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Bowlby remained attached to his psychoanalytic roots and conceptualised treatment in terms of one-to-one relationships, albeit acknowledging the need for a family formulation. Bowlby's five therapeutic tasks were never adapted to the current understanding of working with the relationships fostering the development and maintenance of children's attachment strategies. This paper goes through each of Bowlby's five tasks and adapts them to our current understanding of development, with consequences for prioritising family approaches, rather than a secure base alone with a therapist. In doing so I will review the process of achieving security, seeing it as more similar to an allostatic process than a state of homeostasis.

Diagnostic systems are not conducive to compassionate health-bringing psychiatric treatment. The systems were built around the fallacy that the politics of biomedicine could be reliably applied to the emergent properties of human psychological suffering and enable diagnosis-specific treatment packages. The resulting industrialised medicine, which reified people, failed to facilitate the compassion needed for healing. This article outlines an approach to psychiatric practice that involves understanding children's suffering and vulnerabilities in terms of their attachment strategies and adaptation to their context and takes a mindful approach to developing compassionate collaborative treatment goals (intelligent kindness). A shift towards mindful psychiatric medicine would encourage politicians to serve the people by addressing the contexts associated with human suffering and what makes people vulnerable, especially social inequalities. Healthy societies in which the psychiatric dis-ease of the population is adequately addressed will not be built with limited biomedical understanding of dis-ease.

Cellular homoeostatic pathways such as macroautophagy (hereinafter autophagy) are regulated by basic mechanisms that are conserved throughout the eukaryotic kingdom. However, it remains poorly understood how these mechanisms further evolved in higher organisms. Here we describe a modification in the autophagy pathway in vertebrates, which promotes its activity in response to oxidative stress. We have identified two oxidation-sensitive cysteine residues in a prototypic autophagy receptor SQSTM1/p62, which allow activation of pro-survival autophagy in stress conditions. The Drosophila p62 homologue, Ref(2)P, lacks these oxidation-sensitive cysteine residues and their introduction into the protein increases protein turnover and stress resistance of flies, whereas perturbation of p62 oxidation in humans may result in age-related pathology. We propose that the redox-sensitivity of p62 may have evolved in vertebrates as a mechanism that allows activation of autophagy in response to oxidative stress to maintain cellular homoeostasis and increase cell survival. The cellular mechanisms underlying autophagy are conserved; however it is unclear how they evolved in higher organisms. Here the authors identify two oxidation-sensitive cysteine residues in the autophagy receptor SQSTM1/p62 in vertebrates which allow activation of pro-survival autophagy in stress conditions.

Macroautophagy can regulate cell signalling and tumorigenesis via elusive molecular mechanisms. We establish a RAS mutant cancer cell model where the autophagy gene ATG5 is dispensable in A549 cells in vitro, yet promotes tumorigenesis in mice. ATG5 represses transcriptional activation by the TGFβ-SMAD gene regulatory pathway. However, autophagy does not terminate cytosolic signal transduction by TGFβ. Instead, we use proteomics to identify selective degradation of the signalling scaffold TRAF3. TRAF3 autophagy is driven by RAS and results in activation of the NF-κB family member RELB. We show that RELB represses TGFβ target promoters independently of DNA binding at NF-κB recognition sequences, instead binding with SMAD family member(s) at SMAD-response elements. Thus, autophagy antagonises TGFβ gene expression. Finally, autophagy-deficient A549 cells regain tumorigenicity upon SMAD4 knockdown. Thus, at least in this setting, a physiologic function for autophagic regulation of gene expression is tumour growth. Macroautophagy can regulate cell signalling and tumorigenesis but the molecular mechanisms are unclear. Here the authors show selective degradation of the signalling scaffold TRAF3 by autophagy and consequent activation of the NF-κB family member RELB regulate gene expression via antagonism of SMAD proteins.

K-Ras dependent non-small cell lung cancer (NSCLC) cells are 'addicted' to basal autophagy that reprograms cellular metabolism in a lysosomal-sensitive manner. Here we demonstrate that the xenophagy-associated kinase TBK1 drives basal autophagy, consistent with its known requirement in K-Ras-dependent NSCLC proliferation. Furthermore, basal autophagy in this context is characterised by sequestration of the xenophagy cargo receptor Ndp52 and its paralogue Tax1bp1, which we demonstrate here to be a bona fide cargo receptor. Autophagy of these cargo receptors promotes non-canonical NF-κB signalling. We propose that this TBK1-dependent mechanism for NF-κB signalling contributes to autophagy addiction in K-Ras driven NSCLC.

