Identifying the research priorities for schema therapy : A Delphi consensus study

Despite the popularity of schema therapy, there exist several important gaps in research on the schema therapy model and its effectiveness. The number of gaps makes it difficult to determine the research areas of the highest strategic priority to advance schema therapy. The objective of this study was to establish consensus among schema therapy clinicians and researchers on the priority areas for future schema therapy research. A panel of experts in schema therapy (43 clinicians and 13 researchers) participated in a Delphi consensus study. The research areas rated were developed by interviewing the founder of schema therapy, Jeffrey Young, conducting a focus group with the executive board of the International Society for Schema Therapy and screening recent reviews on schema therapy for recommendations for future research. The panel rated 81 research areas in terms of priority across three rounds. Nineteen research areas were rated by 75% of the panel as ‘Very high priority’ or ‘High priority’. These priorities reflected four broad themes: (1) schema therapy constructs and measures, (2) the theoretical assumptions underlying schema therapy, (3) schema therapy and theory in relation to different contexts and outcomes and (4) schema therapy effectiveness and mechanisms of change. The findings are important for establishing a clear research agenda for the future of schema therapy

Early maladaptive schemas, emotion regulation difficulties, and alexithymia : A systematic review and meta-analysis

Background Emotion regulation is an integral part of the schema therapy model. The aim of this systematic review and meta-analysis was to synthesize the evidence on the associations between early maladaptive schemas (EMSs), difficulties with emotion regulation and alexithymia. Method PsycINFO, PubMed and CINAHL Complete databases were searched on 28 May 2022 and 3 February 2023 in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Included studies were in English, in peer-reviewed journals and reported on the association between one or more of the 18 EMSs or five schema domains and emotion regulation difficulties or alexithymia. Methodological quality was assessed using the Appraisal Tool for Cross-Sectional Studies. Meta-analyses were conducted to examine difficulties with emotion regulation and alexithymia as correlates of each EMS and domain. Results A total of 19 studies published between 2008 and 2022 were included (Pooled N = 5957). Difficulties with emotion regulation were positively correlated with all 18 EMSs (range: entitlement r(7) = .28, 95% CI [.13, .42] to negativity pessimism r(5) = .53, 95% CI [.23, .74]) and schema domains (range: impaired limits r(5) = .34, 95% CI [.08, .56] to disconnection rejection r(5) = .44, 95% CI [.33, .73]). Alexithymia was positively correlated with the other-directedness domain (r(2) = .40, 95% CI [.09, .64]) and 16 of the 18 EMSs (range: unrelenting standards r(5) = .21, 95% CI [.12, .28] to emotional inhibition r(5) = .50, 95% CI [.34, .63]). Conclusions The findings suggested that almost all 18 EMSs are implicated in emotion regulation difficulties and alexithymia, particularly those relating to unmet needs for attachment and autonomy

LNK (SH2B3): paradoxical effects in ovarian cancer.

LNK (SH2B3) is an adaptor protein studied extensively in normal and malignant hematopoietic cells. In these cells, it downregulates activated tyrosine kinases at the cell surface resulting in an antiproliferative effect. To date, no studies have examined activities of LNK in solid tumors. In this study, we found by in silico analysis and staining tissue arrays that the levels of LNK expression were elevated in high-grade ovarian cancer. To test the functional importance of this observation, LNK was either overexpressed or silenced in several ovarian cancer cell lines. Remarkably, overexpression of LNK rendered the cells resistant to death induced by either serum starvation or nutrient deprivation, and generated larger tumors using a murine xenograft model. In contrast, silencing of LNK decreased ovarian cancer cell growth in vitro and in vivo. Western blot studies indicated that overexpression of LNK upregulated and extended the transduction of the mitogenic signal, whereas silencing of LNK produced the opposite effects. Furthermore, forced expression of LNK reduced cell size, inhibited cell migration and markedly enhanced cell adhesion. Liquid chromatography-mass spectroscopy identified 14-3-3 as one of the LNK-binding partners. Our results suggest that in contrast to the findings in hematologic malignancies, the adaptor protein LNK acts as a positive signal transduction modulator in ovarian cancers

Loss-of-function of the ciliopathy protein Cc2d2a disorganizes the vesicle fusion machinery at the periciliary membrane and indirectly affects Rab8-trafficking in zebrafish photoreceptors

