| 1. |
- Santangelo, James S., et al.
(författare)
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Global urban environmental change drives adaptation in white clover
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375
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Tidskriftsartikel (refereegranskat)abstract
- Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural dines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale.
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| 2. |
- Iacopetta, B, et al.
(författare)
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Functional categories of TP53 mutation in colorectal cancer: results of an International Collaborative Study.
- 2006
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Ingår i: Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. - : Elsevier BV. - 0923-7534. ; 17:5, s. 842-7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Loss of TP53 function through gene mutation is a critical event in the development and progression of many tumour types including colorectal cancer (CRC). In vitro studies have found considerable heterogeneity amongst different TP53 mutants in terms of their transactivating abilities. The aim of this work was to evaluate whether TP53 mutations classified as functionally inactive (< or=20% of wildtype transactivation ability) had different prognostic and predictive values in CRC compared with mutations that retained significant activity. MATERIALS AND METHODS: TP53 mutations within a large, international database of CRC (n = 3583) were classified according to functional status for transactivation. RESULTS: Inactive TP53 mutations were found in 29% of all CRCs and were more frequent in rectal (32%) than proximal colon (22%) tumours (P < 0.001). Higher frequencies of inactive TP53 mutations were also seen in advanced stage tumours (P = 0.0003) and in tumours with the poor prognostic features of vascular (P = 0.006) and lymphatic invasion (P = 0.002). Inactive TP53 mutations were associated with significantly worse outcome only in patients with Dukes' stage D tumours (RR = 1.71, 95%CI 1.25-2.33, P < 0.001). Patients with Dukes' C stage tumours appeared to gain a survival benefit from 5-fluorouracil-based chemotherapy regardless of TP53 functional status for transactivation ability. CONCLUSIONS: Mutations that inactivate the transactivational ability of TP53 are more frequent in advanced CRC and are associated with worse prognosis in this stage of disease.
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| 3. |
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| 4. |
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| 5. |
- Altenburger, A., et al.
(författare)
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Dimorphism in cryptophytes—The case of Teleaulax amphioxeia/Plagioselmis prolonga and its ecological implications
- 2020
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 6:37
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Tidskriftsartikel (refereegranskat)abstract
- Growing evidence suggests that sexual reproduction might be common in unicellular organisms, but observations are sparse. Limited knowledge of sexual reproduction constrains understanding of protist ecology. Although Teleaulax amphioxeia and Plagioselmis prolonga are common marine cryptophytes worldwide, and are also important plastid donors for some kleptoplastic ciliates and dinoflagellates, the ecology and development of these protists are poorly known. We demonstrate that P. prolonga is the haploid form of the diploid T. amphioxeia and describe the seasonal dynamics of these two life stages. The diploid T. amphioxeia dominates during periods of high dissolved inorganic nitrogen (DIN) and low irradiance, temperature, and grazing (winter and early spring), whereas the haploid P. prolonga becomes more abundant during the summer, when DIN is low and irradiance, temperature, and grazing are high. Dimorphic sexual life cycles might explain the success of this species by fostering high genetic diversity and enabling endurance in adverse conditions.
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| 6. |
- Gelin, Johan, 1948, et al.
(författare)
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The role of the adrenals in the acute phase response to interleukin-1 and tumor necrosis factor-alpha.
- 1993
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Ingår i: The Journal of surgical research. - 0022-4804. ; 54:1, s. 70-8
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to investigate the role of the adrenals, particularly the glucocorticoids, in the acute phase response following daily injections for 5 days of recombinant human interleukin-1 alpha,beta and tumor necrosis factor-alpha (TNF alpha). Adult weight-stable freely fed or pair-fed (to cytokine-injected mice) mice (C57Bl/6J) with and without adrenals were used. Adrenalectomized animals showed a sensitivity to both IL-1 alpha and -1 beta (40 ng IL-1/day) greater than 10-fold higher than that of normal mice (420 ng IL-1/day) in regard to mortality and anorexia. Microscopic examination of tissue specimens from adrenalectomized IL-1 alpha,beta-injected mice did not reveal any histologic alterations in lung, kidney, liver, brain, or gastrointestinal tract to explain the mortality. This mortality was not prevented by physiologic replacement doses of hydrocortisone (10-20 micrograms/day); however, a pharmacological dose of 2.5 mg hydrocortisone/day abolished completely the increased toxicity to IL-1 alpha,beta and the anorectic response to IL-1 alpha,beta and TNF alpha. Increased toxicity (mortality) was not observed in adrenalectomized animals with TNF alpha at the dose interval used (450 ng TNF alpha/day and lower). The hepatic acute phase response (liver weight and RNA and liver protein content) was increased by both IL-1 alpha,beta and TNF alpha in a glucocorticoid-independent way. The cytokine-induced alterations of plasma concentrations of acute phase proteins (serum amyloid P, transferrin, complement C3) were significantly dependent on glucocorticoids, while the decline in plasma albumin was not.(ABSTRACT TRUNCATED AT 250 WORDS)
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| 7. |
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| 8. |
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| 9. |
- Altman, D, et al.
