From LAL-D to MASLD:Insights into the role of LAL and Kupffer cells in liver inflammation and lipid metabolism

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent liver pathology worldwide, closely associated with obesity and metabolic disorders. Increasing evidence suggests that macrophages play a crucial role in the development of MASLD. Several human studies have shown an inverse correlation between circulating lysosomal acid lipase (LAL) activity and MASLD. LAL is the sole enzyme known to degrade cholesteryl esters (CE) and triacylglycerols in lysosomes. Consequently, these substrates accumulate when their enzymatic degradation is impaired due to LAL deficiency (LAL[sbnd]D). This study aimed to investigate the role of hepatic LAL activity and liver-resident macrophages (i.e., Kupffer cells (KC)) in MASLD. To this end, we analyzed lipid metabolism in hepatocyte-specific (hep)Lal−/− mice and depleted KC with clodronate treatment. When fed a high-fat/high-cholesterol diet (HF/HCD), hepLal−/− mice exhibited CE accumulation and an increased number of macrophages in the liver and significant hepatic inflammation. KC were depleted upon clodronate administration, whereas infiltrating/proliferating CD68-expressing macrophages were less affected. This led to exacerbated hepatic CE accumulation and dyslipidemia, as evidenced by increased LDL-cholesterol concentrations. Along with proteomic analysis of liver tissue, these findings indicate that hepatic LAL-D in HF/HCD-fed mice leads to macrophage infiltration into the liver and that KC depletion further exacerbates hepatic CE concentrations and dyslipidemia.</p

Toward a New Standard of Dissensus: Notes on De-standardising Teacher Education

In a range of international contexts, professional standards have been developed and adopted as vehicles for codifying and governing the work of teachers. The putative rationale for developing professional standards is that they provide a shared language for talking about teachers, teaching, and learning and thus serve as a common reference point for pedagogical, professional and promotion-related conversations. At the same time, critical questions have been raised about the potential of standards as vehicles, not just for professional development, but for monitoring and controlling teachers. Concerns have also been raised regarding the degree to which standards inhibit professional autonomy and creativity. In this chapter, we ‘propose’, ironically and paradoxically, a standard of dissensus for teacher education, recognising that the Global Education Reform Movement (GERM) has imposed a seductive consensus around shared professional standards as an unquestioned common ‘good’. It is such ‘goodness’ we want to problematise and discuss in this chapter. Standards are often linked to testing and curriculum as well as to regulation of teachers’ work in many jurisdictions around the globe. As members of ITERC, we are broadly interested in thinking about how teacher educators might build a non-self-congratulatory solidarity that appreciates a standard of dissensus ‘from below’ in order to arrest and challenge the progress and influence of GERM. To that end, we want to offer some thoughtful notes that may serve as a starting point for a reconfiguration of the contemporary (im)possibilities in education

A co-created self-care and informal support intervention targeting women with gestational diabetes mellitus in northern Vietnam (VALID-II):a protocol for a two-arm non-randomised feasibility study

Background: Gestational diabetes mellitus (GDM) is a transitory form of diabetes that presents during pregnancy with frequent adverse maternal and neonatal health consequences if left untreated. The prevalence of GDM is rapidly increasing in low- and middle-income countries such as Vietnam, and early sustainable interventions are important. The overall aim of this study—henceforth referred to as VALID-II—is to assess the feasibility of a co-created self-care and informal support intervention targeted at pregnant women with GDM. Further, the aim is to assess the potential efficacy of the intervention in reducing maternal and neonatal health complications compared with standard care. Methods: VALID-II is a two-site, two-arm, non-randomised feasibility intervention study in Thai Binh Province in northern Vietnam with a delayed start for the intervention group. The intervention study is nested in a larger cohort. In total, 2000 pregnant women will be screened for GDM, with an estimated 400 women screening positive according to the World Health Organisation—International Association of Diabetes and Pregnancy Study Group diagnostic criteria. First, 200 women who screen positive for GDM will be assigned to a control group that will receive standard care. Among the 200 women, 20 will take part in an in-depth ethnographic study along with their family members, and the intervention will be co-created with them. Second, once the intervention has been created, 200 women will be assigned to the intervention group, which will receive the intervention plus standard care. Twenty women and their families from the intervention group will also take part in an ethnographic study. The primary outcome is to evaluate how feasible the self-care intervention is (composite outcome: recruitment, retention, and acceptability). Other secondary outcomes include the number of new-borns born large for gestational age, prevalence and risk factors for GDM, self-care agency, self-care, and breastfeeding practices. Discussion: This study provides knowledge of the feasibility of informal/self-care and social support interventions and their preliminary impact on maternal and child health outcomes among women with GDM in northern Vietnam. Furthermore, it will inform parameters such as effect size and variance, which are essential for calculating the sample size needed to achieve the desired power in a future full-scale trial. This may guide decision makers in how to optimise the management of GDM in low- and middle-income contexts. Trial registration: NCT05744856. Trial status: Recruiting.</p

