| 11. |
- Lawenius, Lina, et al.
(author)
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Development of a synbiotic that protects against ovariectomy-induced trabecular bone loss
- 2022
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In: American Journal of Physiology-Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 322:4
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Journal article (peer-reviewed)abstract
- The gut microbiome has the capacity to regulate bone mass. The aim of this study was to develop a nutritional synbiotic dietary assemblage at an optimal dose to maintain bone mass in ovariectomized (Ovx) mice. We performed genomic analyses and in vitro experiments in a large collection of bacterial and fungal strains (>4,000) derived from fresh fruit and vegetables to identify candidates with the synergistic capacity to produce bone-protective short-chain fatty acids (SCFA) and vitamin K2. The candidate SBD111-A, composed of Lactiplantibacillus plantarum, Levilactobacillus brevis, Leuconostoc mesenteroides, Pseudomonas fluorescens, and Pichia kudriavzevii together with prebiotic dietary fibers, produced high levels of SCFA in vitro and protected against Ovx-induced trabecular bone loss in a dose-dependent manner in mice. Metagenomic sequencing revealed that SBD111-A changed the taxonomic composition and enriched specific pathways for synthesis of bone-protective SCFA, vitamin K2, and branched-chain amino acids in the gut microbiome. NEW & NOTEWORTHY We performed genomic analyses and in vitro experiments in a collection of bacterial and fungal strains. We identified a combination (SBD111-A) that produced high levels of SCFA in vitro and protected against ovariectomy-induced bone loss in a dose-dependent manner in mice. Metagenomic sequencing revealed that SBD111-A changed the taxonomic composition and function of the gut microbiome and enriched pathways for synthesis of bone-protective SCFA, vitamin K2, and branched-chain amino acids.
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| 12. |
- Lawenius, Lina, et al.
(author)
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Pasteurized Akkermansia muciniphila protects from fat mass gain but not from bone loss
- 2020
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In: American Journal of Physiology-Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 318:4
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Journal article (peer-reviewed)abstract
- Probiotic bacteria can protect from ovariectomy (ovx)-induced bone loss in mice. Akkermansia muciniphila is considered to have probiotic potential due to its beneficial effect on obesity and insulin resistance. The purpose of the present study was to determine if treatment with pasteurized Akkermansia muciniphila (pAkk) could prevent ovx-induced bone loss. Mice were treated with vehicle or pAkk for 4 wk, starting 3 days before ovx or sham surgery. Treatment with pAkk reduced fat mass accumulation confirming earlier findings. However, treatment with pAkk decreased trabecular and cortical bone mass in femur and vertebra of gonadal intact mice and did not protect from ovx-induced bone loss. Treatment with pAkk increased serum parathyroid hormone (PTH) levels and increased expression of the calcium transporter Trpv5 in kidney suggesting increased reabsorption of calcium in the kidneys. Serum amyloid A 3 (SAA3) can suppress bone formation and mediate the effects of PTH on bone resorption and bone loss in mice and treatment with pAkk increased serum levels of SAA3 and gene expression of Saa3 in colon. Moreover, regulatory T cells can be protective of bone and pAkk-treated mice had decreased number of regulatory T cells in mesenteric lymph nodes and bone marrow. In conclusion, treatment with pAkk protected from ovx-induced fat mass gain but not from bone loss and reduced bone mass in gonadal intact mice. Our findings with pAkk differ from some probiotics that have been shown to protect bone mass, demonstrating that not all prebiotic and probiotic factors have the same effect on bone.
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| 13. |
- Liu, Meng, 1976, et al.
(author)
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Targeting the protein prenyltransferases efficiently reduces tumor development in mice with K-RAS-induced lung cancer
- 2010
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 107:14, s. 6471-6476
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Journal article (peer-reviewed)abstract
- RAS and RHO proteins, which contribute to tumorigenesis and metastasis, undergo posttranslational modification with an isoprenyl lipid by protein farnesyltransferase (FTase) or protein geranylgeranyltransferase-I (GGTase-I). Inhibitors of FTase and GGTase-I were developed to block RAS-induced malignancies, but their utility has been difficult to evaluate because of off-target effects, drug resistance, and toxicity. Moreover, the impact of FTase deficiency and combined FTase/GGTase-I deficiency has not been evaluated with genetic approaches. We found that inactivation of FTase eliminated farnesylation of HDJ2 and H-RAS, prevented H-RAS targeting to the plasma membrane, and blocked proliferation of primary and K-RAS(G12D)-expressing fibroblasts. FTase inactivation in mice with K-RAS-induced lung cancer reduced tumor growth and improved survival, similar to results obtained previously with inactivation of GGTase-I. Simultaneous inactivation of FTase and GGTase-I markedly reduced lung tumors and improved survival without apparent pulmonary toxicity. These data shed light on the biochemical and therapeutic importance of FTase and suggest that simultaneous inhibition of FTase and GGTase-I could be useful in cancer therapeutics.
