| 1. |
- Söderström, A, et al.
(författare)
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A large Escherichia coli O157 outbreak in Sweden associated with locally produced lettuce.
- 2008
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Ingår i: Foodborne pathogens and disease. - : Mary Ann Liebert Inc. - 1556-7125 .- 1535-3141. ; 5:3, s. 339-49
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Tidskriftsartikel (refereegranskat)abstract
- In 2005 a large outbreak of verotoxin-producing Escherichia coli (VTEC) occurred in Sweden. Cases were interviewed and cohort and case-control studies were conducted. Microbiological investigations were performed using polymerase chain reaction (PCR) to detect the Shiga-like toxin (Stx) genes followed by cultivation and pulsed-field gel electrophoresis. A total of 135 cases were recorded, including 11 cases of hemolytic uremic syndrome. The epidemiological investigations implicated lettuce as the most likely source of the outbreak, with an OR of 13.0 (CI 2.94-57.5) in the case-control study. The lettuce was irrigated by water from a small stream, and water samples were positive for Stx 2 by PCR. The identical VTEC O157 Stx 2 positive strain was isolated from the cases and in cattle at a farm upstream from the irrigation point. An active surveillance and reporting system was crucial and cooperation between all involved parties was essential for quickly identifying the cause of this outbreak. Handling of fresh greens from farm to table must be improved to minimize the risk of contamination.
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| 2. |
- Clavero, AL, et al.
(författare)
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MDM2 inhibitors, nutlin-3a and navtemadelin, retain efficacy in human and mouse cancer cells cultured in hypoxia
- 2023
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 13:1, s. 4583-
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Tidskriftsartikel (refereegranskat)abstract
- Activation of p53 by small molecule MDM2 inhibitors can induce cell cycle arrest or death in p53 wildtype cancer cells. However, cancer cells exposed to hypoxia can develop resistance to other small molecules, such as chemotherapies, that activate p53. Here, we evaluated whether hypoxia could render cancer cells insensitive to two MDM2 inhibitors with different potencies, nutlin-3a and navtemadlin. Inhibitor efficacy and potency were evaluated under short-term hypoxic conditions in human and mouse cancer cells expressing different p53 genotypes (wild-type, mutant, or null). Treatment of wild-type p53 cancer cells with MDM2 inhibitors reduced cell growth by > 75% in hypoxia through activation of the p53–p21 signaling pathway; no inhibitor-induced growth reduction was observed in hypoxic mutant or null p53 cells except at very high concentrations. The concentration of inhibitors needed to induce the maximal p53 response was not significantly different in hypoxia compared to normoxia. However, inhibitor efficacy varied by species and by cell line, with stronger effects at lower concentrations observed in human cell lines than in mouse cell lines grown as 2D and 3D cultures. Together, these results indicate that MDM2 inhibitors retain efficacy in hypoxia, suggesting they could be useful for targeting acutely hypoxic cancer cells.
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| 3. |
- Lerma Clavero, A, et al.
(författare)
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MDM2 inhibitors, nutlin-3a and navtemadelin, retain efficacy in human and mouse cancer cells cultured in hypoxia
- 2023
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 13:1, s. 4583-
-
Tidskriftsartikel (refereegranskat)abstract
- Activation of p53 by small molecule MDM2 inhibitors can induce cell cycle arrest or death in p53 wildtype cancer cells. However, cancer cells exposed to hypoxia can develop resistance to other small molecules, such as chemotherapies, that activate p53. Here, we evaluated whether hypoxia could render cancer cells insensitive to two MDM2 inhibitors with different potencies, nutlin-3a and navtemadlin. Inhibitor efficacy and potency were evaluated under short-term hypoxic conditions in human and mouse cancer cells expressing different p53 genotypes (wild-type, mutant, or null). Treatment of wild-type p53 cancer cells with MDM2 inhibitors reduced cell growth by > 75% in hypoxia through activation of the p53–p21 signaling pathway; no inhibitor-induced growth reduction was observed in hypoxic mutant or null p53 cells except at very high concentrations. The concentration of inhibitors needed to induce the maximal p53 response was not significantly different in hypoxia compared to normoxia. However, inhibitor efficacy varied by species and by cell line, with stronger effects at lower concentrations observed in human cell lines than in mouse cell lines grown as 2D and 3D cultures. Together, these results indicate that MDM2 inhibitors retain efficacy in hypoxia, suggesting they could be useful for targeting acutely hypoxic cancer cells.
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| 4. |
- Osbjer, Kristina, et al.
(författare)
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Risk factors associated with Campylobacter detected by PCR in humans and animals in rural Cambodia
- 2016
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Ingår i: Epidemiology and Infection. - 0950-2688 .- 1469-4409. ; 144:14, s. 2979-2988
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Tidskriftsartikel (refereegranskat)abstract
- Campylobacter are worldwide-occurring zoonotic bacteria, with the species Campylobacter jejuni and C. coli commonly associated with diarrhoea in children in low-income countries. In this cross-sectional study, the prevalence of C. jejuni and C. coli in human and livestock faecal samples was detected by PCR and zoonotic risk factors associated with human Campylobacter positivity were identified. In total 681 humans and 753 livestock (chickens, ducks, pigs, cattle) from 269 households were sampled. Children aged < 16 years were more frequently Campylobacter positive (19%) than adults (8%) and multilevel logistic models revealed that human C. jejuni positivity was associated with the following household practices: home-slaughtering [odds ratio (OR) 2.4, P = 0.01], allowing animals access to sleeping and food preparation areas (OR 2.8, P = 0.02), and eating undercooked meat (OR 6.6, P = 0.05), while frequent consumption of beef was protective (OR 0.9, P = 0.05). Associations were stronger for home-slaughtering (OR 4.9, P = 0.004) with C. jejuni infection in children only. Campylobacter was highly prevalent in pigs (72%) and chickens (56%) and risk factors associated with human Campylobacter positivity were identified throughout the meat production chain. The findings underline the importance of studying source attributions throughout the production chain and the need for upgraded understanding of Campylobacter epidemiology in low-income countries.
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