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TNFSF8/CD30 ligand is a TNF superfamily member expressed on several major immune cell types, including activated monocytes, B, and T cells. The signaling of CD30 ligand through its cognate CD30 receptor has been shown to have effects on cell differentiation, cell death/survival, and cytokine production. The signaling pair has been implicated in hematopoietic malignancies and inflammatory disease, and a chemotherapy–CD30 antibody combination for the treatment of Hodgkin and other lymphomas has been developed. There are two recorded isoforms of CD30 ligand. All hitherto studies of CD30 ligand are of the first, canonical isoform, while the second isoform has never been described. This study aims to elucidate the properties and signaling functions of the second CD30 ligand isoform. We have found mRNA expression of both isoforms in the PBMCs of all six healthy donors tested. Through methods in cell biology and biochemistry, we were able to discover that the second CD30 ligand isoform has no discernable pro-inflammatory function and, in fact, isoform 2 can restrict the capacity of the canonical isoform to signal through the CD30 receptor by preventing their interaction. This discovery has implications for the future development of therapeutics targeting the CD30/CD30 ligand signaling pair in cancer and inflammatory disease.

In this article, we report on a mixed-methods study which investigated teachers' attitudes towards and experiences with teaching environmental issues within their ELT classes. Given the rising importance of ecoliteracy and its inclusion as a transversal learning objective for all subjects in many national state curricula, it is critically important to understand how ELT educators can be best supported in addressing simultaneously both linguistic and environmentally related teaching goals. Data were collected via an online international survey (n = 91) and a series of in-depth, semi-structured interviews (n = 5). Analysis of the data reveals the specific strategies ELT teachers employ when integrating environmental issues alongside linguistic issues, what their motivations for doing so are, what resources and materials they use, and what challenges they face. The article offers valuable insights into the factors that facilitate the sustainable and effective teaching of both language and environmental issues in diverse ELT contexts across the globe.

Abstract Strength training recommendations have been embedded within the UK’s Chief Medical Officers’ physical activity guidelines since 2011. There is limited evidence that these recommendations are used by exercise instructors in the community to underpin strength training prescription in the older adult population. This study aimed to explore exercise instructors’ awareness and utilisation of the guidelines when prescribing strength training to older adults. Fifteen exercise instructors working with older adults in the UK participated in one online interview. A general inductive approach was conducted and thematic analysis allowed for major themes to be identified from the raw data. We found that most exercise instructors (n = 9), but not all (n = 6), were aware of the guidelines. Only one instructor (n = 1) had reportedly implemented the guidelines into their practice; other instructors reported that the guidelines were irrelevant. Instead, each of the instructors had their preferred sources of information that they relied on to underpin their exercise prescription, and each had their own interpretation of ‘evidence-based strength training.’ This individualised interpretation resulted in exceptionally varied prescription in the community and does not necessarily align with the progressive, evidence-based prescription known to build muscular strength. We suggest that (i) more detail on how to build muscular strength be embedded within the guidelines, (ii) a handbook on how to implement the guidelines be made available, (iii) theoretical and practical teaching materials and courses be updated, and/or (iv) a re-(education) of exercise instructors already in the field may be necessary to bring about a consistent, evidence-based strength prescription necessary for the best possible health and longevity outcomes for our ageing population.

The aim of this study was to assess changes in mental health and wellbeing measures across a 50-day physical activity workplace program. The secondary aims assessed the relationship between demographic and pre-program physical activity self-reported variables, mental health, wellbeing and program engagement measures. The study utilized a naturalistic longitudinal design with a study population of 2903 people. Participants were engaged in the 10,000 step daily physical activity program for 50-days and measures of engagement were tracked. 1320 participants provided full pre/post-program data across a range of standardized mental health and wellbeing measures alongside demographic and program engagement measures. For individuals providing pre and post program data there was a significant reduction in anxiety (18.2%, p = .008), stress (13.0%, p = .014) and sleep related impairment (6.9%, p < .001) alongside a significant improvement in overall wellbeing (6.7%, p = .001). The data further showed no significant mental health differences were identified between individuals who recorded below versus equal to or above 10,000 steps. Regression analyses indicated numerous group and personal variables impacted mental health, wellbeing and program engagement. The study highlights improvements in a range of mental health and wellbeing scores occurred over the 50-day activity program for people who complete the program. Finally, the study identified a range of protective and risk factors for mental health benefits of these programs and level of engagement. Whilst there were similarities in the pre-program mental health and wellbeing scores of those who completed and those lost to follow-up, further research is required to better characterize and understand this group., Author(s): Karen T. Hallam [sup.1] [sup.2] , Anna Peeters [sup.3] , A. Gupta [sup.3] , S. Bilsborough [sup.2] Author Affiliations: (1) grid.1021.2, 0000 0001 0526 7079, Institute for Mental and [...]

