Basic science of osteoarthritis

Osteoarthritis (OA) is a prevalent, disabling disorder of the joints that affects a large population worldwide and for which there is no definitive cure. This review provides critical insights into the basic knowledge on OA that may lead to innovative end efficient new therapeutic regimens. While degradation of the articular cartilage is the hallmark of OA, with altered interactions between chondrocytes and compounds of the extracellular matrix, the subchondral bone has been also described as a key component of the disease, involving specific pathomechanisms controlling its initiation and progression. The identification of such events (and thus of possible targets for therapy) has been made possible by the availability of a number of animal models that aim at reproducing the human pathology, in particular large models of high tibial osteotomy (HTO). From a therapeutic point of view, mesenchymal stem cells (MSCs) represent a promising option for the treatment of OA and may be used concomitantly with functional substitutes integrating scaffolds and drugs/growth factors in tissue engineering setups. Altogether, these advances in the fundamental and experimental knowledge on OA may allow for the generation of improved, adapted therapeutic regimens to treat human OA.(undefined

Evaluation of mid-level management training in immunisation in the African Region

Objective: The Mid-Level Management (MLM) training course provides managers of immunisation programmes with new, advanced skills in planning, management, monitoring and evaluation. An evaluation was conducted of the MLM training courses held between 2000 and 2004 in the African Region, in order to assess its effectiveness and impact, and its contribution to the management of the Extended Programme on Immunisation (EPI) at country level.Methods: Evaluation methods included: a desk review of the MLM course reports, WHO/AFRO MLM modules and reference documents; interviews with MLM course participants, facilitators, supervisors, Ministry of Health officials and country-based partners; focus group discussions; and questionnaires.Results: During 2000-2004, eleven MLM courses were held and 642 participants were trained. Of the 151 course participants interviewed, 85% rated the course as very useful and 15% as useful. Modules on new vaccines, immunisation safety, cold chain and vaccine management, communication and problem solving were most appreciated. According to supervisors, the MLM training has contributed to significant improvements in the performance of the staff after attending the MLM course. Using DTP3 as an indicator, immunisation coverage in the African Region increased from 49% in 1991 to 53% in 2001 and 69% in 2004.Conclusions: The MLM training has increased the performance of the trained staff and therefore contributed to the improvement of EPI coverage in the African Region. However, MLM training remains a predominantly vertical event and should be harmonised with other health training programmes for various levels of the health system

Leukocyte methylomic imprints of exposure to the genocide against the Tutsi in Rwanda: a pilot epigenome-wide analysis

Aim & methods: We conducted a pilot epigenome-wide association study of women from Tutsi ethnicity exposed to the genocide while pregnant and their resulting offspring, and a comparison group of women who were pregnant at the time of the genocide but living outside of Rwanda.Results: Fifty-nine leukocyte-derived DNA samples survived quality control: 33 mothers (20 exposed, 13 unexposed) and 26 offspring (16 exposed, 10 unexposed). Twenty-four significant differentially methylated regions (DMRs) were identified in mothers and 16 in children. Conclusions: In utero genocide exposure was associated with CpGs in three of the 24 DMRs: BCOR, PRDM8 and VWDE, with higher DNA methylation in exposed versus unexposed offspring. Of note, BCOR and VWDE show significant correlation between brain and blood DNA methylation within individuals, suggesting these peripherally derived signals of genocide exposure may have relevance to the brain. Lay abstract The 1994 Rwandan genocide against ethnic Tutsi has been associated with adverse mental health outcomes in survivors decades later, but the molecular mechanisms that contribute to this association remain poorly characterized. Epigenetic mechanisms such as DNA methylation regulate gene function and change in response to life experiences. We identified differentially methylated regions (DMRs) in genocide-exposed versus unexposed mothers and children. In utero genocide exposure was linked with methylation differences in three maternal DMRs, with higher methylation in exposed offspring. Two of three DMRs show correlation between brain and blood methylation within individuals, suggesting that peripherally derived signals of genocide exposure may be relevant to the brain. en

Community engagement in epigenomic and neurocognitive research on post-traumatic stress disorder in Rwandans exposed to the 1994 genocide against the Tutsi: lessons learned

Epigenomic and neurocognitive studies have provided new perspectives on post-traumatic stress disorder and its intergenerational transmission. This article outlines the lessons learned from community engagement (CE) in such research on Rwandan genocide survivors. A strong trauma-related response was observed within the research project-targeted community (genocide survivors) during explanation of the project. CE also revealed privacy concerns, as community members worried that any leakage of genetic/(epi)genomic data could affect not only themselves but also their close relatives. Adopting a culture of CE in the process of research implementation enables the prioritization of targeted community needs and interests. Furthermore, CE has stimulated the development of mental healthcare interventions, which married couples can apply to protect their offspring and thus truly break the cycle of inherited vulnerability. Studies of how human genes are affected by the environment (epigenomic studies) have provided new perspectives on post-traumatic stress disorder and its intergenerational transmission. This article describes the lessons learned from community engagement (CE) in this type of research in a Rwandan genocide-exposed population. A strong trauma-related response was observed within the community while explaining the project. CE also revealed the participants' privacy concerns related to leakage of genetic/(epi)genomic data that could also affect their close relatives. Adopting a culture of CE in the process of research implementation enables the prioritization of community needs and interests. CE has furthermore stimulated the development of preventive interventions for married couples to protect their offspring and thus truly break the cycle of inherited vulnerability. en

