Autoethnographic Reflections on Mental Distress and Medication Management: Conceptualising Biomedical and Recovery Models of Mental Health.

This article uses autoethnography to explore the author's lived experiences of mental distress and how she has conceptualised and explained these symptoms to herself using both the biomedical and recovery models of care. Autoethnography is a process of personal reflection that enables connection between the personal and the political. Experiences of mental distress are recounted alongside the decision to reduce medication.

Exploring the Efficacy of an Online Training Programme to Introduce Mental Health Recovery to Carers.

Family carers often support people with mental ill-health, however, there is a dearth of research on the importance of recovery to mental health carers. This article describes the delivery and qualitative evaluation of an online training programme on recovery to a group of eleven carers. The participants considered their understanding of the meaning of recovery, differentiating between its personal and clinical nature.

At the Crossroads of Life and Death: The Proteins That Influence Cell Fate Decisions.

When a cell is damaged, it must decide how to respond. As a consequence of a variety of stresses, cells can induce well-regulated programmes such as senescence, a persistent proliferative arrest that limits their replication. Alternatively, regulated programmed cell death can be induced to remove the irreversibly damaged cells in a controlled manner.

Experiences of Being Cared-For: The Perspective of an Expert-by-Experience in Mental Health.

It is difficult to understand what it feels like for people with mental ill-health to be cared-for and supported by family members; this experience is often little-explored. Narratives about caring have been increasingly written alongside first-person accounts of recovery, however, there is a dearth of literature written to gain the perspective of being cared-for because of mental distress. Thus, using autoethnography, I present three critical incidents occurring at different points in my recovery to enable exploration of experiences of being cared-for.

Shared Decision-Making: An Autoethnography About Service User Perspectives in Making Choices About Mental Health Care and Treatment.

Shared decision-making (SDM) between mental health medication prescribers and service users is a central pillar in the recovery approach, because it supports people experiencing mental ill-health to explore their care and treatment options to promote their well-being and to enable clinicians to gain knowledge of the choices the service user prefers. SDM is receiving increasing recognition both in the delivery of physical and mental health services; and as such, is of significance to current practice. As an expert-by-experience with over 30 years of receiving mental health treatment, I have made many choices about taking medication and accessing other forms of support.

Exorcising memories of internalised stigma: The demons of lived experience.

Public stigma and self-stigma impact negatively on the lives of people with mental health issues. Many people in society stereotype and discriminate against people with mental ill-health, and often this negative process of marginalisation is internalised by people with lived experiences. Thus, this negative internalisation leads to the development of self-stigma.

Cryo-EM structural analysis of FADD:Caspase-8 complexes defines the catalytic dimer architecture for co-ordinated control of cell fate.

Regulated cell death is essential in development and cellular homeostasis. Multi-protein platforms, including the Death-Inducing Signaling Complex (DISC), co-ordinate cell fate via a core FADD:Caspase-8 complex and its regulatory partners, such as the cell death inhibitor c-FLIP. Here, using electron microscopy, we visualize full-length procaspase-8 in complex with FADD.

Targeting cell death signalling in cancer: minimising 'Collateral damage'.

Targeting apoptosis for the treatment of cancer has become an increasingly attractive strategy, with agents in development to trigger extrinsic apoptosis via TRAIL signalling, or to prevent the anti-apoptotic activity of BCL-2 proteins or inhibitor of apoptosis (IAP) proteins. Although the evasion of apoptosis is one of the hallmarks of cancer, many cancers have intact apoptotic signalling pathways, which if unblocked could efficiently kill cancerous cells. However, it is becoming increasing clear that without a detailed understanding of both apoptotic and non-apoptotic signalling, and the key proteins that regulate these pathways, there can be dose-limiting toxicity and adverse effects associated with their modulation.

BMX Negatively Regulates BAK Function, Thereby Increasing Apoptotic Resistance to Chemotherapeutic Drugs.

The ability of chemotherapeutic agents to induce apoptosis, predominantly via the mitochondrial (intrinsic) apoptotic pathway, is thought to be a major determinant of the sensitivity of a given cancer to treatment. Intrinsic apoptosis, regulated by the BCL2 family, integrates diverse apoptotic signals to determine cell death commitment and then activates the nodal effector protein BAK to initiate the apoptotic cascade. In this study, we identified the tyrosine kinase BMX as a direct negative regulator of BAK function.

Resistance to UV-induced apoptosis by β-HPV5 E6 involves targeting of activated BAK for proteolysis by recruitment of the HERC1 ubiquitin ligase.

UV exposure is the main etiological agent in the development of non-melanoma skin cancer (NMSC), but mounting evidence suggests a co-factorial role for β-genus HPV types early in tumor initiation or progression. UV damage initiates an apoptotic response, driven at the mitochondrial level by BCL-2 family proteins, that eliminates damaged cells that may accumulate deleterious mutations and acquire tumorigenic properties. BAK is a pro-apoptotic BCL-2 protein that functions ultimately to form pores that permeabilize the mitochondrial outer membrane, thereby committing a cell to death, a process involving changes in BAK phosphorylation and conformation.

Blockade of the BAK hydrophobic groove by inhibitory phosphorylation regulates commitment to apoptosis.

The BCL-2 family protein BAK is a key regulator of mitochondrial apoptosis. BAK activation first involves N-terminal conformational changes that lead to the transient exposure of the BAK BH3 domain that then inserts into a hydrophobic groove on another BAK molecule to form symmetric dimers. We showed recently that post-translational modifications are important in the regulation of BAK conformational change and multimerization, with dephosphorylation at tyrosine 108 constituting an initial step in the BAK activation process.

Intra-individual and inter-individual variation in breath alcohol pharmacokinetics: The effect of food on absorption.

Eight male and 8 female subjects underwent serial breath alcohol concentration (BrAC) measurements in the fasting state, following a snack of crisps and following a light meal. BrAC versus time curves were constructed for each subject and the values of peak BrAC (C(max)), theoretical (extrapolated) BrAC at zero time (C(0)), time taken to reach peak (T(max)) and rate of elimination (ß) were recorded directly from the curves. In all subjects values of C(0) extrapolated from the post-meal BrAC-time curves were significantly lower than in the fasting and snack fed states.

"Licensed to kill": tyrosine dephosphorylation and Bak activation.

The genomes of multi-cellular organisms are under constant assault from a host of environmental agents. The efficient elimination of cells harbouring damage is essential to avoid the accumulation of deleterious changes that may promote tumorigenesis. Consequently, a complex and elaborate series of damage responses have evolved to either ensure that correct repair of the DNA has been carried out, or alternatively, to initiate programmes that result in the ablation of the damaged cell.

Tyrosine dephosphorylation is required for Bak activation in apoptosis.

Activation of the cell-death mediator Bak commits a cell to mitochondrial apoptosis. The initial steps that govern Bak activation are poorly understood. To further clarify these pivotal events, we have investigated whether post-translational modifications of Bak impinge on its activation potential.