(författare)
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Risk of renal cell carcinoma after hysterectomy
- 2010
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Ingår i: Archives of internal medicine. - : American Medical Association (AMA). - 1538-3679 .- 0003-9926. ; 170:22, s. 2011-2016
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Tidskriftsartikel (refereegranskat)
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| 10. |
- Altman, D., et al.
(författare)
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Somatic Comorbidity in Women with Overactive Bladder Syndrome
- 2016
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Ingår i: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 196:2, s. 473-477
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: We explore the influence of co-occurring somatic illnesses on prevalent overactive bladder in women of premenopausal age. Materials and Methods: Data for the present study were derived from a nationwide survey on complex diseases among all twins in the Swedish Twin Registry born 1959 to 1985. The present study was limited to female twins participating in the survey (12,850). Generalized estimating equations were used to estimate odds ratios with 95% CIs. Environmental and genetic influences were assessed in co-twin control analysis. Results: Generalized estimating equations analysis showed a significant association between overactive bladder and migraine (OR 1.34, 95% CI 1.15-1.57), fibromyalgia (1.83, 1.54-2.18), chronic fatigue (1.81, 1.49-2.19) and eating disorders (1.56, 1.24-1.96). There was also a significant association with allergic disorders including asthma (1.24, 1.01-1.52) and eczema (1.22, 1.04-1.43). Among reproductive disorders, urinary tract infections (1.60, 1.40-1.84), dysmenorrhea (1.53, 1.33-1.76) and pelvic pain (1.60, 1.31-1.94) showed the strongest association with overactive bladder. Results from co-twin control analysis indicated that the significant associations observed in generalized estimating equations analysis were influenced by environmental and genetic factors without a common pathway model. Conclusions: Our results suggest a multifactorial and complex pathogenesis of overactive bladder in which associations between various somatic illnesses and overactive bladder may be affected by environmental and genetic factors.
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| 11. |
- Altman, Daniel, et al.
(författare)
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The genetic and environmental contribution to the occurrence of bladder pain syndrome: an empirical approach in a nationwide population sample.
- 2011
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Ingår i: European urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 59:2, s. 280-5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aetiology of bladder pain syndrome (BPS) remains poorly understood, and a number of pathogenic mechanisms have been proposed. The importance of genetic factors for BPS is receiving growing attention, but data so far are of a preliminary nature. OBJECTIVE: To empirically assess the genetic and environmental contribution to BPS in a population-based sample of twins. DESIGN, SETTING, AND PARTICIPANTS: The study included >25 000 twins born between 1959 and 1985. Individuals with BPS were identified using latent class cluster analysis (LCCA) based on self-reported symptoms from a nationwide screening for complex diseases in the Swedish Twin Registry. By comparing monozygotic and dizygotic twins, we estimated twin similarity and the relative proportions of phenotypic variance resulting from genetic and environmental factors. MEASUREMENTS: Twin similarity was measured. RESULTS AND LIMITATIONS: The LCCA yielded an overall BPS prevalence of 1.1% and 2.4% for males and females, respectively. In males, the contribution of genetic effects to BPS could not be assessed because of the small number of concordant twin pairs. In women, twin similarity estimates indicated a genetic component for the aetiology of BPS, but genetic factors contributed less than one-third of the total variation in susceptibility to BPS. Nonshared environmental factors accounted for more than two-thirds of the variance, whereas early nongenetic factors shared within the family were of little or no consequence to the risk of developing BPS later in life. Use of self-reported symptoms to define the disease phenotype is a limitation of the study. CONCLUSIONS: The influence of environmental factors in the development of BPS in women is substantial, whereas genetic influences are of only modest importance for the possibility of developing the disease.
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| 12. |
- Beckley, Amber L., et al.
