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- Chatterjee, Neal A, et al.
(author)
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Increasing sex differences in the use of cardiac resynchronization therapy with or without implantable cardioverter-defibrillator
- 2017
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In: European Heart Journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 38:19, s. 1485-1494
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Journal article (peer-reviewed)abstract
- AIMS: Previous studies have identified sex disparities in the use of cardiac resynchronization therapy (CRT) and implantable cardioverter defibrillators (ICD), although the basis of underutilization in women remains poorly understood. The aim of this study was to assess sex differences in patterns of CRT use with our without ICD.METHODS AND RESULTS: In this cross-sectional study using the National Inpatient Sample database we identified 311 009 patients undergoing CRT implantation in the United States between 2006 and 2012. Demographic and clinical characteristics were compared between men and women undergoing CRT implantation, with special attention to clinical predictors of left ventricular reverse remodelling (CRT response, score range: 0-4) and reduced ICD efficacy (score range: 0-7). When compared to men, women undergoing CRT implantation were significantly more likely to have ≥ 3 predictors of CRT response (47.3 vs. 33.2%, P < 0.001) and less likely to have ≥3 predictors of reduced ICD efficacy (27.0 vs. 37.3%, P < 0.001). Despite this, men were significantly more likely to undergo CRT with ICD (CRT-D) as the type of CRT (88.6 vs. 80.1% of all CRT implants). Compared to those with the greatest likelihood of CRT response (score ≥ 3), those with the least likelihood of CRT response had a significant decreased odds of CRT-D implant (adj odds ratio 0.27 [0.24-0.31], P < 0.001), with a greater decreased odds in women compared to men (P, for sex interaction <0.001). The difference in the % of CRT-D implant in men vs. women increased over the study period (P, sex Δ time trend = 0.012).CONCLUSION: In this large, contemporary cohort, sex differences in CRT-D implantation were inversely related to predicted CRT efficacy and have increased over time. Future efforts to narrow the gap in CRT-D implantation in men and women may help better align device selection with those most likely to benefit.
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- Lindvall, Charlotta
(author)
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Molecular studies of acute myeloid leukemia and the telomerase reverse transcriptase gene
- 2002
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Doctoral thesis (other academic/artistic)abstract
- Multiple chromosome rearrangements (MCRs) are detected in approximately 10% of patients with acute myeloid leukemia (AML), and are associated with an adverse prognosis. Comprehensive analysis of the chromosome rearrangements in these complex karyotypes has previously been hampered by the limitations of conventional cytogenetic techniques such as G-banding. As a consequence, our knowledge concerning the genetic alterations in these malignancies is limited. We applied spectral karyotyping (SKY), comparative genomic hybridization (CGH) and cDNA microarrays to bone marrow cells from AML patients with MCRs in order to characterize these rearrangements on the genomic and transcriptional level. Using SKY and CGH we resolved 12 complex AML karyotypes, and also detected novel chromosome rearrangements. We showed that many of the deletions scored by G-banding harboured cryptic chromosome rearrangements. Ile majority were unbalanced translocations and most frequently resulted in chromosome loss of 5q, 7q and 17p, and chromosome gain of 11q. In addition, the SKY analysis revealed a number of balanced translocations that had not been described before. Some seem recurrent and may reflect novel fusion genes directly involved in leukemogenesis. (Paper I) The chimeric transcripts of one reciprocal translocation detected by SKY, a t(8;16)(p11;p13);(MOZCBP), was analyzed at the sequence level using RT-PCR. The resulting RT-PCR method could be diagnostically useful, since the detection of t(8;16) in AML has clinical ramifications and may be difficult to identify by chromosome banding alone. (Paper II) In order to investigate the transcriptional profiles of leukemic cells with MCRs we also developed and applied a high-density cDNA microarray assay. We showed that most of the chromosome rearrangements were manifested in aberrant gene expression profiles in a gene-dosage dependent manner. (Paper III) We also investigated the role of hTERT/telomerase in tumorigenesis and disease. Telomeres, which constitute the ends of chromosomes and are essential for genomic stability and integrity, are synthesized by a ribonucleoprotein reverse transcriptase called telomerase. Telomerase consists of an RNA template, a reverse transcriptase (hTERT) and telomerase