| 1. |
- Dupraz, Julien, et al.
(författare)
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Use of healthcare services and assistive devices among centenarians : results of the cross-sectional, international 5-COOP study
- 2020
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 10:3
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To measure the use of healthcare services and assistive devices by centenarians in five countries. Design Cross-sectional study using a survey questionnaire. Setting Community-dwelling and institutionalised centenarians living in Japan, France, Switzerland, Sweden and Denmark. Participants 1253 participants aged 100 or in their 100th year of life, of whom 1004 (80.1%) were female and 596 (47.6%) lived in institutions. Main outcome measures Recent use of medical visits, nursing care at home, home-delivered meals, acute care hospital stays overnight, professional assessments such as sight tests, mobility aids and other assistive devices. A set of national healthcare system indicators was collected to help interpret differences between countries. Results There was considerable variability in the healthcare services and assistive devices used by centenarians depending on their country and whether they were community-dwelling or institutionalised. In contrast to the relatively homogeneous rates of hospitalisation in the past year (around 20%), community-dwelling centenarians reported widely ranging rates of medical visits in the past 3 months (at least one visit, from 32.2% in Japan to 86.6% in France). The proportion of community-dwellers using a mobility device to get around indoors (either a walking aid or a wheelchair) ranged from 48.3% in Japan to 79.2% in Sweden. Participants living in institutions and reporting the use of a mobility device ranged from 78.6% in Japan to 98.2% in Denmark. Conclusions Our findings suggest major differences in care received by centenarians across countries. Some may result from the characteristics of national healthcare systems, especially types of healthcare insurance coverage and the amounts of specific resources available. However, unexplored factors also seem to be at stake and may be partly related to personal health and cultural differences.
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| 2. |
- Fujita, Hidetoshi, et al.
(författare)
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The E3 ligase synoviolin controls body weight and mitochondrial biogenesis through negative regulation of PGC-1 beta
- 2015
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Ingår i: EMBO Journal. - : EMBO. - 1460-2075 .- 0261-4189. ; 34:8, s. 1042-1055
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is a major global public health problem, and understanding its pathogenesis is critical for identifying a cure. In this study, a gene knockout strategy was used in post-neonatal mice to delete synoviolin (Syvn) 1/Hrd1/Der3, an ER-resident E3 ubiquitin ligase with known roles in homeostasis maintenance. Syvn1 deficiency resulted in weight loss and lower accumulation of white adipose tissue in otherwise wild-type animals as well as in genetically obese (ob/ob and db/db) and adipose tissue-specific knockout mice as compared to control animals. SYVN1 interacted with and ubiquitinated the thermogenic coactivator peroxisome proliferator-activated receptor coactivator (PGC)-1 beta, and Syvn1 mutants showed upregulation of PGC-1 beta target genes and increase in mitochondrion number, respiration, and basal energy expenditure in adipose tissue relative to control animals. Moreover, the selective SYVN1 inhibitor LS-102 abolished the negative regulation of PGC-1 beta by SYVN1 and prevented weight gain in mice. Thus, SYVN1 is a novel post-translational regulator of PGC-1 beta and a potential therapeutic target in obesity treatment.
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| 3. |
- Kanayama, Kengo, et al.
(författare)
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Genome-wide mapping of bivalent histone modifications in hepatic stem/progenitor cells
- 2019
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Ingår i: Stem Cells International. - : Hindawi Limited. - 1687-966X .- 1687-9678. ; 2019
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Tidskriftsartikel (refereegranskat)abstract
- The “bivalent domain,” a distinctive histone modification signature, is characterized by repressive trimethylation of histone H3 at lysine 27 (H3K27me3) and active trimethylation of histone H3 at lysine 4 (H3K4me3) marks. Maintenance and dynamic resolution of these histone marks play important roles in regulating differentiation processes in various stem cell systems. However, little is known regarding their roles in hepatic stem/progenitor cells. In the present study, we conducted the chromatin immunoprecipitation (ChIP) assay followed by high-throughput DNA sequencing (ChIP-seq) analyses in purified delta-like 1 protein (Dlk + ) hepatic stem/progenitor cells and successfully identified 562 genes exhibiting bivalent domains within 2 kb of the transcription start site. Gene ontology analysis revealed that these genes were enriched in developmental functions and differentiation processes. Microarray analyses indicated that many of these genes exhibited derepression after differentiation toward hepatocyte and cholangiocyte lineages. Among these, 72 genes, including Cdkn2a and Sox4, were significantly upregulated after differentiation toward hepatocyte or cholangiocyte lineages. Knockdown of Sox4 in Dlk + cells suppressed colony propagation and resulted in increased numbers of albumin + /cytokeratin 7 + progenitor cells in colonies. These findings implicate that derepression of Sox4 expression is required to induce normal differentiation processes. In conclusion, combined ChIP-seq and microarray analyses successfully identified bivalent genes. Functional analyses of these genes will help elucidate the epigenetic machinery underlying the terminal differentiation of hepatic stem/progenitor cells.
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| 4. |
- Nakajima, Yoko, et al.
(författare)
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Clinical, biochemical and molecular analysis of 13 Japanese patients with beta-ureidopropionase deficiency demonstrates high prevalence of the c.977G > A (p.R326Q) mutation
- 2014
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Ingår i: Journal of Inherited Metabolic Disease. - : Wiley. - 0141-8955 .- 1573-2665. ; 37:5, s. 801-812
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Tidskriftsartikel (refereegranskat)abstract
- beta-ureidopropionase (beta UP) deficiency is an autosomal recessive disease characterized by N-carbamyl-beta-amino aciduria. To date, only 16 genetically confirmed patients with beta UP deficiency have been reported. Here, we report on the clinical, biochemical and molecular findings of 13 Japanese beta UP deficient patients. In this group of patients, three novel missense mutations (p.G31S, p.E271K, and p.I286T) and a recently described mutation (p.R326Q) were identified. The p.R326Q mutation was detected in all 13 patients with eight patients being homozygous for this mutation. Screening for the p.R326Q mutation in 110 Japanese individuals showed an allele frequency of 0.9 %. Transient expression of mutant beta UP enzymes in HEK293 cells showed that the p.E271K and p.R326Q mutations cause profound decreases in activity (a parts per thousand currency sign 1.3 %). Conversely, beta UP enzymes containing the p.G31S and p.I286T mutations possess residual activities of 50 and 70 %, respectively, suggesting we cannot exclude the presence of additional mutations in the non-coding region of the UPB1 gene. Analysis of a human beta UP homology model revealed that the effects of the mutations (p.G31S, p.E271K, and p.R326Q) on enzyme activity are most likely linked to improper oligomer assembly. Highly variable phenotypes ranging from neurological involvement (including convulsions and autism) to asymptomatic, were observed in diagnosed patients. High prevalence of p.R326Q in the normal Japanese population indicates that beta UP deficiency is not as rare as generally considered and screening for beta UP deficiency should be included in diagnosis of patients with unexplained neurological abnormalities.
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