| 1. |
- Lundgren, Markus, et al.
(författare)
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Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
- 2017
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Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
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| 2. |
- Ganesh, Santhi K., et al.
(författare)
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Loci influencing blood pressure identified using a cardiovascular gene-centric array
- 2013
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 22:8, s. 1663-1678
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Tidskriftsartikel (refereegranskat)abstract
- Blood pressure (BP) is a heritable determinant of risk for cardiovascular disease (CVD). To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP), we genotyped 50 000 single-nucleotide polymorphisms (SNPs) that capture variation in 2100 candidate genes for cardiovascular phenotypes in 61 619 individuals of European ancestry from cohort studies in the USA and Europe. We identified novel associations between rs347591 and SBP (chromosome 3p25.3, in an intron of HRH1) and between rs2169137 and DBP (chromosome1q32.1 in an intron of MDM4) and between rs2014408 and SBP (chromosome 11p15 in an intron of SOX6), previously reported to be associated with MAP. We also confirmed 10 previously known loci associated with SBP, DBP, MAP or PP (ADRB1, ATP2B1, SH2B3/ATXN2, CSK, CYP17A1, FURIN, HFE, LSP1, MTHFR, SOX6) at array-wide significance (P 2.4 10(6)). We then replicated these associations in an independent set of 65 886 individuals of European ancestry. The findings from expression QTL (eQTL) analysis showed associations of SNPs in the MDM4 region with MDM4 expression. We did not find any evidence of association of the two novel SNPs in MDM4 and HRH1 with sequelae of high BP including coronary artery disease (CAD), left ventricular hypertrophy (LVH) or stroke. In summary, we identified two novel loci associated with BP and confirmed multiple previously reported associations. Our findings extend our understanding of genes involved in BP regulation, some of which may eventually provide new targets for therapeutic intervention.
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| 3. |
- Tragante, Vinicius, et al.
(författare)
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Gene-centric Meta-analysis in 87,736 Individuals of European Ancestry Identifies Multiple Blood-Pressure-Related Loci.
- 2014
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 94:3, s. 349-360
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Tidskriftsartikel (refereegranskat)abstract
- Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ∼50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p < 6 × 10(-7)) and confirmed 27 previously reported associations. Bioinformatic analysis of the 11 loci provided support for a putative role in hypertension of several genes, such as CDK6 and NUCB2. Analysis of potential pharmacological targets in databases of small molecules showed that ten of the genes are predicted to be a target for small molecules. In summary, we identified previously unknown loci associated with BP. Our findings extend our understanding of genes involved in BP regulation, which may provide new targets for therapeutic intervention or drug response stratification.
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| 4. |
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| 5. |
- Gazdagh, Gabriella, et al.
(författare)
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Extending the phenotypes associated with TRIO gene variants in a cohort of 25 patients and review of the literature
- 2023
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Ingår i: American Journal of Medical Genetics. Part A. - : Wiley-Blackwell. - 1552-4825 .- 1552-4833. ; 191:7, s. 1722-1740
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Forskningsöversikt (refereegranskat)abstract
- The TRIO gene encodes a rho guanine exchange factor, the function of which is to exchange GDP to GTP, and hence to activate Rho GTPases, and has been described to impact neurodevelopment. Specific genotype-to-phenotype correlations have been established previously describing striking differentiating features seen in variants located in specific domains of the TRIO gene that are associated with opposite effects on RAC1 activity. Currently, 32 cases with a TRIO gene alteration have been published in the medical literature. Here, we report an additional 25, previously unreported individuals who possess heterozygous TRIO variants and we review the literature. In addition, functional studies were performed on the c.4394A > G (N1465S) and c.6244-2A > G TRIO variants to provide evidence for their pathogenicity. Variants reported by the current study include missense variants, truncating nonsense variants, and an intragenic deletion. Clinical features were previously described and included developmental delay, learning difficulties, microcephaly, macrocephaly, seizures, behavioral issues (aggression, stereotypies), skeletal problems including short, tapering fingers and scoliosis, dental problems (overcrowding/delayed eruption), and variable facial features. Here, we report clinical features that have not been described previously, including specific structural brain malformations such as abnormalities of the corpus callosum and ventriculomegaly, additional psychological and dental issues along with a more recognizable facial gestalt linked to the specific domains of the TRIO gene and the effect of the variant upon the function of the encoded protein. This current study further strengthens the genotype-to-phenotype correlation that was previously established and extends the range of phenotypes to include structural brain abnormalities, additional skeletal, dental, and psychiatric issues.
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| 6. |
- Lindahl, Johanna, et al.
