4 research outputs found
Tnni3k Modifies Disease Progression in Murine Models of Cardiomyopathy
The Calsequestrin (Csq) transgenic mouse model of cardiomyopathy exhibits wide variation in phenotypic progression dependent on genetic background. Seven heart failure modifier (Hrtfm) loci modify disease progression and outcome. Here we report Tnni3k (cardiac Troponin I-interacting kinase) as the gene underlying Hrtfm2. Strains with the more susceptible phenotype exhibit high transcript levels while less susceptible strains show dramatically reduced transcript levels. This decrease is caused by an intronic SNP in low-transcript strains that activates a cryptic splice site leading to a frameshifted transcript, followed by nonsense-mediated decay of message and an absence of detectable protein. A transgenic animal overexpressing human TNNI3K alone exhibits no cardiac phenotype. However, TNNI3K/Csq double transgenics display severely impaired systolic function and reduced survival, indicating that TNNI3K expression modifies disease progression. TNNI3K expression also accelerates disease progression in a pressure-overload model of heart failure. These combined data demonstrate that Tnni3k plays a critical role in the modulation of different forms of heart disease, and this protein may provide a novel target for therapeutic intervention
Perceived infertility and contraceptive use in the female, reproductive-age cancer survivor
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Perceived infertility and contraceptive use in the female, reproductive-age cancer survivor
ObjectiveTo estimate the association between perceived fertility potential and contraception use and to characterize factors important in contraceptive decision making in reproductive-age, female cancer survivors.DesignCross-sectional study.SettingParticipants were from two state cancer registries, physician referrals, and cancer survivor advocacy groups in the United States.Patient(s)A total of 483 female survivors aged 18-40 years.Intervention(s)Online questionnaire.Main outcome measure(s)Contraception use.Result(s)Eighty-four percent of participants used contraception; 49.7% used highly effective, World Health Organization tiers I and II methods (surgical sterilization, intrauterine devices, contraceptive implant, combined hormonal contraceptives, medroxyprogesterone acetate, progestin-only pills, contraceptive diaphragm). Contraception non-use was more common among survivors who perceived themselves to be infertile, compared with survivors who perceived themselves to be as or more fertile than similarly aged peers (prevalence ratio 4.0, 95% confidence interval 2.5-7.4). In mediation analysis that adjusted for clinical infertility, 59% of the association between prior chemotherapy and contraception non-use was explained by perceived infertility. Contraception efficacy (n = 62, 25.8%) and ease of use (n = 50, 20.8%) were the most cited reasons for using tier I/II methods; compared with lack of hormones (n = 81, 49.7%) as the predominant reason for using less-effective, tier III/IV methods.Conclusion(s)Although female, reproductive-age cancer survivors had high uptake of contraception, those who perceived themselves to be infertile were less likely to use contraception. Throughout survivorship, clinicians should counsel survivors on fertility potential in the context of their prior cancer treatments and on factors, including contraceptive efficacy and hormone-free contraception, that inform reproductive decision making in this population