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- Hallström, Hadar, et al.
(author)
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Probiotic supplements and debridement of peri-implant mucositis : a randomized controlled trial
- 2015
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In: Acta Odontologica Scandinavica. - : Taylor & Francis. - 0001-6357 .- 1502-3850. ; 74:1, s. 60-66
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Journal article (peer-reviewed)abstract
- Objective. The aim of this double-blind randomized placebo-controlled trial was to evaluate the effects of probiotic supplements in adjunct to conventional management of peri-implant mucositis.Materials and methods.Forty-nine adult patients with peri-implant mucositis were consecutively recruited after informed consent. After initial mechanical debridement and oral hygiene instructions, the patients received a topical oil application (active or placebo) followed by twice-daily intake of lozenges (active or placebo) for 3 months. The active products contained a mix of two strains of Lactobacillus reuteri. Patients were clinically monitored and sampled at baseline and after 1, 2, 4, 12 and 26 weeks. The clinical end-points were pocket-probing depth (PPD), plaque index (PI) and bleeding on probing (BOP). In addition, the subgingival microbiota was processed with checkerboard DNA-DNA hybridization and samples of gingival crevicular fluid (GCF) were analyzed for selected cytokines with the aid of multiplex immunoassays.Results.After 4 and 12 weeks, all clinical parameters were improved in both the test and the placebo group. PPD and BOP were significantly reduced compared with baseline (p < 0.05), but no significant differences were displayed between the groups. The clinical improvements persisted 3 months after the intervention. No major alterations of the subgingival microflora were disclosed and the levels of inflammatory mediators in GCF did not differ between the groups.Conclusions.Mechanical debridement and oral hygiene reinforcement resulted in clinical improvement of peri-implant mucositis and a reduction in cytokine levels. Probiotic supplements did not provide added benefit to placebo.
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- Knutsson, Sofie, et al.
(author)
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Noncovalent Inhibitors of Mosquito Acetylcholinesterase 1 with Resistance-Breaking Potency
- 2018
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In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 61:23, s. 10545-10557
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Journal article (peer-reviewed)abstract
- Resistance development in insects significantly threatens the important benefits obtained by insecticide usage in vector control of disease-transmitting insects. Discovery of new chemical entities with insecticidal activity is highly desired in order to develop new insecticide candidates. Here, we present the design, synthesis, and biological evaluation of phenoxyacetamide-based inhibitors of the essential enzyme acetylcholinesterase 1 (AChE1). AChE1 is a validated insecticide target to control mosquito vectors of, e.g., malaria, dengue, and Zika virus infections. The inhibitors combine a mosquito versus human AChE selectivity with a high potency also for the resistance-conferring mutation G122S; two properties that have proven challenging to combine in a single compound. Structure activity relationship analyses and molecular dynamics simulations of inhibitor protein complexes have provided insights that elucidate the molecular basis for these properties. We also show that the inhibitors demonstrate in vivo insecticidal activity on disease-transmitting mosquitoes. Our findings support the concept of noncovalent, selective, and resistance-breaking inhibitors of AChE1 as a promising approach for future insecticide development.
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- Taal, H. Rob, et al.
(author)
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Common variants at 12q15 and 12q24 are associated with infant head circumference
- 2012
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:5, s. 532-538
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Journal article (peer-reviewed)abstract
- To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 x 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 x 10(-10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height(1), their effects on infant head circumference were largely independent of height (P = 3.8 x 10(-7) for rs7980687 and P = 1.3 x 10(-7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P = 3.9 x 10(-6)). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume(2), Parkinson's disease and other neurodegenerative diseases(3-5), indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life.
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- Willems, S. M., et al.
(author)
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Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness
- 2017
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Journal article (peer-reviewed)abstract
- Hand grip strength is a widely used proxy of muscular fitness, a marker of frailty, and predictor of a range of morbidities and all-cause mortality. To investigate the genetic determinants of variation in grip strength, we perform a large-scale genetic discovery analysis in a combined sample of 195,180 individuals and identify 16 loci associated with grip strength (P<5 × 10-8) in combined analyses. A number of these loci contain genes implicated in structure and function of skeletal muscle fibres (ACTG1), neuronal maintenance and signal transduction (PEX14, TGFA, SYT1), or monogenic syndromes with involvement of psychomotor impairment (PEX14, LRPPRC and KANSL1). Mendelian randomization analyses are consistent with a causal effect of higher genetically predicted grip strength on lower fracture risk. In conclusion, our findings provide new biological insight into the mechanistic underpinnings of grip strength and the causal role of muscular strength in age-related morbidities and mortality. © The Author(s) 2017.
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