| 1. |
- Astengo, Marco, et al.
(författare)
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Ability of noninvasive criteria to predict hemodynamically significant aortic obstruction in adults with coarctation of the aorta.
- 2017
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Ingår i: Congenital heart disease. - : Computers, Materials and Continua (Tech Science Press). - 1747-0803 .- 1747-079X. ; 12:2, s. 174-180
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Tidskriftsartikel (refereegranskat)abstract
- Coarctation of the aorta (CoA) is a common condition. Adult patients with newly diagnosed CoA and patients with recurring or residual CoA require evaluation of the severity of aortic obstruction. Cardiac catheterization is considered the gold standard for the evaluation of hemodynamically significant CoA. The European Society of Cardiology (ESC) Guidelines for the management of grown-up congenital heart disease (GUCH) include noninvasive criteria for identifying significant CoA. Our aim was to investigate the ability of the Class I and Class IIa ESC recommendations to identify significant CoA at cardiac catheterization.Sixty-six adult patients with native or recurrent CoA underwent diagnostic cardiac catheterization at the GUCH unit at the Sahlgrenska University Hospital in Gothenburg from October 1998 to November 2013. Clinical and imaging data, as well as data about cardiac catheterization were retrospectively collected from patient records.The Class I ESC recommendations predicted significant CoA with a sensitivity of 0.57, a specificity of 0.63, a positive predictive value of 0.67, and a negative predictive value of 0.53. The combination of Class I and Class IIa recommendations predicted significant CoA with a sensitivity of 0.75, a specificity of 0.42, a positive predictive value of 0.66 and a negative predictive value of 0.52.the noninvasive criteria proposed by the ESC guidelines to identify subjects with significant CoA performed poorly in our dataset. Further research is needed to develop more accurate, noninvasive criteria to evaluate CoA severity and thereby reduce the number of unnecessary cardiac catheterizations.
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| 2. |
- Ekblom Bak, Elin, 1981-, et al.
(författare)
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Accelerometer derived physical activity and subclinical coronary and carotid atherosclerosis : cross-sectional analyses in 22 703 middle-aged men and women in the SCAPIS study
- 2023
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 13:11
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim included investigation of the associations between sedentary (SED), low-intensity physical activity (LIPA), moderate-to-vigorous intensity PA (MVPA) and the prevalence of subclinical atherosclerosis in both coronaries and carotids and the estimated difference in prevalence by theoretical reallocation of time in different PA behaviours.DESIGN: Cross-sectional.SETTING: Multisite study at university hospitals.PARTICIPANTS: A total of 22 670 participants without cardiovascular disease (51% women, 57.4 years, SD 4.3) from the population-based Swedish CArdioPulmonary bioImage study were included. SED, LIPA and MVPA were assessed by hip-worn accelerometer.PRIMARY AND SECONDARY OUTCOMES: Any and significant subclinical coronary atherosclerosis (CA), Coronary Artery Calcium Score (CACS) and carotid atherosclerosis (CarA) were derived from imaging data from coronary CT angiography and carotid ultrasound.RESULTS: High daily SED (>70% ≈10.5 hours/day) associated with a higher OR 1.44 (95% CI 1.09 to 1.91), for significant CA, and with lower OR 0.77 (95% CI 0.63 to 0.95), for significant CarA. High LIPA (>55% ≈8 hours/day) associated with lower OR for significant CA 0.70 (95% CI 0.51 to 0.96), and CACS, 0.71 (95% CI 0.51 to 0.97), but with higher OR for CarA 1.41 (95% CI 1.12 to 1.76). MVPA above reference level, >2% ≈20 min/day, associated with lower OR for significant CA (OR range 0.61-0.67), CACS (OR range 0.71-0.75) and CarA (OR range 0.72-0.79). Theoretical replacement of 30 min of SED into an equal amount of MVPA associated with lower OR for significant CA, especially in participants with high SED 0.84 (95% CI 0.76 to 0.96) or low MVPA 0.51 (0.36 to 0.73).CONCLUSIONS: MVPA was associated with a lower risk for significant atherosclerosis in both coronaries and carotids, while the association varied in strength and direction for SED and LIPA, respectively. If causal, clinical implications include avoiding high levels of daily SED and low levels of MVPA to reduce the risk of developing significant subclinical atherosclerosis.
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| 3. |
- Gad, Helge, et al.
(författare)
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MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
- 2014
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
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Tidskriftsartikel (refereegranskat)abstract
- Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
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