| 51. |
- Aryal, Umesh R., 1973, et al.
(författare)
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Perceived risks and benefits of cigarette smoking among Nepalese adolescents: a population-based cross-sectional study.
- 2013
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Ingår i: BMC public health. - : Springer Science and Business Media LLC. - 1471-2458. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The perceived risks and benefits of smoking may play an important role in determining adolescents' susceptibility to initiating smoking. Our study examined the perceived risks and benefits of smoking among adolescents who demonstrated susceptibility or non susceptibility to smoking initiation. METHODS: In October--November 2011, we conducted a population-based cross-sectional study in Jhaukhel and Duwakot Villages in Nepal. Located in the mid-hills of Bhaktapur District, 13 kilometers east of Kathmandu, Jhaukhel and Duwakot represent the prototypical urbanizing villages that surround Nepal's major urban centers, where young people have easy access to tobacco products and are influenced by advertising. Jhaukhel and Duwakot had a total population of 13,669, of which 15% were smokers. Trained enumerators used a semi-structured questionnaire to interview 352 randomly selected 14- to 16-year-old adolescents. The enumerators asked the adolescents to estimate their likelihood (0%--100%) of experiencing various smoking-related risks and benefits in a hypothetical scenario. RESULTS: Principal component analysis extracted four perceived risk and benefit components, excluding addiction risk: (i) physical risk I (lung cancer, heart disease, wrinkles, bad colds) ;(ii) physical risk II (bad cough, bad breath, trouble breathing);(iii) social risk (getting into trouble, smelling like an ashtray); and (iv) social benefit(looking cool, feeling relaxed, becoming popular, and feeling grown-up). The adjusted odds ratio of susceptibility increased 1.20-fold with each increased quartile in perception of physical Risk I. Susceptibility to smoking was 0.27- and 0.90-fold less among adolescents who provided the highest estimates of physical Risk II and social risk, respectively. Similarly, susceptibility was 2.16-fold greater among adolescents who provided the highest estimates of addiction risk. Physical risk I, addiction risk, and social benefits of cigarette smoking related positively, and physical risk II and social risk related negatively, with susceptibility to smoking. CONCLUSION: To discourage or prevent adolescents from initiating smoking, future intervention programs should focus on communicating not only the health risks but also the social and addiction risks as well as counteract the social benefits of smoking.
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| 52. |
- Asp, Julia, 1973, et al.
(författare)
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Comparison of human cardiac gene expression profiles in paired samples of right atrium and left ventricle collected in vivo
- 2012
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Ingår i: Physiological Genomics. - : American Physiological Society. - 1094-8341 .- 1531-2267. ; 44:1, s. 89-98
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Tidskriftsartikel (refereegranskat)abstract
- Studies of expressed genes in human heart provide insight into both physiological and pathophysiological mechanisms. This is of importance for extended understanding of cardiac function as well as development of new therapeutic drugs. Heart tissue for gene expression studies is generally hard to obtain, particularly from the ventricles. Since different parts of the heart have different functions, expression profiles should likely differ between these parts. The aim of the study was therefore to compare the global gene expression in cardiac tissue from the more accessible auricula of the right atrium to expression in tissue from the left ventricle. Tissue samples were collected from five men undergoing aortic valve replacement or coronary artery bypass grafting. Global gene expression analysis identified 542 genes as differentially expressed between the samples extracted from these two locations, corresponding to similar to 2% of the genes covered by the microarray; 416 genes were identified as abundantly expressed in right atrium, and 126 genes were abundantly expressed in left ventricle. Further analysis of the differentially expressed genes according to available annotations, information from curated pathways and known protein interactions, showed that genes with higher expression in the ventricle were mainly associated with contractile work of the heart. Transcription in biopsies from the auricula of the right atrium on the other hand indicated a wider area of functions, including immunity and defense. In conclusion, our results suggest that biopsies from the auricula of the right atrium may be suitable for various genetic studies, but not studies directly related to muscle work.
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| 53. |
- Asplund, Annika, 1979-, et al.
