Synovial cell metabolism and chronic inflammation in rheumatoid arthritis

Metabolomic studies of body fluids show that immune-mediated inflammatory diseases such as rheumatoid arthritis (RA) are associated with metabolic disruption. This is likely to reflect the increased bioenergetic and biosynthetic demands of sustained inflammation and changes to nutrient and oxygen availability in damaged tissue. The synovial membrane lining layer is the principle site of inflammation in RA. Here the resident cells are the fibroblast-like synoviocytes (FLS) and the synovial tissue macrophages (STM), which are transformed toward overproduction of enzymes which degrade cartilage and bone, and cytokines which promote immune cell infiltration. Recent studies have shown metabolic changes in both FLS and macrophages from RA patients and these may be therapeutically targetable. However, as the origins and subset specific functions of synoviocytes are poorly understood and the signaling modules which control metabolic deviation in RA synovial cells are yet to be explored, significant additional research is needed to translate these findings toward clinical application. Furthermore, in many inflamed tissues, different cell types can forge metabolic collaborations through solute carriers (SLC) in their membranes, to meet a high demand for energy or biomolecules. Such relationships are likely to exist in the synovium and are yet to be explored. Finally, it is not yet known whether metabolic change is a consequence of disease or if primary changes to cellular metabolism might underlie or contribute to early stage disease pathogenesis. This article collates what is known about metabolism in synovial tissue cells and highlights future research directions in this area

Recomanacions per als puzles en l'aprenentatge de la construcció

Aquesta comunicació presenta recomanacions d’utilitat per a la realització d’activitats puzle dirigides a l’aprenentatge de la construcció a l’arquitectura. Aquestes recomanacions es basen en l’experiència d’utilitzar l’activitat puzle en classes de construcció del Departament de Construccions Arquitectòniques I (CA1) de l’Etsab, UPC. Aquestes activitats s’han dut a terme en assignatures de segon curs (Construcció 1); tercer curs (Construcció IV) i Postgrau (Màster universitari en Tecnologia a l’Arquitectura). Aquests puzles han incorporat variacions respecte la tècnica puzle convencional. N’hi ha hagut sobre detalls constructius d’edificis, sobre solucions davant de conflictes reals a l’obra, d’externs... Durant aquests puzles s’han recollit diversos indicadors: pretests i posttests, enquestes de satisfacció, temps de dedicació, fitxes d’aprenentatge... Analitzant aquests indicadors és possible: a) confirmar que l’alumnat valora positivament aquesta activitat; i b) recollir i ordenar l’experiència acumulada mitjançant les recomanacions que es presenten en aquesta comunicació.Peer Reviewe

Urban way of life as survival: navigating everyday life in a pluriversal global south

Southern cities have become increasingly inscribed in broader postcolonial and neoliberal development forces. In tandem with global pandemics, digital threats, and migration and climate crises, these forces have posed critical implications for all residents, decimating the middle class, widening the gap between elites and masses, deepening the cost of living for the urban majority, and making it harder to rise through the ladder. In such an environment, navigating everyday life increasingly becomes synonymous with survival, constituting a proactive process of inhabiting the city, where the self and the urban are always in the making. This paper examines prominent accounts of the urban way of life as survival. We take one large city of Nairobi in eastern Africa as a representative case, highlighting manifold rhythms and ensembles of survival, such as how residents make ends meet, optimize for a soft life, niche social infrastructures, and cultivate technological infrastructures. In their material manifestations, these rhythms and ensembles demonstrate the role and centrality of urban residents as proactive producers and co-creators of multiple urban forms. They draw us to a mode of survival that is continuous rather than intermittent and of inhabitation that is reparative rather than castigatory

Determinants of the empiric use of antibiotics by general practitioners in South Africa : observational, analytic, cross-sectional study

The overuse of antibiotics is the main driver of antimicrobial resistance (AMR). However, there has been limited surveillance data on AMR and antibiotic prescribing at a primary healthcare level in South Africa. An observational, analytic, cross-sectional study was undertaken to assess key factors associated with empiric antibiotic prescribing among private sector general practitioners (GPs) in the eThekwini district in South Africa, particularly for patients with acute respiratory infections (ARIs). A semi-structured web-based questionnaire was used between November 2020 – March 2021. One hundred and sixteen (55.5%) responding GPs prescribed antibiotics empirically for patients with ARIs more than 70% of the time, primarily for symptom relief and the prevention of complications. GPs between the ages of 35-44 years (OR: 3,38; 95%CI: 1,15-9,88), > 55 years (OR: 4,75; 95% CI 1,08-21) and in practice < 15 years (OR: 2,20; 95%CI: 1,08-4,51) were significantly more likely to prescribe antibiotics empirically. Three factors - workload/time pressures; diagnostic uncertainty, and the use of a formulary, were significantly associated with empiric prescribing. GPs with more experience and working alone were slightly less likely to prescribe antibiotics empirically. These findings indicate that a combination of environmental factors are important underlying contributors to the development of AMR. As a result, guide appropriate interventions using a health system approach, which includes pertinent prescribing indicators and targets