Ciliopathies are human disorders caused by dysfunction of primary cilia, ubiquitous organelles involved in transduction of environmental signals such as light sensation in photoreceptors. Concentration of signal detection proteins such as opsins in the ciliary membrane is achieved by RabGTPase-regulated polarized vesicle trafficking and by a selective barrier at the ciliary base, the transition zone (TZ). Dysfunction of the TZ protein CC2D2A causes Joubert/Meckel syndromes in humans and loss of ciliary protein localization in animal models, including opsins in retinal photoreceptors. The link between the TZ and upstream vesicle trafficking has been little explored to date. Moreover, the role of the small GTPase Rab8 in opsin-carrier vesicle (OCV) trafficking has been recently questioned in a mouse model. Using correlative light and electron microscopy and live imaging in zebrafish photoreceptors, we provide the first live characterization of Rab8-mediated trafficking in photoreceptors in vivo. Our results support a possibly redundant role for both Rab8a/b paralogs in OCV trafficking, based on co-localization of Rab8 and opsins in vesicular structures, and joint movement of Rab8-tagged particles with opsin. We further investigate the role of the TZ protein Cc2d2a in Rab8-mediated trafficking using cc2d2a zebrafish mutants and identify a requirement for Cc2d2a in the latest step of OCV trafficking, namely vesicle fusion. Progressive accumulation of opsin-containing vesicles in the apical portion of photoreceptors lacking Cc2d2a is caused by disorganization of the vesicle fusion machinery at the periciliary membrane with mislocalization and loss of the t-SNAREs SNAP25 and Syntaxin3 and of the exocyst component Exoc4. We further observe secondary defects on upstream Rab8-trafficking with cytoplasmic accumulation of Rab8. Taken together, our results support participation of Rab8 in OCV trafficking and identify a novel role for the TZ protein Cc2d2a in fusion of incoming ciliary-directed vesicles, through organization of the vesicle fusion machinery at the periciliary membrane

Estimation of Breast Cancer Incident Cases and Medical Care Costs Attributable to Alcohol Consumption Among Insured Women Aged <45 Years in the U.S.

This study estimated the percentage of breast cancer cases, total number of incident cases, and total annual medical care costs attributable to alcohol consumption among insured younger women (aged 18–44 years) by type of insurance and stage at diagnosis

Reengineering the clinical research enterprise to involve more community clinicians

<p>Abstract</p> <p>Background</p> <p>The National Institutes of Health has called for expansion of practice-based research to improve the clinical research enterprise.</p> <p>Methods</p> <p>This paper presents a model for the reorganization of clinical research to foster long-term participation by community clinicians.</p> <p>Based on the literature and interviews with clinicians and other stakeholders, we posited a model, conducted further interviews to test the viability of the model, and further adapted it.</p> <p>Results</p> <p>We propose a three-dimensional system of checks and balances to support community clinicians using research support organizations, community outreach, a web-based registry of clinicians and studies, web-based training services, quality audits, and a feedback mechanism for clinicians engaged in research.</p> <p>Conclusions</p> <p>The proposed model is designed to offer a systemic mechanism to address current barriers that prevent clinicians from participation in research. Transparent mechanisms to guarantee the safety of patients and the integrity of the research enterprise paired with efficiencies and economies of scale are maintained by centralizing some of the functions. Assigning other responsibilities to more local levels assures flexibility with respect to the size of the clinician networks and the changing needs of researchers.</p

Correlative super-resolution and electron microscopy to resolve protein localization in zebrafish retina

We present a method to investigate the subcellular protein localization in the larval zebrafish retina by combining super-resolution light microscopy and scanning electron microscopy. The sub-diffraction limit resolution capabilities of super-resolution light microscopes allow improving the accuracy of the correlated data. Briefly, 110 nanometer thick cryo-sections are transferred to a silicon wafer and, after immunofluorescence staining, are imaged by super-resolution light microscopy. Subsequently, the sections are preserved in methylcellulose and platinum shadowed prior to imaging in a scanning electron microscope (SEM). The images from these two microscopy modalities are easily merged using tissue landmarks with open source software. Here we describe the adapted method for the larval zebrafish retina. However, this method is also applicable to other types of tissues and organisms. We demonstrate that the complementary information obtained by this correlation is able to resolve the expression of mitochondrial proteins in relation with the membranes and cristae of mitochondria as well as to other compartments of the cell