Exploring the ‘fit-for-work’ principle:The association between occupational physical activity, cardio-respiratory fitness, and mortality – a meta-analysis of male worker data

Objectives This individual participant data meta-analysis investigates the association between occupational physical activity (OPA) and both cardiovascular mortality and all-cause mortality across different cardio-respi-ratory fitness (CRF) groups among male workers. Methods Data were pooled from five European cohort studies. OPA was categorized into three levels and CRF into low, moderate, and high tertiles. OPA was assessed using self-reports and CRF through objective measure-ments. Two-stage meta-analyses were conducted. First, we analyzed each cohort using Cox-regression models then we pooled results with random effects model to evaluate the associations between OPA and both cardiovascular and all-cause mortality, stratified by CRF. Models were adjusted for age, body mass index, smoking status, leisure-time physical activity, and educational level. Results Among 9922 men (mean age 46.8, standard deviation 6.7, years), 55.7% died during an average 25.6-year follow-up, of which 29.3% died from cardiovascular causes. Individuals with low CRF and high levels of OPA showed increased risks of cardiovascular [hazard ratio (HR) 1.27, 95% confidence interval (CI) 1.04–1.55] and all-cause mortality (HR 1.22, 95% CI 1.07–1.40) compared to those with low CRF and low levels of OPA. High CRF mitigated cardiovascular mortality risk (HR 1.08, 95% CI 0.79–1.48) but not all-cause mortality (HR 1.27, 95% CI 0.98–1.83) for those with high OPA. Conclusions Our findings for cardiovascular mortality suggest that high CRF levels may protect workers with physically demanding jobs from adverse cardiovascular outcomes, supporting the ‘fit-for-work’ principle. How-ever, this protective effect was not observed for all-cause mortality.</p

Making sense of digital communication between students, parents, teachers and school leaders in Danish state schools

Communication in Danish schools takes place with the aid of digital platforms developed and/or subsidised by the public sector and has done so for more than two decades. Within the same time frame, commercial social media platforms have emerged and become successfully integrated with key communicative practices. In order to understand how these communicative practices come about, we conducted interviews with students (from two different age groups), parents, teachers and school leaders in two primary and lower secondary schools in Denmark. The interviews focus on sense-making processes in digital communication and were analysed using Lomborg’s concept of communicative genres in social media. The analysis yielded four analytical categories through which the meaningfulness of using different digital platforms was assessed: (1) importance, (2) precision, (3) speed and (4) frequency. The findings are discussed in the framework of platformisation as well as the notion of technology paternalism. We argue that critical reflection on the use of commercial platforms in public institutions is needed. When key communicative practices in this arena rely on the services of data broking commercial actors, we risk further normalisation of problematic datafication.</p

Changing Narrative Through Theatre. The Case of Bergamo ER Theatre Covid Play

In recent years, historical approaches to management and organization research have gained significant momentum, after being considered peripheral to the field for many decades. According to Marcelo Bucheli and R. Daniel Wadhwani (Bucheli and Wadhwani, Organizations in time: History, theory, methods, Oxford University Press, 2014), the growing focus on history within business and organizational research mirrors a broader trend across the social sciences and mainstream intellectual discussions toward developing approaches that emphasize the historical context in the study of economic and social behavior.Bucheli &amp; Wadhwani identify the specificity of historical reasoning in its capacity to emphasise: “temporally contextualized explanations of organizations and markets and the methodological challenges of assigning significance and meaning to incomplete and temporally distant evidence from the past” (Bucheli and Wadhwani, Organizations in time: History, theory,methods, Oxford University Press, 2014, p. 4). However, as several scholars have pointed out—also in this collection—this process is not neutral, objective and easily reconstructed