(författare)
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One Standardized Differentiation Procedure Robustly Generates Homogenous Hepatocyte Cultures Displaying Metabolic Diversity from a Large Panel of Human Pluripotent Stem Cells
- 2016
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Ingår i: Stem Cell Reviews and Reports. - : Springer Science and Business Media LLC. - 1550-8943 .- 1558-6804. ; 12:1, s. 90-104
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Tidskriftsartikel (refereegranskat)abstract
- Human hepatocytes display substantial functional inter-individual variation regarding drug metabolizing functions. In order to investigate if this diversity is mirrored in hepatocytes derived from different human pluripotent stem cell (hPSC) lines, we evaluated 25 hPSC lines originating from 24 different donors for hepatic differentiation and functionality. Homogenous hepatocyte cultures could be derived from all hPSC lines using one standardized differentiation procedure. To the best of our knowledge this is the first report of a standardized hepatic differentiation procedure that is generally applicable across a large panel of hPSC lines without any adaptations to individual lines. Importantly, with regard to functional aspects, such as Cytochrome P450 activities, we observed that hepatocytes derived from different hPSC lines displayed inter-individual variation characteristic for primary hepatocytes obtained from different donors, while these activities were highly reproducible between repeated experiments using the same line. Taken together, these data demonstrate the emerging possibility to compile panels of hPSC-derived hepatocytes of particular phenotypes/genotypes relevant for drug metabolism and toxicity studies. Moreover, these findings are of significance for applications within the regenerative medicine field, since our stringent differentiation procedure allows the derivation of homogenous hepatocyte cultures from multiple donors which is a prerequisite for the realization of future personalized stem cell based therapies.
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| 54. |
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| 55. |
- Awe, Julius Adebayo, et al.
(författare)
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Filtration-based enrichment of circulating tumor cells from all prostate cancer risk groups
- 2017
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Ingår i: Urologic Oncology-Seminars and Original Investigations. - : Elsevier BV. - 1078-1439 .- 1873-2496. ; 35:5, s. 300-309
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To combine circulating tumor cell (CTC) isolation by filtration and immunohistochemistry to investigate the presence of CTCs in low, intermediate, and high-risk prostate cancer (PCa). CTCs isolated from these risk groups stained positive for both cytokeratin and androgen receptors, but negative for CD45. Patients and methods: Blood samples from 41 biopsy confirmed patients with PCa at different clinical stages such as low, intermediate, and high risk were analyzed. The samples were processed with the ScreenCell filtration device and PCa CTCs were captured for all patients. The isolated CTCs were confirmed PCa CTCs by the presence of androgen receptors and cytokeratins 8, 18, and 19 that occurred in the absence of CD45 positivity. PCa CTC nuclear sizes were measured using the TeloView program. Results: The filtration-based isolation method used permitted the measurement of the average nuclear size of the captured CTCs. CTCs were identified by immunohistochemistry in low, intermediate, and high-risk groups of patients with PCa. Conclusion: CTCs may be found in all stages of PCa. These CTCs can be used to determine the level of genomic instability at any stage of PCa; this will, in the future, enable personalized patient management. (C) 2017 The Authors. Published by Elsevier Inc.
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| 56. |
- Awe, Julius Adebayo, et al.
(författare)
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Three-Dimensional Telomeric Analysis of Isolated Circulating Tumor Cells (CTCs) Defines CTC Subpopulations
- 2013
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Ingår i: Translational Oncology. - : Elsevier BV. - 1944-7124 .- 1936-5233. ; 6:1, s. 51-U184
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Tidskriftsartikel (refereegranskat)abstract
- Circulating tumor cells (CTCs) have been identified with the potential to serve as suitable biomarkers for tumor stage and progression, but the availability of effective isolation technique(s) coupled with detailed molecular characterization have been the challenges encountered in making CTCs clinically relevant. For the first time, we combined isolation of CTCs using the ScreenCell filtration technique with quantitative analysis of CTC telomeres by TeloView. This resulted in the identification and molecular characterization of different subpopulations of CTCs in the same patient. Three-dimensional (3D) telomeric analysis was carried out on isolated CTCs of 19 patients that consisted of four different tumor types, namely, prostate, colon, breast, melanoma, and one lung cancer cell line. With telomeric analysis of the filter-isolated CTCs, the level of chromosomal instability (CIN) of the CTCs can be determined. Our study shows that subpopulations of CTCs can be identified on the basis of their 3D telomeric properties.
