This open access book provides insight on how to interpret capability in ageing – one’s individual ability to perform actions in order to reach goals one has reason to value – from a ...multidisciplinary approach. With for the first time in history there being more people in the world aged 60 years and over than there are children below the age of 5, the book describes this demographic trends as well as the large global challenges and important societal implications this will have such as a worldwide increase in the number of persons affected with dementia, and in the ratio of retired persons to those still in the labor market. Through contributions from many different research areas, it discussed how capability depends on interactions between the individual (e.g. health, genetics, personality, intellectual capacity), environment (e.g. family, friends, home, work place), and society (e.g. political decisions, ageism, historical period). The final chapter summarizes the differences and similarities in these contributions. As such this book provides an interesting read for students, teachers and researchers at different levels and from different fields interested in capability and multidisciplinary research.
The incidence of breast cancer is increasing in the Western world and there is an urgent need for studies of the mechanisms of sex steroids in order to develop novel preventive strategies. Diet ...modifications may be among the means for breast cancer prevention. Angiogenesis, key in tumor progression, is regulated by the balance between pro- and anti-angiogenic factors, which are controlled in the extracellular space. Sampling of these molecules at their bioactive compartment is therefore needed. The aims of this study were to explore if tamoxifen, one of the most used anti-estrogen treatments for breast cancer affected some of the most important endogenous angiogenesis regulators, vascular endothelial growth factor (VEGF), angiogenin, and endostatin in normal breast tissue in vivo and if a diet supplementation with flaxseed had similar effects as tamoxifen in the breast. Microdialysis was used for in situ sampling of extracellular proteins in normal breast tissue of women before and after six weeks of tamoxifen treatment or before and after addition of 25 g/day of ground flaxseed to the diet or in control women. We show significant correlations between estradiol and levels of VEGF, angiogenin, and endostatin in vivo, which was verified in ex vivo breast tissue culture. Moreover, tamoxifen decreased the levels of VEGF and angiogenin in the breast whereas endostatin increased significantly. Flaxseed did not alter VEGF or angiogenin levels but similar to tamoxifen the levels of endostatin increased significantly. We conclude that one of the mechanisms of tamoxifen in normal breast tissue include tipping of the angiogenic balance into an anti-angiogenic state and that flaxseed has limited effects on the pro-angiogenic factors whereas the anti-angiogenic endostatin may be modified by diet. Further studies of diet modifications for breast cancer prevention are warranted.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Protein intake is higher in formula-fed than in breast-fed infants during infancy, which may lead to an increased risk of being overweight. Applying alpha-lactalbumin (α-lac)-enriched whey or casein ...glycomacropeptide (CGMP)-reduced whey to infant formula may enable further reduction of formula protein by improving the amino acid profile. Growth, nutrient intake, and protein metabolites were evaluated in a randomized, prospective, double-blinded intervention trial where term infants received standard formula (SF:2.2 g protein/100 kcal;
= 83) or low-protein formulas with α-lac-enriched whey (α-lac-EW;1.75 g protein/100 kcal;
= 82) or CGMP-reduced whey (CGMP-RW;1.76 g protein/100 kcal;
= 80) from 2 to 6 months. Breast-fed infants (BF;
= 83) served as reference. Except between 4 and 6 months, when weight gain did not differ between α-lac-EW and BF (
= 0.16), weight gain was higher in all formula groups compared to BF. Blood urea nitrogen did not differ between low-protein formula groups and BF during intervention, but was lower than in SF. Essential amino acids were similar or higher in α-lac-EW and CGMP-RW compared to BF. Conclusion: Low-protein formulas enriched with α-lac-enriched or CGMP-reduced whey supports adequate growth, with more similar weight gain in α-lac-enriched formula group and BF, and with metabolic profiles closer to that of BF infants.
