Self-Compassion Moderates the Mediating Effect of Self-Criticism in the Link Between Childhood Maltreatment and Psychopathology

Childhood maltreatment (CM) has been associated with psychological symptoms (i.e., psychopathology) among clinical and nonclinical samples. The mechanisms underlying this link have been understudied, especially among well-functioning adults. Arguably, exposure to CM may be translated into negative and critical self-appraisals and self-blame, reflected in high self-criticism. CM may also result in difficulty in extending kindness towards oneself, that is, low self-compassion. These characteristics are linked with elevated psychopathology. Nevertheless, no study has yet tested the extent to which self-criticism and self-compassion may serve as independent mechanisms linking CM and psychopathology and whether in this context self-compassion buffers the link between self-criticism and psychopathology. Here, we tested an integrative model in which the relation between CM and psychopathology was mediated by self-compassion and self-criticism, and the path between self-criticism and psychopathology was moderated by self-compassion. A convenience sample of 914 individuals completed online self-report questionnaires. Results indicated that CM was related to psychopathology through the mediation of self-compassion and self-criticism, with a significant interaction between self-criticism and self-compassion. Showing a moderated-mediational effect, the link between self-criticism and psychopathology was weaker under high than under low levels of self-compassion. Our findings highlight the importance of self-compassion, a robust resilience factor related to reduced psychopathology and moderating the link between self-criticism, a potent transdiagnostic risk factor, and psychopathology in the context of CM. These results thus provide empirical evidence for the relevance of compassion and mindfulness in counseling settings, particularly with CM survivors, who are at greater risk for psychopathology

The Legacy of ERA, Privatization and the Policy Ratchet

This article explores the ways in which the neo-liberal impetus toward the privatization of state schooling signalled in the Education Reform Act 1988 (ERA) has become embedded in the English school system. Four main points are made. First, that ERA itself was of huge strategic rather than substantive importance as far as privatization is concerned. Second, by tracing the lineage of privatization from ERA onwards a 'ratchet' effect of small and incremental policy moves can be identified, which have disseminated, embedded and naturalized privatization within public sector provision. Third, that while privatization has been taken up and taken much further by New Labour than it had been by the Conservatives there are differences between the two sets of governments in the role of privatization in education policy and the role of the state. Fourth, the participation of private providers in the planning and delivery of state services has put the private sector at the very heart of policy. At points the article draws upon interviews conducted with private sector providers. © 2008 Sage Publications

Challenging the orthodoxy: union learning representatives as organic intellectuals

Teacher education and continuing professional development have become a key areas of controversy in England since the period of school sector restructuring following the 1988 Education Reform Act. More recently teacher training and professional development have often been used to promote and reinforce a narrow focus on the government’s ‘standards agenda’. However, the emerging discourse of ‘new professionalism’ has raised the profile of professional development in schools, and together with union learning representatives, there are opportunities to secure real improvements in teachers’ access to continuing professional development. This paper argues however that union learning representatives must go beyond advocating for better access to professional development and should raise more fundamental questions about the nature of professional development and the education system it serves. Drawing on Gramsci’s notion of the ‘organic intellectual’, the paper argues that union learning representatives have a key role as organisers of ideas – creating spaces in which the ideological dominance of current policy orthodoxy might be challenged

Fecal Lipocalin 2, a Sensitive and Broadly Dynamic Non- Invasive Biomarker for Intestinal Inflammation

Inflammation has classically been defined histopathologically, especially by the presence of immune cell infiltrates. However, more recent studies suggest a role for low-grade inflammation in a variety of disorders ranging from metabolic syndrome to cancer, which is defined by modest elevations in pro-inflammatory gene expression. Consequently, there is a need for cost-effective, non-invasive biomarkers that, ideally, would have the sensitivity to detect low-grade inflammation and have a dynamic range broad enough to reflect classic robust intestinal inflammation. Herein, we report that, for assessment of intestinal inflammation, fecal lipocalin 2 (Lcn-2), measured by ELISA, serves this purpose. Specifically, using a well-characterized mouse model of DSS colitis, we observed that fecal Lcn-2 and intestinal expression of pro-inflammatory cytokines (IL-1b, CXCL1, TNFa) are modestly but significantly induced by very low concentrations of DSS (0.25 and 0.5%), and become markedly elevated at higher concentrations of DSS (1.0 and 4.0%). As expected, careful histopathologic analysis noted only modest immune infiltrates at low DSS concentration and robust colitis at higher DSS concentrations. In accordance, increased levels of the neutrophil product myeloperoxidase (MPO) was only detected in mice given 1.0 and 4.0% DSS. In addition, fecal Lcn-2 marks the severity of spontaneous colitis development in IL-10 deficient mice. Unlike histopathology, MPO, and q-RT-PCR, the assay of fecal Lcn-2 requires only a stool sample, permits measurement over time, and can detect inflammation as early as 1 day following DSS administration. Thus, assay of fecal Lcn-2 by ELISA can function as a non-invasive, sensitive, dynamic, stable and cost-effective means to monitor intestinal inflammation in mice