(författare)
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Association of height and violent criminality : results from a Swedish total population study
- 2014
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 43:3, s. 835-842
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Tidskriftsartikel (refereegranskat)abstract
- Background: Violent criminality is at least moderately heritable, but the mechanisms behind this remain largely unexplained. Height, a highly heritable trait, may be involved but no study has estimated the effect of height on crime while simultaneously accounting for important demographic, biological and other heritable confounders. Methods: We linked nationwide, longitudinal registers for 760 000 men who underwent mandatory military conscription from 1980 through 1992 in Sweden, to assess the association between height and being convicted of a violent crime. We used Cox proportional hazard modelling and controlled for three types of potential confounders: physical characteristics, childhood demographics and general cognitive ability (intelligence). Results: In unadjusted analyses, height had a moderate negative relationship to violent crime; the shortest of men were twice as likely to be convicted of a violent crime as the tallest. However, when simultaneously controlling for all measured confounders, height was weakly and positively related to violent crime. Intelligence had the individually strongest mitigating effect on the height-crime relationship. Conclusions: Although shorter stature was associated with increased risk of violent offending, our analyses strongly suggested that this relationship was explained by intelligence and other confounding factors. Hence, it is unlikely that height, a highly heritable physical characteristic, accounts for much of the unexplained heritability of violent criminality.
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| 13. |
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| 14. |
- Bryzgalova, G, et al.
(författare)
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Mechanisms of antidiabetogenic and body weight-lowering effects of estrogen in high-fat diet-fed mice
- 2008
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Ingår i: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 295:4, s. E904-E912
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Tidskriftsartikel (refereegranskat)abstract
- The high-fat diet (HFD)-fed mouse is a model of obesity, impaired glucose tolerance, and insulin resistance. The main objective of this study was to elucidate the molecular mechanisms underlying the antidiabetogenic and weight-lowering effects of 17β-estradiol (E2) in this mouse model. C57BL/6 female mice (8 wk old) were fed on a HFD for 10 mo. E2, given daily (50 μg/kg sc) during the last month of feeding, decreased body weight and markedly improved glucose tolerance and insulin sensitivity. Plasma levels of insulin, leptin, resistin, and adiponectin were decreased. We demonstrated that E2treatment decreased the expression of genes encoding resistin and leptin in white adipose tissue (WAT), whereas adiponectin expression was unchanged. Furthermore, in WAT we demonstrated decreased expression levels of sterol regulatory element-binding protein 1c (SREBP1c) and its lipogenic target genes, such as fatty acid synthase and stearoyl-CoA desaturase 1 (SCD1). In the liver, the expression levels of transcription factors such as liver X receptor α and SREBP1c were not changed by E2treatment, but the expression of the key lipogenic gene SCD1 was reduced. This was accompanied by decreased hepatic triglyceride content. Importantly, E2decreased the hepatic expression of glucose-6-phosphatase (G-6-Pase). We conclude that E2treatment exerts antidiabetic and antiobesity effects in HFD mice and suggest that this is related to decreased expression of lipogenic genes in WAT and liver and suppression of hepatic expression of G-6-Pase. Decreased plasma levels of resistin probably also play an important role in this context.
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| 15. |
- Ericsson, Malin, et al.
(författare)
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Childhood social class and cognitive aging in the Swedish Adoption/Twin Study of Aging
- 2017
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 114:27, s. 7001-7006
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Tidskriftsartikel (refereegranskat)abstract
- In this report we analyzed genetically informative data to investigate within-person change and between-person differences in late-life cognitive abilities as a function of childhood social class. We used data from nine testing occasions spanning 28 y in the Swedish Adoption/Twin Study of Aging and parental social class based on the Swedish socioeconomic index. Cognitive ability included a general factor and the four domains of verbal, fluid, memory, and perceptual speed. Latent growth curve models of the longitudinal data tested whether level and change in cognitive performance differed as a function of childhood social class. Between-within twin-pair analyses were performed on twins reared apart to assess familial confounding. Childhood social class was significantly associated with mean-level cognitive performance at age 65 y, but not with rate of cognitive change. The association decreased in magnitude but remained significant after adjustments for level of education and the degree to which the rearing family was supportive toward education. A between-pair effect of childhood social class was significant in all cognitive domains, whereas within-pair estimates were attenuated, indicating genetic confounding. Thus, childhood social class is important for cognitive performance in adulthood on a population level, but the association is largely attributable to genetic influences.
