Two-year real-world outcome data from a single tertiary centre shows reduced ustekinumab persistence in a non-bio-naïve Crohn's disease cohort with penetrating disease, -ostomies and sarcopenia

BACKGROUND: Ustekinumab was approved in 2016 for the treatment of moderate-severe Crohn's disease (CD). Clinical trials and real-world studies have suggested ustekinumab to be a safe and effective treatment; however, studies to date infrequently use imaging techniques to predict response to biologics in CD. OBJECTIVES: We assessed the 2-year real-world effectiveness and safety of ustekinumab in a tertiary CD cohort with the use of novel imaging techniques. DESIGN: Retrospective cohort study. METHODS: Retrospective data were collected between 2016 and 2021. Study end points included ustekinumab persistence, biological and/or clinical response and remission at 12, 18 and 24 months. Statistical analysis included demographic and inferential analyses. RESULTS: In all, 131 CD patients [57.3% female, median age of 26.0 (21.0-37.0)] were included. Patients were non-bio naïve, and the majority received ustekinumab as third- or fourth-line treatment. At 24 months, 61.0% (80/131) persisted with ustekinumab [52.7% (69/131) steroid free]. Clinical response was reported in 55.2% (37/67), clinical remission in 85.7% (57/67), biological response in 46.8% (22/47) and biological remission in 31.9% (15/47) of patients at 24 months. The low outcome numbers were attributable to missing data. Improvements in routine disease markers, including C-reactive protein and Harvey-Bradshaw Index, were also reflected in magnetic resonance imaging-derived disease scores. The presence of penetrating CD, an -ostomy and sarcopenia were all predictors of poorer ustekinumab outcomes (p < 0.05). CONCLUSION: Ustekinumab is effective in non-bio-naïve CD patients with non-stricturing, non-penetrating disease with an unremarkable safety profile but may be less effective in those with penetrating disease, -ostomies and sarcopenia

Post-transcriptional Gene Silencing Induced by Short Interfering RNAs in Cultured Transgenic Plant Cells

Short interfering RNA (siRNA) is widely used for studying post-transcriptional gene silencing and holds great promise as a tool for both identifying function of novel genes and validating drug targets. Two siRNA fragments (siRNA-a and -b), which were designed against different specific areas of coding region of the same target green fluorescent protein (GFP) gene, were used to silence GFP expression in cultured gfp transgenic cells of rice (Oryza sativa L.; OS), cotton (Gossypium hirsutum L.; GH), Fraser fir [Abies fraseri (Pursh) Poir; AF], and Virginia pine (Pinus virginiana Mill.; PV). Differential gene silencing was observed in the bombarded transgenic cells between two siRNAs, and these results were consistent with the inactivation of GFP confirmed by laser scanning microscopy, Northern blot, and siRNA analysis in tested transgenic cell cultures. These data suggest that siRNA-mediated gene inactivation can be the siRNA specific in different plant species. These results indicate that siRNA is a highly specific tool for targeted gene knockdown and for establishing siRNA-mediated gene silencing, which could be a reliable approach for large-scale screening of gene function and drug target validation

Effects of Genetic Variation in Protease Activated Receptor 4 after an Acute Coronary Syndrome: Analysis from the TRACER trial

© 2018 Elsevier Inc. This manuscript version is made available under the CC-BY-NC-ND 4.0 license: http://creativecommons.org/licenses/by-nc-nd/4.0/ This author accepted manuscript is made available following 12 month embargo from date of publication (Sept 2018) in accordance with the publisher’s archiving policyVariation in platelet response to thrombin may affect the safety and efficacy of PAR antagonism. The Thr120 variant of the common single nucleotide polymorphism (SNP) rs773902 in the protease-activated receptor (PAR) 4 gene is associated with higher platelet aggregation compared to the Ala120 variant. We investigated the relationship between the rs773902 SNP with major bleeding and ischemic events, safety, and efficacy of PAR1 inhibition in 6177 NSTE ACS patients in the TRACER trial. There was a lower rate of GUSTO moderate/severe bleeding in patients with the Thr120 variant. The difference was driven by a lower rate in the smaller homozygous group (recessive model, HR 0.13 [0.02–0.92] P = 0.042). No significant differences were observed in the ischemic outcomes. The excess in bleeding observed with PAR1 inhibition was attenuated in patients with the Thr120 variant, but the interactions were not statistically significant. In summary, lower major bleeding rates were observed in the overall TRACER cohort with the hyperreactive PAR4 Thr120 variant. The increase in bleeding with vorapaxar was attenuated with the Thr120 variant, but we could not demonstrate an interaction with PAR1 inhibition. These findings warrant further exploration, including those of African ancestry where the A allele (Thr120) frequency is ~65%.This work was supported by the National Institutes of Health [grant number HL102482]; the University of Utah Division of Hematology and Hematologic Malignancies; and the Cardeza Foundation for Hematologic Research

