| 1. |
- Artigas Soler, María, et al.
(författare)
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Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function.
- 2011
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1082-90
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Tidskriftsartikel (refereegranskat)abstract
- Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 × 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.
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| 2. |
- Barnard, Katharine, et al.
(författare)
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Impact of Chronic Sleep Disturbance for People Living With T1 Diabetes.
- 2016
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Ingår i: Journal of diabetes science and technology. - : SAGE Publications. - 1932-2968. ; 10:3, s. 762-767
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to explore personal experiences and to determine the impact of impaired sleep on well-being and diabetes-related activities/decision making among a cohort of people living with T1D.
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| 3. |
- Barnard, Katharine, et al.
(författare)
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Impact of Type 1 Diabetes Technology on Family Members/Significant Others of People With Diabetes.
- 2016
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Ingår i: Journal of diabetes science and technology. - : SAGE Publications. - 1932-2968. ; 10:4, s. 824-30
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to explore the impact of diabetes-related technology to ensure that such devices are used in a way that returns maximum benefit from a medical and psychological perspective.Spouses and caregivers of people with type 1 diabetes were invited to complete an online questionnaire about their experiences with diabetes technologies used by their family members. Participants were recruited via the Glu online community website. Questions explored impact on daily living, frequency and severity of hypoglycemia, and diabetes-related distress.In all, 100 parents/caregivers and 74 partners participated in this survey. Average (mean) duration of living with a person with type 1 diabetes was 16 years (SD = 13) for partners, with duration of diabetes for children being 4.2 ± 3.2 years. Average duration of current therapy was 8.3 ± 7.3 years for adults and 3.4 ± 2.9 years for children. Of the participants, 86% partners and 82% parents/caregivers reported diabetes technology had made it easier for their family members to achieve blood glucose targets. Compared to partners, parents/caregivers reported more negative emotions (P < .001) and decreased well-being (P < .001) related to their family members type 1 diabetes. Diabetes-related distress was common, as was sleep disturbance associated with device alarms and fear of hypoglycemia. Reduced frequency and severity of hypoglycemia related to device use was reported by approximately half of participants.There is little doubt about the medical benefit of diabetes technologies and their uptake is increasing but some downsides were reported. Barriers to uptake of technologies lie beyond the mechanics of diabetes management. Supporting users in using diabetes technology to achieve the best possible glycemic control, in the context of their own life, is crucial. Furthermore, understanding these issues with input from the type 1 diabetes community including family members and caregivers will help innovation and design of new technology.
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| 4. |
- Daly, Sarah B, et al.
(författare)
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Mutations in HPSE2 cause urofacial syndrome.
- 2010
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Ingår i: American journal of human genetics. - 1537-6605. ; 86:6, s. 963-9
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Tidskriftsartikel (refereegranskat)abstract
- Urinary voiding dysfunction in childhood, manifesting as incontinence, dysuria, and urinary frequency, is a common condition. Urofacial syndrome (UFS) is a rare autosomal recessive disease characterized by facial grimacing when attempting to smile and failure of the urinary bladder to void completely despite a lack of anatomical bladder outflow obstruction or overt neurological damage. UFS individuals often have reflux of infected urine from the bladder to the upper renal tract, with a risk of kidney damage and renal failure. Whole-genome SNP mapping in one affected individual defined an autozygous region of 16 Mb on chromosome 10q23-q24, within which a 10 kb deletion encompassing exons 8 and 9 of HPSE2 was identified. Homozygous exonic deletions, nonsense mutations, and frameshift mutations in five further unrelated families confirmed HPSE2 as the causative gene for UFS. Mutations were not identified in four additional UFS patients, indicating genetic heterogeneity. We show that HPSE2 is expressed in the fetal and adult central nervous system, where it might be implicated in controlling facial expression and urinary voiding, and also in bladder smooth muscle, consistent with a role in renal tract morphology and function. Our findings have broader implications for understanding the genetic basis of lower renal tract malformations and voiding dysfunction.
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| 5. |
- Johnson, Wade T, et al.
(författare)
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Immunomodulatory Nanoparticles for Modulating Arthritis Flares
- 2023
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Ingår i: ACS nano. - 1936-086X. ; 18:3, s. 1892-1906
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Tidskriftsartikel (refereegranskat)abstract
- Disease-modifying drugs have improved the treatment for autoimmune joint disorders, such as rheumatoid arthritis, but inflammatory flares are a common experience. This work reports the development and application of flare-modulating poly(lactic-co-glycolic acid)-poly(ethylene glycol)-maleimide (PLGA-PEG-MAL)-based nanoparticles conjugated with joint-relevant peptide antigens, aggrecan70-84 and type 2 bovine collagen256-270. Peptide-conjugated PLGA-PEG-MAL nanoparticles encapsulated calcitriol, which acted as an immunoregulatory agent, and were termed calcitriol-loaded nanoparticles (CLNP). CLNP had a ∼200 nm hydrodynamic diameter with a low polydispersity index. In vitro, CLNP induced phenotypic changes in bone marrow derived dendritic cells (DC), reducing the expression of costimulatory and major histocompatibility complex class II molecules, and proinflammatory cytokines. Bulk RNA sequencing of DC showed that CLNP enhanced expression of Ctla4, a gene associated with downregulation of immune responses. In vivo, CLNP accumulated in the proximal lymph nodes after intramuscular injection. Administration of CLNP was not associated with changes in peripheral blood cell numbers or cytokine levels. In the collagen-induced arthritis and SKG mouse models of autoimmune joint disorders, CLNP reduced clinical scores, prevented bone erosion, and preserved cartilage proteoglycan, as assessed by high-resolution microcomputed tomography and histomorphometry analysis. The disease protective effects were associated with increased CTLA-4 expression in joint-localized DC and CD4+ T cells but without generalized suppression of T cell-dependent immune response. The results support the potential of CLNP as modulators of disease flares in autoimmune arthropathies.
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