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| 14. |
- Ohlsson, Claes, 1965, et al.
(author)
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Inducible Wnt16 inactivation: WNT16 regulates cortical bone thickness in adult mice.
- 2018
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In: The Journal of endocrinology. - 1479-6805. ; 237:2, s. 113-122
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Journal article (peer-reviewed)abstract
- Substantial progress has been made in the therapeutic reduction of vertebral fracture risk in patients with osteoporosis, but non-vertebral fracture risk has been improved only marginally. Human genetic studies demonstrate that the WNT16 locus is a major determinant of cortical bone thickness and non-vertebral fracture risk and mouse models with life-long Wnt16 inactivation revealed that WNT16 is a key regulator of cortical thickness. These studies, however, could not exclude that the effect of Wnt16 inactivation on cortical thickness might be caused by early developmental and/or growth effects. To determine the effect of WNT16 specifically on adult cortical bone homeostasis, Wnt16 was conditionally ablated in young adult and old mice through tamoxifen-inducible Cre-mediated recombination using CAG-Cre-ER; Wnt16flox/flox (Cre-Wnt16flox/flox) mice. First, 10-week-old Cre-Wnt16flox/flox and Wnt16flox/flox littermate control mice were treated with tamoxifen. Four weeks later, Wnt16 mRNA levels in cortical bone were reduced and cortical thickness in femur was decreased in Cre-Wnt16flox/flox mice compared to Wnt16flox/flox mice. Then, inactivation of Wnt16 in 47-week-old mice (evaluated four weeks later) resulted in a reduction of Wnt16 mRNA levels, cortical thickness and cortical bone strength with no effect on trabecular bone volume fraction. Mechanistic studies demonstrated that the reduced cortical bone thickness was caused by a combination of increased bone resorption and reduced periosteal bone formation. In conclusion, WNT16 is a crucial regulator of cortical bone thickness in young adult and old mice. We propose that new treatment strategies targeting the adult regulation of WNT16 might be useful to reduce fracture risk at cortical bone sites.
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| 15. |
- Sjögren, Anna-Karin, 1980, et al.
(author)
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GGTase-I deficiency reduces tumor formation and improves survival in mice with K-RAS-induced lung cancer
- 2007
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In: J Clin Invest. - 0021-9738. ; 117:5, s. 1294-304
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Journal article (peer-reviewed)abstract
- Protein geranylgeranyltransferase type I (GGTase-I) is responsible for the posttranslational lipidation of CAAX proteins such as RHOA, RAC1, and cell division cycle 42 (CDC42). Inhibition of GGTase-I has been suggested as a strategy to treat cancer and a host of other diseases. Although several GGTase-I inhibitors (GGTIs) have been synthesized, they have very different properties, and the effects of GGTIs and GGTase-I deficiency are unclear. One concern is that inhibiting GGTase-I might lead to severe toxicity. In this study, we determined the effects of GGTase-I deficiency on cell viability and K-RAS-induced cancer development in mice. Inactivating the gene for the critical beta subunit of GGTase-I eliminated GGTase-I activity, disrupted the actin cytoskeleton, reduced cell migration, and blocked the proliferation of fibroblasts expressing oncogenic K-RAS. Moreover, the absence of GGTase-I activity reduced lung tumor formation, eliminated myeloproliferative phenotypes, and increased survival of mice in which expression of oncogenic K-RAS was switched on in lung cells and myeloid cells. Interestingly, several cell types remained viable in the absence of GGTase-I, and myelopoiesis appeared to function normally. These findings suggest that inhibiting GGTase-I may be a useful strategy to treat K-RAS-induced malignancies.
