Inflammation in the hippocampus affects IGF1 receptor signaling and contributes to neurological sequelae in rheumatoid arthritis.

Rheumatoid arthritis (RA) is an inflammatory joint disease with a neurological component including depression, cognitive deficits, and pain, which substantially affect patients' quality of daily life. Insulin-like growth factor 1 receptor (IGF1R) signaling is one of the factors in RA pathogenesis as well as a known regulator of adult neurogenesis. The purpose of this study was to investigate the association between IGF1R signaling and the neurological symptoms in RA. In experimental RA, we demonstrated that arthritis induced enrichment of IBA1+ microglia in the hippocampus. This coincided with inhibitory phosphorylation of insulin receptor substrate 1 (IRS1) and up-regulation of IGF1R in the pyramidal cell layer of the cornus ammoni and in the dentate gyrus, reproducing the molecular features of the IGF1/insulin resistance. The aberrant IGF1R signaling was associated with reduced hippocampal neurogenesis, smaller hippocampus, and increased immobility of RA mice. Inhibition of IGF1R in experimental RA led to a reduction of IRS1 inhibition and partial improvement of neurogenesis. Evaluation of physical functioning and brain imaging in RA patients revealed that enhanced functional disability is linked with smaller hippocampus volume and aberrant IGF1R/IRS1 signaling. These results point to abnormal IGF1R signaling in the brain as a mediator of neurological sequelae in RA and provide support for the potentially reversible nature of hippocampal changes.

[Health services for children and the implementation of IMCI in Monkey Bay, Malawi]. / Heilbrigdisthjónusta vid veik börn med IMCI vinnuferlum í Monkey Bay, Malaví.

OBJECTIVES: Examine primary health care services for ill children in a sub-Saharan African country, assess the appropriateness of the Integrated Management of Childhood Illness (IMCI) in such a setting and evaluate its implementation. MATERIAL AND METHODS: The study was carried out in March, 2005 in the Monkey Bay area, Malawi, in two state-run health facilities that provide services free of charge and in three privately run facilities that charge user fees. Data was collected from each facility regarding all out-patient visits but in particular of children under five years of age (U5s). Interviews were conducted with health workers and drug inventories were carried out in the facilities. RESULTS: Eight out of 10 health workers were trained in IMCI. It was 1.22 times more likely (RR, 95% CI 1.18-1.26) that U5s were brought to a state-run facility than a private one. Around 4/5 of all disease classifications during the research period are dealt with in the IMCI. About half of U5s were classified with malaria, 28% with other respiratory infections, 6% with pneumonia, and 5% with diarrhoea. Most IMCI-recommended drugs were in stock at the time of inspection but all facilities lacked at least one recommended drug. CONCLUSION: Results show that IMCI reaches the periphery of the health care system in a low-income country such as Malawi. They confirm that IMCI deals with the majority of diseases affecting U5s in such a setting. User fees seem to influence health care seeking behaviour. It is important to support and strengthen health services for ill children in the area, support continuous education of staff and ensure availability of drugs and equipment.