| 1. |
- Sandestig, Anna, et al.
(författare)
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A Novel DLG3 Mutation Expanding the Phenotype of X-Linked Intellectual Disability Caused by DLG3 Nonsense Variants
- 2019
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Ingår i: Molecular Syndromology. - : KARGER. - 1661-8769 .- 1661-8777. ; 10:5, s. 281-285
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Tidskriftsartikel (refereegranskat)abstract
- The DLG3 gene is located at Xq13.1 and encodes SAP102, a member of the MAGUK protein family, extensively expressed in the brain and involved in synaptic function. Mutations in DLG3 are associated with a rare nonsyndromic form of X-linked intellectual disability (XLID) and have been described in 11 families to date. All affected males presented with intellectual disability, and some showed additional clinical features. The majority of female carriers were reported asymptomatic or mildly affected, due to skewed X-inactivation, rarely severely affected. We report a family, a boy and his mother, with a novel nonsense mutation in the DLG3 gene, c.1720Camp;gt;T; p.Arg574*. The boy, hemizygous for the variant, showed intellectual disability, short stature due to growth hormone deficiency, dysmorphic features, and pectus excavatum. The mother, who presented with learning disabilities and borderline cognitive development, is a heterozygous carrier of the variant, which had arisen de novo. X-inactivation test was noninformative. This case report broadens the phenotypic spectrum of XLID caused by DLG3 nonsense variants. The dysmorphic features of the affected males may be more frequent than previously thought.
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| 2. |
- Andersson, Anna-Karin, et al.
(författare)
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Triage in the emergency department : A qualitative study of the factors which nurses consider when making decisions
- 2006
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Ingår i: Nursing in Critical Care. - 1362-1017 .- 1478-5153. ; 11:3, s. 136-145
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Tidskriftsartikel (refereegranskat)abstract
- Triage, as a concept, is relatively new in Sweden and means 'sorting'. The triage process was developed to grade patients who needed immediate care. Triage is currently important for the emergency treatment system, and nurses are expected to work with it professionally. The aim of this study is to describe how nurses implement triage when patients arrive at the emergency department of a county hospital, situated in a rural area of Sweden, as well as to highlight the factors considered when prioritizing, in connection with nurses' decision-making. The method used was observations of 19 nurses, with minimal disturbance in their triage work, followed by a short tape-recorded interview, during which the nurses were asked to reflect upon their decision of priorities. Qualitative content analysis of data has been used. The results were divided into two areas, internal factors and external factors. The internal factors reflect the nurse skills and personal capacity. The external factors reflect work environment, including high workload and practical arrangements, and should always be perceived and taken into consideration. Using these factors as a basis, the patients' clinical condition, clinical history, various examinations and tests form an assessment, which subsequently results in a prioritization.
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| 3. |
- Björklund, Peyman, et al.
(författare)
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The internally truncated LRP5 receptor presents a therapeutic target in breast cancer
- 2009
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 4:1, s. e4243-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Breast cancer is a common malignant disease, which may be caused by a number of genes deregulated by genomic or epigenomic events. Deregulated WNT/beta-catenin signaling with accumulation of beta-catenin is common in breast tumors, but mutations in WNT signaling pathway components have been rare. An aberrantly spliced internally truncated LRP5 receptor (LRP5Delta666-809, LRP5Delta) was shown recently to be resistant to DKK1 inhibition, and was required for beta-catenin accumulation in hyperparathyroid tumors and parathyroid tumor growth. METHODOLOGY/PRINCIPAL FINDINGS: Here we show, by reverse transcription PCR and Western blot analysis, that LRP5Delta is frequently expressed in breast tumors of different cancer stage (58-100%), including carcinoma in situ and metastatic carcinoma. LRP5Delta was required in MCF7 breast cancer cells for the non-phosphorylated active beta-catenin level, transcription activity of beta-catenin, cell growth in vitro, and breast tumor growth in a xenograft SCID mouse model. WNT3 ligand, but not WNT1 and WNT3A augmented the endogenous beta-catenin activity of MCF7 cells in a DKK1-insensitive manner. Furthermore, an anti-LRP5 antibody attenuated beta-catenin activity, inhibited cell growth, and induced apoptosis in LRP5Delta-positive MCF7 and T-47D breast cancer cells, but not in control cells. CONCLUSIONS/SIGNIFICANCE: Our results suggest that the LRP5Delta receptor is strongly implicated in mammary gland tumorigenesis and that its aberrant expression present an early event during disease progression. LRP5 antibody therapy may have a significant role in the treatment of breast cancer.