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| 16. |
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| 17. |
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| 18. |
- Sjögren, Karin, et al.
(author)
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Organisational and environmental characteristics of residential aged care units providing highly person-centred care : a cross sectional study
- 2017
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In: BMC Nursing. - : Springer Science and Business Media LLC. - 1472-6955. ; 16
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Journal article (peer-reviewed)abstract
- BACKGROUND: Few studies have empirically investigated factors that define residential aged care units that are perceived as being highly person-centred. The purpose of this study was to explore factors characterising residential aged care units perceived as being highly person-centred, with a focus on organisational and environmental variables, as well as residents' and staff' characteristics.METHODS: A cross-sectional design was used. Residents (n = 1460) and staff (n = 1213) data from 151 residential care units were collected, as well as data relating to characteristics of the organisation and environment, and data measuring degree of person-centred care. Participating staff provided self-reported data and conducted proxy ratings on residents. Descriptive and comparative statistics, independent samples t-test, Chi(2) test, Eta Squared and Phi coefficient were used to analyse data.RESULTS: Highly person-centred residential aged care units were characterized by having a shared philosophy of care, a satisfactory leadership, interdisciplinary collaboration and social support from colleagues and leaders, a dementia-friendly physical environment, staff having time to spend with residents, and a smaller unit size. Residential aged care units with higher levels of person-centred care had a higher proportion of staff with continuing education in dementia care, and a higher proportion of staff receiving regular supervision, compared to units with lower levels of person-centred care.CONCLUSIONS: It is important to target organisational and environmental factors, such as a shared philosophy of care, staff use of time, the physical environment, interdisciplinary support, and support from leaders and colleagues, to improve person-centred care in residential care units. Managers and leaders seeking to facilitate person-centred care in daily practice need to consider their own role in supporting, encouraging, and supervising staff.
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| 19. |
- Sjögren, Karin, 1953-
(author)
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Personcentrerad vård i särskilda boenden för äldre
- 2013
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Doctoral thesis (other academic/artistic)abstract
- Bakgrund: Andelen äldre i befolkningen ökar nationellt och internationellt, och med ökande ålder ökar både fysisk och psykisk ohälsa. Äldre personer med ohälsa i form av kognitiv svikt (oftast demenssjukdom) kan bli beroende av vård och omsorg i särskilda boenden för äldre för att kunna känna trygghet och välbefinnande samt ha ett gott liv, i gemenskap med andra. Dock visar utvärderingar av särskilda boenden för äldre att vården ofta kan vara uppgiftscentrerad och inte motsvara de äldres individuella behov och önskemål. Personcentrerad vård är en vårdmodell som beskrivs kunna tillgodose äldre personers multidimensionella behov och önskemål, genom att personens livshistoria, personlighet, kapacitet och perspektiv uppmärksammas, respekteras och inkluderas i vården. Den vetenskapliga litteraturen inom området visar dock att det finns begränsad kunskap om förekomsten av personcentrerad vård i särskilda boenden för äldre i Sverige och internationellt, liksom om vilka faktorer som är mest betydelsefulla för att särskilda boenden för äldre ska bedriva en personcentrerad vård.Syfte: Syftet med denna avhandling var att beskriva faktorer som samvarierar med förekomst av personcentrerad vård i särskilda boenden för äldre i Sverige.Metod: Samtliga delstudier var tvärsnittstudier och data samlades in genom enkäter till äldre med kognitiv svikt och personal i särskilda boenden för äldre i Sverige. I studie I bestod insamlad data av skattningar av personcentrerad vård från vårdpersonal (n=1465) i 182 särskilda boendeenheter. I studie II insamlades data i form av vårdpersonalens (n=1169) skattningar av personcentrerad vård och proxyskattningar av de äldres (n=1261) livskvalitet, ADL-förmågor, smärta, depressiva symtom och agitation i 151 särskilda boendeenheter. Delstudie III baserades på data i form av personalskattningar (n=1169) av personcentrerad vård, tillfredställelse med arbete och vård, samvetsstress, arbetsbelastning och