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| 16. |
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| 17. |
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| 18. |
- Hammarsten, Peter, et al.
(författare)
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Immunoreactivity for prostate specific antigen and Ki67 differentiates subgroups of prostate cancer related to outcome
- 2019
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Ingår i: Modern Pathology. - : Elsevier BV. - 0893-3952 .- 1530-0285. ; 32, s. 1310-1319
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Tidskriftsartikel (refereegranskat)abstract
- Based on gene-expression profiles, prostate tumors can be subdivided into subtypes with different aggressiveness and response to treatment. We investigated if similar clinically relevant subgroups can be identified simply by the combination of two immunohistochemistry markers: one for tumor cell differentiation (prostate specific antigen, PSA) and one for proliferation (Ki67). This was analyzed in men with prostate cancer diagnosed at transurethral resection of the prostate 1975–1991 (n = 331) where the majority was managed by watchful waiting. Ki67 and PSA immunoreactivity was related to outcome and to tumor characteristics previously associated with prognosis. Increased Ki67 and decreased PSA were associated with poor outcome, and they provided independent prognostic information from Gleason score. A combinatory score for PSA and Ki67 immunoreactivity was produced using the median PSA and Ki67 levels as cut-off (for Ki67 the upper quartile was also evaluated) for differentiation into subgroups. Patients with PSA low/Ki67 high tumors showed higher Gleason score, more advanced tumor stage, and higher risk of prostate cancer death compared to other patients. Their tumor epithelial cells were often ERG positive and expressed higher levels of ErbB2, phosphorylated epidermal growth factor receptor (pEGF-R) and protein kinase B (pAkt), and their tumor stroma showed a reactive response with type 2 macrophage infiltration, high density of blood vessels and hyaluronic acid, and with reduced levels of caveolin-1, androgen receptors, and mast cells. In contrast, men with PSA high/Ki67 low tumors were characterized by low Gleason score, and the most favorable outcome amongst PSA/Ki67-defined subgroups. Men with PSA low/Ki67 low tumors showed clinical and tumor characteristics intermediate of the two groups above. A combinatory PSA/Ki67 immunoreactivity score identifies subgroups of prostate cancers with different epithelial and stroma phenotypes and highly different outcome but the clinical usefulness of this approach needs to be validated in other cohorts. © 2019, The Author(s).
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| 19. |
- Havland, Ida, et al.
(författare)
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The observed association between maternal anxiety and adolescent asthma : children of twin design suggest familial effects
- 2013
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Ingår i: PLoS One. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1932-6203. ; 42
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Previous studies indicate that maternal anxiety is associated with asthma in the adolescent child, but mechanisms are unclear. OBJECTIVE: To investigate the association between maternal anxiety and maternal, self- and register-based report of asthma in the adolescent child, and whether the association remains after control of familial confounding (shared environmental and genetic factors). METHOD: From the Twin and Offspring Study of Sweden, 1691 mothers (1058 twins) and their adolescent child were included. The association between maternal self-reported anxiety (Beck Anxiety Inventory (BAI) and Karolinska Scales of Personality (KSP) somatic or psychic anxiety) and asthma based on subjective (maternal or child report) or objective (register-based diagnosis and medication) measures were analysed using logistic regression. The children-of-twins design was used to explore whether genes or environment contribute to the association. RESULTS: Maternal BAI anxiety (OR 2.02, CI 1.15-3.55) was significantly associated with adolescent asthma reported by the mother. Maternal KSP somatic anxiety (OR 1.74, CI 1.04-2.91) and psychic anxiety (OR 1.74, CI 1.05-2.86) was significantly associated with breathlessness reported by the adolescent child. In contrast, maternal anxiety was not associated with increased risk for the register-based outcomes of asthma diagnosis or medication. The results remained also after adjusting for covariates and the children-of-twins analyses which indicate that the association was due to familial confounding. CONCLUSIONS: We found some associations between maternal anxiety and subjectively reported offspring asthma or breathlessness which may be due to familial effects. A likely candidate for explaining this familial confounding is heritable personality traits associated with both anxiety and subjective measures of asthma.
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| 20. |
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| 21. |
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| 22. |
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| 23. |
- Hyltander, Anders, 1954, et al.