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| 4. |
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| 5. |
- Novak, Daniel, et al.
(författare)
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Altered cortical bone strength and lean mass in young women with long-duration (19 years) type 1 diabetes
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- To investigate bone health and body composition in young women with long-duration type 1 diabetes (T1D) in relation to matched controls. Twenty-three Swedish women, age 19.2-27.9 years, with a T1D duration of 10 years or more were recruited from the Swedish National Diabetes Registry (NDR). An age-, gender- and geography-matched control group was recruited. Bone mass and body composition were assessed by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. Data was retrieved from the NDR and SWEDIABKIDS registries. T1D individuals had a mean diabetes duration of 19 years. T1D individuals had reduced lean mass (40.0 +/- 6.1 kg vs. 43.9 +/- 4.9 kg) and were shorter (1.66 +/- 0.06 m vs. 1.71 +/- 0.06 m) although comparable BMI. Subjects with T1D had lower muscle area (P = 0.0045). No differences were observed for fractures; physical activity; total, lumbar spine or femur areal bone mineral density. The cortical bone strength strain index was lower for TD1 patients (1875 +/- 399 mm(3) vs. 2277 +/- 332 mm(3)). In conclusion, young women with long-term diabetes duration showed reduced cortical bone strength, decreased periosteal circumference, endosteal circumference and altered body composition. These factors contribute to the health burden of TD1, which warrants further attention for advancing bone health in women with T1D.
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| 6. |
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| 7. |
- Pettersson, Cecilia, 1962, et al.
(författare)
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Dietary intake and nutritional status in adolescents and young adults with anorexia nervosa: A 3-year follow-up study
- 2021
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Ingår i: Clinical Nutrition. - : Elsevier BV. - 0261-5614. ; 40:10, s. 5391-5398
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Tidskriftsartikel (refereegranskat)abstract
- Background & aims: Patients with anorexia nervosa (AN) restrict their dietary intake leading to malnutrition. Information is scarce on nutrition status during recovery. The aim of the study was to investigate dietary intake, body composition, biochemistry, and status in young women three years after hospital treatment due to severe restrictive AN. Methods: Dietary intake from four-day food records were compared to a reference group and the Nordic Nutrition Recommendations. Body composition was assessed by dual-energy X-ray absorptiometry (DXA). Serum levels of vitamin A, E, D, folate, and ferritin were assessed. Results: Three years after hospital treatment for AN, 12 subjects (60%) were recovered or in partial remission from AN. Subnormal values of body fat and skeletal muscle mass were present in 30% and 25%. Energy intake was 1730 kcal/day (min-max 705-2441) or 33 kcal/kg/day (16-54). Most (80%) had a total energy intake/day below the estimated needs and 6 (32%) had energy intakes below 1550 kcal/day. Micronutrient intakes from food were low; 16 (85%) had intakes below recommendations of iron, folate, and vitamin D. Serum levels of vitamins A, E, D, and folate were on average adequate; but a subnormal value (<50 nmol/L) of vitamin D was found in 20%. Ferritin levels were significantly lower at follow-up, and 25% had values below reference range. Return of menstruation was dependent of energy intake and body fat. Conclusions: A regular and careful assessment of nutritional status along with nutritional counseling during recovery is recommended to reduce malnutrition in patients with AN. (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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| 8. |
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| 9. |
- Prescott, Eva, et al.
(författare)
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Safety and efficacy of the 5-lipoxygenase-activating protein inhibitor AZD5718 in patients with recent myocardial infarction: The phase 2a FLAVOUR study.
