Treatment of adult-onset Still's disease: a review

Adult-onset Still's disease (AOSD) is a rare inflammatory disorder that has been recently classified as a polygenic autoinflammatory disorder. The former classification, based on the disease course, seems to be quite dated. Indeed, there is accumulating evidence that AOSD can be divided into two distinct phenotypes based on cytokine profile, clinical presentation, and outcome, ie, a "systemic" pattern and an "articular" pattern. The first part of this review deals with the treatments that are currently available for AOSD. We then present the different strategies based on the characteristics of the disease according to clinical presentation. To do so, we focus on the two subsets of the disease. Finally, we discuss the management of life-threatening complications of AOSD, along with the therapeutic options during pregnancy

Tautologies toponymiques : comment apprivoiser l’espace entre continuités et fractures

On ne peut réduire les tautologies – dénominations dont la forme condense deux expressions transmettant un seul et même concept – en toponymie à une simple question étymologique. Elles posent, au-delà de la nécessité de la motivation toujours renouvelée des désignations toponymiques, le problème des contacts entre populations et traduisent la façon dont ces contacts ont pu s’établir. A partir d’une réalité géomorphologique commune, soit la combinaison d’espace géophysique et anthropisé, langues et cultures différentes peuvent réaliser des partitions sémantiques visant à apprivoiser l’espace extralinguistique. L’étude des tautologies, s’inscrivant dans une succession historique liée à l’occupation des lieux, représente un outil permettant de repérer et formuler les enjeux de continuité et fracture qui se jouent dans nos sociétés contemporaines.Toponymic tautologies – denominations whose form condenses two expressions conveying one and the same concept – cannot be reduced to a simple etymological question. Beyond the need for an ever-renewed motivation for toponymic designations, they address the problem of contacts between populations and reflect the way these contacts have been established. From a shared geomorphological reality, i.e. the combination of geophysical and anthropized spaces, different languages and cultures can produce semantic partitions that aim to tame extra-linguistic space. The study of tautologies, which are part of a historical succession linked to the occupation of the places, represent a useful tool for identifying and formulating the issues of continuity and fracture that are at stake in our contemporary societies

Crystal structure of (E)-4-benzylidene-6-phenyl-1,2,3,4,7,8,9,10-octahydrophenanthridine

The preparation of the title compound, C26H25N, was achieved by the condensation of an ethano­lic mixture of benzaldehyde, cyclo­hexa­none and ammonium acetate in a 2:1:1 molar ratio. There are two crystallographically independent mol­ecules in the asymmetric unit. The two cyclo­hexyl rings adopt an anti-envelope conformation with the benzyl moiety adopting a cis conformation with respect to the nitro­gen atom of the phenanthridine segment. In the crystal, mol­ecules are linked through C—H⋯N inter­actions into hydrogen-bonded chains that are further arranged into distinct layers by weak offset π–π inter­actions

Single-arm, open-label pilot intervention study to investigate an effect of oral 5-aminolevulinic acid plus sodium ferrous citrate on glucocorticoid reduction in patients with adult-onset Still disease

BACKGROUND: Glucocorticoids are an important class of medication for patients with adult-onset Still disease (AOSD), however, relapse following glucocorticoid reduction and adverse events due to long-term effects of glucocorticoid are still problematic. It is of course essential to minimize the risk of treatment. Immunosuppressive therapies such as methotrexate and biologics including tocilizumab are used in glucocorticoid-dependent patients with AOSD, but no second-line treatments for patients with glucocorticoid dependence have been established yet. Given that these drugs also have the potential to cause adverse events, alternative treatments are sought. Recently, elevated heme oxygenase-1 (HO-1) has been reported in the serum of patients with AOSD, suggesting that HO-1 activity contributes to AOSD pathogenesis and may represent a new therapeutic target for the treatment of AOSD. The amino acid 5-aminolevulinic acid (5-ALA) is a non-proteinogenic δ amino acid in human body. An addition of ferrous iron to 5-ALA enhances heme biosynthesis. The increase in heme in vivo induces HO-1 production, a heme-degrading enzyme. Elevated HO-1 has been suggested to contribute to the pathogenesis of AOSD, and administration of 5-ALA and ferrous iron may be a potential treatment for AOSD. METHODS/DESIGN: This study is a single-arm, open-label pilot intervention study using clinical endpoints to investigate the effects of oral 5-ALA with sodium ferrous citrate on glucocorticoid reduction in patients with AOSD receiving glucocorticoid therapy. DISCUSSION: This pilot intervention study will provide evidence regarding the effectiveness and safety of 5-ALA/sodium ferrous citrate as a potential new therapeutic agent for glucocorticoid-dependent patients with AOSD. TRIAL REGISTRATION: This study was registered in the Japan Registry of Clinical Trials (https://jrct.niph.go.jp) on January 14, 2020 as jRCTs071190042

Hypersensitivity pneumonitis: antigen diversity and disease implications

Article in PressHypersensitivity pneumonitis (HP) is an immune-mediated syndrome triggered by inhalation of a wide variety of allergens, to which an individual has previously been sensitized. More than 200 agents responsible for the disease have already been identified; however, HP occurs only in a small number of individuals exposed to causal antigens. The present report provides an overview of the role of antigen role in HP, highlighting its diversity, research methods, and prevention strategies, as well as the impact on disease prognosis following elimination of antigen. HP is an underdiagnosed disease and, therefore, it is difficult to accurately estimate its incidence. Triggering antigens can be divided into six broad categories: bacteria, fungi, mycobacteria, animal and plant proteins, chemicals, and metals, represented by disease prototypes. The identification of causal antigen is a major challenge; it is impossible to obtain in about 30-60% of cases. The acute form of HP, with early detection and immediate eviction of causal antigen, tends to have an excellent prognosis. In the chronic form, partial recovery of disease is still possible; however, some cases tend to progress to fibrosis, even after removal from exposure. In conclusion, HP diagnosis should be based on a proactive search for potential antigen sources, although their identification is hampered by the lack of standardized methods of demonstrating the specific antigen sensitization. Antigen avoidance is a critical determinant in disease prognosis.(undefined)info:eu-repo/semantics/acceptedVersio

Neanderthal Use of Fish, Mammals, Birds, Starchy Plants and Wood 125-250,000 Years Ago

Neanderthals are most often portrayed as big game hunters who derived the vast majority of their diet from large terrestrial herbivores while birds, fish and plants are seen as relatively unimportant or beyond the capabilities of Neanderthals. Although evidence for exploitation of other resources (small mammals, birds, fish, shellfish, and plants) has been found at certain Neanderthal sites, these are typically dismissed as unusual exceptions. The general view suggests that Neanderthal diet may broaden with time, but that this only occurs sometime after 50,000 years ago. We present evidence, in the form of lithic residue and use-wear analyses, for an example of a broad-based subsistence for Neanderthals at the site of Payre, Ardèche, France (beginning of MIS 5/end of MIS 6 to beginning of MIS 7/end of MIS 8; approximately 125–250,000 years ago). In addition to large terrestrial herbivores, Neanderthals at Payre also exploited starchy plants, birds, and fish. These results demonstrate a varied subsistence already in place with early Neanderthals and suggest that our ideas of Neanderthal subsistence are biased by our dependence on the zooarchaeological record and a deep-seated intellectual emphasis on big game hunting