Integrated transcriptomics establish macrophage polarization signatures and have potential applications for clinical health and disease

Growing evidence defines macrophages (Mφ) as plastic cells with wide-ranging states of activation and expression of different markers that are time and location dependent. Distinct from the simple M1/M2 dichotomy initially proposed, extensive diversity of macrophage phenotypes have been extensively demonstrated as characteristic features of monocyte-macrophage differentiation, highlighting the difficulty of defining complex profiles by a limited number of genes. Since the description of macrophage activation is currently contentious and confusing, the generation of a simple and reliable framework to categorize major Mφ phenotypes in the context of complex clinical conditions would be extremely relevant to unravel different roles played by these cells in pathophysiological scenarios. In the current study, we integrated transcriptome data using bioinformatics tools to generate two macrophage molecular signatures. We validated our signatures in in vitro experiments and in clinical samples. More importantly, we were able to attribute prognostic and predictive values to components of our signatures. Our study provides a framework to guide the interrogation of macrophage phenotypes in the context of health and disease. The approach described here could be used to propose new biomarkers for diagnosis in diverse clinical settings including dengue infections, asthma and sepsis resolution

Community perceptions of the impact of war on unintended pregnancy and induced abortion in Protection of Civilian sites in Juba, South Sudan

Conflict and mass displacement into Protection of Civilian (POCs) sites in South Sudan led to the breakdown of community and family structures, increasing women and girls’ vulnerability to gender-based violence and exacerbating already poor sexual and reproductive health outcomes. As one component of a study on post-abortion care, this study explores community perceptions of unintended pregnancy and abortion in a POC in Juba. Four focus group discussions were conducted with 36 women and married men aged 18-45 living in the POC. Although initial reactions to induced abortion were generally negative, participants discussed that unintended pregnancy and induced abortion appeared to have increased during the current conflict. Their discussion of abortion became less condemnatory as they described changes in people’s situation due to war, including instability and poverty, transactional sex, disruption of marital norms, rape, and low contraceptive use. This is one of the first studies to investigate community perceptions and practices related to unintended pregnancy and abortion in South Sudan. Despite beliefs that these are taboo topics, the discussions provide an opening to reduce abortion stigma. To ensure lasting stigma reduction, investment in women and girls to improve gender equity is needed

Altered thymic differentiation and modulation of arthritis by invariant NKT cells expressing mutant ZAP70

Various subsets of invariant natural killer T (iNKT) cells with different cytokine productions develop in the mouse thymus, but the factors driving their differentiation remain unclear. Here we show that hypomorphic alleles of Zap70 or chemical inhibition of Zap70 catalysis leads to an increase of IFN-gamma-producing iNKT cells (NKT1 cells), suggesting that NKT1 cells may require a lower TCR signal threshold. Zap70 mutant mice develop IL-17-dependent arthritis. In a mouse experimental arthritis model, NKT17 cells are increased as the disease progresses, while NKT1 numbers negatively correlates with disease severity, with this protective effect of NKT1 linked to their IFN-gamma expression. NKT1 cells are also present in the synovial fluid of arthritis patients. Our data therefore suggest that TCR signal strength during thymic differentiation may influence not only IFN-gamma production, but also the protective function of iNKT cells in arthritis

Telomere length and epigenetic age acceleration in adolescents with anxiety disorders

Evidence on the relationship between genetics and mental health are flourishing. However, few studies are evaluating early biomarkers that might link genes, environment, and psychopathology. We aimed to study telomere length (TL) and epigenetic age acceleration (AA) in a cohort of adolescents with and without anxiety disorders (N = 234). We evaluated a representative subsample of participants at baseline and after 5 years (n = 76) and categorized them according to their anxiety disorder diagnosis at both time points: (1) control group (no anxiety disorder, n = 18), (2) variable group (anxiety disorder in one evaluation, n = 38), and (3) persistent group (anxiety disorder at both time points, n = 20). We assessed relative mean TL by real-time quantitative PCR and DNA methylation by Infinium HumanMethylation450 BeadChip. We calculated AA using the Horvath age estimation algorithm and analyzed differences among groups using generalized linear mixed models. The persistent group of anxiety disorder did not change TL over time (p = 0.495). The variable group had higher baseline TL (p = 0.003) but no accelerated TL erosion in comparison to the non-anxiety control group (p = 0.053). Furthermore, there were no differences in AA among groups over time. Our findings suggest that adolescents with chronic anxiety did not change telomere length over time, which could be related to a delay in neuronal development in this period of life