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《European journal of medical genetics》2014,57(2-3):95-102
Patients with congenital adrenal hyperplasia (CAH) with tenascin-X deficiency (CAH-X syndrome) have both endocrine imbalances and characteristic Ehlers Danlos syndrome phenotypes. Unlike other subtypes, tenascin-X-related Ehlers Danlos syndrome is caused by an extracellular matrix protein deficiency rather than a defect in fibrillar collagen or a collagen-modifying enzyme, and the understanding of the disease mechanisms is limited. We hypothesized that transforming growth factor-β pathway dysregulation may, in part, be responsible for connective tissue phenotypes observed in CAH-X, due to this pathway's known role in connective tissue disorders.Fibroblasts and direct tissue from human skin biopsies from CAH-X probands and age- and sex-matched controls were screened for transforming growth factor-β biomarkers known to be dysregulated in other hereditary disorders of connective tissue. In CAH-X fibroblast lines and dermal tissue, pSmad1/5/8 was significantly upregulated compared to controls, suggesting involvement of the bone morphogenetic protein pathway. Additionally, CAH-X samples compared to controls exhibited significant increases in fibroblast-secreted TGF-β3, a cytokine important in secondary palatal development, and in plasma TGF-β2, a cytokine involved in cardiac function and development, as well as palatogenesis. Finally, MMP-13, a matrix metalloproteinase important in secondary palate formation and tissue remodeling, had significantly increased mRNA and protein expression in CAH-X fibroblasts and direct tissue.Collectively, these results demonstrate that patients with CAH-X syndrome exhibit increased expression of several transforming growth factor-β biomarkers and provide a novel link between this signaling pathway and the connective tissue dysplasia phenotypes associated with tenascin-X deficiency. 相似文献
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《Vaccine》2018,36(6):779-787
In Italy, in 2016, we conducted a cross-sectional survey to estimate vaccine hesitancy and investigate its determinants among parents of children aged 16–36 months.Data on parental attitudes and beliefs about vaccinations were collected through a questionnaire administered online or self-administered at pediatricians’ offices and nurseries. Parents were classified as pro-vaccine, vaccine-hesitant or anti-vaccine, according to self-reported tetanus and measles vaccination status of their child. Multivariable logistic regression was used to investigate factors associated with hesitancy.A total of 3130 questionnaires were analysed: 83.7% of parents were pro-vaccine, 15.6% vaccine-hesitant and 0.7% anti-vaccine. Safety concerns are the main reported reason for refusing (38.1%) or interrupting (42.4%) vaccination. Anti-vaccine and hesitant parents are significantly more afraid than pro-vaccine parents of short-term (85.7 and 79.7% vs 60.4%) and long-term (95.2 and 72.3% vs 43.7%) vaccine adverse reactions. Most pro-vaccine and hesitant parents agree about the benefits of vaccinations. Family pediatricians are considered a reliable source of information by most pro-vaccine and hesitant parents (96.9 and 83.3% respectively), against 45% of anti-vaccine parents. The main factors associated with hesitancy were found to be: not having received from a paediatrician a recommendation to fully vaccinate their child [adjusted odds ratio (AOR): 3.21, 95% CI: 2.14–4.79], having received discordant opinions on vaccinations (AOR: 1.64, 95% CI: 1.11–2.43), having met parents of children who experienced serious adverse reactions (AOR: 1.49, 95% CI: 1.03–2.15), and mainly using non-traditional medical treatments (AOR: 2.05, 95% CI: 1.31–3.19).Vaccine safety is perceived as a concern by all parents, although more so by hesitant and anti-vaccine parents. Similarly to pro-vaccine parents, hesitant parents consider vaccination an important prevention tool and trust their family pediatricians, suggesting that they could benefit from appropriate communication interventions. Training health professionals and providing homogenous information about vaccinations, in line with national recommendations, are crucial for responding to their concerns. 相似文献
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目的核查放射治疗计划系统(TPS)计算病人治疗剂量的非均匀野剂量校正。方法将插有TLD的聚苯乙烯固体模体,聚苯乙烯/肺固体模体,聚苯乙烯/骨固体模体分别经CT扫描,影像分别传入TPS并计算高能X射线下监督单位数,使传递给中心束轴TLD剂量为2 Gy。在高能X射线下完成TLD照射,照射后的TLD经测量、剂量计算,D(TLD)与D(TPS)剂量比值在0.95~1.05范围为可接受范围。结果核查结果表明,光子线束均匀模体轴上(P)剂量和非均匀骨模体轴上(BP)剂量核查结果较好。非均匀肺模体轴上(LP)和离轴(LL)剂量核查结果误差很大。结论光子线束非均匀性剂量校正在放射治疗中是非常重要,尤其是肺组织。校正不当,对于肺组织剂量误差也可达到11.1%,离轴情况下更多达18.4%。对于骨组织剂量误差较小。 相似文献