Abatacept in difficult-to-treat juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children and an important cause of short-term and long-term disability. Gene changes in the immune system can predispose to JIA and regulation of the immune system is crucial in the pathogenesis. The goal of therapy is complete disease control using disease-modifying antirheumatic drugs (DMARDS). Activated T-cells may play a role in the immunopathology of JIA. Therefore, targeting T-cell activation is a rational approach for the treatment of JIA. Abatacept (ABA), a selective co-stimulation modulator, has been shown to be effective in treating all JIA subtypes and is generally safe and well tolerated in JIA. Neutralizing antibodies were found in 6/9 (67%) of seropositive patients, but anti-ABA antibodies did not appear to be associated with disease flare, serious adverse events, acute infusional adverse events, hypersensitivity, autoimmune disorders, or low ABA serum concentrations. Anti-ABA antibodies were more frequent when ABA concentrations were below therapeutic levels. Although information on ABA in JIA is still limited, available data suggest a potential role in difficult to treat JIA patients previously treated with other biologic agents and for non-responders to TNF-blockade

Public finances, service delivery, and mine closure in Koffiefontein (Free State, South Africa): From stepping stone to stumbling block

This article examines the interrelationship between mining activities, the local municipality, and public finance in Koffiefontein (Letsemeng Local Municipality). The international literature suggests that, all over the world, mine closure has had a severe negative influence on municipal and public finances. Furthermore, addressing the influence of mine closure requires the involvement of all spheres of government. After being historically dependent on the mining industry, the beginning of the 1990s saw a major downscaling of this industry. The existing symbiosis benefits the municipality to a large degree; but in view of possible mine closure, a high level of dependence has been created in Koffiefontein. It is argued in the article that mine closure will influence negatively municipal revenue and service delivery and will increase the number of indigent households. In order to address these problems, specific planning should be conducted for mine closure. The contribution of various spheres of government is also needed, since such planning cannot be managed by the Local Municipality alone

Role of the Hepatic Parenchyma in Liver Transplant Tolerance: A Paradigm Revisited

Unlike other solid organs, liver transplants are spontaneously accepted in a wide range of animal models. In the clinic, transplanted livers also display privileged immunological properties allowing weaning of immunosuppression therapy in up to 20% of selected patients. To explain this phenomenon, many studies have focused on the role of donor-derived ‘passenger’ leukocytes that are thought to induce antigen-specific tolerance by migrating from the graft into recipient secondary lymphoid tissues. Although convincing evidence exists that these cells are able to elicit antiallograft T cell hyporesponsiveness, several studies argue against an exclusive role for this cell population and even question whether it is critical in conferring donor MHC-specific tolerance. Instead, these studies suggest that the hepatic parenchyma plays a more critical role in this phenomenon. In this review we will reinterpret the results of old and more recent literature in light of recent advances in the field of liver immunology to explain the contribution of both passenger leukocytes and liver tissue in the liver tolerance effect

Genomic Health Literacy Interventions in Pediatrics:Scoping Review

BACKGROUND: The emergence of genetic and genomic sequencing approaches for pediatric patients has raised questions about the genomic health literacy levels, attitudes toward receiving genomic information, and use of this information to inform treatment decisions by pediatric patients and their parents. However, the methods to educate pediatric patients and their parents about genomic concepts through digital health interventions have not been well-established. OBJECTIVE: The primary objective of this scoping review is to investigate the current levels of genomic health literacy and the attitudes toward receiving genomic information among pediatric patients and their parents. The secondary aim is to investigate patient education interventions that aim to measure and increase genomic health literacy among pediatric patients and their parents. The findings from this review will be used to inform future digital health interventions for patient education. METHODS: A scoping review using PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines and protocols was completed using the following databases: MEDLINE, Embase, CINAHL, and Scopus. Our search strategy included genomic information inclusive of all genetic and genomic terms, pediatrics, and patient education. Inclusion criteria included the following: the study included genetic, genomic, or a combination of genetic and genomic information; the study population was pediatric (children and adolescents <18 years) and parents of patients with pediatric illnesses or only parents of patients with pediatric illnesses; the study included an assessment of the knowledge, attitudes, and intervention regarding genomic information; the study was conducted in the last 12 years between 2008 and 2020; and the study was in the English language. Descriptive data regarding study design, methodology, disease population, and key findings were extracted. All the findings were collated, categorized, and reported thematically. RESULTS: Of the 4618 studies, 14 studies (n=6, 43% qualitative, n=6, 43% mixed methods, and n=2, 14% quantitative) were included. Key findings were based on the following 6 themes: knowledge of genomic concepts, use of the internet and social media for genomic information, use of genomic information for decision-making, hopes and attitudes toward receiving genomic information, experiences with genetic counseling, and interventions to improve genomic knowledge. CONCLUSIONS: This review identified that older age is related to the capacity of understanding genomic concepts, increased genomic health literacy levels, and the perceived ability to participate in decision-making related to genomic information. In addition, internet-searching plays a major role in obtaining genomic information and filling gaps in communication with health care providers. However, little is known about the capacity of pediatric patients and their parents to understand genomic information and make informed decisions based on the genomic information obtained. More research is required to inform digital health interventions and to leverage the leading best practices to educate these genomic concepts