114 research outputs found

    DAP12/TREM2 Deficiency Results in Impaired Osteoclast Differentiation and Osteoporotic Features

    Get PDF
    Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), Nasu-Hakola disease, is a globally distributed recessively inherited disease. PLOSL is characterized by cystic bone lesions, osteoporotic features, and loss of white matter in the brain leading to spontaneous bone fractures and profound presenile dementia. We have earlier characterized the molecular genetic background of PLOSL by identifying mutations in two genes, DAP12 and TREM2. DAP12 is a transmembrane adaptor protein that associates with the cell surface receptor TREM2. The DAP12–TREM2 complex is involved in the maturation of dendritic cells. To test a hypothesis that osteoclasts would be the cell type responsible for the bone pathogenesis in PLOSL, we analyzed the differentiation of peripheral blood mononuclear cells isolated from DAP12- and TREM2-deficient PLOSL patients into osteoclasts. Here we show that loss of function mutations in DAP12 and TREM2 result in an inefficient and delayed differentiation of osteoclasts with a remarkably reduced bone resorption capability in vitro. These results indicate an important role for DAP12–TREM2 signaling complex in the differentiation and function of osteoclasts

    Dietary fatty acid intake in childhood and the risk of islet autoimmunity and type 1 diabetes : the DIPP birth cohort study

    Get PDF
    Publisher Copyright: © 2022, The Author(s).Purpose The aim was to study the associations between dietary intake of fatty acids in childhood and the risk of islet autoimmunity and type 1 diabetes (T1D). Methods The prospective Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Study included children with genetic susceptibility to T1D born between 1996 and 2004. Participants were followed up every 3 to 12 months up to 6 years for diet, islet autoantibodies, and T1D. Dietary intake of several fatty acids at the age of 3 months to 6 years was assessed 1-8 times per participant with a 3-day food record. Joint models adjusted for energy intake, sex, HLA genotype and familial diabetes were used to investigate the associations of longitudinal intake of fatty acids and the development of islet autoimmunity and T1D. Results During the 6-year follow-up, 247 (4.4%) children of 5626 developed islet autoimmunity and 94 (1.7%) children of 5674 developed T1D. Higher intake of monounsaturated fatty acids (HR 0.63; 95% CI 0.47, 0.82), arachidonic acid (0.69; 0.50, 0.94), total n-3 fatty acids (0.64; 0.48, 0.84), and long-chain n-3 fatty acids (0.14; 0.04, 0.43), was associated with a decreased risk of islet autoimmunity with and without energy adjustment. Higher intake of total fat (0.73; 0.53, 0.98), and saturated fatty acids (0.55; 0.33, 0.90) was associated with a decreased risk of T1D only when energy adjusted. Conclusion Intake of several fatty acids was associated with a decreased risk of islet autoimmunity or T1D among high-risk children. Our findings support the idea that dietary factors, including n-3 fatty acids, may play a role in the disease process of T1D.Peer reviewe

    PERBANDINGAN PERFORMA KOLEKTOR SURYA POINT PARABOLIC CONCENTRATING ANTARA REFLEKTOR ALUMINIUM FOIL DAN REFLEKTOR CERMIN KACA

    Get PDF
    Aluminium foil merupakan reflektor yang sering digunakan pada penelitian kolektor surya, salah satunya pada kolektor surya poin parabolic concentrating. Namun efisisensi yang dihasilkan masih kecil sehingga dikembangkan penggunaan cermin kaca sebagai reflektor. Namun, pada pengujian sebelumnya tidak ada variable control yang jelas sehingga performa antara kedua reflektor kolektor surya tersebut tidak dapat dibandingkan. Oleh sebab itu, untuk mengetahui reflektor yang memiliki performa paling baik diperlukan penelitian dengan membandingkan kolektor surya reflektor aluminium foil dengan reflektor cermin kaca. Untuk mengetahui performa kolektor surya, pada penelitian ini dilakukan dengan metode eksperimen, dimana kolektor surya divariasikan menggunakan reflektor aluminium foil dan reflektor cermin kaca. Pengujian dilakukan pada pukul 10.00 WIB sampai pukul 14.00 WIB dengan interval 25 menit selama 3 hari. Pada penelitian yang telah dilakukan, didapatkan hasil bahwa perubahan temperatur kolektor surya reflektor cermin kaca lebih tinggi dibandingkan reflektor aluminium foil. Begitu juga dengan efisiensi yang didapatkan, kolektor surya reflektor cermin kaca memiliki efisiensi tertinggi 87,11%, sedangkan pada kolekor surya reflektor aluminium foil memiliki efisiensi tertinggi sebesar 59,75%. Dari percobaan yang telah dilakukan dapat disimpulkan bahwa kolektor surya reflektor cermin kaca lebih baik dari pada kolektor surya reflektor aluminium foil. Kata Kunci: kolektor surya, reflektor aluminium foil, reflektor cermin kaca, temperatur, efisiens

    Enterovirus Infections Are Associated With the Development of Celiac Disease in a Birth Cohort Study

    Get PDF
    Enterovirus and adenovirus infections have been linked to the development of celiac disease. We evaluated this association in children who developed biopsy-proven celiac disease (N = 41) during prospective observation starting from birth, and in control children (N = 53) matched for the calendar time of birth, sex, and HLA-DQ genotype. Enterovirus and adenovirus infections were diagnosed by seroconversions in virus antibodies in longitudinally collected sera using EIA. Enterovirus infections were more frequent in case children before the appearance of celiac disease-associated tissue transglutaminase autoantibodies compared to the corresponding period in control children (OR 6.3, 95% CI 1.8-22.3; p = 0.005). No difference was observed in the frequency of adenovirus infections. The findings suggest that enterovirus infections may contribute to the process leading to celiac disease

