Lived experience codesign of self-harm interventions: a scoping review.

OBJECTIVES: This study aims to map existing literature describing how people with lived experience of self-harm have engaged in codesigning self-harm interventions, understand barriers and facilitators to this engagement, and how the meaningfulness of codesign has been evaluated. DESIGN: Scoping review by Joanna Briggs Institute methodology. A protocol was published online (http://dx.doi.org/10.17605/OSF.IO/P52UD). DATA SOURCES: PubMed, Embase, PsycINFO, Web of Science, Cochrane Library, PROSPERO, ClinicalTrials.gov and relevant websites were searched on 24 December 2022 (repeated 4 November 2023). ELIGIBILITY CRITERIA: We included studies where individuals with lived experience of self-harm (first-hand or caregiver) have codesigned self-harm interventions. DATA EXTRACTION AND SYNTHESIS: Results were screened at title and abstract level, then full-text level by two researchers independently. Prespecified data were extracted, charted and sorted into themes. RESULTS: We included 22 codesigned interventions across mobile health, educational settings, prisons and emergency departments. Involvement varied from designing content to multistage involvement in planning, delivery and dissemination. Included papers described the contribution of 159 female, 39 male and 21 transgender or gender diverse codesigners. Few studies included contributors from a minoritised ethnic or LGBTQIA+ group. Six studies evaluated how meaningfully people with lived experience were engaged in codesign: by documenting the impact of contributions on intervention design or through postdesign reflections. Barriers included difficulties recruiting inclusively, making time for meaningful engagement in stretched services and safeguarding concerns for codesigners. Explicit processes for ensuring safety and well-being, flexible schedules, and adequate funding facilitated codesign. CONCLUSIONS: To realise the potential of codesign to improve self-harm interventions, people with lived experience must be representative of those who use services. This requires processes that reassure potential contributors and referrers that codesigners will be safeguarded, remunerated, and their contributions used and valued

Unparticle Physics in Single Top Signals

We study the single production of top quarks in $e^+e^-, ep$ and $pp$ collisions in the context of unparticle physics through the Flavor Violating (FV) unparticle vertices and compute the total cross sections for single top production as functions of scale dimension d_{\U}. We find that among all, LHC is the most promising facility to probe the unparticle physics via single top quark production processes.Comment: 14 pages, 10 figure

Effects of pollution on adolescent mental health: a systematic review protocol.

BACKGROUND: Whilst there is little uncertainty about the deleterious impact of pollution on human and planetary health, pollution's impact on adolescent mental health is less well understood. This is particularly true for young people in underdeveloped and developing world contexts, about whom research is generally lacking. Furthermore, although adolescent resilience continues to be a research priority, little attention has been paid to adolescent pathways of resilience in the face or aftermath of pollution exposure. The objective of this study will be to examine the associations between pollution and mental health in 10- to 24-year-olds (i.e. adolescents). METHODS: We designed and registered a study protocol for a systematic review of studies which link pollution and mental health in adolescents. We will include observational studies (e.g. cohort, case-control, time series analyses) that assess the associations between exposure to any form of pollution and the mental health of 10- to 24-year-olds. The primary outcome will be symptoms associated with neurodevelopmental disorders; disruptive, impulse-control, and conduct disorders; depressive disorders; anxiety disorders; substance disorders; and schizophrenia. No secondary outcomes will be considered. Literature searches will be conducted in multiple electronic databases (from inception onwards), including PubMed, MEDLINE, SCOPUS, Web of Science, CINAHL, PsycINFO, SciELO, ERIC, and Africa-Wide. Two investigators will independently screen all citations, full-text articles, and abstract data. The methodological quality (or bias) of included studies will be appraised using appropriate tools. We will provide a narrative synthesis of the evidence. DISCUSSION: This systematic review will evaluate the evidence on the associations between pollution and the mental health of 10- to 24-year-olds. Our findings will be of potential interest to multiple audiences (including adolescent patients/clients, their families, caregivers, healthcare professionals, scientists, and policy makers) and could be used to develop prevention and intervention strategies as well as focus future research. Results will be published in a peer-reviewed journal. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020176664

Retrospective cohort analysis of Spanish national trends of coronary artery bypass grafting and percutaneous coronary intervention from 1998 to 2017