IN SEARCH OF CREATIVE EXPRESSION: THE DIALECTICS OF RACE, POLITICS, AND LITERATURE IN CARIBBEAN DUB POETRY / IEŠKANT KŪRYBINĖS IŠRAIŠKOS: RASĖS, POLITIKOS IR LITERATŪROS DIALEKTIKA KARIBŲ DUB ŽANRO POEZIJOJE

This article examines dub poetry as an artistic form located along several borderlines, both spatial and cultural. Formulated by poets of African descent, the creative language of dub poets was often conceptualized through the framework of identity politics and an anti-colonial approach. Yet from the 1980s, dub poetry became institutionalized simultaneously within the pop culture industry and in “respectable” venues such as academic research, a process that calls its initial political orientation into question. In light of its differentiated formations, audiences, mediating devices, and forms of reception, however, we might view and evaluate dub poetry not exclusively through the prism of political speech, but also as a cultural form. Based on texts, recordings and performance analysis this article is a call to acknowledge dub poetry, and artistic expression in general, as the result of aesthetic decisions rather than exclusively moral ones. Santrauka Straipsnyje tyrinėjama dub žanro poezija kaip meninė forma, vyraujanti ties kai kuriais paribiais – tiek erdviniais, tiek kultūriniais. Formuluota Afrikos nuosmukio laikotarpio poetų, kūrybinė dub žanro poetų kalba politikos ir antikolonijiniu požiūriais dažnai buvo konceptualizuojama ieškant tapatumo. Nuo XX a. 9-ojo dešimtmečio dub poezija tapo institucionalizuota tiek popkultūros industrijoje, tiek „gerbiamose“ srityse, tokiose kaip akademiniai tyrimai – tai procesas, kvestionuojantis savąją vidinę politinę orientaciją. Šio proceso diferencijuotų formacijų, auditorijų, medijuojančių priemonių ir priėmimo formų fone vis dėlto galima į dub poeziją žvelgti ir ją vertinti ne išimtinai per politinės kalbos prizmę, bet ir kaip kultūrinę formą. Pagrįstas tekstų, įrašų ir performansų analize, šis straipsnis – tai kvietimas pripažinti dub poeziją ir meninę išraišką apskritai ne tiek kaip išskirtinai moralinių, kiek estetinių sprendimų rezultatą. Reikšminiai žodžiai: juodumas, Karibų dub žanro poezija, Jamaika, performansas, rasė, regis

Biogeochemical plant-soil microbe feedback in response to climate warming in peatlands

Peatlands act as global sinks of atmospheric carbon (C) through the accumulation of organic matter(1), primarily made up of decay-resistant litter of peat mosses(2). However, climate warming has been shown to promote vascular plant growth in peatlands, especially ericaceous shrubs(3). A change in vegetation cover is in turn expected to modify above-ground/below-ground interactions(4), but the biogeochemical mechanisms involved remain unknown. Here, by selecting peatlands at different altitudes to simulate a natural gradient of soil temperature, we show that the expansion of ericaceous shrubs with warming is associated with an increase of polyphenol content in both plant litter and pore water. In turn, this retards the release of nitrogen (N) from decomposing litter, increases the amount of dissolved organic N and reduces N immobilization by soil microbes. A decrease of soil water content with increasing temperature promotes the growth of fungi, which feeds back positively on ericaceous shrubs by facilitating the symbiotic acquisition of dissolved organic N. We also observed a higher release of labile C from vascular plant roots at higher soil temperatures, which promotes the microbial investment in C-degrading enzymes. Our data suggest that climate-induced changes in plant cover can reduce the productivity of peat mosses and potentially prime the decomposition of organic matter by affecting the stoichiometry of soil enzymatic activity

Sequestration of soil nitrogen as tannin-protein complexes may improve the competitive ability of sheep laurel (Kalmia angustifolia) relative to black spruce (Picea mariana)

The role of litter tannins in controlling soil nitrogen (N) cycling may explain the competitive ability of Kalmia relative to black spruce (Picea mariana), although this has not been demonstrated experimentally. Here, the protein-precipitation capacities of purified tannins and leaf extracts from Kalmia and black spruce were compared. The resistance to degradation of tannin protein precipitates from both species were compared by monitoring carbon (C) and N dynamics in humus amended with protein, purified tannins or protein-tannin precipitates. The purity of the precipitates was verified using solid-state C-13 nuclear magnetic resonance (NMR) spectra. The ability of mycorrhizal fungi associated with both species to grow on media amended with tannin-protein complexes as the principal N source was also compared. The protein precipitation capacity of Kalmia tannins was superior to those of black spruce. Humus amended with protein increased both mineral and microbial N, whereas humus amended with tannin-protein precipitates increased dissolved organic N. Mycorrhizal fungi associated with Kalmia showed better growth than those associated with black spruce when N was provided as tannin-protein precipitates. These data suggest that Kalmia litter increases the amount of soil N sequestered as tannin-protein complexes, which may improve the competitive ability of Kalmia relative to black spruce by favouring N uptake by mycorrhizas associated with the former