psykosocialt klimat i samma 151 särskilda boendeenheter. Även delstudie IV baserades på data från de 151 särskilda boendeenheterna och inkluderade skattningar av de äldre och vårdpersonal, men också skattningar av organisation och miljö vid dessa enheter (n=151). Samtliga studiernas data analyserades med hjälp av statistiska analyser, beskrivande, bivariata och multivariata analysmetoder.Resultat: Studie I visade att enkätinstrumentet The Person-Centred Care Assessment Tool (P-CAT) har tillfredställande psykometriska egenskaper för intern konsistens och test-retest-reliabilitet. Instrumentet består av två subskalor: Individualisering av vården och Stöd från organisation och miljö. Delstudie II visade att de boendes ADL-förmågor och livskvalitet skattades bättre vid enheter som kan beskrivas som mer personcentrerade. Delstudie III visade att en mer personcentrerad vård har samband med att personalen upplever ett positivt psykosocialt klimat, mindre samvetsstress, lägre arbetsbelastning samt högre tillfredställelse med vård och arbete. Studien visade också att personcentrerad vård var positivt relaterat till i vilken omfattning vårdarna hade vidareutbildning i demensvård. Delstudie IV visade att vårdmiljön var mest betydelsefull för förekomsten av personcentrerad vård vid boendeenheterna och att en gynnsam vårdmiljö innebar att personal upplevde att det var ett positivt psykosocialt klimat på enheten, att de hade tid att prata med eller bara vara med de boende samt att de upplevde sig ha en gemensam värdegrund, låg arbetsbelastning och en fysisk miljö som var anpassad till de boendes behov.Slutsatser: Resultaten i avhandlingen visar att den svenska versionen av P-CAT kan användas för valida och reliabla utvärderingar av personcentrerad vård samt att den kan rekommenderas för fortsatt forskning och vårdutveckling inom särskilda boenden för äldre. Resultatet visar också att den vård- och arbetsmiljö som omger de äldre och vårdpersonal i särskilda boenden för äldre är betydelsefull för förekomsten av personcentrerad vård. Dessa aspekter behöver fokuseras ytterligare för att kunna erbjuda en personcentrerad vård. Vidare är det psykosociala klimatet och förekomsten av en upplevd gemensam värdegrund viktig att förstå och prioritera om vården ska utvecklas mot en ökad personcentrering. Fortsatt forskning och kliniskt utvecklingsarbete behövs för att operationalisera och implementera de komponenter som bidrar till ett positivt psykosocialt klimat och en personcentrerad värdegrund på särskilda boenden för äldre. Dessutom behövs en ökad förståelse för hur en sådan värdegrund kan omsättas i personcentrerade interaktioner, handlingar, aktiviteter och prioriteringar. Det vore alltså önskvärt att äldrevården utvecklades mot ett mer personcentrat förhållningssätt, eftersom avhandlingens resultat visar att högre grad av personcentrerad vård i särskilda boenden för äldre var positivt relaterat till välbefinnande och tillfredställelse för såväl de äldre som för vårdpersonal.
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| 20. |
- Sjögren, Karin, et al.
(author)
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Psychometric evaluation of the swedish version of the person-centered care assessment tool (P-CAT)
- 2012
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In: International psychogeriatrics. - : Cambridge University Press. - 1041-6102 .- 1741-203X. ; 24:3, s. 406-415
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Journal article (peer-reviewed)abstract
- Background: Person-centered care is a multidimensional concept describing good care, especially within aged care and care for people with dementia. Research studies evaluating person-centered care interventions seldom use direct measurement of levels of person-centeredness. Existing scales that measure person-centeredness need further testing. This study evaluated the psychometric properties of the Swedish version of the Person-Centered Care Assessment Tool (P-CAT). Methods: A cross-sectional sample of 1465 staff from 195 residential care units for older people in Sweden participated in the study. Validity, reliability, and discrimination ability of the scale were evaluated. Results: Confirmatory factor analysis, parallel analysis and exploratory factor analysis supported the construct validity of a two-factor solution. Reliability and homogeneity were satisfactory for the whole P-CAT as demonstrated by a Cronbach's α of 0.75. Test-retest reliability showed temporal stability of the scale, and the discrimination ability of the scale was satisfactory. Conclusion: The Swedish version of the P-CAT was found to be valid, reliable, and applicable for further use. Two subscales are recommended for the Swedish version. © 2011 International Psychogeriatric Association.
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