'It's always difficult when it's family. . . whereas when you're talking to a therapist. . .': Parents' views of cognitive-behaviour therapy for depressed adolescents

BACKGROUND: Parents are key to helping their adolescent child access psychological therapy for mental health problems such as depression. However, little is known about how parents experience their child's psychological therapy. We aimed to explore parents' experiences of their adolescent child's cognitive behaviour therapy for depression. METHOD: We applied Thematic Analysis (TA) to qualitative data from in-depth interviews with parents (N = 16) whose adolescent child was randomly allocated to CBT in a large multisite RCT for adolescent depression (the IMPACT trial). Interviews were conducted at the end of treatment. RESULTS: We generated two main themes: parents' perceptions of the adolescent's journey through therapy, and parents' perceptions of the therapeutic setting and process. Each included four sub-themes. Parents talked about key factors that impacted on their child's progress through treatment, including the adolescent's readiness for therapy and the adolescent-therapist relationship. CONCLUSION: Parents' insights confirm the foundations of what is considered good clinical practice of CBT for adolescent depression, including tailoring therapy to the adolescent, and establishing a strong adolescent-therapist relationship. Parents recognised that, for CBT to be helpful, their child had to be willing to engage in therapy and able to develop a trusting relationship with their therapist

Rate-limiting transport of positively charged arginine residues through the Sec-machinery is integral to the mechanism of protein secretion

Transport of proteins across and into membranes is a fundamental biological process with the vast majority being conducted by the ubiquitous Sec machinery. In bacteria, this is usually achieved when the SecY-complex engages the cytosolic ATPase SecA (secretion) or translating ribosomes (insertion). Great strides have been made towards understanding the mechanism of protein translocation. Yet, important questions remain – notably, the nature of the individual steps that constitute transport, and how the proton-motive force (PMF) across the plasma membrane contributes. Here, we apply a recently developed high-resolution protein transport assay to explore these questions. We find that pre-protein transport is limited primarily by the diffusion of arginine residues across the membrane, particularly in the context of bulky hydrophobic sequences. This specific effect of arginine, caused by its positive charge, is mitigated for lysine which can be deprotonated and transported across the membrane in its neutral form. These observations have interesting implications for the mechanism of protein secretion, suggesting a simple mechanism through which the PMF can aid transport by enabling a 'proton ratchet', wherein re-protonation of exiting lysine residues prevents channel re-entry, biasing transport in the outward direction

Loneliness and mental health in children and adolescents with pre-existing mental health problems: A rapid systematic review

Objectives: Periods of social isolation are associated with loneliness in children and young people, and loneliness is associated with poor mental and physical health. Children and young people with pre-existing mental health difficulties may be prone to loneliness. Containment of COVID-19 has necessitated widespread social isolation, with unprecedented school closures and restrictions imposed on social interactions. This rapid review aimed to establish what is known about the relationship between loneliness and mental health problems in children and young people with pre-existing mental health problems. Methods: We sought to identify all primary research that examined the cross-sectional and longitudinal associations between loneliness/perceived social isolation and mental health in children and young people with pre-existing mental health problems. We also aimed to identify effective interventions that reduce the adverse impact of loneliness. A rapid systematic search was conducted using MEDLINE, PsycINFO, and Web of Science. Results: Of 4,531 papers screened, 15 included children and young people with pre-existing mental health conditions. These 15 studies included 1,536 children and young people aged between 6 and 23 years with social phobia, anxiety and/or depression, and neurodevelopmental disorders. Loneliness was associated with anxiety and depression both cross-sectionally and prospectively in children and young people with mental health problems and neurodevelopmental conditions. We found preliminary evidence that psychological treatments can help to reduce feelings of loneliness in this population. Conclusions: Loneliness is associated with depression and anxiety in children and young people with pre-existing mental health conditions, and this relationship may be bidirectional. Existing interventions to address loneliness and/or mental health difficulties in other contexts may be applied to this population, although they may need adaptation and testing in younger children and adolescents. Practitioner points: Loneliness is common in children and young people, and during periods of enforced social isolation such as during COVID-19, children and young people report high levels of loneliness (or increased rates of loneliness). The review showed that loneliness is associated, both cross-sectionally and prospectively, in children and young people with mental health problems and also in children and young people with neurodevelopmental conditions, such as autism spectrum disorder. Thus, loneliness is a possible risk factor of which mental health providers should be aware. Maintaining social contact both by direct and by indirect means, especially through the Internet, could be important in mitigating loneliness. Interventions to address loneliness should be further developed and tested to help children and young people with pre-existing mental health problems who are lonely by preventing exacerbation of their mental health difficulties, in particular anxiety and depression