(författare)
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Supportive nutrition on recovery of metabolism, nutritional state, health-related quality of life, and exercise capacity after major surgery: a randomized study
- 2005
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Ingår i: Clinical gastroenterology and hepatology. - 1542-3565. ; 3:5, s. 466-74
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: The aim of this study was to investigate whether specialized supportive enteral and parenteral feeding have superior effects compared to oral nutrition on recovery during long-term postoperative treatment of cancer patients with preoperative weight loss and reduced maximum exercise capacity. METHODS: One hundred twenty-six patients referred for resection of the esophagus (n = 48), stomach (n = 28), or pancreas (n = 50) were considered to be included before operation. Included patients (n = 80) received supportive enteral or parenteral nutrition postoperatively at home corresponding to 1000 kcal/d until the patients did not wish to continue with artificial nutrition for any reason. Patients randomized to oral nutrition only served as control subjects. Caloric intake, body composition (dual-energy x-ray absorptiometry), and respiratory gas exchanges at rest and during exercise were measured including health-related quality of life. RESULTS: Survival and hospital stay did not differ among the groups, whereas overall complications were higher on artificial nutrition (P < .05). Changes in resting energy expenditure and biochemical tests did not differ during follow-up among the groups. Body weight and whole body fat declined similarly over time in all groups (P < .005), whereas lean body mass was unchanged during follow-up compared to preoperative values. Maximum exercise capacity and maximum oxygen consumption were normalized within 6 months postoperatively in all groups. There was no difference in recovery of food intake among the groups. Parenteral feeding was associated with the highest rate of nutrition-related complications, whereas enteral feeding reduced quality of life most extensively. CONCLUSION: After major surgery, specialized supportive enteral and parenteral nutrition are not superior to oral nutrition only when guided by a dietitian.
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| 24. |
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| 25. |
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| 26. |
- Köhn, M., et al.
(författare)
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Medical yoga for patients with stress-related symptoms and diagnosis in primary health care : a randomized control trial
- 2013
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Ingår i: Evidence-based Complementary and Alternative Medicine. - New York, USA : Hindawi Publishing Corporation. - 1741-427X .- 1741-4288.
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Tidskriftsartikel (refereegranskat)abstract
- An increasing number of patients are suffering from stress-related symptoms and diagnoses. The purpose of this study was to evaluate the medical yoga treatment in patients with stress-related symptoms and diagnoses in primary health care. A randomized controlled study was performed at a primary health care centre in Sweden from March to June, 2011. Patients were randomly allocated to a control group receiving standard care or a yoga group treated with medical yoga for 1 hour, once a week, over a 12-week period in addition to the standard care. A total of 37 men and women, mean age of years were included. General stress level (measured using Perceived Stress Scale (PSS)), burnout (Shirom-Melamed Burnout Questionnaire (SMBQ)), anxiety and depression (Hospital Anxiety and Depression Scale (HADS)), insomnia severity (Insomnia Severity Index (ISI)), pain (visual analogue scale (VAS)), and overall health status (Euro Quality of Life VAS (EQ-VAS)) were measured before and after 12 weeks. Patients assigned to the Yoga group showed significantly greater improvements on measures of general stress level ( ), anxiety ( ), and overall health status ( ) compared to controls. Treatment with medical yoga is effective in reducing levels of stress and anxiety in patients with stress-related symptoms in primary health care.
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| 27. |
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| 28. |
- Liu, Bojing, et al.
(författare)
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β2-adrenoreceptor agonists, montelukast, and Parkinson's disease risk
- 2023
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Ingår i: Annals of Neurology. - : John Wiley & Sons. - 0364-5134 .- 1531-8249. ; 93:5, s. 1023-1028
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study was undertaken to examine the association between montelukast use, beta 2-adrenoreceptor (beta 2AR) agonist use, and later Parkinson disease (PD).Methods: We ascertained use of beta 2AR agonists (430,885 individuals) and montelukast (23,315 individuals) from July 1, 2005 to June 30, 2007, and followed 5,186,886 PD-free individuals from July 1, 2007 to December 31, 2013 for incident PD diagnosis. We estimated hazard ratios and 95% confidence intervals using Cox regressions.Results: We observed 16,383 PD cases during on average 6.1 years of follow-up. Overall, use of beta 2AR agonists and montelukast were not related to PD incidence. A 38% lower PD incidence was noted among high-dose montelukast users when restricted to PD registered as the primary diagnosis.Interpretation: Overall, our data do not support inverse associations between beta 2AR agonists, montelukast, and PD. The prospect of lower PD incidence with high-dose montelukast exposure warrants further investigation, especially with adjustment for high-quality data on smoking. ANN NEUROL 2023
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| 29. |
- Ljungdahl, M, et al.
