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- Ljungman, L., et al.
(författare)
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Sexual Dysfunction and Reproductive Concerns in Young Men Diagnosed With Testicular Cancer : An Observational Study
- 2019
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Ingår i: Journal of Sexual Medicine. - : Elsevier. - 1743-6095 .- 1743-6109. ; 16:7, s. 1049-1059
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The survival rates for testicular cancer are excellent; still, there is a lack of knowledge regarding important survivorship issues, such as sexual dysfunction and reproductive concerns.AIM: The aim of this study was to investigate the prevalence and predictors of sexual dysfunction and reproductive concerns and the potential association between these issues in young men ∼2 years after a diagnosis of testicular cancer.METHODS: Data were collected from 111 men (response rate = 50%) diagnosed with testicular cancer at age 16-39. Patients were identified via the Swedish National Quality Registry for Testicular Cancer and approached with a survey, including standardized measures of sexual function, reproductive concerns, body image, and health-related quality of life. The survey was sent to participants approximately 2 years after their cancer diagnosis. Clinical variables were collected from the registry. Predictors were identified by multivariable linear regression analyses.MAIN OUTCOME MEASURES: The main outcomes were sexual function, assessed with the Patient-Reported Outcomes Measurement Information System Sexual Function and Satisfaction measure version 2.0, and reproductive concerns, assessed with the Reproductive Concerns After Cancer scale.RESULTS: Sexual dysfunction was reported by 26% of men, and a high level of reproductive concerns was reported by 28%. Lower satisfaction with sex life was associated with older age (β = -0.41), negative body image (β = -0.42), not having a partner (β = 4.8), and dissatisfaction with sex life before cancer (β = 8.31). Negative body image was associated with reproductive concerns in the dimensions of fertility potential (β = 0.06), partner disclosure (β = 0.08), and child's health (β = 0.07), whereas having had fertility preservation predicted higher levels of concerns with regard to personal health (β = 0.52) and achieving pregnancy (β = 0.53). Clinical variables did not predict either sexual function or reproductive concerns.CLINICAL IMPLICATIONS: Our results show that the majority of young men diagnosed with testicular cancer do not report sexual dysfunction or reproductive concerns 2 years after diagnosis. A sizeable minority, however, does report dysfunction or reproductive concerns, which should be recognized in the follow-up care of this population.STRENGTHS & LIMITATIONS: A strength of the study is the use of high-quality registry data and validated instruments. The lack of Swedish norms for sexual function and reproductive concerns is a possible limitation.CONCLUSION: A subgroup of young men treated for testicular cancer report sexual dysfunction or reproductive concerns approximately 2 years after diagnosis. Factors associated with these issues seem to mainly be psychological, rather than medical, nature. Ljungman L, Eriksson LE, Flynn KE, et al. Sexual Dysfunction and Reproductive Concerns in Young Men Diagnosed With Testicular Cancer: An Observational Study. J Sex Med 2019;16:1049-1059.
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- Bazaz, S, et al.
(författare)
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Novel Orthogonally Hydrocarbon-Modified Cell-Penetrating Peptide Nanoparticles Mediate Efficient Delivery of Splice-Switching Antisense Oligonucleotides In Vitro and In Vivo
- 2021
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Ingår i: Biomedicines. - : MDPI AG. - 2227-9059. ; 9:8
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Tidskriftsartikel (refereegranskat)abstract
- Splice-switching therapy with splice-switching oligonucleotides (SSOs) has recently proven to be a clinically applicable strategy for the treatment of several mis-splice disorders. Despite this, wider application of SSOs is severely limited by the inherently poor bioavailability of SSO-based therapeutic compounds. Cell-penetrating peptides (CPPs) are a class of drug delivery systems (DDSs) that have recently gained considerable attention for improving the uptake of various oligonucleotide (ON)-based compounds, including SSOs. One strategy that has been successfully applied to develop effective CPP vectors is the introduction of various lipid modifications into the peptide. Here, we repurpose hydrocarbon-modified amino acids used in peptide stapling for the orthogonal introduction of hydrophobic modifications into the CPP structure during peptide synthesis. Our data show that α,α-disubstituted alkenyl-alanines can be successfully utilized to introduce hydrophobic modifications into CPPs to improve their ability to formulate SSOs into nanoparticles (NPs), and to mediate high delivery efficacy and tolerability both in vitro and in vivo. Conclusively, our results offer a new flexible approach for the sequence-specific introduction of hydrophobicity into the structure of CPPs and for improving their delivery properties.
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- Gupta, Dhanu, et al.
(författare)
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Amelioration of systemic inflammation via the display of two different decoy protein receptors on extracellular vesicles
- 2021
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Ingår i: Nature Biomedical Engineering. - Stockholm : Karolinska Institutet, Dept of Laboratory Medicine. - 2157-846X.
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Tidskriftsartikel (refereegranskat)abstract
- Extracellular vesicles (EVs) can be functionalized to display specific protein receptors on their surface. However, surface-display technology typically labels only a small fraction of the EV population. Here, we show that the joint display of two different therapeutically relevant protein receptors on EVs can be optimized by systematically screening EV-loading protein moieties. We used cytokine-binding domains derived from tumour necrosis factor receptor 1 (TNFR1) and interleukin-6 signal transducer (IL-6ST), which can act as decoy receptors for the pro-inflammatory cytokines tumour necrosis factor alpha (TNF-α) and IL-6, respectively. We found that the genetic engineering of EV-producing cells to express oligomerized exosomal sorting domains and the N-terminal fragment of syntenin (a cytosolic adaptor of the single transmembrane domain protein syndecan) increased the display efficiency and inhibitory activity of TNFR1 and IL-6ST and facilitated their joint display on EVs. In mouse models of systemic inflammation, neuroinflammation and intestinal inflammation, EVs displaying the cytokine decoys ameliorated the disease phenotypes with higher efficacy as compared with clinically approved biopharmaceutical agents targeting the TNF-α and IL-6 pathways.
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