Introduction Spain is one of the countries with the lowest rates of revascularisation and highest ratio of percutaneous coronary intervention (PCI) to coronary artery bypass grafting (CABG). Objectives To investigate the changes and trends in the two revascularisation procedures between 1998 and 2017 in Spain. Design Retrospective cohort study. Analysis of in-hospital outcomes. Setting Minimum basic data set from the Spanish National Department of Health: mandatory database collecting information of patients who are attended in the Spanish public National Health System. Participants 603 976 patients who underwent isolated CABG or PCI in the Spanish National Health System. The study period was divided in four 5-year intervals. Patients with acute myocardial infarction on admission were excluded. Primary and secondary outcomes We investigated the volume of procedures nationwide, the changes of the risk profile of patients and in-hospital mortality of both techniques. Results We observed a 2.2-fold increase in the rate of any type of myocardial revascularisation per million inhabitants-year: 357 (1998) to 776 (2017). 93 682 (15.5%) had a coronary surgery. PCI to CABG ratio rose from 2.2 (1998-2002) to 8.1 (2013-2017). Charlson's index increased by 0.8 for CABG and 1 for PCI. The median annual volume of PCI/hospital augmented from 136 to 232, while the volume of CABG was reduced from 137 to 74. In the two decades, we detected a significant reduction of CABG in-hospital mortality (6.5% vs 2.6%, p<0.001) and a small increase in PCI (1.2% vs 1.5%, p<0.001). Risk adjusted mortality rate was reduced for both CABG (1.51 vs 0.48, p<0.001), and PCI (1.42 vs 1.05, p<0.001). Conclusion We detected a significant increase in the volume of revascularisations (particularly PCI) in Spain. Risk-adjusted in-hospital mortality was significantly reduce

Protein kinase activity of phosphoinositide 3-kinase regulates cytokine-dependent cell survival

Extent: 14 p.The dual specificity protein/lipid kinase, phosphoinositide 3-kinase (PI3K), promotes growth factor-mediated cell survival and is frequently deregulated in cancer. However, in contrast to canonical lipid-kinase functions, the role of PI3K protein kinase activity in regulating cell survival is unknown. We have employed a novel approach to purify and pharmacologically profile protein kinases from primary human acute myeloid leukemia (AML) cells that phosphorylate serine residues in the cytoplasmic portion of cytokine receptors to promote hemopoietic cell survival. We have isolated a kinase activity that is able to directly phosphorylate Ser585 in the cytoplasmic domain of the interleukin 3 (IL-3) and granulocyte macrophage colony stimulating factor (GM-CSF) receptors and shown it to be PI3K. Physiological concentrations of cytokine in the picomolar range were sufficient for activating the protein kinase activity of PI3K leading to Ser585 phosphorylation and hemopoietic cell survival but did not activate PI3K lipid kinase signaling or promote proliferation. Blockade of PI3K lipid signaling by expression of the pleckstrin homology of Akt1 had no significant impact on the ability of picomolar concentrations of cytokine to promote hemopoietic cell survival. Furthermore, inducible expression of a mutant form of PI3K that is defective in lipid kinase activity but retains protein kinase activity was able to promote Ser585 phosphorylation and hemopoietic cell survival in the absence of cytokine. Blockade of p110α by RNA interference or multiple independent PI3K inhibitors not only blocked Ser585 phosphorylation in cytokine-dependent cells and primary human AML blasts, but also resulted in a block in survival signaling and cell death. Our findings demonstrate a new role for the protein kinase activity of PI3K in phosphorylating the cytoplasmic tail of the GM-CSF and IL-3 receptors to selectively regulate cell survival highlighting the importance of targeting such pathways in cancer.Daniel Thomas, Jason A. Powell, Benjamin D. Green, Emma F. Barry, Yuefang Ma, Joanna Woodcock, Stephen Fitter, Andrew C.W. Zannettino, Stuart M. Pitson, Timothy P. Hughes, Angel F. Lopez, Peter R. Shepherd, Andrew H. Wei, Paul G. Ekert and Mark A. Guthridg

Apolipoprotein E, periodontal disease and the risk for atherosclerosis: a review

Foundation of Support to the Scientific and Technological Development of the State of Ceara/Brazil (FUNCAP) PPSUS grant, the Brazilian Coordination for the Improvement of Higher Education Personnel (CAPES) Procad (071/2013 # 144494), and by the National Council for Science and Technological Development (CNPq, grant number 467143/2014-5)

Cytokine Production but Lack of Proliferation in Peripheral Blood Mononuclear Cells from Chronic Chagas' Disease Cardiomyopathy Patients in Response to T. cruzi Ribosomal P Proteins