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| 57. |
- Axelsson, Kristian F, et al.
(författare)
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Association Between Alendronate Use and Hip Fracture Risk in Older Patients Using Oral Prednisolone
- 2017
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Ingår i: Jama-Journal of the American Medical Association. - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 318:2, s. 146-155
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Oral glucocorticoid treatment increases fracture risk, and evidence is lacking regarding the efficacy of alendronate to protect against hip fracture in older patients using glucocorticoids. OBJECTIVE To investigate whether alendronate treatment in older patients using oral prednisolone is associated with decreased hip fracture risk and adverse effects. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study using a national database (N = 433 195) of patients aged 65 years or older undergoing a health evaluation (baseline) at Swedish health care facilities; 1802 patients who were prescribed alendronate after at least 3 months of oral prednisolone treatment (>= 5mg/d) were identified. Propensity score matching was used to select 1802 patients without alendronate use from 6076 patients taking prednisolone with the same dose and treatment time criteria. Follow-up occurred between January 2008 and December 2014. EXPOSURES Alendronate vs no alendronate use; no patients had previously taken alendronate at the time of prednisolone initiation. MAIN OUTCOMES AND MEASURES The primary outcome was incident hip fracture. RESULTS Of the 3604 included patients, the mean age was 79.9 (SD, 7.5) years, and 2524 (70%) were women. After a median follow-up of 1.32 years (interquartile range, 0.57-2.34 years), there were 27 hip fractures in the alendronate group and 73 in the no-alendronate group, corresponding to incidence rates of 9.5 (95% CI, 6.5-13.9) and 27.2 (95% CI, 21.6-34.2) fractures per 1000 person-years, with an absolute rate difference of -17.6 (95% CI, -24.8 to -10.4). The use of alendronate was associated with a lower risk of hip fracture in a multivariable-adjusted Cox model (hazard ratio, 0.35; 95% CI, 0.22-0.54). Alendronate treatment was not associated with increased risk of mild upper gastrointestinal tract symptoms (alendronate vs no alendronate, 15.6 [95% CI, 11.6-21.0] vs 12.9 [95% CI, 9.3-18.0] per 1000 person-years; P=.40) or peptic ulcers (10.9 [95% CI, 7.7-15.5] vs 11.4 [95% CI, 8.0-16.2] per 1000 person-years; P=.86). There were no cases of incident drug-induced osteonecrosis and only 1 case of femoral shaft fracture in each group. CONCLUSIONS AND RELEVANCE Among older patients using medium to high doses of prednisolone, alendronate treatment was associated with a significantly lower risk of hip fracture over a median of 1.32 years. Although the findings are limited by the observational study design and the small number of events, these results support the use of alendronate in this patient group.
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| 58. |
- Axelsson, K. F., et al.
(författare)
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Effectiveness of a minimal resource fracture liaison service
- 2016
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Ingår i: Osteoporosis International. - : Springer. - 0937-941X .- 1433-2965. ; 27:11, s. 3165-3175
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The purpose of this study was to investigate if a 2-year intervention with a minimal resource fracture liaison service (FLS) was associated with increased investigation and medical treatment and if treatment was related to reduced re-fracture risk.METHODS: The FLS started in 2013 using existing secretaries (without an FLS coordinator) at the emergency department and orthopaedic wards to identify risk patients. All patients older than 50 years of age with a fractured hip, vertebra, shoulder, wrist or pelvis were followed during 2013-2014 (n = 2713) and compared with their historic counterparts in 2011-2012 (n = 2616) at the same hospital. Re-fractures were X-ray verified. A time-dependent adjusted (for age, sex, previous fracture, index fracture type, prevalent treatment, comorbidity and secondary osteoporosis) Cox model was used.RESULTS: The minimal resource FLS increased the proportion of DXA-investigated patients after fracture from 7.6 to 39.6 % (p < 0.001) and the treatment rate after fracture from 12.6 to 31.8 %, which is well in line with FLS types using the conventional coordinator model. Treated patients had a 51 % lower risk of any re-fracture than untreated patients (HR 0.49, 95 % CI 0.37-0.65 p < 0.001).CONCLUSIONS: We found that our minimal resource FLS was effective in increasing investigation and treatment, in line with conventional coordinator-based services, and that treated patients had a 51 % reduced risk of new fractures, indicating that also non-coordinator based fracture liaison services can improve secondary prevention of fractures.