- 2022
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Ingår i: International journal of cardiology. - : Elsevier BV. - 1874-1754 .- 0167-5273. ; 365, s. 34-40
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Tidskriftsartikel (refereegranskat)abstract
- Leukotrienes are pro-inflammatory vasoactive lipid mediators implicated in the pathophysiology of atherosclerotic cardiovascular disease. We studied the effect of the 5-lipoxygenase-activating protein inhibitor AZD5718 on leukotriene biosynthesis and coronary microvascular function in a single-blind, phase 2a study.Patients 7-28days after myocardial infarction (±ST elevation), with <50% left anterior descending coronary artery stenosis and Thrombolysis in Myocardial Infarction flow grade≥2 after percutaneous coronary intervention, were randomized 2:1:2 to once-daily AZD5718 200mg or 50mg, or placebo, in 4- and 12-week cohorts. Change in urine leukotriene E4 (uLTE4) was the primary endpoint, and coronary flow velocity reserve (CFVR; via echocardiography) was the key secondary endpoint.Of 129 randomized patients, 128 received treatment (200mg, n=52; 50mg, n=25; placebo, n=51). Statistically significant reductions in uLTE4 levels of >80% were observed in both AZD5718 groups versus the placebo group at 4 and 12weeks. No significant changes in CFVR were observed for AZD5718 versus placebo. Adverse events (AEs) occurred in 12/18, 3/6 and 6/13 patients receiving 200mg, 50mg and placebo, respectively, in the 4-week cohort, and in 27/34, 14/19 and 24/38 patients, respectively, in the 12-week cohort. Serious AEs in seven patients receiving AZD5718 and four receiving placebo were not treatment-related, and there were no deaths.In patients with recent myocardial infarction, AZD5718 was well tolerated, and leukotriene biosynthesis was dose-dependently inhibited. No significant changes in CFVR were detected.gov identifier: NCT03317002.
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| 10. |
- Sallinger, Katja, et al.
(författare)
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Spatial tumour gene signature discriminates neoplastic from non-neoplastic compartments in colon cancer : unravelling predictive biomarkers for relapse
- 2023
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Ingår i: Journal of Translational Medicine. - 1479-5876. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Opting for or against the administration of adjuvant chemotherapy in therapeutic management of stage II colon cancer remains challenging. Several studies report few survival benefits for patients treated with adjuvant therapy and additionally revealing potential side effects of overtreatment, including unnecessary exposure to chemotherapy-induced toxicities and reduced quality of life. Predictive biomarkers are urgently needed. We, therefore, hypothesise that the spatial tissue composition of relapsed and non-relapsed colon cancer stage II patients reveals relevant biomarkers.Methods: The spatial tissue composition of stage II colon cancer patients was examined by a novel spatial transcriptomics technology with sub-cellular resolution, namely in situ sequencing. A panel of 176 genes investigating specific cancer-associated processes such as apoptosis, proliferation, angiogenesis, stemness, oxidative stress, hypoxia, invasion and components of the tumour microenvironment was designed to examine differentially expressed genes in tissue of relapsed versus non-relapsed patients. Therefore, FFPE slides of 10 colon cancer stage II patients either classified as relapsed (5 patients) or non-relapsed (5 patients) were in situ sequenced and computationally analysed.Results: We identified a tumour gene signature that enables the subclassification of tissue into neoplastic and non-neoplastic compartments based on spatial expression patterns obtained through in situ sequencing. We developed a computational tool called Genes-To-Count (GTC), which automates the quantification of in situ signals, accurately mapping their position onto the spatial tissue map and automatically identifies neoplastic and non-neoplastic tissue compartments. The GTC tool was used to quantify gene expression of biological processes upregulated within the neoplastic tissue in comparison to non-neoplastic tissue and within relapsed versus non-relapsed stage II colon patients. Three differentially expressed genes (FGFR2, MMP11 and OTOP2) in the neoplastic tissue compartments of relapsed patients in comparison to non-relapsed patients were identified predicting recurrence in stage II colon cancer.Conclusions: In depth spatial in situ sequencing showed potential to provide a deeper understanding of the underlying mechanisms involved in the recurrence of disease and revealed novel potential predictive biomarkers for disease relapse in colon cancer stage II patients. Our open-access GTC-tool allowed us to accurately capture the tumour compartment and quantify spatial gene expression in colon cancer tissue.
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