Inflammasome expression is higher in ovarian tumors than in normal ovary

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Luborsky, J., Barua, A., Edassery, S., Bahr, J. M., & Edassery, S. L. Inflammasome expression is higher in ovarian tumors than in normal ovary. Plos One, 15(1), (2020): e0227081, doi:10.1371/journal.pone.0227081.Chronic inflammation fundamentally influences cancer risk and development. A mechanism of chronic inflammation is the formation of inflammasome complexes which results in the sustained secretion of the pro-inflammatory cytokines IL1β and IL18. Inflammasome expression and actions vary among cancers. There is no information on inflammasome expression in ovarian cancer (OvCa). To determine if ovarian tumors express inflammasome components, mRNA and protein expression of NLRP3 (nucleotide-binding domain, leucine-rich repeat family, pyrin domain containing 3), caspase-1, IL1β, and IL18 expression in hen and human OvCa was assessed. Chicken (hen) OvCa a valid model of spontaneous human OvCa. Hens were selected into study groups with or without tumors using ultrasonography; tumors were confirmed by histology, increased cellular proliferation, and expression of immune cell marker mRNA. mRNA expression was higher for hallmarks of inflammasome activity (caspase-1, 5.9x increase, p = 0.04; IL1β, 4x increase, p = 0.04; and IL18, 7.8x increase, p = 0.0003) in hen OvCa compared to normal ovary. NLRP3, caspase-8 and caspase-11 mRNA did not differ significantly between tumor and non-tumor containing ovaries. Similar results occurred for human OvCa. Protein expression by immunohistochemistry paralleled mRNA expression and was qualitatively higher in tumors. Increased protein expression of caspase-1, IL1β, and IL18 occurred in surface epithelium, tumor cells, and immune cells. The aryl hydrocarbon receptor (AHR), a potential tumor suppressor and NLRP3 regulator, was higher in hen (2.4x increase, p = 0.002) and human tumors (1.8x increase, p = 0.038), suggesting a role in OvCa. Collectively, the results indicate that inflammasome expression is associated with hen and human OvCa, although the NLR sensor type remains to be determined.This research was made possible by NIH grant NCI R03CA182120 (JL), DOD grant W81XWH-08-1-0203 (JL) and Swim Across America (AB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Strengthening Competence of Therapists-in-Training in the Treatment of Health Anxiety (Hypochondriasis): Validation of the Assessment of Core CBT Skills (ACCS)

Although the observation and assessment of psychotherapeutic competences is central to training, supervision, patient care, quality control, and life‐long practice, structured instruments are used only occasionally. In the current study, an observation‐based tool for the Assessment of Core CBT Skills (ACCS) was translated into German and adapted, and its psychometric properties were pilot evaluated. Competence of therapists‐in‐training was assessed in a random sample of n = 30 videos on cognitive‐behavioral therapy including patients diagnosed with hypochondriasis. Two of three raters independently assessed the competences demonstrated in the entire, active treatment sessions (n = 60). In our sample, internal consistency was excellent, and interrater reliability was good. Convergent validity (Cognitive Therapy Scale) and discriminant validity (Helping Alliance Questionnaire) were within the expected ranges. The ACCS total score did not significantly predict the reduction of symptoms of hypochondriasis, and a one‐factorial structure of the instrument was found. By providing multiple opportunities for feedback, self‐reflection and supervision, the ACCS may complement current tools for the assessment of psychotherapeutic competences and importantly, support competence‐based training and supervision

Differences in client and therapist views of the working alliance in drug treatment

Background - There is growing evidence that the therapeutic alliance is one of the most consistent predictors of retention and outcomes in drug treatment. Recent psychotherapy research has indicated that there is a lack of agreement between client, therapist and observer ratings of the therapeutic alliance; however, the clinical implications of this lack of consensus have not been explored. Aims - The aims of the study are to (1) explore the extent to which, in drug treatment, clients and counsellors agree in their perceptions of their alliance, and (2) investigate whether the degree of disagreement between clients and counsellors is related to retention in treatment. Methods - The study recruited 187 clients starting residential rehabilitation treatment for drug misuse in three UK services. Client and counsellor ratings of the therapeutic alliance (using the WAI-S) were obtained during weeks 1-12. Retention was in this study defined as remaining in treatment for at least 12 weeks. Results - Client and counsellor ratings of the alliance were only weakly related (correlations ranging from r = 0.07 to 0.42) and tended to become more dissimilar over the first 12 weeks in treatment. However, whether or not clients and counsellors agreed on the quality of their relationship did not influence whether clients were retained in treatment. Conclusions - The low consensus between client and counsellor views of the alliance found in this and other studies highlights the need for drug counsellors to attend closely to their clients' perceptions of the alliance and to seek regular feedback from clients regarding their feelings about their therapeutic relationship

The hen model of human ovarian cancer develops anti-mesothelin autoantibodies in response to mesothelin expressing tumors

