The inhibitor profiling of the caspase family of proteases using substrate-derived peptide glyoxals.

A series of substrate-based a-keto-ß-aldehyde (glyoxal) sequences have been synthesised and evaluated as inhibitors of the caspase family of cysteine proteases. A number of potent inhibitor sequences have been identified. For example, a palmitic acid containing sequence pal-Tyr-Val-Ala-Asp-glyoxal was demonstrated to be an extremely effective inhibitor of caspase-1, inhibiting not only the action of the protease against synthetic fluorogenic substrates (Ki = 0.3 nM) but also blocking its processing of pro-interleukin-1beta (pro-IL-1ß). In addition, the peptide Ac-Asp-Glu-Val-Asp-glyoxal, which is based on the consensus cleavage sequence for caspase-3, is a potent inhibitor of this protease (Ki = 0.26 nM) yet only functions as a comparatively modest inhibitor of caspase-1 (Ki = 451 nM). Potent inhibitor sequences were also identified for caspases-6 and -8. However, the degree of discrimination between the family members is limited. The ability of Ac-Asp-Glu-Val-Asp-glyoxal to block caspase-3 like activity in whole cells and to delay the development of apoptosis was assessed. When tested against caspase-3 like activity in cell lysates, Ac-Asp-Glu-Val-Asp-glyoxal displayed effective inhibition similar to that observed against recombinant caspase-3. Treatment of whole cells with this potent caspase-3 inhibitor was however, not sufficient to significantly stall the development of apoptosis in-vitro.

Keeping it in the Family: Surviving Political Exile, 1870-1917

A sentence of exile was a regular feature of the Russian revolutionary’s underground career. In order to survive this punishment and continue their struggle against Tsarism, revolutionaries relied on help from their fellow exiles, their party, the Political Red Cross and, often, their families. Historians have rarely acknowledged the role of kin in supporting the revolutionary movement and very few studies have noted the attempts by families to mitigate the worst aspects of a sentence of exile. This article explores the ways in which spouses and siblings, parents and children obtained concessions from the Tsarist authorities regarding their loved ones’ sentences of exile, helped off-set the poverty to which many exiles were reduced, and, above all, combated the sense of loneliness and depression to which those in exile were exposed. This article argues that such familial support had a collective and positive impact on revolutionaries’ experience of exile. More broadly it provides an illuminating case study of the blurred space between public and private which the revolutionary occupied and highlights the way in which the movement depended on help from sympathisers and family members in order to function effectively on a daily basis.

A systematic review of instruments related to family caregivers of palliative care patients

Support for family caregivers is a core function of palliative care. However, there is a lack of consistency in the way needs are assessed, few longitudinal studies to examine the impact of caregiving, and a dearth of evidence-based interventions. In order to help redress this situation, identification of suitable instruments to examine the caregiving experience and the effectiveness of interventions is required. A systematic literature review was undertaken incorporating representatives of the European Association for Palliative Care’s International Palliative Care Family Caregiver Research Collaboration and Family Carer Taskforce. The aim of the review was to identify articles that described the use of instruments administered to family caregivers of palliative care patients (pre and post-bereavement). Fourteen of the 62 instruments targeted satisfaction with service delivery and less than half were developed specifically for the palliative care context. In approximately 25% of articles psychometric data were not reported. Where psychometric results were reported, validity data were reported in less than half (42%) of these cases. While a considerable variety of instruments have been administered to family caregivers, the validity of some of these requires further consideration. We recommend that others be judicious before developing new instruments for this population.

Teaching family carers about home based palliative care: Final results from a group education program

Without the considerable support provided by family carers, many patients receiving palliative care would be unable to remain at home. However, family carers typically lack the required information and skills to prepare them for such a role. Pilot work has demonstrated that group education programs for family carers can be readily developed; they are feasible, accessible, and useful. This project sought to build on our pilot research to further examine the effectiveness of a group education program by evaluating the outcomes with a larger number of participants. The program aimed to prepare primary family carers for the role of supporting a relative with advanced, noncurative cancer at home. The psycho-educational program consisted of three consecutive weekly sessions presented in a group format, conducted at six home-based palliative care services across metropolitan and regional Victoria, Australia. The following dependent variables were measured at three time points: carer competence, preparedness, rewards, and information needs. The three time points were: commencement of the program (Time 1), upon completion (Time 2), and two weeks later (Time 3). A total of 156 participants (including the pilot phase) completed Time 1 questionnaires and 96 completed all three time periods (62%). Between Time 1 and Time 2, the intervention had a statistically significant positive effect on preparedness, competence, rewards, and having informational needs met. Outcomes were maintained at Time 3. There was no difference in the effectiveness of the intervention for participants in regional areas compared to participants in metropolitan areas.

This study demonstrated that a group education program to prepare family carers for the role of supporting a dying relative at home was effective. Implications for further research and practice are outlined.

Psychological and social profile of family caregivers upon commencement of palliative care provision

Context
Palliative care services are required to support patients who have advanced, life-threatening, noncurable disease, and their family caregivers. Comprehensive psychological and social support for bereaved family members also is expected. However, recent systematic reviews have demonstrated significant gaps in evidence-based approaches for such support. Furthermore, a comprehensive understanding of the psychological and social response to the family caregiver role is required for support to be optimized.

Objectives
We sought to examine the psychological and social profile of family caregivers on commencement of receiving palliative care services.

Methods
A self-report questionnaire was administered to primary family caregivers of patients within two weeks of admission to three palliative care services in Melbourne, Australia. The questionnaire incorporated six instruments that measured 11 family caregiver-related psychosocial factors; four instruments that measured caregiver psychological distress factors; 14 mental health lifetime risk factors; and a sociodemographic questionnaire.

Results
Three hundred and two family caregivers participated. Nearly half (44%) of the caregivers had a probable anxiety and/or depressive disorder, with 40% scoring more than the cutoff score for probable anxiety and 20% scoring more than the cutoff score for probable depression. Additionally, approximately 15% of caregivers met the criteria for pre-loss grief, and around 10% reported moderate to severe levels of demoralization. Caregivers who had a probable anxiety and/or depressive disorder also reported higher levels of pre-loss grief.

Conclusion
This study provides further evidence of the prevalence of poor psychosocial well-being in this population. The results reinforce the need to develop suitable strategies for psychological and social support for family caregivers.