Exploration of the process of implementing Short Term Psychoanalytic Psychotherapy (STPP) within a Child and Adolescent Psychotherapy team working in an NHS Trust: An Interpretative Phenomenological Analysis.

This study aims to explore the implementation of Short-Term Psychoanalytic Psychotherapy (STPP) in Children and Young People’s mental health services (CYPS) in an NHS Trust. It focuses on the perspectives of the Child and Adolescent Psychotherapists (CAPTs), investigating their thoughts and feelings as they implemented STPP. Particular focus is given to how these thoughts and feelings changed over the year of this process. The participants were four qualified CAPTs working across three CYPS within one NHS Trust. This constituted the majority of the Trust’s CAPT team. Data was gathered via transcription of audio recordings of the participant’s interviews at two time points: Time 1 as CAPTs were beginning to use STPP and Time 2 a year into its implementation. Interpretative Phenomenological Analysis was then used to elicit themes from the data. Particular attention was paid to how these themes changed or did not change over the two interview time points. Three relevant superordinate themes were found: Theme 1- Is STPP ‘psychotherapy-light’ ? Existential questions. Theme 2- The ‘hard reality’ of time, could there be ‘enough’ ? Theme 3- ‘People are very depleted’ - the need for organisational holding and containment. The findings are explored and discussed in relation to relevant research and psychoanalytic theory. Reflexivity and the countertransference of the researcher are also used to further embed and illuminate the findings. The fantasies, thoughts and feelings CAPTs have in relation to STPP are central when introducing this way of working. The importance of organisational culture, and a holding and containing environment in allowing space for innovation is highlighted

Epigallocatechin Gallate Modulates Microglia Phenotype to Suppress Pro-Inflammatory Signalling Cues and Inhibit Phagocytosis

Microglia are crucial players in the pathogenesis of late onset Alzheimer’s Disease (AD), with evidence for both deleterious and beneficial effects. Identifying interventions to modulate microglial responsiveness, to promote Amyloid β (Aβ) clearance, disrupt plaque formation, or to dampen excessive inflammation has therapeutic potential. Bioavailable flavonoids, such as the flavan 3-ols, are of interest due to their antioxidant, metal chelating, signalling and anti-inflammatory potential. Primary microglia were treated with a series of structurally related flavanol 3-ols to assess effects on phagocytosis, cytokine release and transcriptional responses by RNA sequencing. Data indicated that the extent of hydroxylation and the presence of the galloyl moiety were strong determinants of flavan 3-ol activity. Epigallocatechin gallate (EGCG) was the most effective flavan-3-ol tested and strongly inhibited phagocytosis of Aβ independent of any metal chelating properties, suggesting a more direct modulation of microglia responsiveness. EGCG was broadly anti-inflammatory, reducing cytokine release and downregulating transcription, particularly of components of the microglia extracellular matrix such as MMP3 and SerpinB2. Collectively, this brings new insight into the actions of flavonoids on microglial responsiveness with potential implications for the therapeutic use of EGCG and structurally related flavanol-3-ols in AD

TauP301L disengages from the proteosome core complex and neurogranin coincident with enhanced neuronal network excitability

Tauopathies are characterised by the pathological accumulation of misfolded tau. The emerging view is that toxic tau species drive synaptic dysfunction and potentially tau propagation before measurable neurodegeneration is evident, but the underlying molecular events are not well defined. Human non-mutated 0N4R tau (tauWT) and P301L mutant 0N4R tau (tauP301L) were expressed in mouse primary cortical neurons using adeno-associated viruses to monitor early molecular changes and synaptic function before the onset of neuronal loss. In this model tauP301L was differentially phosphorylated relative to tauwt with a notable increase in phosphorylation at ser262. Affinity purification - mass spectrometry combined with tandem mass tagging was used to quantitatively compare the tauWT and tauP301L interactomes. This revealed an enrichment of tauP301L with ribosomal proteins but a decreased interaction with the proteasome core complex and reduced tauP301L degradation. Differences in the interaction of tauP301L with members of a key synaptic calcium-calmodulin signalling pathway were also identified, most notably, increased association with CaMKII but reduced association with calcineurin and the candidate AD biomarker neurogranin. Decreased association of neurogranin to tauP301L corresponded with the appearance of enhanced levels of extracellular neurogranin suggestive of potential release or leakage from synapses. Finally, analysis of neuronal network activity using micro-electrode arrays showed that overexpression of tauP301L promoted basal hyperexcitability coincident with these changes in the tau interactome and implicating tau in specific early alterations in synaptic function

TauP301L disengages from the proteosome core complex and neurogranin coincident with enhanced neuronal network excitability

Tauopathies are characterised by the pathological accumulation of misfolded tau. The emerging view is that toxic tau species drive synaptic dysfunction and potentially tau propagation before measurable neurodegeneration is evident, but the underlying molecular events are not well defined. Human non-mutated 0N4R tau (tauWT) and P301L mutant 0N4R tau (tauP301L) were expressed in mouse primary cortical neurons using adeno-associated viruses to monitor early molecular changes and synaptic function before the onset of neuronal loss. In this model tauP301L was differentially phosphorylated relative to tauwt with a notable increase in phosphorylation at ser262. Affinity purification - mass spectrometry combined with tandem mass tagging was used to quantitatively compare the tauWT and tauP301L interactomes. This revealed an enrichment of tauP301L with ribosomal proteins but a decreased interaction with the proteasome core complex and reduced tauP301L degradation. Differences in the interaction of tauP301L with members of a key synaptic calcium-calmodulin signalling pathway were also identified, most notably, increased association with CaMKII but reduced association with calcineurin and the candidate AD biomarker neurogranin. Decreased association of neurogranin to tauP301L corresponded with the appearance of enhanced levels of extracellular neurogranin suggestive of potential release or leakage from synapses. Finally, analysis of neuronal network activity using micro-electrode arrays showed that overexpression of tauP301L promoted basal hyperexcitability coincident with these changes in the tau interactome and implicating tau in specific early alterations in synaptic function

POZylation: a new approach to enhance nanoparticle diffusion through mucosal barriers

The increasing use of nanoparticles in the pharmaceutical industry is generating concomitant interest in developing nanomaterials that can rapidly penetrate into, and permeate through, biological membranes to facilitate drug delivery and improve the bioavailability of active pharmaceutical ingredients. Here, we demonstrate that the permeation of thiolated silica nanoparticles through porcine gastric mucosa can be significantly enhanced by their functionalization with either 5 kDa poly(2-ethyl-2-oxazoline) or poly(ethylene glycol). Nanoparticle diffusion was assessed using two independent techniques; Nanoparticle Tracking Analysis, and fluorescence microscopy. Our results show that poly(2-ethyl-2-oxazoline) and poly(ethylene glycol) have comparable abilities to enhance diffusion of silica nanoparticles in mucin dispersions and through the gastric mucosa. These findings provide a new strategy in the design of nanomedicines, by surface modification or nanoparticle core construction, for enhanced transmucosal drug delivery