MLKL is the essential effector of necroptosis, a form of programmed lytic cell death. We have isolated a mouse strain with a single missense mutation, MlklD139V, that alters the two-helix ‘brace’ that connects the killer four-helix bundle and regulatory pseudokinase domains. This confers constitutive, RIPK3 independent killing activity to MLKL. Homozygous mutant mice develop lethal postnatal inflammation of the salivary glands and mediastinum. The normal embryonic development of MlklD139V homozygotes until birth, and the absence of any overt phenotype in heterozygotes provides important in vivo precedent for the capacity of cells to clear activated MLKL. These observations offer an important insight into the potential disease-modulating roles of three common human MLKL polymorphisms that encode amino acid substitutions within or adjacent to the brace region. Compound heterozygosity of these variants is found at up to 12-fold the expected frequency in patients that suffer from a pediatric autoinflammatory disease, chronic recurrent multifocal osteomyelitis (CRMO).

Aims and objectives: To evaluate acceptability, efficiency, and quality of a new digital care management system in a residential aged care home (RACH).Background: Improving care quality and efficiency in RACH, while simultaneously upgrading data management, is a priority for communities and governments.Design: Participatory action research with mixed methods data collection was employed to evaluate a digital care management system implemented at a 169-bed RACH. This paper reports qualitative findings of the 2-year evaluation.Methods: Qualitative data were collected using focus groups with residents, visitors, nurses, managers, care workers, and consultants; resident/visitor and staff hallway interviews and responses to open-ended questions in online staff surveys. Data were analysed thematically under the four predetermined study objectives. Reporting adhered to COREQ guidelines.Results: 325 data captures from 88 participants, over seven data sources were coded.Findings indicate that the system was acceptable to both residents and staff due to perceptions of time-saving and improved quality of care. Increased efficiency was perceived through timeliness as well as reduced time spent retrieving and documenting information. Quality of care was improved through care scheduling individualised to resident needs, with reminders to avoid missed care. Relatives were reassured and activities were scheduled to loved one's preferences. The co-design implementation | 175 BAIL et AL.

To systematically evaluate evidence regarding the unmet supportive care needs of men and women affected by chemotherapy induced alopecia (CIA) to inform clinical practice guidelines. Methods:We performed a review of CINAHL, MEDLINE, PsychINFO, Scopus, the Cochrane Library (CCRT and CDSR) controlled trials databases and clinicaltrials.gov from January 1990 to June 2019 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Twenty-seven publications were selected for inclusion in this analysis.Results: Included reports used qualitative (ten) and quantitative (seventeen) studies. Across these studies men and women reported the major impact that CIA had on their psychological well-being, quality of life and body image. Hair loss had a negative impact irrespective of gender, which resulted in feelings of vulnerability and visibility of being a "cancer patient". Men and women described negative feelings, often similar, related to CIA with a range of unmet supportive care needs.Conclusions: Some patients are not well prepared for alopecia due to a lack of information and resources to reduce the psychological burden associated with CIA. Hair loss will affect each patient and their family differently, therefore intervention and support must be tailored at an individual level of need to optimise psychological and physical well-being and recovery.Implications for Cancer Survivors: People affected by CIA may experience a range of unmet supportive care needs and oncology doctors and nurses are urged to use these findings in their everyday consultations to ensure effective, person-centred care and timely intervention to minimise the sequalae associated with CIA.