, a total of 11,952 drivers participated in the two surveys among which 11,574 provided a breath sample (96.8%), 8,177 a saliva sample (68.4%) and 5,931 a urine sample (49.6%). Cocaine was detected in 1.1% of urine samples and 1.0% of saliva samples of the driving population. In both fatally injured drivers and driving population, cocaine was found mostly (> 90%) in four main types of combination: cocaine alone, cocaine + cannabis, cocaine + alcohol, cocaine + cannabis + alcohol. The data collected allowed two different analyses: a case-control (urine/urine) and a responsibility analysis (case-case approach) that compares cocaine cases to drug-free cases. Despite some data limitations, all analyses for the four main types of combination clearly suggest that cocaine use plays a role in fatal crashes.

Care planning in home care: an exploratory study.

Care Planning is one of the most important responsibilities of the case manager in home care. Research on how care plan decisions are made is scarce in the case management literature. The purpose of this exploratory study was to determine the factors that influence the decision-making process of case managers within the Edmonton Home Care Program (EHCP) when developing care plans. A volunteer sample of six EHCP case managers from three different disciplines was selected: two registered nurses (BScN), two occupational therapists (BScoT), and two social workers (BSW). With the use of fictional case studies, these professionals were asked to construct care plans. Individual semi-structured interviews and a group session permitted in-depth exploration of their decision-making process. Findings suggest that client and/or caregiver characteristics appear to be the most influential in determining care plans. It was also found that case managers are not comfortable with fiscal accountability.