Mapping the dynamics of Nrf2 antioxidant and NFκB inflammatory responses by soft electrophilic chemicals in human liver cells defines the transition from adaptive to adverse responses.

A comprehensive understanding of the dynamic activation and crosstalk between different cellular stress response pathways that drive cell adversity is crucial in chemical safety assessment. Various chemicals have electrophilic properties that drive cell injury responses in particular oxidative stress signaling and inflammatory signaling. Here we used bacterial artificial chromosome-based GFP cellular stress reporters with live cell confocal imaging, to systematically monitor the differential modulation of the dynamics of stress pathway activation by six different soft electrophiles: sulforaphane, andrographolide, diethyl maleate, CDDO-Me, ethacrynic acid and tert-butyl hydroquinone. The various soft electrophiles showed differential potency and dynamics of Nrf2 activation and nuclear translocation. These differences in Nrf2 dynamics correlated with distinct activation pattern of Nrf2 downstream targets SRNX1 and HMOX1. All soft electrophiles caused a strong dose dependent suppression of a cytokine-induced NFĸB response represented by suppression of NFĸB nuclear oscillation and inhibition of the downstream target gene activation A20 and ICAM1, which followed the potency of Nrf2 modulation but occurred at higher concentration close to saturation of Nrf2 activation. RNAi-based depletion of RelA resulted in a prolonged presence of Nrf2 in the nucleus after soft electrophile treatment; depletion of Nrf2 caused the induction of NFĸB signaling and activation of its downstream targets A20 and ICAM1. A systematic transcriptome analysis confirmed these effects by soft electrophiles on Nrf2 and NFκB signaling crosstalk in human induced-pluripotent stem cell-derived hepatocyte-like cells. Altogether our data indicate that modulation of Nrf2 by soft electrophiles may have consequences for efficient inflammatory signaling.

Fractured Care: A Window Into Emergency Transitions in Care for LTC Residents With Complex Health Needs.

Objective: For long-term care (LTC) residents, transfers to emergency departments (EDs) can be associated with poor health outcomes. We aimed to describe characteristics of residents transferred, factors related to decisions during transfer, care received in emergency medical services (EMS), ED settings, outcomes on return to LTC, and times of transfer segments along the transition. Method: We prospectively followed 637 transitions to an ED in British Columbia and Alberta, Canada, over a 12-month period. Data were captured through an electronic Transition Tracking Tool and interviews with health care professionals. Results: Common events triggering transfer were falls (26.8%), sudden change in condition (23.5%), and shortness of breath (19.8%). Discrepancies existed between reason for transfer, EMS reported chief complaint, and ED diagnosis. Many transfers resulted in resident return directly to LTC (42.7%). Discussion: Avoidable transfers may put residents at risk of receiving inappropriate care. Standardized communication strategies to highlight changes in resident condition are warranted.

C-621/15 - W and Others v Sanofi Pasteur: An Example of Judicial Distortion and Indifference to Science.

This case commentary examines the CJEU's recent decision in C-621/15 W and Others v Sanofi Pasteur MSD SNC [2017] ECR I. This commentary critically examines the decision through the lens of the cultural conflict between law and science. We argue that the CJEU's decision reflects both a distortion of scientific knowledge and an improper indifference to the legitimate methods by which scientific knowledge is generated in the context of vaccines. These judicial approaches may, the authors argue, inadvertently fuel the vaccine scepticism that is growing across the developed world, and in particular in Europe.

Invisible no more: a scoping review of the health care aide workforce literature.

BACKGROUND: Healthcare aides (HCAs) are the primary caregivers for vulnerable older persons. They have many titles and are largely unregulated, which contributes to their relative invisibility. The objective of this scoping review was to evaluate the breadth and depth of the HCA workforce literature. METHODS: We conducted a search of seven online bibliographic databases. Studies were included if published since 1995 in English, peer-reviewed journals. Results were iteratively synthesized within and across the following five categories: education, supply, use, demand and injury and illness. RESULTS: Of 5,045 citations screened, 82 studies met inclusion criteria. Few examined HCA education; particularly trainee characteristics, program location, length and content. Results in supply indicated that the average HCA was female, 36-45 years and had an education level of high school or less. Home health HCAs were, on average, older and were more likely to be immigrants than those working in other settings. The review of studies exploring HCA use revealed that their role was unclear - variation in duties, level of autonomy and work setting make describing "the" role of an HCA near impossible. Projected increased demand for HCAs and high rates of turnover, both at the profession and facility-level, elicit predictions of future HCA shortages. Home health HCAs experienced comparatively lower job stability, earned less, worked the fewest hours and were less likely to have fringe benefits than HCAs employed in hospitals and nursing homes. The review of studies related to HCA illness and injury revealed that they were at comparatively higher risk of injury than registered nurses and licensed practical nurses. CONCLUSIONS: This is the largest, most comprehensive scoping review of HCA workforce literature to date. Our results indicate that the HCA workforce is both invisible and ubiquitous; as long as this is the case, governments and healthcare organizations will be limited in their ability to develop and implement feasible, effective HCA workforce plans. The continued undervaluation of HCAs adversely impacts care providers, the institutions they work for and those who depend on their care. Future workforce planning and research necessitates national HCA registries, or at minimum, directories.