Periodic sulphur dioxide degassing from the Soufriere Hills Volcano related to deep magma supply

Soufrière Hills Volcano produced prodigious quantities of sulphur dioxide (SO2) gas throughout 1995–2013. An unprecedented, detailed record of SO2 flux shows that high SO2 fluxes were sustained through eruptive pauses and for two years after the end of lava extrusion and are decoupled from lava extrusion rates. Lava extrusion rates have exhibited strong 1- to 2-year cyclicity. Wavelet analysis demonstrates periodicities of c. 5 months and c. 2 years within the SO2 time series, as well as the shorter cycles identified previously. The latter period is similar to the wavelength of cycles in lava extrusion, albeit non-systematically offset. The periodicities are consistent with pressure changes accompanying deformation in a coupled magma reservoir system whereby double periodic behaviour may arise from limited connectivity between two reservoirs. During periods of lava extrusion SO2 is released together with the lava (yielding the c. 2 year period), albeit with some offset. In contrast, when magma cannot flow because of its yield strength, SO2 is released independently from lava (yielding the c. 5 month period). Our results have implications for eruption forecasting. It seems likely that, when deep supply of magma ceases, gas fluxes will cease to be periodic

Compositional characteristics and spatial distribution of enriched Icelandic mantle components

Author Posting. © The Authors, 2010. This is the author's version of the work. It is posted here by permission of Oxford University Press for personal use, not for redistribution. The definitive version was published in Journal of Petrology 51 (2010): 1447-1475, doi:10.1093/petrology/egq025.We present compositional data on a suite of 18 primitive neovolcanic alkali basalts from three flank zone regions in Iceland (Vestmannaeyjar in the south, Snæfell in the east, and Snæfellsnes in the west) that are peripheral to the main rift zones that are dominated by tholeiitic basalts. This study integrates He isotope data with radiogenic isotope data (Sr-Nd-Pb-Hf), stable isotope data (δ18O), and trace element data to characterise the compositional features of the trace-elementenriched components of the Icelandic mantle. We also present high-precision Pb isotope data on an additional 57 lava samples from the flank zones (including Öræfajökull in the south-east) and the Northern and Eastern rift zones. Most Icelandic lavas have negative Δ207Pb (–4 to –1), with higher values (–1 to +4) found only in samples from Öræfajökull, Snæfell, and parts of the Reykjanes Peninsula. At Snæfell, this EM1-type component is characterised by a low δ18Oolivine signature (+4.1‰ to +4.6‰), moderate 206Pb/204Pb values (18.4-18.6) and MORB-like 3He/4He (6.9-7.5 R/RA). Samples from Vestmannaeyjar and Snæfellsnes have mantle-like δ18Oolivine (+4.9‰ to +5.0‰), and radiogenic 206Pb/204Pb values (18.9-19.3) that fall on the NHRL for 208Pb/204Pb (Δ208Pb –5 to +5). Compared to the Vestmannaeyjar lavas, Snæfellsnes lavas have higher La/YbN (5-11 vs. 3-5), lower εNd (5.5-6.5 vs. 6.8-7.6) and lower 3He/4He (6.3-8.6 R/RA vs. 11.4-13.5 R/RA). Therefore, the most trace element enriched components in the Icelandic mantle are not the carriers of the high 3He/4He values (> 15 R/RA) found in some lavas on Iceland and the adjacent ridges, and instead are consistent with degassed, recycled components. Even after excluding the EM1-type high Δ207Pb samples, high-precision Pb isotope data produce a kinked array on an 206Pb/204Pb vs. 208Pb/204Pb plot, which is not consistent with simple binary mixing between two end-members. This requires significant lateral heterogeneity within the Icelandic mantle and the presence of more than just two compositionally-distinct local mixing end-member components. Samples from each of the main axial rift zones define different trends. Despite the tectonic continuity between the Northern Volcanic Zone and the Eastern Volcanic Zone, lavas from these two rift zones define separate sub-parallel linear arrays. Lavas from the adjacent Western Volcanic Zone and the Eastern Volcanic Zone define oblique linear arrays that converge on a common local end-member that is not involved in the magmatism of the Northern Volcanic Zone. Therefore, there is a distinct NE-SW compositional heterogeneity within the Icelandic mantle.work was funded primarily by the Danish National Research Foundation through a grant to the former Danish Lithosphere Centre, with additional funding from the University of Iowa for the oxygen isotope analyses