BACKGROUND AND AIMS: The host receptor for severe acute respiratory syndrome coronavirus 2, angiotensin-converting enzyme 2 (ACE2), is highly expressed in small bowel (SB). Our aim was to identify factors influencing intestinal ACE2 expression in Crohns disease (CD), ulcerative colitis (UC), and non-inflammatory bowel disease (IBD) controls. METHODS: Using bulk RNA sequencing or microarray transcriptomics from tissue samples (4 SB and 2 colonic cohorts; n = 495; n = 387 UC; n = 94 non-IBD), we analyzed the relationship between ACE2 with demographics and disease activity and prognosis. We examined the outcome of anti-tumor necrosis factor and anti-interleukin-12/interleukin-23 treatment on SB and colonic ACE2 expression in 3 clinical trials. Univariate and multivariate regression models were fitted. RESULTS: ACE2 levels were consistently reduced in SB CD and elevated in colonic UC compared with non-IBD controls. Elevated SB ACE2 was also associated with demographic features (age and elevated body mass index) associated with poor coronavirus disease 2019 outcomes. Within CD, SB ACE2 was reduced in patients subsequently developing complicated disease. Within UC, colonic ACE2 was elevated in active disease and in patients subsequently requiring anti-tumor necrosis factor rescue therapy. SB and colonic ACE2 expression in active CD and UC were restored by anti-cytokine therapy, most notably in responders. CONCLUSIONS: Reduced SB but elevated colonic ACE2 levels in IBD are associated with inflammation and severe disease, but normalized after anti-cytokine therapy, suggesting compartmentalization of ACE2-related biology in SB and colonic inflammation. The restoration of ACE2 expression with anti-cytokine therapy might be important in the context of severe acute respiratory syndrome coronavirus 2 infection and potentially explain reports of reduced morbidity from coronavirus disease 2019 in IBD patients treated with anti-cytokines.

BACKGROUND AND AIMS: Heterogeneity in Crohns disease [CD] provides a challenge for the development of effective therapies. Our goal was to define a unique molecular signature for severe, refractory CD to enable precision therapy approaches to disease treatment and to facilitate earlier intervention in complicated disease. METHODS: We analysed clinical metadata, genetics, and transcriptomics from uninvolved ileal tissue from CD patients who underwent a single small bowel resection. We determined transcriptional risk scores, cellular signatures, and mechanistic pathways that define patient subsets in refractory CD. RESULTS: Within refractory CD, we found three CD patient subgroups [CD1, CD2, and CD3]. Compared with CD1, CD3 was enriched for subjects with increased disease recurrence after first surgery [OR = 6.78, p = 0.04], enhanced occurrence of second surgery [OR = 5.07, p = 0.016], and presence of perianal CD [OR = 3.61, p = 0.036]. The proportion of patients with recurrence-free survival was smaller in CD3 than in CD1 (p = 0.02, median survival time [months] in CD1 = 10 and CD3 = 6). Overlaying differential gene expression between CD1 and CD3 on CD subgroup-associated genetic polymorphisms identified 174 genes representing both genetic and biological differences between the CD subgroups. Pathway analyses using this unique gene signature indicated eukaryotic initiation factor 2 [eIF2] and cyclic adenosine monophosphate [cAMP] signalling to be dominant pathways associated with CD3. Furthermore, the severe, refractory subset, CD3, was associated with a higher transcriptional risk score and enriched with eosinophil and natural killer T [NKT] cell gene signatures. CONCLUSION: We characterized a subset of severe, refractory CD patients who may need more aggressive treatment after first resection and who are likely to benefit from targeted therapy based on their genotype and tissue gene expression signature.

Periods of economic downturn are of keen interest to the law. The legal literature primarily focuses on how laws and legal markets affect – by contributing to or abating – economic downturns. This focus has left a sizeable gap in the literature analyzing the converse: how economic downturns affect law practice. The conventional wisdom is that economic downturns harm legal markets overall, and transaction practices in particular, but supporting data are not well studied. This paper helps fill the empirical gap by surveying and interviewing Bay Area attorneys from various law firms on their perception of the effects of economic downturns on legal markets. We find evidence to support the conventional wisdom at a high level of generality, but the granularity of our data lead to findings that significantly complicate the general picture. We find, for example, that personal-injury litigation is negatively affected by economic downturns, investment-management law is resilient, and healthcare transactional work can be positively affected. Our study reveals a highly complex picture of the effects of economic downturns on legal markets, effects that are dependent upon a constellation of factors. Overall, our study offers a more nuanced understanding of economic downturns and the legal profession. [ABSTRACT FROM AUTHOR]

Abstract Background An increased awareness of the health benefits of walking has emerged with the development and refinement of accelerometer equipment. Evidence is beginning to highlight the value of promoting walking, particularly focusing on the Japanese mark of obtaining 10,000 steps per day. Workplace based step challenges have become popular to engage large cohorts in increasing their daily physical activity in a sustainable and enjoyable way. Findings are now highlighting the positive health effects of these medium-term programs (typically conducted over a few months) in terms of cardiovascular health, reducing diabetes risk and improving lifestyle factors such as weight and blood pressure. As yet, research has not focused on whether similar improvements in psychological health and wellbeing are present. Methods This study investigated the impact of a 100-day, 10,000 step program on signs of depression, anxiety and stress as well as general wellbeing using standardised psychological scales. Results The results indicated a small but consistent effect on all of these measures of mental health over the term of the program. This effect appeared irrespective of whether a person reached the 10,000 step mark. Conclusions These results highlight improved mental health and wellbeing in people undertaking this 100-day 10,000 step program and indicates the efficacy and potential of these programs for a modest, yet important improvement in mental health. Notably, targets reached may be less important than participation itself.

In this article, we report on a mixed-methods study which investigated teachers' attitudes towards and experiences with teaching environmental issues within their ELT classes. Given the rising importance of ecoliteracy and its inclusion as a transversal learning objective for all subjects in many national state curricula, it is critically important to understand how ELT educators can be best supported in addressing simultaneously both linguistic and environmentally related teaching goals. Data were collected via an online international survey (n = 91) and a series of in-depth, semi-structured interviews (n = 5). Analysis of the data reveals the specific strategies ELT teachers employ when integrating environmental issues alongside linguistic issues, what their motivations for doing so are, what resources and materials they use, and what challenges they face. The article offers valuable insights into the factors that facilitate the sustainable and effective teaching of both language and environmental issues in diverse ELT contexts across the globe. [ABSTRACT FROM AUTHOR]