Background:Trypanosoma cruzi ribosomal P proteins, P2β and P0, induce high levels of antibodies in patients with chronic Chagas' disease Cardiomyopathy (CCC). It is well known that these antibodies alter the beating rate of cardiomyocytes and provoke apoptosis by their interaction with β1-adrenergic and M2-muscarinic cardiac receptors. Based on these findings, we decided to study the cellular immune response to these proteins in CCC patients compared to non-infected individuals.Methodology/Principal findings:We evaluated proliferation, presence of surface activation markers and cytokine production in peripheral blood mononuclear cells (PBMC) stimulated with P2β, the C-terminal portion of P0 (CP0) proteins and T. cruzi lysate from CCC patients predominantly infected with TcVI lineage. PBMC from CCC patients cultured with P2β or CP0 proteins, failed to proliferate and express CD25 and HLA-DR on T cell populations. However, multiplex cytokine assays showed that these antigens triggered higher secretion of IL-10, TNF-α and GM-CSF by PBMC as well as both CD4+ and CD8+ T cells subsets of CCC subjects. Upon T. cruzi lysate stimulation, PBMC from CCC patients not only proliferated but also became activated within the context of Th1 response. Interestingly, T. cruzi lysate was also able to induce the secretion of GM-CSF by CD4+ or CD8+ T cells.Conclusions/Significance:Our results showed that although the lack of PBMC proliferation in CCC patients in response to ribosomal P proteins, the detection of IL-10, TNF-α and GM-CSF suggests that specific T cells could have both immunoregulatory and pro-inflammatory potential, which might modulate the immune response in Chagas' disease. Furthermore, it was possible to demonstrate for the first time that GM-CSF was produced by PBMC of CCC patients in response not only to recombinant ribosomal P proteins but also to parasite lysate, suggesting the value of this cytokine to evaluate T cells responses in T. cruzi infection.Fil: Longhi, Silvia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Atienza, Augusto. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Perez Prados, Graciela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Buying, Alcinette. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Balouz, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Buscaglia, Carlos Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Santos, Radleigh. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Tasso, Laura Mónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Bonato, Ricardo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Chiale, Pablo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Pinilla, Clemencia. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Judkowski, Valeria A.. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Gomez, Karina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin

Characterisation of feline renal cortical fibroblast cultures and their transcriptional response to transforming growth factor beta 1

Chronic kidney disease (CKD) is common in geriatric cats, and the most prevalent pathology is chronic tubulointerstitial inflammation and fibrosis. The cell type predominantly responsible for the production of extra-cellular matrix in renal fibrosis is the myofibroblast, and fibroblast to myofibroblast differentiation is probably a crucial event. The cytokine TGF-β1 is reportedly the most important regulator of myofibroblastic differentiation in other species. The aim of this study was to isolate and characterise renal fibroblasts from cadaverous kidney tissue of cats with and without CKD, and to investigate the transcriptional response to TGF-β1

Pseudomonas aeruginosa Adaptation to Lungs of Cystic Fibrosis Patients Leads to Lowered Resistance to Phage and Protist Enemies

Pathogenic life styles can lead to highly specialized interactions with host species, potentially resulting in fitness trade-offs in other ecological contexts. Here we studied how adaptation of the environmentally transmitted bacterial pathogen, Pseudomonas aeruginosa, to cystic fibrosis (CF) patients affects its survival in the presence of natural phage (14/1, ΦKZ, PNM and PT7) and protist (Tetrahymena thermophila and Acanthamoebae polyphaga) enemies. We found that most of the bacteria isolated from relatively recently intermittently colonised patients (1-25 months), were innately phage-resistant and highly toxic for protists. In contrast, bacteria isolated from long time chronically infected patients (2-23 years), were less efficient in both resisting phages and killing protists. Moreover, chronic isolates showed reduced killing of wax moth larvae (Galleria mellonella) probably due to weaker in vitro growth and protease expression. These results suggest that P. aeruginosa long-term adaptation to CF-lungs could trade off with its survival in aquatic environmental reservoirs in the presence of microbial enemies, while lowered virulence could reduce pathogen opportunities to infect insect vectors; factors that are both likely to result in poorer environmental transmission. From an applied perspective, phage therapy could be useful against chronic P. aeruginosa lung infections that are often characterized by multidrug resistance: chronic isolates were least resistant to phages and their poor growth will likely slow down the emergence of beneficial resistance mutations

Effects of Inhibiting CoQ10 Biosynthesis with 4-nitrobenzoate in Human Fibroblasts

Coenzyme Q10 (CoQ10) is a potent lipophilic antioxidant in cell membranes and a carrier of electrons in the mitochondrial respiratory chain. We previously characterized the effects of varying severities of CoQ10 deficiency on ROS production and mitochondrial bioenergetics in cells harboring genetic defects of CoQ10 biosynthesis. We observed a unimodal distribution of ROS production with CoQ10 deficiency: cells with <20% of CoQ10 and 50–70% of CoQ10 did not generate excess ROS while cells with 30–45% of CoQ10 showed increased ROS production and lipid peroxidation. Because our previous studies were limited to a small number of mutant cell lines with heterogeneous molecular defects, here, we treated 5 control and 2 mildly CoQ10 deficient fibroblasts with varying doses of 4-nitrobenzoate (4-NB), an analog of 4-hydroxybenzoate (4-HB) and inhibitor of 4-para-hydroxybenzoate:polyprenyl transferase (COQ2) to induce a range of CoQ10 deficiencies. Our results support the concept that the degree of CoQ10 deficiency in cells dictates the extent of ATP synthesis defects and ROS production and that 40–50% residual CoQ10 produces maximal oxidative stress and cell death