‘Walking in their shoes’:How does externally worn diabetes technology mediate with the lifeworld of adolescents with type 1 diabetes

Despite the high prevalence of Type 1 Diabetes (T1D) among young people, there is limited understanding of how diabetes technologies affect their lives. What is it like to be a young person grappling with the challenges of T1D? How do therapeutic approaches sculpt their experiences? In what ways are medical devices constitutive of their embodiment? Through interviews with adolescents, this phenomenological study explores how insulin pumps, continuous glucose monitors, and other paraphernalia affect adolescents' lived experiences. Key existential themes are articulated as an experience of: living interrupted, being made visible, living monitored, and the ambiguity of technological dependency. We show the potential complexity of adolescents' experiences with T1D technologies. While the technologies function as helpful tools, they may also be experienced as burdensome and intrusive on adolescents living of their lives. By being attentive to adolescents experiences, this study contributes to the development of patient-centered approaches to T1D care and offers critical reflections on the role of wearable technologies in chronic disease management.</p

Longitudinal Follow-up Reveals Peripheral Immunological Changes Upon Tick Bite in α-Gal–Sensitized Individuals

Background: α-Gal syndrome is characterized by specific IgE (sIgE) antibodies to the carbohydrate galactose-α-1,3-galactose (α-Gal) and delayed onset of allergic symptoms after ingestion of mammalian meat. While tick bites are assumed to mediate sensitization, the immune response to tick bites has not yet been investigated. Objective: To investigate the peripheral immune response to tick bites in humans over time. Methods: In a longitudinal cohort study, immunological reactions associated with tick bites (Ixodes species) were analyzed within 1 day (V1), 2 weeks (V2), 1 month (V3), and 3 months (V4) after the occurrence of a bite. sIgE, sIgG, and sIgG subclass levels, as well as 10 cytokines, were quantified. Deep immune phenotyping was performed using mass cytometry. Results: A total of 4 controls and 10 patients were bitten by a tick and followed up over 3 months. None of the controls developed sIgE to α-Gal, and sIgE increased in all patients from V1 until V2/V3, as did IL-8 levels. We noted a significant increase in CD19 + B cells and B-cell subpopulations, as well as a decrease in γδ CD56 + T cells in patients between V0 and V1. At V1, frequencies of plasmacytoid dendritic cells (pDCs) and γδ CD56 + T cells were lower in patients than in controls. Conclusion: Our study provides evidence of significant changes in several immune cell populations in α-Gal–sensitized patients, along with increased levels of IL-8 and sIgE. This is the first exploratory study to investigate longitudinal peripheral immune profiles in patients and controls bitten by ticks.</p

Afghanistan

This chapter traces the history of NATO and Afghanistan and pinpoints the principal strengths and weaknesses of the Alliance’s operational involvement in the country. NATO’s security assistance mission (ISAF) and the subsequent training mission Resolute Support) ultimately failed, and NATO was forced to withdraw chaotically in August 2021. The record of Alliance involvement in Afghanistan defies easy interpretation. NATO was layered into a counter-insurgency campaign partly run by a US-led coalition and partly by United Nations agencies. NATO went big in terms of operational footprint, but its hand on the political steering wheel was always light. NATO demonstrated endurance, capacity, and political legitimacy, and yet Afghanistan became the graveyard of its good intentions. Three frameworks of interpretation help make sense of all this—highlighting, respectively, strategic leadership, institutionalized ideas, and the contingency of multinational warfare. In engaging these frameworks, the chapter demonstrates how, even as we now know the beginning and the end of NATO in Afghanistan, the full meaning of the intervention is still emerging. The case thus merits further scholarly attention