(författare)
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Do vaccination interventions have effects? : A study on how poultry vaccination interventions change smallholder farmer knowledge, attitudes, and practice in villages in Kenya and Tanzania
- 2019
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Ingår i: Tropical Animal Health and Production. - : Springer Science and Business Media LLC. - 0049-4747 .- 1573-7438. ; 51:1, s. 213-220
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Tidskriftsartikel (refereegranskat)abstract
- Poultry are important for many poor households in developing countries, but there are many constraints to poultry production, including disease. One of the most important diseases of chickens is Newcastle disease (ND). Even though there are effective vaccines against this disease available in most countries, uptake by small-scale poultry keepers is often low. In this study, two areas in Kenya and Tanzania were studied, where some villages had received additional support to get vaccination and other villages had not. In Kenya, 320 households from 10 villages were interviewed, of which half of the villages had active promotion of vaccination through village-based advisors. In Tanzania, 457 households were interviewed, of which 241 came from villages that have had active support through either a project or government extension services. Knowledge about vaccines and the attitudes towards vaccinating against ND was evaluated using mixed multivariable logistic models. Results indicate that in Kenya, the most important determinants for understanding the function of a vaccine were having had support in the village and to have knowledge about ND signs, while in Tanzania gender and previous vaccine use were important in addition to having had support. Attitudes towards vaccination were mainly determined by knowledge, where more knowledge about how vaccines work in general or about ND contributed to more positive attitudes. Among Kenyan farmers that had never used the vaccine before, the amount of birds they lost to disease and predators also influenced attitudes. In conclusion, this study supports the notion that knowledge is a very important component of extension support and that simply making vaccines available may not be sufficient for high levels of uptake.
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| 7. |
- Vontell, Regina, et al.
(författare)
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Cellular mechanisms of toll-like receptor-3 activation in the thalamus are associated with white matter injury in the developing brain.
- 2015
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Ingår i: Journal of neuropathology and experimental neurology. - 1554-6578. ; 74:3, s. 273-85
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Tidskriftsartikel (refereegranskat)abstract
- Toll-like receptor-3 (TLR3) has been identified in a variety of intracellular structures (e.g. endosomes and endoplasmic reticulum); it detects viral molecular patterns and damage-associated molecular patterns. We hypothesized that, after white matter injury (WMI) has occurred, localization and activation of TLR3 are altered in gray matter structures in response to damage-associated molecular patterns and activated glia. Therefore, we investigated the subcellular localization of TLR3 and its downstream signaling pathway in postmortem brain sections from preterm infants with and without WMI (7 patients each). We assessed astroglia (glial fibrillary acidic protein-positive), microglia (ionized calcium-binding adaptor molecule-1-positive), and neuronal populations in 3 regions of the thalamus and in the posterior limb of the internal capsule and analyzed TLR3 messenger RNA and protein expression in the ventral lateral posterior thalamic region, an area associated with impaired motor function. We also assessed TLR3 colocalization with late endosomes (lysosome-associated membrane protein-1) and phagosomal compartments in this region. Glial fibrillary acidic protein, ionized calcium-binding adaptor molecule-1, and TLR3 immunoreactivity and messenger RNA expression were increased in cases with WMI compared with controls. In ventral lateral posterior neurons, TLR3 was colocalized with the endoplasmic reticulum and the autophagosome, suggesting that autophagy may be a stress response associated with WMI. Thus, alterations in TLR3 expression in WMI may be an underlying molecular mechanism associated with impaired development in preterm infants.
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| 8. |
- Wyatt, Katherine H., et al.
(författare)
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Integrated and innovative scenario approaches for sustainable development planning in The Bahamas
- 2021
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Ingår i: Ecology and Society. - 1708-3087. ; 26:4
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Tidskriftsartikel (refereegranskat)abstract
- Using alternative future scenarios in development planning supports the integration of diverse perspectives and the joint consideration of the needs of humans and nature. Here, we report on the use of scenarios as an integral part of a two-year sustainable development planning process for Andros Island, The Bahamas. We combined qualitative and quantitative approaches to link stakeholder visions of the future of their island with quantitative assessments of the likely impacts of those visions on future conditions. We highlight knowledge gains for scenarios in three key areas: (1) inclusion of participatory mapping as both a mechanism for eliciting stakeholder knowledge and aspirations, and as an input for risk assessment; (2) participation of a transdisciplinary team to guide the scenario creation process and enable better understanding of the range of stakeholder visions and values; and (3) use of cumulative risk assessment as a framework to bring together quantitative and qualitative information and provide objective comparisons between alternatives. We convened over 560 people in 35 meetings and worked with 13 government ministries to create and compare four alternative scenarios consisting of storylines and maps of habitat risk of degradation. We found that one scenario, featuring intensive development, would pose the greatest risk to habitats and worked together to understand which activities could lead to such a future and what interventions could be taken to help avoid it. Ultimately, our collaborative process yielded objective comparisons between alternative future scenarios, incorporated diverse visions and values of stakeholders into the island-wide master plan, and informed investments in the sustainable management of coastal ecosystems and infrastructure critical for the livelihoods of island communities. This process can serve as an example for scientists and practitioners worldwide seeking to use scenarios to inform sustainable development planning.
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