High protein intake during infancy results in accelerated early weight gain and potentially later obesity. The aim of this follow-up study at 12 months was to evaluate if modified low-protein ...formulas fed during early infancy have long-term effects on growth and metabolism. In a double-blinded RCT, the ALFoNS study, 245 healthy-term infants received low-protein formulas with either alpha-lactalbumin-enriched whey (α-lac-EW; 1.75 g protein/100 kcal), casein glycomacropeptide-reduced whey (CGMP-RW; 1.76 g protein/100 kcal), or standard infant formula (SF; 2.2 g protein/100 kcal) between 2 and 6 months of age. Breastfed (BF) infants served as a reference. At 12 months, anthropometrics and dietary intake were assessed, and serum was analyzed for insulin, C-peptide, and insulin-like growth factor 1 (IGF-1). Weight gain between 6 and 12 months and BMI at 12 months were higher in the SF than in the BF infants (
= 0.019;
< 0.001, respectively), but were not significantly different between the low-protein formula groups and the BF group. S-insulin and C-peptide were higher in the SF than in the BF group (
< 0.001;
= 0.003, respectively), but more alike in the low-protein formula groups and the BF group. Serum IGF-1 at 12 months was similar in all study groups. Conclusion: Feeding modified low-protein formula during early infancy seems to reduce insulin resistance, resulting in more similar growth, serum insulin, and C-peptide concentrations to BF infants at 6-months post intervention. Feeding modified low-protein formula during early infancy results in more similar growth, serum insulin, and C-peptide concentrations to BF infants 6-months post intervention, probably due to reduced insulin resistance in the low-protein groups.
Angiogenin, a 14.2-kDa polypeptide member of the RNase A superfamily, has potent angiogenic effects. Nuclear accumulation of angiogenin is essential for its angiogenic activity. Increased angiogenin ...expression has been associated with the transition of normal breast tissue into invasive breast carcinoma. In this article, we investigated whether estradiol (E(2)) affected angiogenin in breast tissue.
We used microdialysis for sampling of extracellular angiogenin in vivo. In vitro cultures of whole normal breast tissue, breast cancer cells, and endothelial cells were used.
We show that extracellular angiogenin correlated significantly with E(2) in normal human breast tissue in vivo and that exposure of normal breast tissue biopsies to E(2) stimulated angiogenin secretion. In breast cancer patients, the in vivo angiogenin levels were significantly higher in tumors compared with the adjacent normal breast tissue. In estrogen receptor-positive breast cancer cells, E(2) increased and tamoxifen decreased angiogenin secretion. Moreover, E(2)-induced angiogenin derived from cancer cells significantly increased endothelial cell proliferation. Tamoxifen reversed this increase as well as inhibited nuclear translocation of angiogenin. In vivo, in experimental breast cancer, tamoxifen decreased angiogenin levels and decreased angiogenesis. Additionally, treating tumor-bearing mice with an antiangiogenin antibody resulted in tumor stasis, suggesting a role for angiogenin in estrogen-dependent breast cancer growth.
Our results suggest previously unknown mechanisms by which estrogen and antiestrogen regulate angiogenesis in normal human breast tissue and breast cancer. This may be important for estrogen-driven breast cancer progression and a molecular target for therapeutic interventions.
Electrophilically reactive compounds have the ability to form adducts with nucleophilic sites in DNA and proteins, constituting a risk for toxic effects. Mass spectrometric detection of adducts to ...N-terminal valine in hemoglobin (Hb) after detachment by modified Edman degradation procedures is one approach for in vivo monitoring of exposure to electrophilic compounds/metabolites. So far, applications have been limited to one or a few selected reactive species, such as acrylamide and its metabolite glycidamide. This article presents a novel screening strategy for unknown Hb adducts to be used as a basis for an adductomic approach. The method is based on a modified Edman procedure, FIRE, specifically developed for LC–MS/MS analysis of N-terminal valine adducts in Hb detached as fluorescein thiohydantoin (FTH) derivatives. The aim is to detect and identify a priori unknown Hb adducts in human blood samples. Screening of valine adducts was performed by stepwise scanning of precursor ions in small mass increments, monitoring four fragments common for the FTH derivative of valine with different N-substitutions in the multiple-reaction mode, covering a mass range of 135 Da (m/z 503–638). Samples from six smokers and six nonsmokers were analyzed. Control experiments were performed to compare these results with known adducts and to check for artifactual formation of adducts. In all samples of smokers and nonsmokers, seven adducts were identified, of which six have previously been studied. Nineteen unknown adducts were observed, and 14 of those exhibited fragmentation patterns similar to earlier studied FTH derivatives of adducts to valine. Identification of the unknown adducts will be the focus of future work. The presented methodology is a promising screening tool using Hb adducts to indicate exposure to potentially toxic electrophilic compounds and metabolites.
