| 1. |
- Ali, Imran, et al.
(författare)
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Cadmium-induced effects on cellular signaling pathways in the liver of transgenic estrogen reporter mice.
- 2012
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Ingår i: Toxicological Sciences. - : Oxford University Press (OUP). - 1096-6080 .- 1096-0929. ; 127:1, s. 66-75
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Tidskriftsartikel (refereegranskat)abstract
- Estrogen-like effects of cadmium (Cd) have been reported in several animal studies, and recent epidemiological findings suggest increased risk of hormone-dependent cancers after Cd exposure. The mechanisms underlying these effects are still under investigation. Our aim was to study the effects of Cd on cellular signaling pathways in vivo with special focus on estrogen signaling and to perform benchmark dose analysis on the effects. Transgenic adult ERE-luciferase male mice were exposed subcutaneously to 0.5-500 μg CdCl(2) per kg body weight (bw) or 17α-ethinylestradiol (EE2) for 3 days. These doses had no effects on organ and bw or testicular histology, indicating subtoxic exposure levels. The transgene luciferase, reporting genomic estrogen response, was significantly increased by EE2 but not by Cd. However, Cd significantly affected kinase phosphorylation and endogenous gene expression. Interestingly, gene expression changes displayed a traditional dose-response relationship, with benchmark dose levels for the expression of Mt1, Mt2, p53, c-fos, and Mdm2 being 92.9, 19.9, 7.6, 259, and 25.9 μg/kg bw, respectively, but changes in kinase phosphorylation were only detected at low exposure levels. Phosphorylation of Erk1/2 was significantly increased even in the lowest dose group, 0.5 μg/kg bw, rendering pErk1/2 a more sensitive sensor of exposure than changes in gene expression. Collectively, our data suggest that the effects triggered by Cd in vivo are markedly concentration dependent. Furthermore, we conclude that the estrogen-like effects of Cd are likely to result from a mechanism different from steroidal estrogens.
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| 2. |
- Berglund, Annika, et al.
(författare)
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Face Arm Speech Time Test use in the prehospital setting, better in the ambulance than in the emergency medical communication center
- 2014
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Ingår i: Cerebrovascular Diseases. - Basel, Switzerland : S. Karger. - 1015-9770 .- 1421-9786. ; 37:3, s. 212-216
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Prehospital identification of acute stroke increases the possibility of early treatment and good outcome. To increase identification of stroke, the Face Arm Speech Time (FAST) test was introduced in the Emergency Medical Communication Center (EMCC). This substudy aims to evaluate the implementation of the FAST test in the EMCC and the ambulance service.METHODS: The study was conducted in the region of Stockholm, Sweden during 6 months. The study population consisted of all calls to the EMCC concerning patients presenting at least one FAST symptom or a history/finding making the EMCC or ambulance personnel to suspect stroke within 6 h. Positive FAST was compared to diagnosis at discharge. Positive predictive values (PPV) for a stroke diagnosis at discharge were calculated.RESULTS: In all, 900 patients with a median age of 71 years were enrolled, 667 (74%) by the EMCC and 233 (26%) by the ambulances. At discharge, 472 patients (52%) were diagnosed with stroke/transient ischemic attack (TIA), 337 identified by the EMCC (71%) and 135 (29%) by the ambulances. The PPV for a discharge diagnosis of stroke/TIA was 51% (CI 47-54%) in EMCC-enrolled and 58% (CI 52-64%) in ambulance-enrolled patients. With a positive FAST the PPV of a correct stroke/TIA diagnosis increased to 56% (CI 52-61%) and 73% (CI 66-80%) in EMCC- and ambulance-enrolled patients, respectively. Positive FAST from EMCC was also found in 44% of patients with a nonstroke diagnosis at discharge. A stroke/TIA diagnosis at discharge but negative FAST was found in 58 and 27 patients enrolled by the EMCC and ambulances, respectively.CONCLUSIONS: The PPV of FAST is higher when used on the scene by ambulance than by EMCC. FAST may be a useful prehospital tool to identify stroke/TIA but has limitations as the test can be negative in true strokes, can be positive in nonstrokes, and FAST symptoms may be present but not identified in the emergency call. For the prehospital care situation better identification tools are needed.
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| 3. |
- Berglund, Annika, et al.