(författare)
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Bacterial translocation in experimental shock is dependent on the strains in the intestinal flora.
- 2000
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 35, s. 389-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Enteric microorganisms are responsible for a significant proportion of post-surgical infections. Intestinal mucosal injury may permit translocation of bacteria and endotoxin. This study investigates translocation in peritonitis and ischemia/reperfusion by inoculating different bacterial species into the small intestine.METHODS: Twenty-five pigs were monitored hemodynamically and divided into three groups: controls (C), ischemia/reperfusion (I/R), and peritonitis (P). Intramucosal pH (pHi) was calculated tonometrically. A perfusion tube was positioned in the ileum for inoculation of the bacterial strains. In a first study period a non-pathogenic bacterium was used, whereas Escherichia coli strains with known ability to translocate were used in a second. Blood and mesenteric lymph nodes (MLNs) were obtained for bacterial culture and endotoxin analyses.RESULTS: Mesenteric arterial blood flow and pHi decreased in groups I/R and P. Endotoxin levels increased in these groups in period 1, whereas in period 2 an increase over time was only observed in group P. No bacterial translocation to blood or MLNs occurred in period 1. In period 2 bacteria translocated to MLNs in all animals, including controls. Translocation to central and/or mesenteric venous blood was found in all groups, but mainly in I/R and P. The incidence of mucosal injury was similar in the two periods.CONCLUSIONS: Since positive blood and MLN samples were only found in period 2, we conclude that translocation of bacteria seems to be more dependent on the presence of translocating strains in the intestinal bacterial flora than on the mucosal insult.
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| 30. |
- Lundholm, Kent, 1945, et al.
(författare)
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Insulin treatment in cancer cachexia: effects on survival, metabolism, and physical functioning
- 2007
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Ingår i: Clinical cancer research. - 1078-0432. ; 13:9, s. 2699-706
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The present study was designed to evaluate whether daily insulin treatment for weight-losing cancer patients attenuates the progression of cancer cachexia and improves metabolism and physical functioning in palliative care. EXPERIMENTAL DESIGN: One hundred and thirty-eight unselected patients with mainly advanced gastrointestinal malignancy were randomized to receive insulin (0.11 +/- 0.05 units/kg/d) plus best available palliative support [anti-inflammatory treatment (indomethacin), prevention of anemia (recombinant erythropoietin), and specialized nutritional care (oral supplements + home parenteral nutrition)] according to individual needs. Control patients received the best available palliative support according to the same principles. Health-related quality of life, food intake, resting energy expenditure, body composition, exercise capacity, metabolic efficiency during exercise, and spontaneous daily physical activity as well as blood tests were evaluated during follow-up (30-824 days) according to intention to treat. RESULTS: Patient characteristics at randomizations were almost identical in study and control groups. Insulin treatment for 193 +/- 139 days (mean +/- SD) significantly stimulated carbohydrate intake, decreased serum-free fatty acids, increased whole body fat, particularly in trunk and leg compartments, whereas fat-free lean tissue mass was unaffected. Insulin treatment improved metabolic efficiency during exercise, but did not increase maximum exercise capacity and spontaneous physical activity. Tumor markers in blood (CEA, CA-125, CA 19-9) did not indicate the stimulation of tumor growth by insulin; a conclusion also supported by improved survival of insulin-treated patients (P<0.03). CONCLUSION: Insulin is a significant metabolic treatment in multimodal palliation of weight-losing cancer patients.
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| 31. |
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| 33. |
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| 35. |
- Lundholm, L, et al.