•Fewer 85-year-olds reported any passive/active suicidal ideation in 2008 and 2015 than in 1986, the decrease was driven by reductions in passive ideation.•Rates of any passive/active suicidal ...ideation remained stable from 2008 to 2015.•Social factors associated with any passive/active suicidal ideation in 85-year-olds differed in women and men. For women, feeling lonely was associated with any passive/active suicidal ideation, for men having no partner was associated with such ideation.
Older adults have high suicide rates. We investigated potential time trends in the prevalence of passive and active suicidal ideation in 85-year-olds. Further, we examined factors associated with such ideation in this age group.
Population-based samples of 85-year-olds were interviewed in 1986 (N = 347), 2008 (N = 426) and 2015 (N = 320). Past-month passive/active suicidal ideation was evaluated with the Paykel questions.
Reporting any type of passive or active suicidal ideation was less common in 2008 (7.3%, p < 0.001) and 2015 (7.2%, p < 0.001) compared to 1986 (16.4%). The change was driven by decreases in passive ideation. Passive/active suicidal ideation was associated with higher MADRS score (OR: 1.2, 95% CI: 1.1–1.2, p < 0.001), institution residence (OR: 3.9, 95% CI: 1.7–8.9, p = 0.001) and feelings of loneliness (OR: 2.7, 95% CI: 1.4–5.2, p = 0.003). When stratified by sex, it was associated with institution residence (OR: 3.7, 95% CI: 1.4–9.9, p = 0.008) and feelings of loneliness (OR: 3.0, 95% CI: 1.4–6.3, p = 0.005) in women. In men, we observed a tenfold higher risk in those without partners (OR: 9.8, 95% CI: 2.9–33.5, p < 0.001).
While differential three-year mortality was not observed in 1986, mortality was higher among non-participants in 2008 and 2015. This might have inflated cohort differences in passive/active suicidal ideation.
An initial decrease in the prevalence of passive/active suicidal ideation in 85-year-olds was observed but this positive trend did not persist. Results underline that preventive strategies targeting loneliness and focusing on institutional settings are needed, as are interventions for men without partners.
Sex steroids play a dominant role in breast carcinogenesis by still largely unknown mechanisms. Matrix metalloproteinases (MMPs) have been extensively studied in the context of matrix biology but it ...is not known if sex steroids affect MMPs in breast cancer. MMPs degrade extracellular matrix components enabling tumor cell invasion and metastasis, but may also regulate the bioavailability of a variety of biologically active molecules such as anti-angiogenic fragments, which may be beneficial for the host. This study shows that estradiol and tamoxifen regulate MMP-2 and MMP-9 as well as TIMP-1 and TIMP-2 in ER + PR + human breast cancer cells. The main finding was a significant effect of tamoxifen exposure, which increased intracellular and secreted protein levels whereas estradiol induced a significant decrease. The overall net effect of these alterations resulted in increased MMP-2/MMP-9 activity by tamoxifen treatment, which also significantly increased extracellular endostatin levels. We conclude that estradiol and tamoxifen have the ability to modulate MMP-2/MMP-9 activity, and endostatin levels in human breast cancer in vitro. The results suggest a possible role of MMP modulation associated with a generation of anti-angiogenic fragments in the therapeutic effect of tamoxifen in breast cancer.
Vad vill vi med historielärarutbildningen? Bagerius, Henric; Hallberg, Erik; Lundqvist, Pia ...
Historisk tidskrift (Stockholm),
2022, Letnik:
142, Številka:
4
Magazine Article
Recenzirano
En central del av verksamheten vid nästan alla institutioner som bedriver undervisning och forskning i historia är att utbilda historielärare. Historiker av facket diskuterar emellertid sällan frågor ...om lärarutbildningens innehåll och uppläggning, utöver de som knyter an till specifika historievetenskapliga sakområden. Vad behöver framtida historielärare kunna, och hur skiljer det sig eventuellt från vad framtida historiker bör kunna? Hur förhåller sig ämnesstudier till ämnesdidaktik och utbildningsvetenskap? Svaren på den typen av frågor har stor betydelse inte bara för lärarutbildningen utan för universitetsämnet historia och dess utövare i stort. Hur ska vi som historiker förhålla oss till det?