(författare)
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Higher prehospital priority level of stroke improves thrombolysis frequency and time to stroke unit : the Hyper Acute STroke Alarm (HASTA) study
- 2012
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Ingår i: Stroke. - New York : American Heart Association. - 0039-2499 .- 1524-4628. ; 43:10, s. 2666-2670
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Early initiated treatment of stroke increases the chances of a good recovery. This randomized controlled study evaluates how an increased priority level for patients with stroke, from level 2 to 1, from the Emergency Medical Communication Center influences thrombolysis frequency, time to stroke unit, and whether other medical emergencies reported negative consequences.METHODS: Patients aged 18 to 85 years in Stockholm, Sweden, with symptoms of stroke within 6 hours were randomized from the Emergency Medical Communication Center or emergency medical services to an intervention group, priority level 1, immediate call of an ambulance, or to a control group with standard priority level, that is, priority level 2 (within 30 minutes). Before study start, an educational program on identification of stroke and importance of early initiated treatment was directed to all medical dispatchers and ambulance and emergency department personnel.RESULTS: During 2008, 942 patients were randomized of which 53% (n=496) had a final stroke/transient ischemic attack diagnosis. Patients in the Emergency Medical Communication Center randomized intervention group reached the stroke unit 26 minutes earlier than the control group (P<0.001) after the emergency call. Thrombolysis was given to 24% of the patients in the intervention group compared with 10% of the control subjects (P<0.001). The higher priority level showed no negative effect on other critical ill patients requiring priority level 1 prehospital attention.CONCLUSIONS: This randomized study shows negligible harm to other medical emergencies, a significant increase in thrombolysis frequency, and a shorter time to the stroke unit for patients with stroke upgraded to priority level 1 from the Emergency Medical Communication Center and through the acute chain of stroke care.
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| 4. |
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| 5. |
- Berglund, Karin, 1967-, et al.
(författare)
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Engaged Sisters : studying the entrepreneurship and innovation support system from ‘within’
- 2013
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Konferensbidrag (refereegranskat)abstract
- Entrepreneurship and innovation support has grown into large institutions in a society that cherishes an enterprising culture. Individuals are encouraged to be entrepreneurial and innovative in general, and to start up their own companies in particular. To support individuals in their business creation processes, policy stresses the need of providing with measures. Together these measures comprise a support system, directed towards supporting new and established entrepreneurs. It has however been recognized that the entrepreneurship and innovation public support system is highly gendered, favoring men and male businesses, whilst programs targeting women put the onus on individual women to start and grow businesses. As well it has been recognized that the policy support system tends to exclude ‘othered’ groups rather than including them in enterprising activities. The subtext of entrepreneurship support points to how some people “are” entrepreneurs, whilst others need support in order to become more entrepreneurial. Hence, there is a need to change the support system of entrepreneurship and innovation since it tends to disempower rather than to empower ‘othered’ groups in society.“Sisters in Business” make up an organization of wo/men entrepreneurs who have joined forces to address this need. Their vision is that entrepreneurship should reflect the society at large. During the last year they have therefore taken several initiatives to make this happen and is today one of the support organizations in a medium sized Swedish town. In this paper three Sisters are working together with a researcher within this area. Together we have formed a group of “engaged sisters´”. In our dialogue the dichotomy between ‘practice’ and ‘theory’ have temporarily dissolved in favor of creating narratives, from episodes, experiences and the everyday life of sister´s, to illustrate how the support system works from ‘within’. This led us to questioning whether the ‘support system’ really is a support system, or something else? Furthermore, this insight made it apparent that there exists ‘other’ support system, tough concealed and silenced. Finally, suggestions are proposed for how ‘practitioners’ can work together with ‘academics’ to change the rules of the game.
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| 6. |
- Berglund, Karin, et al.
(författare)
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Transformation from entrepreneurship to entrepreneurships : creating alternatives?
- 2014
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- In this paper our ambition is to provide with theoretical and empirical inspiration for studying contemporary constitutions of entrepreneurship. In specific, we seek to highlight how the transformation from entrepreneurship into forms of entrepreneurships has unfolded on various arenas. This means tracing the interplay between criticism of (traditional) entrepreneurship and the outbreak and dissemination of alternative entrepreneurships. In specific, we focus on the positive connotations that come with the alternative forms, a goodness that lures behind each and every corner, to see what it shapes as well as what shape entrepreneurship takes. Even if entrepreneurship research does pay some interest to the changing conditions for entrepreneurship, it seldom links these to changes in conditions for people, organizations and societies.
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| 7. |
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| 8. |
- 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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| 9. |
- Herlitz, Johan, 1949, et al.
(författare)
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Early identification and delay to treatment in myocardial infarction and stroke: differences and similarities.
- 2010
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Ingår i: Scandinavian journal of trauma, resuscitation and emergency medicine. - : Springer Science and Business Media LLC. - 1757-7241. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- The two major complications of atherosclerosis are acute myocardial infarction (AMI) and acute ischemic stroke. Both are life-threatening conditions characterised by the abrupt cessation of blood flow to respective organs, resulting in an infarction. Depending on the extent of the infarction, loss of organ function varies considerably. In both conditions, it is possible to limit the extent of infarction with early intervention. In both conditions, minutes count. This article aims to describe differences and similarities with regard to the way patients, bystanders and health care providers act in the acute phase of the two diseases with the emphasis on the pre-hospital phase.
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| 10. |
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