<p>Abstract</p> <p>Objective</p> <p>Study of the hen immune system led to seminal contributions to basic immunological principles. Recent studies of spontaneous ovarian cancer in the laying hen show strikingly similar tumor types and antigen expression compared to human ovarian cancer, suggesting hens would be valuable for studies of tumor immunology and pre-clinical vaccine development. Circulating mesothelin is a relatively specific marker for human ovarian cancer and autoantibodies to mesothelin were reported. We hypothesized that hen tumors express mesothelin and that circulating anti-mesothelin antibodies occur in response to tumors.</p> <p>Methods</p> <p>Mesothelin mRNA expression was analyzed by RT-PCR in hen ovarian tumors and normal ovaries. Mesothelin protein expression was evaluated by immunohistochemistry (IHC) and two-dimensional SDS-PAGE Western blots. Anti-mesothelin antibodies were assessed by immunoassay of sera from hens with normal ovaries and with ovarian tumors.</p> <p>Results</p> <p>Significant mesothelin mRNA expression was observed in 57% (12/21) of hen ovarian tumors but not in normal ovaries and was found predominantly in serous tumors as in humans. Mesothelin protein was detected in tumors with mesothelin mRNA by IHC and 2D Western blots, but not in normal ovaries or tumors without mesothelin mRNA. Circulating anti-mesothelin antibodies occurred in 44% (n = 4/9) of hens with ovarian tumors which express mesothelin mRNA and were not found in hens with tumors that did not express mesothelin (n = 0/5) or normal ovaries (n = 0/5).</p> <p>Conclusion</p> <p>The results support the utility of the hen as a novel model for preclinical studies of mesothelin as a biomarker and a target for immunotherapy.</p

How Qualitative Methods Contribute to Understanding Combination Antiretroviral Therapy Adherence

Strict adherence to medication regimens is generally required to obtain optimal response to combination antiretroviral therapy (ART). Yet, we have made limited progress in developing strategies to decrease the prevalence of nonadherence. As we work to understand adherence in developed countries, the introduction of ART in resource-poor settings raises novel challenges. Qualitative research is a scientific approach that uses methods such as observation, interviews, and verbal interactions to gather rich in-depth information about how something is experienced. It seeks to understand the beliefs, values, and processes underlying behavioral patterns. Qualitative methods provide powerful tools for understanding adherence. Culture-specific influences, medication beliefs, access, stigma, reasons for nonadherence, patterns of medication taking, and intervention fidelity and measurement development are areas ripe for qualitative inquiry. A disregard for the social and cultural context of adherence or the imposition of adherence models inconsistent with local values and practices is likely to produce irrelevant or ineffective interventions. Qualitative methods remain underused in adherence research. We review appropriate qualitative methods for and provide an overview of the qualitative research on ART nonadherence. We discuss the rationales for using qualitative methods, present 2 case examples illustrating their use, and discuss possible institutional barriers to their acceptance

Curie Temperatures for Three-Dimensional Binary Ising Ferromagnets

Using the Swendsen and Wang algorithm, high accuracy Monte Carlo simulations were performed to study the concentration dependence of the Curie temperature in binary, ferromagnetic Ising systems on the simple-cubic lattice. Our results are in good agreement with known mean-field like approaches. Based on former theoretical formulas we propose a new way of estimating the Curie temperature of these systems.Comment: nr. of pages:13, LATEX. Version 2.09, Scientific Report :02/1994 (Univ. of Bergen, Norway), 7 figures upon reques

Singaporean caregivers’ experiences of placing a relative into long term care

Caregivers experience many difficulties and challenges with the process of providing care particularly at times of transition, such as when the care recipient moves into a nursing home. This qualitative study aims to understand caregiver experiences of this important process. Methods: Twelve interviews were conducted with caregivers with an older relative in a nursing home in Singapore. The resulting data was analysed through thematic analysis. Results: Five themes were identified: Filial and cultural expectations shape caregivers’ experience of pre-placement decisions and post-placement; View of the placement decision; Continued impact of caring; Engagement with the institution and Maintaining the relationship. Conclusions: Caregivers were found to place significant emphasis on cultural values, specifically on filial piety. This impacted their caregiving role prior to placement, when making the decision to place their relative into a nursing home and in their continued involvement after placement. Despite the changing role, the placement experience was fraught with persisting difficulties involving maintaining the relationship with the resident and developing a new relationship with the nursing home

Exchange bias effect in alloys and compounds

The phenomenology of exchange bias effects observed in structurally single-phase alloys and compounds but composed of a variety of coexisting magnetic phases such as ferromagnetic, antiferromagnetic, ferrimagnetic, spin-glass, cluster-glass and disordered magnetic states are reviewed. The investigations on exchange bias effects are discussed in diverse types of alloys and compounds where qualitative and quantitative aspects of magnetism are focused based on macroscopic experimental tools such as magnetization and magnetoresistance measurements. Here, we focus on improvement of fundamental issues of the exchange bias effects rather than on their technological importance