Mitochondrial proteins Bnip3 and Bnip3L are involved in anthrax lethal toxin-induced macrophage cell death

Anthrax lethal toxin (LeTx) induces rapid cell death of RAW246.7 macrophages. We recently found that a small population of these macrophages is spontaneously and temporally refractory to LeTx-induced cytotoxicity. Analysis of genome-wide transcripts of a resistant clone before and after regaining LeTx sensitivity revealed that a reduction of two closely related mitochondrial proteins, Bcl-2/adenovirus E1B 19-kDa interacting protein 3 (Bnip3) and Bnip3-like (Bnip3L), correlates with LeTx resistance. Down-regulation of Bnip3 and Bnip3L was also found in "toxin-induced resistance" whereby sublethal doses of LeTx induce resistance to subsequent exposure to cytolytic toxin doses. The role of Bnip3 and Bnip3L in LeTx-induced cell death was confirmed by showing that overexpression of either Bnip3 or Bnip3L rendered the resistant cells susceptible to LeTx, whereas down-regulation of Bnip3 and Bnip3L in wild-type macrophages conferred resistance. The down-regulation of Bnip3 and Bnip3L mRNAs by LeTx occurred at both transcriptional and mRNA stability levels. Inhibition of the p38 pathway by lethal factor was responsible for the destabilization of Bnip3/Bnip3L mRNAs as confirmed by showing that p38 inhibitors stabilized Bnip3 and Bnip3L mRNAs and conferred resistance to LeTx cytotoxicity. Therefore, Bnip3/Bnip3L play a crucial role in LeTx-induced cytotoxicity, and down-regulation of Bnip3/Bnip3L is a mechanism of spontaneous or toxin-induced resistance of macrophages.

Sudden death and sudden birth of entanglement in common structured reservoirs

We study the exact entanglement dynamics of two qubits in a common structured reservoir. We demonstrate that for certain classes of entangled states, entanglement sudden death occurs, while for certain initially factorized states, entanglement sudden birth takes place. The backaction of the non-Markovian reservoir is responsible for revivals of entanglement after sudden death has occurred, and also for periods of disentanglement following entanglement sudden birth.

Preferences for place of care and place of death among informal caregivers of the terminally ill

Objectives: (1) To determine informal caregivers perceptions about place of care and place of death; and (2) to identify variables associated with a home death among terminally ill individuals who received in-home support services in a publicly funded home care system. Participants and design: A total of 216 informal caregivers participated in a bereavement interview. Data collection included care recipient and informal caregiver characteristics, the use of and satisfaction with community services, and preferences about place of death. Results: Most caregivers reported that they and the care recipient had a preferred place of death (77 and 68%, respectively) with over 63% reporting home as the preferred place of death. Caregivers had a greater preference for an institutional death (14%) than care recipients (4.7%). While 30% of care recipients did not die in their preferred location, most caregivers (92%) felt, in retrospect, that where the care recipient died was the appropriate place of death. Most caregivers reported being satisfied with the care that was provided. The odds of dying at home were greater when the care recipient stated a preference for place of death (OR: 2.92; 95% CI: 1.25, 6.85), and the family physician made home visits during the care recipients last month of life (Univariate odds ratios (OR): 4.42; 95% CI: 1.46, 13.36). Discussion: The ethic of self-control and choice for the care recipient must be balanced with consideration for the well being of the informal caregiver and responsiveness of the community service system. © 2005 Edward Arnold (Publishers) Ltd.