UK guideline on transition of adolescent and young persons with chronic digestive diseases from paediatric to adult care

The risks of poor transition include delayed and inappropriate transfer that can result in disengagement with healthcare. Structured transition care can improve control of chronic digestive diseases and long-term health-related outcomes. These are the first nationally developed guidelines on the transition of adolescent and young persons (AYP) with chronic digestive diseases from paediatric to adult care. They were commissioned by the Clinical Services and Standards Committee of the British Society of Gastroenterology under the auspices of the Adolescent and Young Persons (A&YP) Section. Electronic searches for English-language articles were performed with keywords relating to digestive system diseases and transition to adult care in the Medline (via Ovid), PsycInfo (via Ovid), Web of Science and CINAHL databases for studies published from 1980 to September 2014. The quality of evidence and grading of recommendations was appraised using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The limited number of studies in gastroenterology and hepatology required the addition of relevant studies from other chronic diseases to be included. These guidelines deal specifically with the transition of AYP living with a diagnosis of chronic digestive disease and/or liver disease from paediatric to adult healthcare under the following headings; 1. Patient populations involved in AYP transition 2. Risks of failing transition or poor transition 3. Models of AYP transition 4. Patient and carer/parent perspective in AYP transition 5. Surgical perspectiv

Psychology of Prejudice and Discrimination

Psychology of Prejudice and Discrimination provides a comprehensive and compelling overview of what psychological theory and research have to say about the nature, causes, and reduction of prejudice and discrimination. It balances a detailed discussion of theories and selected research with applied examples that ensure the material is relevant to students. This edition has been thoroughly revised and updated and addresses several interlocking themes. It first looks at the nature of prejudice and discrimination, followed by a discussion of research methods. Next come the psychological underpinnings of prejudice: the nature of stereotypes, the conditions under which stereotypes influence responses to other people, contemporary theories of prejudice, and how individuals’ values and belief systems are related to prejudice. Explored next are the development of prejudice in children and the social context of prejudice. The theme of discrimination is developed via discussions of the nature of discrimination, the experience of discrimination, and specific forms of discrimination, including gender, gender identity, sexual orientation, age, ability, and appearance. The concluding theme is the reduction of prejudice. The book is accompanied by a comprehensive website featuring an Instructor Manual that contains activities and tools to help with teaching a prejudice and discrimination course; PowerPoint slides for every chapter; and a Test Bank with short answer and multiple-choice exam questions for every chapter. This book is an essential companion for all students of prejudice and discrimination, including those in psychology, education, social work, business, communication studies, ethnic studies, and other disciplines. In addition to courses on prejudice and discrimination, this book will also appeal to those studying racism and diversity.https://repository.usfca.edu/faculty_books_all/1100/thumbnail.jp