    Serum fatty acids and risk of developing islet autoimmunity : A nested case-control study within the TRIGR birth cohort

    Get PDF
    Background Circulating fatty acids have been linked to development of type 1 diabetes. Objectives To study the prospective associations of serum fatty acids with the risk of islet autoimmunity in high-risk children. Methods A nested case-control selection was carried out within the TRIGR cohort, which included infants with HLA (DQB1 or DQA1)-conferred disease susceptibility and a first-degree relative with type 1 diabetes, born between 2002 and 2007 in 15 countries and followed-up until 2017. The present study included 244 case children positive for at least two islet autoantibodies (ICA, IAA, GADA, and IA-2A) and two control children were matched for country and age. Proportions of 26 serum fatty acids at cord blood and at 6, 12, and 18 months of age were assessed using gas-chromatography. Results The average proportions of the following fatty acids were associated with an increased risk of islet autoimmunity, adjusted for sex, HLA risk, and maternal type 1 diabetes: pentadecanoic acid (15:0) (OR 3.41: 95% CI 1.70, 6.85), heptadecanoic acid (iso 17:0) (2.64: 1.62, 4.28) and (anteiso 17:0) (2.27: 1.39, 3.70), stearic acid (18:0) (23.8: 2.32, 244.6), and conjugated linoleic acid (18:2n-7) (2.60: 1.47, 4.59). Breastfeeding and not having maternal type 1 diabetes were positively associated with levels of the above-mentioned fatty acids. N-3 fatty acids were not consistently associated with islet autoimmunity. Conclusions We found direct associations of pentadecanoic acid, heptadecanoic acid, stearic acid, and conjugated linoleic acid with the risk of islet autoimmunity. Further studies are needed to understand the complex role of fatty acids in the development of type 1 diabetes.Peer reviewe

    Associations Between Serum Fatty Acids and Immunological Markers in Children Developing Islet Autoimmunity-The TRIGR Nested Case-Control Study

    Get PDF
    AimsAltered immune functions as well as fatty acid intake and status have been associated with the development of type 1 diabetes. We aimed to study the relationship between fatty acids and immunological markers in young children with increased genetic risk for type 1 diabetes in order to define putative mechanisms related to development of islet autoimmunity. MethodsSerum samples for fatty acid and immunological marker measurements were obtained in the Trial to Reduce IDDM in the Genetically at Risk (TRIGR) ancillary study (Divia) from children born between 2002 and 2007 in 15 countries. Case children (n = 95) were defined as having repeated positivity for at least two out of four diabetes-associated autoantibodies. For each case child, control children were selected matched for country and date of birth (n = 173). Serum fatty acids and immunological markers were measured from cord serum and at the age of 6 and 12 months. Spearman correlation coefficients were calculated between fatty acids and immunological markers. ResultsCorrelations between circulating fatty acids and immunological markers were different in case children who developed islet autoimmunity than in control children already at birth continuing across the first year of life. In case children, saturated fatty acids (SFAs) showed stronger correlations with immunological markers, while in controls, polyunsaturated fatty acids (PUFAs) showed stronger correlations. ConclusionsIn cases, SFAs were associated with several immunological markers (CXCL10, IL-6, IL-9, IL-17, and CM-CSF) previously linked to the type 1 diabetes disease process. Findings indicate that fatty acids could have immunomodulatory potential in the early phase of the disease development, although causality between fatty acids and the immunological pathways remains to be explored. Trial registry numberNCT00179777Peer reviewe

    Competence areas of health science teachers – A systematic review of quantitative studies

    Get PDF
    BackgroundIn the face of rapid digitalisation and ever-higher educational requirements for healthcare professionals, it is important that health science teachers possess the relevant core competences. The education of health science teachers varies internationally and there is no consensus about the minimum qualifications and experience they require.ObjectiveThe aim of this systematic review was to describe the health science teachers' competences and the factors related to it.DesignSystematic review of original quantitative studies.Data sourcesFour databases were selected from which to retrieve original studies: Cinahl (Ebsco), PubMed, Medic, Eri (ProQuest).Review MethodsThe systematic review used PICOS inclusion criteria. Original peer-reviewed quantitative studies published between 1/2007 and 1/2018 were identified. Screening was conducted by two researchers separately reading the 1885 titles, 600 abstracts, and 63 full-texts that were identified, and then agreed between them. Critical appraisal was performed using the JBI MAStARI evaluation tool. The data was extracted and then analysed narratively.ResultsThe core competences of health science teachers include areas of knowledge, skills and attitudes. Health science teachers evaluate their own competence as high. Only in relation to entrepreneurship and leadership knowledge was evaluated to be average. The most common factors influencing competence were teachers' title/position, healthcare experience, research activities, age, academic degree and for which type of organisation they work.ConclusionIt is important to identify the core competencies required by health science teachers in order to train highly competent healthcare professionals. Based on the findings of this systematic review we suggest that teachers should be encouraged to gain university education and actively participate in research, and that younger teachers should have opportunities to practice the relevant teaching skills to build competence.<br /
    • …
    corecore