Clinical markers for unfavorable course of multiple sclerosis

Objective. To study possible clinical markers associated with the unfavorable course of multiple sclerosis and its transition to a progressive subtype. Materials and methods. This prospective study included healthy volunteers and patients with relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS), primary progressive multiple sclerosis (PPMS). For a comprehensive clinical evaluation, the participants completed the Timed 25-Foot Walk Test (T25-FW), Nine-Hole Peg Test (9-HPT), Symbol Digit Modalities Test (SDMT), Fatigue test, and MSProDiscuss questionnaires. Then we compared the results between the groups. Results. We found significant differences between the groups in regard to most of the tests. Furthermore, we proposed a composite clinical score (CCS) based on T25-FW, SDMT, and 9-HPT results (for both hands). Discussion. Our CCS can be a useful clinical tool to determine the most likely course of multiple sclerosis at a certain timepoint

Mitochondria-Targeted Antioxidant SkQ1 Improves Dermal Wound Healing in Genetically Diabetic Mice

Oxidative stress is widely recognized as an important factor in the delayed wound healing in diabetes. However, the role of mitochondrial reactive oxygen species in this process is unknown. It was assumed that mitochondrial reactive oxygen species are involved in many wound-healing processes in both diabetic humans and animals. We have applied the mitochondria-targeted antioxidant 10-(6′-plastoquinonyl)decyltriphenylphosphonium (SkQ1) to explore the role of mitochondrial reactive oxygen species in the wound healing of genetically diabetic mice. Healing of full-thickness excisional dermal wounds in diabetic C57BL/KsJ-db−/db− mice was significantly enhanced after long-term (12 weeks) administration of SkQ1. SkQ1 accelerated wound closure and stimulated epithelization, granulation tissue formation, and vascularization. On the 7th day after wounding, SkQ1 treatment increased the number of α-smooth muscle actin-positive cells (myofibroblasts), reduced the number of neutrophils, and increased macrophage infiltration. SkQ1 lowered lipid peroxidation level but did not change the level of the circulatory IL-6 and TNF. SkQ1 pretreatment also stimulated cell migration in a scratch-wound assay in vitro under hyperglycemic condition. Thus, a mitochondria-targeted antioxidant normalized both inflammatory and regenerative phases of wound healing in diabetic mice. Our results pointed to nearly all the major steps of wound healing as the target of excessive mitochondrial reactive oxygen species production in type II diabetes

Managing emerging fisheries of the North Kenya Banks in the context of environmental change

The North Kenya Banks have long been considered an important emerging fishery with the potential to spur economic growth for local fishing communities. As a regionally important extension to the otherwise narrow East African continental shelf, the North Kenya Banks remain under studied with implications for efforts to develop a sustainable fisheries management strategy. The local marine ecosystem is known to be strongly influenced by wind driven upwelling processes with seasonal variability driven by the changing monsoon seasons being of particular importance. Nevertheless, the Western Indian Ocean is warming due to anthropogenic climate change with evidence indicating reduced ocean productivity in future. How the ecosystem of the North Kenya Banks will respond is currently uncertain but is of great importance due to the significance of coastal fishery resources to coastal communities, and growing Blue Economy initiatives to exploit the North Kenya Banks fisheries more widely. There is, however, limited knowledge of the processes influencing productivity over the North Kenya Banks regions and currently there is no management plan in place to sustainably manage the fishery resources. Here, information about the North Kenya Banks fisheries are examined in relation to environmental processes and threats from climate change impacts with suggestions for future research and management directions