Loss of function mutation in toll-like receptor-4 does not offer protection against obesity and insulin resistance induced by a diet high in trans fat in mice

<p>Abstract</p> <p>Background</p> <p>Toll-like receptor-4 (TLR4) triggers inflammatory signaling in response to microbial lipoploysaccharide. It has been reported that loss of TLR4 protected against saturated fat-induced inflammation and insulin resistance. It is not known whether loss of TLR4 function offers protection against trans fat (TF) induced obesity, inflammation, and insulin resistance. We investigated whether mice with loss of function mutation in TLR4 were resistant to TF-induced pathologies such as obesity, inflammation, hyperglycemia, and hyperinsulinemia.</p> <p>Methods</p> <p>C57BL/6j and C57BL/10 mice were cross bred to generate TLR4 mutant and wild type (WT). TLR4 mutant (n = 12) and WT (n = 12) mice were fed either low fat (LF) (13.5% fat energy) or high TF diets (60% fat energy) for 12 weeks. <it>In vitro </it>experiments were conducted on mouse macrophage cells (RAW 264.7 and J774A.1) to investigate whether elaidic (trans 18:1) or oleic acid (cis 18:1) would upregulate inflammatory markers.</p> <p>Results</p> <p>TLR4 mutant mice were ~26.4% heavier than WT mice. In both genotypes, mice that received TF diet were significantly heavier than those mice that received LF diet (P < 0.01). TLR4 mutant mice compared to WT mice had significantly higher fasting blood glucose, serum insulin, insulin resistance, serum leptin, and serum cholesterol when they received TF diet (P < 0.05). No upregulation of iNOS or COX2 in response to either elaidic or oleic acid in macrophage cells was observed.</p> <p>Conclusions</p> <p>Loss of function mutation in TLR4 not only did not protect mice from TF-induced obesity, hyperglycemia, hyperinsulinemia, and hypercholesterolemia but also exacerbated the above pathologies suggesting that functional TLR4 is necessary in attenuating TF-induced deleterious effects. It is likely that TF induces pathologies through pathways independent of TLR4.</p

Recognising Desire: A psychosocial approach to understanding education policy implementation and effect

It is argued that in order to understand the ways in which teachers experience their work - including the idiosyncratic ways in which they respond to and implement mandated education policy - it is necessary to take account both of sociological and of psychological issues. The paper draws on original research with practising and beginning teachers, and on theories of social and psychic induction, to illustrate the potential benefits of this bipartisan approach for both teachers and researchers. Recognising the significance of (but somewhat arbitrary distinction between) structure and agency in teachers’ practical and ideological positionings, it is suggested that teachers’ responses to local and central policy changes are governed by a mix of pragmatism, social determinism and often hidden desires. It is the often underacknowledged strength of desire that may tip teachers into accepting and implementing policies with which they are not ideologically comfortable

How do older people discuss their own sexuality? A systematic review of qualitative research studies

This study captured older people’s attitudes and concerns about sex and sexuality in later life by synthesising qualitative research published on this issue. The systematic review was conducted between November 2015 and June 2016 based on a pre-determined protocol. Key words were used to ensure a precise search strategy. Empirically based, qualitative literature from 18 databases was found. Twenty studies met the inclusion criteria. Thomas and Harden’s thematic synthesis was used to generate ‘analytical themes’ which summarise this body of literature. Three main themes were identified: (a) social legitimacy for sexuality in later life; (b) health, not age, is what truly impacts sexuality, and (c) the hegemony of penetrative sex. The themes illustrate the complex and delicate relation between ageing and sexuality. Older adults facing health issues that affect sexual function adopt broader definitions of sexuality and sexual activit

Sorafenib, Rapamycin, and Venetoclax Attenuate Doxorubicin-Induced Senescence and Promote Apoptosis in HCT116 Cells