I present a rationale for two different types of in-patient child psychiatric unit: 24/7 intensive units and 24/5 child and family units. Intensive units address safety requirements. The developing personality of young people is at the centre of in-patient approaches on the child and family units. This requires attachment-informed practice. Families must always be involved and placement of units must facilitate their participation. The primary skill characterising these units is use of the milieu for therapy and combining this with family therapy. In other words, nurses and allied professionals need to be the dominant force in unit development, under the reflective guidance of consultants and clinical psychologists.

In the event of an incident involving the release of a hazardous chemical, first responders may decide to initiate emergency decontamination in order to remove any contaminant from affected casualties. Recent initiatives such as the UK Home Office-led Initial Operational Response Programme have introduced new evidence-based decontamination protocols that reduce the time taken to initiate the decontamination process, including an increased emphasis on rapidly removing contaminated clothing (disrobe), and the use of improvised dry decontamination methods. The current study used a series of focus groups to examine public perceptions of different decontamination interventions and responder management strategies. Results revealed that a decontamination shower was perceived to be more effective than dry decontamination methods and that a management strategy that included effective responder communication resulted in increased willingness to comply with the need for decontamination. This study demonstrates that public understanding and acceptance of novel decontamination methods such as dry decontamination may present additional challenges for first responders. Increased emphasis on effective communication during decontamination is needed. Furthermore, provision of information during the focus group study resulted in an increase in participants' knowledge and confidence in taking recommended decontamination actions, which was maintained three months after the study. The longitudinal nature of these effects suggest that it may be possible to increase public awareness about actions to take during chemical incidents by developing pre-incident public education; however, further research is needed to examine this more fully.

BackgroundChildren undergoing surgery and their parents are at risk of developing post-traumatic stress reactions. We systematically reviewed the literature to understand the prevalence of this issue, as well as potential risk factors.MethodsWe conducted a systematic review and meta-analysis, using PubMed, PsycInfo, Web of Science and Google Scholar, with searches conducted in February 2021. Papers were included if they measured post-traumatic stress in children and/or parents following paediatric surgery and were excluded if they did not use a validated measure of post-traumatic stress. Data were extracted from published reports.FindingsOur search yielded a total of 1672 papers, of which 16 met our inclusion criteria. In meta-analysis, pooled studies of children estimated an overall prevalence of 16% meeting criteria for post-traumatic stress disorder post surgery (N=187, 95% CI 5% to 31%, I2=80%). After pooling studies of parents, overall prevalence was estimated at 23% (N=1444, 95% CI 16% to 31%, I2=91%). Prevalence rates were higher than those reported in the general population. Risk factors reported within studies included length of stay, level of social support and parental mental health.InterpretationThere is consistent evidence of traumatic stress following surgery in childhood which warrants further investigation. Those delivering surgical care to children would benefit from a raised awareness of the potential for post-traumatic stress in their patients and their families, including offering screening and support.

Skin function is not limited to a physical barrier. According to its total surface area, it is also considered as an extra-hepatic metabolizing organ. In vitro engineered human skins have been developed to replace limited ex vivo normal human skin samples (NHS). Thus, assessing and comparing skin models from SkinEthic [Episkin™, RHE™ and the full thickness model (FTM)] with NHS in terms of metabolic capability are essential. The apparent activities of main cutaneous isoforms of cytochrome P450-dependent monooxygenases (CYP1A1/1B1, 2B6/2C18/2E1, 3A5/3A7), esterase, glutathione- S -[(GST), A, M, P, T], N -acetyl-(NAT1), uridinyl-diphosphate glucuronyl-(UDPGT 1A family) and sulfo-(SULT1A1) transferases were determined using probe substrates. Mean activities indicative of CYP1A1/1B1 (expressed as pmol/mg protein/6 h) in RHE™ (2.8) and FTM (2.6) were very similar to NHS (3.0) while Episkin™ showed a higher activity (9.1). Activities of CYP3A5/3A7 in FTM (3.3) and Episkin™ (3.6) were similar to NHS (3.8) while activity in RHE™ (13.3) was higher. CYP2B6/2C18/2E1 activity was below LOQ (0.5) in all skin models and NHS. Comparable intrinsic metabolic clearances were measured between NHS and skin models for esterase, UDPGT, GST and NAT1 activities. SULT1A1 activity toward probe substrates was not detected in skin models and observed at the limit of detection in NHS. Weak cytochrome P450-dependent monooxygenases, high esterase and transferase activities suggested that NHS and skin models exhibited limited functionalization and much greater detoxification (hydrolytic and conjugating) capacities. These results demonstrate that skin models are similar to NHS in terms of metabolic functionality toward xenobiotics investigated and useful tools to assess both the local efficiency and safety of cosmetics.