Strengthening moral reasoning through dedicated ethics training in dietetic preparatory programs.

Moral reasoning skills, associated with the ability to make ethical decisions effectively, must be purposively fostered. Among health professionals, enhanced moral reasoning is linked to superior clinical performance. Research demonstrates that moral reasoning is enhanced through dedicated, discussion-based ethics education offered over a period of 3-12 weeks. Current dietetic students and practicing dietitians seeking to strengthen their moral reasoning skills can undertake elective ethics education. Further research within dietetic preparatory programs is warranted to better inform the development and implementation of ethics courses.

The Older Persons' Transitions in Care (OPTIC) study: pilot testing of the transition tracking tool.

BACKGROUND: OPTIC is a mixed method Partnership for Health System Improvement (http://www.cihr-irsc.gc.ca/e/34348.html) study focused on improving care for nursing home (NH) residents who are transferred to and from emergency departments (EDs) via emergency medical services (EMS). In the pilot study we tested feasibility of concurrently collecting individual resident data during transitions across settings using the Transition Tracking Tool (T3). METHODS: The pilot study tracked 54 residents transferred from NHs to one of two EDs in two western Canadian provinces over a three month period. The T3 is an electronic data collection tool developed for this study to record data relevant to describing and determining success of transitions in care. It comprises 800+ data elements including resident characteristics, reasons and precipitating factors for transfer, advance directives, family involvement, healthcare services provided, disposition decisions, and dates/times and timing. RESULTS: Residents were elderly (mean age = 87.1 years) and the majority were female (61.8%). Feasibility of collecting data from multiple sources across two research sites was established. We identified resources and requirements to access and retrieve specific data elements in various settings to manage data collection processes and allocate research staff resources. We present preliminary data from NH, EMS, and ED settings. CONCLUSIONS: While most research in this area has focused on a unidirectional process of patient progression from one care setting to another, this study established feasibility of collecting detailed data from beginning to end of a transition across multiple settings and in multiple directions.

A dose-response study of graded reoxygenation on the carotid haemodynamics, matrix metalloproteinase-2 activities and amino acid concentrations in the brain of asphyxiated newborn piglets.

PURPOSE: It is controversial to choose an appropriate oxygen concentration to resuscitate asphyxiated newborns regarding the clinical and biochemical oxidative effects. We examined the vasomotor response to reoxygenation with graded reoxygenation and the effects on matrix metalloproteinases and amino acids of the immature brain. METHODS: Thirty-two piglets (1-3 days, 1.5-2.1 kg) were instrumented for continuous monitoring of left common carotid and pulmonary arterial flows (Transonic). Piglets were randomized to a sham-operated control group (without hypoxia/reoxygenation) or 2 h hypoxia induced by decreasing the inspired oxygen concentration to 10-15%, followed by reoxygenation with 21, 50 or 100% oxygen for 1 h and then 21% oxygen for 3 h (n=8 each). The brains were then flash frozen and analyzed for matrix metalloproteinases and amino acid levels by zymography and HPLC, respectively. RESULTS: After 2 h oxygen deprivation, the absolute carotid flow remained similar but accounted for 38% of cardiac output (increased from 17% at baseline, p=0.001). During early reoxygenation, the flow rose in the piglets resuscitated with air (p<0.05), but not in those with supplemental oxygen. Carotid vascular resistance correlated significantly with the arterial partial pressure of oxygen (r=0.7). There was an oxygen-dependent increase in global cerebral activity of matrix metalloproteinase-2 with specific increases in the basal ganglia of all hypoxic-reoxygenated brains. There were no significant differences in glutamate and other amino acids in any brain regions. CONCLUSIONS: Although using high oxygen concentration to resuscitate asphyxiated newborn piglets increased carotid vascular resistance and cerebral matrix metalloproteinase-2 activity, there is no detrimental effect observed in this acute model of hypoxia-reoxygenation.

Dietary manipulation of fatty acid composition in lamb meat and its effect on the volatile aroma compounds of grilled lamb.

The effect on lamb muscle of five dietary supplements high in polyunsaturated fatty acids (PUFA) was measured. The supplements were linseed oil, fish oil, protected lipid (high in linoleic acid (C18:2 n-6) and α-linolenic acid (C18:3 n-3)), fish oil/marine algae (1:1), and protected lipid/marine algae (1:1). Eicosapentaenoic acid (C20:5 n-3) and docosahexaenoic acid (C22:6 n-3) were found in the highest amounts in the meat from lambs fed diets containing algae. Meat from lambs fed protected lipid had the highest levels of C18:2 n-6 and C18:3 n-3, due to the effectiveness of the protection system. In grilled meat from these animals, volatile compounds derived from n-3 fatty acids were highest in the meat from the lambs fed the fish oil/algae diet, whereas compounds derived from n-6 fatty acids were highest in the meat from the lambs fed the protected lipid diet.