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| 59. |
- Axelsson, Kristian F, et al.
(författare)
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Fracture risk after gastric bypass surgery – a retrospective cohort study
- 2018
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Ingår i: Journal of Bone and Mineral Research. - : Wiley-Blackwell Publishing Inc.. - 0884-0431 .- 1523-4681. ; 33:12, s. 2122-2131
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Tidskriftsartikel (refereegranskat)abstract
- Gastric bypass surgery constitutes the most common and effective bariatric surgery to treat obesity. Gastric bypass leads to bone loss, but fracture risk following surgery has been insufficiently studied. Furthermore, the association between gastric bypass and fracture risk has not been studied in patients with diabetes, which is a risk factor for fracture and affected by surgery. In this retrospective cohort study using Swedish national databases, 38 971 obese patients undergoing gastric bypass were identified, 7758 with diabetes and 31 213 without. An equal amount of well-balanced controls were identified through multivariable 1:1 propensity score matching. The risk of fracture and fall injury was investigated using Cox proportional hazards and flexible parameter models. Fracture risk according to weight loss and degree of calcium and vitamin D supplementation one-year post- surgery was investigated. During a median follow-up time of 3.1 (IQR 1.7-4.6) years, gastric bypass was associated with increased risk of any fracture, in patients with and without diabetes using a multivariable Cox model (HR 1.26, 95% CI 1.05- 1.53 and HR 1.32, 95% CI 1.18-1.47, respectively). Using flexible parameter models, the fracture risk appeared to increase with time. The risk of fall injury without fracture was also increased after gastric bypass. Larger weight loss or poor calcium and vitamin D supplementation after surgery were not associated with increased fracture risk. In conclusion, gastric bypass surgery is associated with an increased fracture risk, which appears to be increasing with time and not associated with degree of weight loss or calcium and vitamin D supplementation following surgery. An increased risk of fall injury was seen after surgery, which could contribute to the increased fracture risk. This article is protected by copyright. All rights reserved.
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| 60. |
- Axelsson, K. F., et al.
(författare)
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Hip fracture risk and safety with alendronate treatment in the oldest-old
- 2017
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 282:6, s. 546-559
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Tidskriftsartikel (refereegranskat)abstract
- Background. There is high evidence for secondary prevention of fractures, including hip fracture, with alendronate treatment, but alendronate's efficacy to prevent hip fractures in the oldest-old (80 years old), the population with the highest fracture risk, has not been studied. Objective. To investigate whether alendronate treatment amongst the oldest-old with prior fracture was related to decreased hip fracture rate and sustained safety. Methods. Using a national database of men and women undergoing a fall risk assessment at a Swedish healthcare facility, we identified 90 795 patients who were 80 years or older and had a prior fracture. Propensity score matching (four to one) was then used to identify 7844 controls to 1961 alendronate-treated patients. The risk of incident hip fracture was investigated with Cox models and the interaction between age and treatment was investigated using an interaction term. Results. The case and control groups were well balanced in regard to age, sex, anthropometrics and comorbidity. Alendronate treatment was associated with a decreased risk of hip fracture in crude (hazard ratio (HR) 0.62 (0.49-0.79), P < 0.001) and multivariable models (HR 0.66 (0.51-0.86), P < 0.01). Alendronate was related to reduced mortality risk (HR 0.88 (0.82-0.95) but increased risk of mild upper gastrointestinal symptoms (UGI) (HR 1.58 (1.12-2.24). The alendronate association did not change with age for hip fractures or mild UGI. Conclusion. In old patients with prior fracture, alendronate treatment reduces the risk of hip fracture with sustained safety, indicating that this treatment should be considered in these high-risk patients.
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