Factors associated with home death for individuals who receive homesupportservices:A retrospective cohort study

Objectives: To determine the factors associated with a home death among older adults who received palliative care nursing home services in the home. Methods: The participants in this retrospective cohort study were 151 family caregivers of patients who had died approximately 9 months prior to the study telephone interview. The interview focused on the last year of life and covered two main areas, patient characteristics and informal caregiver characteristics. Results: Odds ratios [OR] and 95% confidence intervals [95% CI] were used to determine which of the 15 potential informal caregiver and seven patient predictor variables were associated with dying at home. Multivariate analysis revealed that the odds of dying at home were greater when the patient lived with a caregiver [OR = 7.85; 95% CI = (2.35, 26.27)], the patient stated a preference to die at home [OR= 6.51; 95% CI = (2.66,15.95)], and the family physician made home visits [OR = 4.79; 95% CI = (1.97,11.64)]. However the odds were lower for patients who had caregivers with fair to poor health status [OR = 0.22; 95% CI = (0.07, 0.65)] and for patients who used hospital palliative care beds [OR = 0.31; 95% CI = (0.12, 0.80)]. Discussion: The findings suggest that individuals who indicated a preference to die at home and resided with a healthy informal caregiver had better odds of dying at home. Home visits by a family physician were also associated with dying at home.

A shared care model pilot for palliative home care in a rural area:Impact on symptoms, distress, and place of death

Context: Shared care models integrating family physician services with interdisciplinary palliative care specialist teams are critical to improve access to quality palliative home care and address multiple domains of end-of-life issues and needs. Objectives: To examine the impact of a shared care pilot program on the primary outcomes of symptom severity and emotional distress (patient and family separately) over time and, secondarily, the concordance between patient preferences and place of death. Methods: An inception cohort of patients (n = 95) with advanced, progressive disease, expected to die within six months, were recruited from three rural family physician group practices (21 physicians) and followed prospectively until death or pilot end. Serial measurement of symptoms, emotional distress (patient and family), and preferences for place of death was performed, with analysis of changes in distress outcomes assessed using t-tests and general linear models. Results: Symptoms trended toward improvement, with a significant reduction in anxiety from baseline to 14 days noted. Symptom and emotional distress were maintained below high severity (7-10), and a high rate of home death compared with population norms was observed. Conclusion: Future controlled studies are needed to examine outcomes for shared care models with comparison groups. Shared care models build on family physician capacity and as such are promising in the development of palliative home care programs to improve access to quality palliative home care and foster health system integration. © 2011 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

"they don't just disappear":Acknowledging death in the long-term care setting

Objective: The purpose of this study was to describe the value of a formal room blessing ritual held within a long-term care facility, from the perspectives of staff, residents, and family members. Method: A qualitative research study involving interviews with staff, residents, and family members was conducted to examine the perceived value of a room blessing ritual. Results: Twenty-four room blessing attendees participated in the study (nine staff, eight residents, and seven family members). Attendees felt that the room blessing provided an opportunity to formally acknowledge the death of the resident and their grief; the majority felt that this was a positive experience and that it provided an element of closure. Staff members and residents expressed their appreciation for the opportunity to connect with family members of the deceased to express their condolences during the ritual. Participants also identified the inclusivity of the ritual (i.e., an open invitation to all staff, residents, and family members) as a positive aspect that served as a reminder that others shared in their grief. Staff members felt that blessing the room for the new resident was an important component of the ritual, helping to bridge the gap between mourning and welcoming a new person. Staff, residents, and family members felt that the room blessing positively reflected the mission and values of the facility. The most highly valued aspect of the ritual for all attendees was the sharing of stories about the deceased to celebrate that person's life. Significance of results: Long-term care facilities need to recognize that formal supports to manage the bereavement needs of staff and residents, such as a room blessing ritual, should be incorporated into their model for managing end-of-life care, given the relationship between the emotional health of staff and the quality of care provided for residents. © 2012 Cambridge University Press.

Desire for hastened death in patients with advanced disease and the evidence base of clinical guidelines:a systematic review

Patients' desire for hastened death within the context of advanced disease and palliative care is a controversial topic, frequently discussed in the international literature. Much of the discussion has focused on opinion and debate about ethical matters related to hastened death. Not many research studies seem to have specifically targeted why palliative care patients may desire hastened death, and few have focused on clinical guidelines for responding to such requests.