Psychology of Prejudice and Discrimination

Psychology of Prejudice and Discrimination provides a comprehensive and compelling overview of what psychological theory and research have to say about the nature, causes, and reduction of prejudice and discrimination. It balances a detailed discussion of theories and selected research with applied examples that ensure the material is relevant to students. This edition has been thoroughly revised and updated and addresses several interlocking themes. It first looks at the nature of prejudice and discrimination, followed by a discussion of research methods. Next come the psychological underpinnings of prejudice: the nature of stereotypes, the conditions under which stereotypes influence responses to other people, contemporary theories of prejudice, and how individuals’ values and belief systems are related to prejudice. Explored next are the development of prejudice in children and the social context of prejudice. The theme of discrimination is developed via discussions of the nature of discrimination, the experience of discrimination, and specific forms of discrimination, including gender, gender identity, sexual orientation, age, ability, and appearance. The concluding theme is the reduction of prejudice. The book is accompanied by a comprehensive website featuring an Instructor Manual that contains activities and tools to help with teaching a prejudice and discrimination course; PowerPoint slides for every chapter; and a Test Bank with short answer and multiple-choice exam questions for every chapter. This book is an essential companion for all students of prejudice and discrimination, including those in psychology, education, social work, business, communication studies, ethnic studies, and other disciplines. In addition to courses on prejudice and discrimination, this book will also appeal to those studying racism and diversity.https://repository.usfca.edu/faculty_books_2022/1011/thumbnail.jp

Clinical service delivery implications of the COVID-19 pandemic on people with Inflammatory bowel disease: a qualitative study

Abstract Background During the COVID-19 pandemic, clinical services were severely disrupted, restricted, or withdrawn across the country. People living with Inflammatory Bowel Disease (IBD) – an auto-immune disorder for which medical treatment often results in immunosuppression, thus requiring regular monitoring—may have struggled to access clinical support. As part of a larger qualitative study, we investigated experiences of access to clinical services during the pandemic, and patient concerns about and preferences for services in the future. Methods This exploratory qualitative study used semi-structured interviews to explore participants’ experiences of clinical services across the UK during the pandemic. All data were collected remotely (March – May 2021) using online video-calling platforms or by telephone. Audio files were transcribed professionally and anonymised for analysis. Data were analysed using thematic analysis. Results Of the eight themes found across all data, four related specifically to accessing GP, local (district) hospital, and specialist (tertiary) referral services for IBD: 1) The Risk of Attending Hospital; 2) Missing Routine Monitoring or Treatment; 3) Accessing Care as Needed, and 4) Remote Access and The Future. Conclusions Our findings support other studies reporting changes in use of health services, and concerns about future remote access methods. Maintenance of IBD services in some form is essential throughout crisis periods; newly diagnosed patients need additional support; future dependence on IBD services could be reduced through use of treatment / self-management plans. As the NHS digitalises it’s future services, the mode of appointment—remote (telephone, video call), or in-person – needs to be flexible and suit the patient

Data from: Voluntary locomotor activity mitigates oxidative damage associated with isolation stress in the prairie vole (Microtus ochrogaster)

Organismal performance directly depends on an individual's ability to cope with a wide array of physiological challenges. For social animals, social isolation is a stressor that has been shown to increase oxidative stress. Another physiological challenge, routine locomotor activity, has been found to decrease oxidative stress levels. Because we currently do not have a good understanding of how diverse physiological systems like stress and locomotion interact to affect oxidative balance, we studied this interaction in the prairie vole (Microtus ochrogaster). Voles were either pair housed or isolated and within the isolation group, voles either had access to a moving wheel or a stationary wheel. We found that chronic periodic isolation caused increased levels of oxidative stress. However, within the vole group that was able to run voluntarily, longer durations of locomotor activity were associated with less oxidative stress. Our work suggests that individuals who demonstrate increased locomotor activity may be better able to cope with the social stressor of isolation

Voluntary locomotor activity mitigates oxidative damage associated with isolation stress in the prairie vole (Microtus ochrogaster)

Organismal performance directly depends on an individual's ability to cope with a wide array of physiological challenges. For social animals, social isolation is a stressor that has been shown to increase oxidative stress. Another physiological challenge, routine locomotor activity, has been found to decrease oxidative stress levels. Because we currently do not have a good understanding of how diverse physiological systems like stress and locomotion interact to affect oxidative balance, we studied this interaction in the prairie vole (Microtus ochrogaster). Voles were either pair housed or isolated and within the isolation group, voles either had access to a moving wheel or a stationary wheel. We found that chronic periodic isolation caused increased levels of oxidative stress. However, within the vole group that was able to run voluntarily, longer durations of locomotor activity were associated with less oxidative stress. Our work suggests that individuals who demonstrate increased locomotor activity may be better able to cope with the social stressor of isolation