(författare)
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The estrogen receptor {alpha}-selective agonist propyl pyrazole triol improves glucose tolerance in ob/ob mice; potential molecular mechanisms
- 2008
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Ingår i: Journal of Endocrinology. - 0022-0795 .- 1479-6805. ; 199:2, s. 275-286
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to validate the role of estrogen receptor alpha (ERalpha) signaling in the regulation of glucose metabolism, and to compare the molecular events upon treatment with the ERalpha-selective agonist propyl pyrazole triol (PPT) or 17beta-estradiol (E(2)) in ob/ob mice. Female ob/ob mice were treated with PPT, E(2) or vehicle for 7 or 30 days. Intraperitoneal glucose and insulin tolerance tests were performed, and insulin secretion was determined from isolated islets. Glucose uptake was assayed in isolated skeletal muscle and adipocytes. Gene expression profiling in the liver was performed using Affymetrix microarrays, and the expression of selected genes was studied by real-time PCR analysis. PPT and E(2) treatment improved glucose tolerance and insulin sensitivity. Fasting blood glucose levels decreased after 30 days of PPT and E(2) treatment. However, PPT and E(2) had no effect on insulin secretion from isolated islets. Basal and insulin-stimulated glucose uptake in skeletal muscle and adipose tissue were similar in PPT and vehicle-treated ob/ob mice. Hepatic lipid content was decreased after E(2) treatment. In the liver, treatment with E(2) and PPT increased and decreased the respective expression levels of the transcription factor signal transducer and activator of transcription 3, and of glucose-6-phosphatase. In summary, our data demonstrate that PPT exerts anti-diabetic effects, and these effects are mediated via ERalpha.
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| 36. |
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| 37. |
- Lundholm, Marie, et al.
(författare)
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Secreted Factors from Colorectal and Prostate Cancer Cells Skew the Immune Response in Opposite Directions
- 2015
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Macrophage infiltration has been associated with an improved prognosis in patients with colorectal cancer (CRC), but a poor prognosis in prostate cancer (PC) patients. In this study, the distribution and prognostic value of proinflammatory M1 macrophages (NOS2(+)) and immunosuppressive M2 macrophages (CD163(+)) was evaluated in a cohort of 234 PC patients. We found that macrophages infiltrating PC were mainly of an M2 type and correlated with a more aggressive tumor and poor patient prognosis. Furthermore, the M1/M2 ratio was significantly decreased in PC compared to CRC. Using in vitro cell culture experiments, we could show that factors secreted from CRC and PC cells induced macrophages of a proinflammatory or immunosuppressive phenotype, respectively. These macrophages differentially affected autologous T lymphocyte proliferation and activation. Consistent with this, CRC specimens were found to have higher degrees of infiltrating T-helper 1 cells and active cytotoxic T lymphocytes, while PC specimens displayed functionally inactive T cells. In conclusion, our results imply that tumour-secreted factors from cancers of different origin can drive macrophage differentiation in opposite directions and thereby regulate the organization of the anti-tumour immune response. Our findings suggest that reprogramming of macrophages could be an important tool in the development of new immunotherapeutic strategies.
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- Svanberg, Elisabeth, 1961, et al.
(författare)
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The role of the growth hormone/insulin-like growth factor I axis in stimulation of protein synthesis in skeletal muscles following oral refeeding.
- 1998
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Ingår i: Endocrinology. - 0013-7227. ; 139:12, s. 4906-10
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Tidskriftsartikel (refereegranskat)abstract
- The mechanisms behind stimulation of protein synthesis in skeletal muscles following oral feeding are not well understood. Previous research has not confirmed that insulin is a major factor behind this stimulation. In the present study we have used genetically altered mice, with either a lack of GH secretion due to a mutational gene inactivation [GH (-/-) dwarf, DW/JOrlBom-dw] or mice with a homozygous site-specific insertion mutation in the insulin-like growth factor-1 gene [IGF-I (m/m)], leading to a deficient IGF-I production. These gene knock-outs were used in comparison to their normal wild types for evaluation of the role that the GH/IGF-I axis may have in activation of nutritionally induced stimulation of protein synthesis in skeletal muscles during oral refeeding. Weight stable adult C57B16 mice served as an additional normal control group. Protein synthesis was measured by a modified flooding dose technique with radioactive L-[14C-U]phenylalanine incorporation into acid precipitated muscle proteins. Fractional protein synthesis in skeletal muscles after an overnight fast was comparable among C57B16 (0.076 +/- 0.009%/h), wild-type IGF-I(+/+) (0.061 +/- 0.008) and IGF-I(m/m) deficient mice (0.068 +/- 0.006%/h), whereas GH(-/-) incompetent mice had a lower fractional synthesis rate compared with GH(+/+) competent mice (0.045 +/- 0.006 vs. 0.068 +/- 0.007, P < 0.05). Refeeding with standard chow diet stimulated protein synthesis in muscles by more than 60% in all animal groups. This response was independent of circulating GH, total IGF-I concentrations in blood, as well as up-regulation of locally produced IGF-I messenger RNA (mRNA) in skeletal muscles.
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