Multiple bactericidal mechanisms of the zinc ionophore PBT2

Published 18 March 2020Globally, more antimicrobials are used in food-producing animals than in humans, and the extensive use of medically important human antimicrobials poses a significant public health threat in the face of rising antimicrobial resistance (AMR). The development of novel ionophores, a class of antimicrobials used exclusively in animals, holds promise as a strategy to replace or reduce essential human antimicrobials in veterinary practice. PBT2 is a zinc ionophore with recently demonstrated antibacterial activity against several Gram-positive pathogens, although the underlying mechanism of action is unknown. Here, we investigated the bactericidal mechanism of PBT2 in the bovine mastitis-causing pathogen, Streptococcus uberis In this work, we show that PBT2 functions as a Zn2+/H+ ionophore, exchanging extracellular zinc for intracellular protons in an electroneutral process that leads to cellular zinc accumulation. Zinc accumulation occurs concomitantly with manganese depletion and the production of reactive oxygen species (ROS). PBT2 inhibits the activity of the manganese-dependent superoxide dismutase, SodA, thereby impairing oxidative stress protection. We propose that PBT2-mediated intracellular zinc toxicity in S. uberis leads to lethality through multiple bactericidal mechanisms: the production of toxic ROS and the impairment of manganese-dependent antioxidant functions. Collectively, these data show that PBT2 represents a new class of antibacterial ionophores capable of targeting bacterial metal ion homeostasis and cellular redox balance. We propose that this novel and multitarget mechanism of PBT2 makes the development of cross-resistance to medically important antimicrobials unlikely.IMPORTANCE More antimicrobials are used in food-producing animals than in humans, and the extensive use of medically important human antimicrobials poses a significant public health threat in the face of rising antimicrobial resistance. Therefore, the elimination of antimicrobial crossover between human and veterinary medicine is of great interest. Unfortunately, the development of new antimicrobials is an expensive high-risk process fraught with difficulties. The repurposing of chemical agents provides a solution to this problem, and while many have not been originally developed as antimicrobials, they have been proven safe in clinical trials. PBT2, a zinc ionophore, is an experimental therapeutic that met safety criteria but failed efficacy checkpoints against both Alzheimer's and Huntington's diseases. It was recently found that PBT2 possessed potent antimicrobial activity, although the mechanism of bacterial cell death is unresolved. In this body of work, we show that PBT2 has multiple mechanisms of antimicrobial action, making the development of PBT2 resistance unlikely.Nichaela Harbison-Price, Scott A. Ferguson, Adam Heikal, George Taiaroa, Kiel Hards ... Christopher A. McDevitt ... et al