Som en utgångspunkt för en sådan diskussion har en grupp historiker verksamma inom lärarutbildningen vid Göteborgs och Örebro universitet genomfört en inventering av historiedidaktiken i ämneslärarutbildningen vid tio av totalt sjutton svenska lärosäten där sådan utbildning med inriktning mot historia inom gymnasieskolan bedrivs idag. Med hjälp av publikt tillgänglig information och en enkät via epost till de ansvariga för utbildningarna har gruppen kartlagt historiedidaktiska kursmål och kurslitteratur, examensarbetenas inriktning och vem som undervisar i historiedidaktik. Medan det finns vissa gemensamma drag i hur målen för utbildningarna formuleras, visar genomgången på betydande variationer mellan lärosätena avseende kurslitteratur, examensarbeten och bemanning. Mot den bakgrunden diskuteras i denna idé- och debattartikel vad likheter och skillnader kan bero på samt om, och i så fall hur, det är ett problem att historielärarutbildningarna är så olika.
Many patients with chronic obstructive pulmonary disease or asthma experience difficulties in coordinating inhalation with pressurized metered-dose inhaler (pMDI) actuation. The use of a spacer ...device can improve drug delivery in these patients. The aim of this study was to establish the relative bioavailability of single doses of Symbicort® (budesonide/formoterol) pMDI 160/4.5 μg/actuation (2 actuations) used with and without a spacer device. In addition, an in vitro study was conducted to characterize performance of the inhaler when used in conjunction with a spacer device.
A Phase I, randomized, open-label, single-dose, single-center, crossover study in 50 healthy volunteers (NCT02934607) assessed the relative bioavailability of single-dose Symbicort® pMDI 160/4.5 μg/actuation (2 actuations) with and without a spacer (AeroChamber Plus® Flow-Vu®). Inhaled doses were administered without or with activated charcoal (taken orally) to estimate total systemic exposure and exposure through the lung, respectively. The in vitro study characterized the effect of the spacer with respect to delivered dose, fine particle dose, and dose during simulated breathing of budesonide and formoterol.
In terms of total systemic exposure, use of the spacer increased the relative bioavailability determined by AUC(0-last) and Cmax by 68% (spacer:no spacer treatment ratio, 167.9%; 90% CI, 144.1 to 195.6) and 99% (ratio, 198.7%; 90% CI, 164.4 to 240.2) for budesonide, and 77% (ratio, 176.6%; 90% CI, 145.1 to 215.0) and 124% (ratio, 223.6%; 90% CI, 189.9 to 263.3) for formoterol, respectively, compared with pMDI alone. Similarly, the lung exposure of budesonide and formoterol increased (AUC(0-last) and Cmax by 146% ratio, 246.0%; 90% CI, 200.7 to 301.6 and 127% ratio, 226.5%; 90% CI, 186.4 to 275.4 for budesonide, and 173% ratio, 272.8%; 90% CI, 202.5 to 367.4 and 136% ratio, 236.2%; 90% CI, 192.6 to 289.6 for formoterol, respectively) when the pMDI was administered through the spacer.
When assessed by AUC(0-last) quartile without spacer, subjects in the lowest exposure quartile (indicating poor inhalation technique) with Symbicort® pMDI 160/4.5 μg/actuation (2 actuations) had markedly increased total systemic and lung exposure when the same dose was administered with the spacer. In contrast, for subjects in the highest exposure quartile with pMDI alone, total systemic and lung exposure of formoterol and budesonide was similar with and without the spacer.
In the in vitro study, the fine particle dose (<5 μm) of both budesonide and formoterol from the spacer at delay time (i.e. pause period after actuation) = 0 s (instantaneous) after actuation was similar to the fine particle dose when not using the spacer. The delivered doses of budesonide and formoterol from the spacer were both lower compared with the doses administered without the spacer. There was also a decrease in delivered dose with increasing delay time.
The clinical study demonstrated that in subjects with poor inhalation technique the use of the AeroChamber Plus® Flow-Vu® spacer increased the bioavailability of Symbicort® pMDI to a level observed in subjects with good inhalation technique without a spacer. The findings from the in vitro study support the fine particle dose characteristics of Symbicort® pMDI with the AeroChamber Plus® Flow-Vu® spacer.
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