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Sökning: WFRF:(Smirnova L.) > Karolinska Institutet

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  • Chalmers, J. R., et al. (författare)
  • Report from the fourth international consensus meeting to harmonize core outcome measures for atopic eczema/dermatitis clinical trials (HOME initiative)
  • 2016
  • Ingår i: British Journal of Dermatology. - : Oxford University Press (OUP). - 0007-0963 .- 1365-2133. ; 175:1, s. 69-79
  • Tidskriftsartikel (refereegranskat)abstract
    • This article is a report of the fourth meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in Malmo, Sweden on 23-24 April 2015 (HOME IV). The aim of the meeting was to achieve consensus over the preferred outcome instruments for measuring patient-reported symptoms and quality of life for the HOME core outcome set for atopic eczema (AE). Following presentations, which included data from systematic reviews, consensus discussions were held in a mixture of whole group and small group discussions. Small groups were allocated a priori to ensure representation of different stakeholders and countries. Decisions were voted on using electronic keypads. For the patient-reported symptoms, the group agreed by vote that itch, sleep loss, dryness, redness/inflamed skin and irritated skin were all considered essential aspects of AE symptoms. Many instruments for capturing patient-reported symptoms were discussed [ including the Patient-Oriented SCOring Atopic Dermatitis index, Patient-Oriented Eczema Measure (POEM), Self-Administered Eczema Area and Severity Index, Itch Severity Scale, Atopic Dermatitis Quickscore and the Nottingham Eczema Severity Score] and, by consensus, POEM was selected as the preferred instrument to measure patient-reported symptoms. Further work is needed to determine the reliability and measurement error of POEM. Further work is also required to establish the importance of pain/soreness and the importance of collecting information regarding the intensity of symptoms in addition to their frequency. Much of the discussion on quality of life concerned the Dermatology Life Quality Index and Quality of Life Index for Atopic Dermatitis; however, consensus on a preferred instrument for measuring this domain could not be reached. In summary, POEM is recommended as the HOME core outcome instrument for measuring AE symptoms.
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  • Isaguliants, M, et al. (författare)
  • Cellular Immune Response Induced by DNA Immunization of Mice with Drug Resistant Integrases of HIV-1 Clade A Offers Partial Protection against Growth and Metastatic Activity of Integrase-Expressing Adenocarcinoma Cells
  • 2021
  • Ingår i: Microorganisms. - : MDPI AG. - 2076-2607. ; 9:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Therapeutic DNA-vaccination against drug-resistant HIV-1 may hinder emergence and spread of drug-resistant HIV-1, allowing for longer successful antiretroviral treatment (ART) up-to relief of ART. We designed DNA-vaccines against drug-resistant HIV-1 based on consensus clade A integrase (IN) resistant to raltegravir: IN_in_r1 (L74M/E92Q/V151I/N155H/G163R) or IN_in_r2 (E138K/G140S/Q148K) carrying D64V abrogating IN activity. INs, overexpressed in mammalian cells from synthetic genes, were assessed for stability, route of proteolytic degradation, and ability to induce oxidative stress. Both were found safe in immunotoxicity tests in mice, with no inherent carcinogenicity: their expression did not enhance tumorigenic or metastatic potential of adenocarcinoma 4T1 cells. DNA-immunization of mice with INs induced potent multicytokine T-cell response mainly against aa 209–239, and moderate IgG response cross-recognizing diverse IN variants. DNA-immunization with IN_in_r1 protected 60% of mice from challenge with 4Tlluc2 cells expressing non-mutated IN, while DNA-immunization with IN_in_r2 protected only 20% of mice, although tumor cells expressed IN matching the immunogen. Tumor size inversely correlated with IN-specific IFN-γ/IL-2 T-cell response. IN-expressing tumors displayed compromised metastatic activity restricted to lungs with reduced metastases size. Protective potential of IN immunogens relied on their immunogenicity for CD8+ T-cells, dependent on proteasomal processing and low level of oxidative stress.
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  • Smirnova, IS, et al. (författare)
  • Hepatitis C virus core protein transforms murine fibroblasts by promoting genomic instability
  • 2006
  • Ingår i: Cellular oncology : the official journal of the International Society for Cellular Oncology. - : Hindawi Limited. - 1570-5870. ; 28:4, s. 177-190
  • Tidskriftsartikel (refereegranskat)abstract
    • The oncogenic potential of hepatitis C virus (HCV) core protein has been demonstrated, but the precise mechanism of cell transformation triggered by HCV core is still unclear. This study shows that constitutive expression of HCV core protein (core) in NIH 3T3 murine fibroblasts triggers malignant transformation. At the preneoplastic stage, clones that expressed HCV core constitutively demonstrated genomic instability seen as disruption of the mitotic spindle cell checkpoint leading to increased ploidy. Transformation was completed by the loss of DNA and resistance to apoptosis induced by serum starvation. Simultaneously, cells acquired a capacity for anchorage independent growth and absence of contact inhibition. Inoculation of these transformed cells into severe combined immune deficiency (SCID) mice led to formation of solid core-expressing tumors. Transformation and tumorigenicity of core-expressing cell lines coincided with a 5- to 10-fold repression of endogenous p53 transactivation. Thus, long-term HCV core expression alone is sufficient for complete transformation of immortal fibroblasts that can then induce tumors in a susceptible host. This data suggests that malignant transformation by HCV core may occur through primary stress, induction of genomic instability, and further HCV core-induced rescue of surviving mutated cells.
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  • Smirnova, Jevgenija, 1988-, et al. (författare)
  • Atopic dermatitis, educational attainment and psychological functioning : a national cohort study
  • 2019
  • Ingår i: British Journal of Dermatology. - : Blackwell Science Ltd.. - 0007-0963 .- 1365-2133. ; 180:3, s. 559-564
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Atopic dermatitis (AD) might adversely affect academic performance, possibly through influences on psychological functioning such as stress resilience.OBJECTIVES: To investigate the association of atopic dermatitis with stress resilience, cognitive function and educational attainment.METHODS: We used data from a national cohort of men who underwent a military conscription examination at ages 17 to 20 years in Sweden between 1969 and 1976. All potential conscripts met a physician who assessed current or previous history of AD. Stress resilience was measured by a psychologist using a semi-structured interview. The conscription assessment included a written cognitive function test. Highest level of achieved education was obtained through record linkage.RESULTS: The study population included 234 715 men, 1 673 (0·7%) had an AD diagnosis. AD was associated with a greater risk of low stress resilience (adjusted relative risk ratio (RRR) 1·60; 95% confidence interval 1·38 to 1·86). AD was associated with higher cognitive function (b coefficient 0·15; 0·05 to 0·24) and higher educational level (RRR 1·29; 1·13 to 1·47) but adjustment for socioeconomic characteristics of the family of origin attenuated the magnitude of the associations and eliminated statistical significance (b coefficient 0·06; -0·03 to 0·15) and (RRR 1·16; 1·00 to 1·35).CONCLUSIONS: Swedish males with AD had lower stress resilience in late adolescence but did not have lower cognitive function or poorer educational attainment. The lower stress resilience associated with AD is consistent with an increased risk of possible long-term adverse health outcomes.
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