5 research outputs found

    The incidence of pelvic fractures and related surgery in the Finnish adult population: a nationwide study of 33,469 patients between 1997 and 2014

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    Background and purpose - Information on the epidemiological trends of pelvic fractures and fracture surgery in the general population is limited. We therefore determined the incidence of pelvic fractures in the Finnish adult population between 1997 and 2014 and assessed the incidence and trends of fracture surgery.Patients and methods - We used data from the Finnish National Discharge Register (NHDR) to calculate the incidence of pelvic fractures and fracture surgery. All patients 18 years of age or older were included in the study. The NHDR covers the whole Finnish population and gives information on health care services and the surgical procedures performed.Results and interpretation - We found that in Finnish adults the overall incidence of hospitalization for a pelvic fracture increased from 34 to 56/100,000 person-years between 1997 and 2014. This increase was most apparent for the low-energy fragility fractures of the elderly female population. The ageing of the population is likely therefore to partly explain this increase. The annual number and incidence of pelvic fracture surgery also rose between 1997 and 2014, from 118 (number) and 3.0 (incidence) in 1997 to 187 and 4.3 in 2014, respectively. The increasing number and incidence of pelvic fractures in the elderly population will increase the need for social and healthcare services. The main focus should be on fracture prevention.Peer reviewe

    Internalization of novel non-viral vector TAT-streptavidin into human cells

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    BACKGROUND: The cell-penetrating peptide derived from the Human immunodeficiency virus-1 transactivator protein Tat possesses the capacity to promote the effective uptake of various cargo molecules across the plasma membrane in vitro and in vivo. The objective of this study was to characterize the uptake and delivery mechanisms of a novel streptavidin fusion construct, TAT(47–57)-streptavidin (TAT-SA, 60 kD). SA represents a potentially useful TAT-fusion partner due to its ability to perform as a versatile intracellular delivery vector for a wide array of biotinylated molecules or cargoes. RESULTS: By confocal and immunoelectron microscopy the majority of internalized TAT-SA was shown to accumulate in perinuclear vesicles in both cancer and non-cancer cell lines. The uptake studies in living cells with various fluorescent endocytic markers and inhibiting agents suggested that TAT-SA is internalized into cells efficiently, using both clathrin-mediated endocytosis and lipid-raft-mediated macropinocytosis. When endosomal release of TAT-SA was enhanced through the incorporation of a biotinylated, pH-responsive polymer poly(propylacrylic acid) (PPAA), nuclear localization of TAT-SA and TAT-SA bound to biotin was markedly improved. Additionally, no significant cytotoxicity was detected in the TAT-SA constructs. CONCLUSION: This study demonstrates that TAT-SA-PPAA is a potential non-viral vector to be utilized in protein therapeutics to deliver biotinylated molecules both into cytoplasm and nucleus of human cells

    The Center of Excellence in Atmospheric Science (2002–2019) — from molecular and biological processes to the global climate

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    The study of atmospheric processes related to climate requires a multidisciplinary approach, encompassing physics, chemistry, meteorology, forest science, and environmental science. The Academy of Finland Centre of Excellence in atmospheric sciences (CoE ATM) responded to that need for 18 years and produced extensive research and eloquent results, which are summarized in this review. The work in the CoE ATM enhanced our understanding in biogeochemical cycles, ecosystem processes, dynamics of aerosols, ions and neutral clusters in the lower atmosphere, and cloud formation and their interactions and feedbacks. The CoE ATM combined continuous and comprehensive long-term in-situ observations in various environments, ecosystems and platforms, ground- and satellitebased remote sensing, targeted laboratory and field experiments, and advanced multi-scale modeling. This has enabled improved conceptual understanding and quantifications across relevant spatial and temporal scales. Overall, the CoE ATM served as a platform for the multidisciplinary research community to explore the interactions between the biosphere and atmosphere under a common and adaptive framework

    Fasting-induced transcription factors repress vitamin D bioactivation, a mechanism for vitamin D deficiency in diabetes

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    Abstract Low 25-hydroxyvitamin D levels correlate with the prevalence of diabetes; however, the mechanisms remain uncertain. Here, we show that nutritional deprivation–responsive mechanisms regulate vitamin D metabolism. Both fasting and diabetes suppressed hepatic cytochrome P450 (CYP) 2R1, the main vitamin D 25-hydroxylase responsible for the first bioactivation step. Overexpression of coactivator peroxisome proliferator–activated receptor γ coactivator 1-α (PGC-1α), induced physiologically by fasting and pathologically in diabetes, resulted in dramatic downregulation of CYP2R1 in mouse hepatocytes in an estrogen-related receptor α (ERRα)–dependent manner. However, PGC-1α knockout did not prevent fasting-induced suppression of CYP2R1 in the liver, indicating that additional factors contribute to the CYP2R1 repression. Furthermore, glucocorticoid receptor (GR) activation repressed the liver CYP2R1, suggesting GR involvement in the regulation of CYP2R1. GR antagonist mifepristone partially prevented CYP2R1 repression during fasting, suggesting that glucocorticoids and GR contribute to the CYP2R1 repression during fasting. Moreover, fasting upregulated the vitamin D catabolizing CYP24A1 in the kidney through the PGC-1α-ERRα pathway. Our study uncovers a molecular mechanism for vitamin D deficiency in diabetes and reveals a novel negative feedback mechanism that controls crosstalk between energy homeostasis and the vitamin D pathway
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