associated proteins. Because hTERT/telomerase activation is critical for cellular immortalization and tumorigenesis we investigated the copy numbers of hTERT in human tumors and found that hTERT is a frequent target for DNA amplification. (Paper IV) Chri-du-Chat syndrome (CdCs) is one of the most common human deletion syndromes and results from a deletion of the distal part of chromosome arm 5p, where the hTERT gene is located. We showed that a heterozygous loss of hTERT is present in CdCs and that hTERT is limiting for telomere maintenance in humans. Therefore, CdCs might be used as a model to study hTERT regulation and telomerase biology in humans. (Paper V) Certain somatic cells can acquire an immortal phenotype by forced expression of hTERT/telomerase. Treatment with exogenous hTERT has been proposed as a cell-based therapy to allow indefinite expansion of normal human cells without damaging their genomes. However, using cDNA microarrays we showed that the gene expression profile of hTERT-immortalized fibroblasts (hTERT-BJ cells) is significantly different from that of normal mortal fibroblasts. One of the highly expressed genes in the hTERT-BJ cells encodes epiregulin and we found its expression was required to maintain the immortal phenotype. Given the significant difference in gene expression profiles between the normal and hTERT-immortalized fibroblasts and the dose relationship between epiregulin and tumorigenesis, we concluded that the use of hTERT for expansion of normal human cells for therapeutic purposes must be approached with great caution. (Paper VI)
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| 5. |
- Lindvall, Charlotta, 1968-
(author)
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The importance of stimulation in school for the well-being of gifted students
- 2023
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In: Konferens i pedagogiskt arbete, 2023. - Linköping : Linköping University Electronic Press. - 9789180752848 - 9789180752831 ; , s. 121-
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Conference paper (peer-reviewed)abstract
- Students who learn quickly and who have a complex way of thinking and analyzing do not always receive the support they need at school in Sweden (Skolinspektionen, 2022). At the same time, international research shows that prolonged lack of stimulation can lead to challenges such as those with neuropsychiatric disorders (Amend & Beljan, 2009) and can lead to school difficulties, such as problematic school absence (Gross, 2009).The purpose of this ongoing research is to find out whether wellbeing differs between the students identified by the school as gifted and the rest of the student population. There are such indications internationally (Casino-García et al., 2021), but no research has yet been done in Sweden to be able to establish that this is indeed the case.The study is part of a larger research project and based on a social constructivist theory with a salutogenic perspective. It has a quantitative approach, and the data collection includes Swedish municipalities that have initiatives aimed at potentially gifted students in grades 4–8. In Sweden, there is no general aptitude testing of students, so to be able to identify the right target group, an estimation tool developed, not a guarantee of giftedness but to give an indication, will be used (Nissen, 2019).Through surveys based on previously published survey tools the results will illustrate whether there is any difference between the well-being of gifted students compared to the wider population. This provides an empirical basis to subsequently explore the effects of school- based interventions, such as acceleration, enrichment, and mentoring, and in turn see whether mental health improves if students are offered such support.ReferencesAmend, E. R., & Beljan, P. (2009). The antecedents of misdiagnosis: When normal behaviors of gifted children are misinterpreted as pathological. Gifted Education International, 25(2), 131–143. https://doi.org/10.1177/026142940902500204Casino-García AM, Llopis-Bueno MJ, Gómez-Vivo MG, JuanGrau A, Shuali-Trachtenberg T and Llinares-Insa LI (2021) “Developing Capabilities”. Inclusive Extracurricular Enrichment Programs to Improve the Well-Being of Gifted Adolescents. Front. Psychol. 12:731591. doi: 10.3389/fpsyg.2021.731591Gross, M. U. M. (2009). Highly gifted children and adolescents. In J. A. Plucker & C. M. Callahan (Eds.), Critical issues and practices in gifted education: What the research says (pp. 241– 251). Prufrock Press Inc.Nissen, P. (2019). Detecting talent from the perspectives of students, parents, and teachers. US-China Education Review B, 9(4), 119-127. https://doi.org/10.17265/2161- 6248/2019.04.001Skolinspektionen (2022). Stimulerande undervisning för elever som ligger långt fram i sin kunskapsutveckling. https://www.skolinspektionen.se/beslut-rapporterstatistik/publikationer/kvalitetsgranskning/2022/stimulerandeundervisning
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