Emerging evidence has shown that the therapy-induced senescent growth arrest in cancer cells is of durable nature whereby a subset of cells can reinstate proliferative capacity. Promising new drugs named senolytics selectively target senescent cells and commit them into apoptosis. Accordingly, senolytics have been proposed as adjuvant cancer treatment to cull senescent tumor cells, and thus, screening for agents that exhibit senolytic properties is highly warranted. Our study aimed to investigate three agents, sorafenib, rapamycin, and venetoclax for their senolytic potential in doxorubicin-induced senescence in HCT116 cells. HCT116 cells were treated with one of the three agents, sorafenib (5 µM), rapamycin (100 nM), or venetoclax (10 µM), in the absence or presence of doxorubicin (1 µM). Senescence was evaluated using microscopy-based and flow cytometry-based Senescence-associated-β-galactosidase staining (SA-β-gal), while apoptosis was assessed using annexin V-FITC/PI, and Muse caspase-3/-7 activity assays. We screened for potential genes through which the three drugs exerted senolytic-like action using the Human Cancer Pathway Finder PCR array. The three agents reduced doxorubicin-induced senescent cell subpopulations and significantly enhanced the apoptotic effect of doxorubicin compared with those treated only with doxorubicin. The senescence genes IGFBP5 and BMI1 and the apoptosis genes CASP7 and CASP9 emerged as candidate genes through which the three drugs exhibited senolytic-like properties. These results suggest that the attenuation of doxorubicin-induced senescence might have shifted HCT116 cells to apoptosis by exposure to the tested pharmacological agents. Our work argues for the use of senolytics to reduce senescence-mediated resistance in tumor cells and to enhance chemotherapy efficacy

Role of Interleukin-1 in Radiation-Induced Cardiomyopathy

Thoracic X-ray therapy (XRT), used in cancer treatment, is associated with increased risk of heart failure. XRT-mediated injury to the heart induces an inflammatory response leading to cardiomyopathy. The aim of this study was to determine the role of interleukin (IL)-1 in response to XRT injury to the heart and on the cardiomyopathy development in the mouse. Female mice with genetic deletion of the IL-1 receptor type I (IL-1R1 knockout mice [IL-1R1 KO]) and treatment with recombinant human IL-1 receptor antagonist anakinra, 10 mg/kg twice daily for 7 d, were used as independent approaches to determine the role of IL-1. Wild-type (wt) or IL-1R1 KO mice were treated with a single session of XRT (20 or 14 gray [Gy]). Echocardiography (before and after isoproterenol challenge) and left ventricular (LV) catheterization were performed to evaluate changes in LV dimensions and function. Masson’s trichrome was used to assess myocardial fibrosis and pericardial thickening. After 20 Gy, the contractile reserve was impaired in wt mice at d 3, and the LV ejection fraction (EF) was reduced after 4 months when compared with sham-XRT. IL-1R1 KO mice had preserved contractile reserve at 3 d and 4 months and LVEF at 4 months after XRT. Anakinra treatment for 1 d before and 7 d after XRT prevented the impairment in contractile reserve. A significant increase in LV end-diastolic pressure, associated with increased myocardial interstitial fibrosis and pericardial thickening, was observed in wt mice, as well as in IL-1R1 KO–or anakinra-treated mice. In conclusion, induction of IL-1 by XRT mediates the development of some, such as the contractile impairment, but not all aspects of the XRT-induced cardiomyopathy, such as myocardial fibrosis or pericardial thickening

Crosstalk Between BCR/ABL Oncoprotein and CXCR4 Signaling through a Src Family Kinase in Human Leukemia Cells

Stromal-derived factor (SDF)-1 and its G protein–coupled receptor, CXCR4, regulate stem/progenitor cell migration and retention in the marrow and are required for hematopoiesis. We show here an interaction between CXCR4 and the Src-related kinase, Lyn, in normal progenitors. We demonstrate that CXCR4-dependent stimulation of Lyn is associated with the activation of phosphatidylinositol 3-kinase (PI3-kinase). This chemokine signaling, which involves a Src-related kinase and PI3-kinase, appears to be a target for BCR/ABL, a fusion oncoprotein expressed only in leukemia cells. We show that the binding of phosphorylated BCR/ABL to Lyn results in the constitutive activation of Lyn and PI3-kinase, along with a total loss of responsiveness of these kinases to SDF-1 stimulation. Inhibition of BCR/ABL tyrosine kinase with STI571 restores Lyn responsiveness to SDF-1 signaling. Thus, BCR/ABL perturbs Lyn function through a tyrosine kinase-dependent mechanism. Accordingly, the blockade of Lyn tyrosine kinase inhibits both BCR/ABL-dependent and CXCR4-dependent cell movements. Our results demonstrate, for the first time, that Lyn-mediated pathological crosstalk exists between BCR/ABL and the CXCR4 pathway in leukemia cells, which disrupts chemokine signaling and chemotaxis, and increases the ability of immature cells to escape from the marrow. These results define a Src tyrosine kinases-dependent mechanism whereby BCR/ABL (and potentially other oncoproteins) dysregulates G protein–coupled receptor signaling and function of mammalian precursors