Marine robots for coastal ocean research in the Western Indian Ocean

Marine robots have the potential to enhance WIO marine research to improve regional adaptation to the challenges presented by climate change by providing enhanced research capacity that bypasses the requirement for expensive infrastructure, such as large research vessels. This paper tests this potential and assesses the readiness of WIO communities to adopt autonomous technologies to meet its marine research priorities. We apply a range of analyses to a marine robots case study undertaken in waters around the island of Pemba, part of the Zanzibar archipelago, in Tanzania in 2019. The campaign formed part of a multinational project focused on increasing WIO capacity to meet food security and ocean sustainability challenges. A community engagement programme with six Tanzanian coastal communities resulted in positive changes in attitudes towards marine robots with reported increases in understanding and acceptance of such technologies. Suspicion of the robots was reduced and a lower risk of removing operational equipment was recorded following the provision of educational material. Cost, risk and benefit analysis shows that marine robots are perceived to provide high level benefits, but come at a high cost that is difficult to achieve using national or regional funding. An assessment of the capacity of WIO marine institutes to adopt such technologies shows that prior to this work, few skills or infrastructure related to marine robots were available to researchers and further confirmed that funding opportunities were perceived to be largely unavailable at institutional, national, regional or international levels. Responses from regional partners following completion of the case study however, revealed an uplift in perceived capacity, particularly related to access to infrastructure and expertise as well as support and opportunities for funding at each level. The presented case study is shown to have been a valuable demonstrator of the benefits of using marine robots to meet WIO coastal ocean research requirements and regional capacity was shown to be substantially increased within the broad range of marine institutes surveyed throughout the case study period. This study demonstrates that taking early steps towards adopting marine autonomous robots has increased WIO regional marine research capacity and increased the confidence and willingness of local researchers to seek alternative solutions to ongoing marine research challenges. Recommendations for future action that will continue to increase the capacity and readiness for regional adoption of marine robots include investment at local, national and regional levels to provide accessible training opportunities and to facilitate regional and international collaborations; investment in a regional hub, or centre of excellence for marine robotic technology; early adoption of newly emerging smaller, cheaper autonomous technologies; investment in local skills and support facilities to aid local buy-in and acceptance while supporting regional capacity

Genome-wide significant association with seven novel multiple sclerosis risk loci

Objective: A recent large-scale study in multiple sclerosis (MS) using the ImmunoChip platform reported on 11 loci that showed suggestive genetic association with MS. Additional data in sufficiently sized and independent data sets are needed to assess whether these loci represent genuine MS risk factors. Methods: The lead SNPs of all 11 loci were genotyped in 10 796 MS cases and 10 793 controls from Germany, Spain, France, the Netherlands, Austria and Russia, that were independent from the previously reported cohorts. Association analyses were performed using logistic regression based on an additive model. Summary effect size estimates were calculated using fixed-effect meta-analysis. Results: Seven of the 11 tested SNPs showed significant association with MS susceptibility in the 21 589 individuals analysed here. Meta-analysis across our and previously published MS case-control data (total sample size n=101 683) revealed novel genome-wide significant association with MS susceptibility (p<5×10−8) for all seven variants. This included SNPs in or near LOC100506457 (rs1534422, p=4.03×10−12), CD28 (rs6435203, p=1.35×10−9), LPP (rs4686953, p=3.35×10−8), ETS1 (rs3809006, p=7.74×10−9), DLEU1 (rs806349, p=8.14×10−12), LPIN3 (rs6072343, p=7.16×10−12) and IFNGR2 (rs9808753, p=4.40×10−10). Cis expression quantitative locus effects were observed in silico for rs6435203 on CD28 and for rs9808753 on several immunologically relevant genes in the IFNGR2 locus. Conclusions: This study adds seven loci to the list of genuine MS genetic risk factors and further extends the list of established loci shared across autoimmune diseases

Genome-wide significant association with seven novel multiple sclerosis risk loci

Objective: A recent large-scale study in multiple sclerosis (MS) using the ImmunoChip platform reported on 11 loci that showed suggestive genetic association with MS. Additional data in sufficiently sized and independent data sets are needed to assess whether these loci represent genuine MS risk factors. Methods: The lead SNPs of all 11 loci were genotyped in 10 796 MS cases and 10 793 controls from Germany, Spain, France, the Netherlands, Austria and Russia, that were independent from the previously reported cohorts. Association analyses were performed using logistic regression based on an additive model. Summary effect size estimates were calculated using fixed-effect meta-analysis. Results: Seven of the 11 tested SNPs showed significant association with MS susceptibility in the 21 589 individuals analysed here. Meta-analysis across our and previously published MS case-control data (total sample size n=101 683) revealed novel genome-wide significant association with MS susceptibility (p<5×10−8) for all seven variants. This included SNPs in or near LOC100506457 (rs1534422, p=4.03×10−12), CD28 (rs6435203, p=1.35×10−9), LPP (rs4686953, p=3.35×10−8), ETS1 (rs3809006, p=7.74×10−9), DLEU1 (rs806349, p=8.14×10−12), LPIN3 (rs6072343, p=7.16×10−12) and IFNGR2 (rs9808753, p=4.40×10−10). Cis expression quantitative locus effects were observed in silico for rs6435203 on CD28 and for rs9808753 on several immunologically relevant genes in the IFNGR2 locus. Conclusions: This study adds seven loci to the list of genuine MS genetic risk factors and further extends the list of established loci shared across autoimmune diseases