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Sickle cell disease (SCD) can be cured by allogeneic hematopoietic stem cell transplant. However, this is only possible when a matched donor is available, making the development of gene therapy using autologous hematopoietic stem cells a highly desirable alternative. We used a culture model of human erythropoiesis to directly compare two insulated, self-inactivating, and erythroid-specific lentiviral vectors, encoding for γ-globin (V5m3-400) or a modified β-globin (βAS3-FB) for production of antisickling hemoglobin (Hb) and correction of red cell deformability after deoxygenation. Bone marrow CD34+ cells from three SCD patients were transduced using V5m3-400 or βAS3-FB and compared with mock-transduced SCD or healthy donor CD34+ cells. Lentiviral transduction did not impair cell growth or differentiation, as gauged by proliferation and acquisition of erythroid markers. Vector copy number averaged approximately one copy per cell, and corrective globin mRNA levels were increased more than sevenfold over mock-transduced controls. Erythroblasts derived from healthy donor and mock-transduced SCD cells produced a low level of fetal Hb that was increased to 23.6 ± 4.1% per vector copy for cells transduced with V5m3-400. Equivalent levels of modified normal adult Hb of 17.6 ± 3.8% per vector copy were detected for SCD cells transduced with βAS3-FB. These levels of antisickling Hb production were sufficient to reduce sickling of terminal-stage red blood cells upon deoxygenation. We concluded that the achieved levels of fetal Hb and modified normal adult Hb would likely prove therapeutic to SCD patients who lack matched donors.

Abstract Background A growing body of epidemiologic evidence links oral health, obesity, and cardiovascular health, though few studies have reported on these relationships in children. While underlying mechanisms are unclear, adult studies have suggested sub-acute systemic inflammation, also implicated in the etiology of both obesity and cardiovascular disease. This study investigated associations between self-reported dental hygiene, obesity, and systemic inflammation in children. Methods 128 children < 19 years of age from rural counties in West Virginia participated in a community-based health screening that included anthropometric assessments, blood collection, and a questionnaire about dental hygiene and self-assessed oral health. Results Participants ranged from 3.0-18.7 years. Univariate analysis demonstrated an association between parent-reported dental hygiene, including frequency of preventive dental care and parent-assessed overall dental health, and markers of systemic inflammation but not obesity. In multivariable regression, parent-assessed overall dental health and obesity were independent predictors of systemic inflammation, after adjustment for age, gender, and parent education. Conclusions This is the first known study of the association between dental hygiene, obesity, and systemic inflammation in children. These results highlight the importance of preventive dental care in overall, systemic health in children and are consistent with previous reports in adults.

Aim: To compare the success rate and complications of adjuvant use of mitomycin C and triamcinolone-impregnated biodegradable nasal packing (TABP) in endoscopic dacryocystorhinostomy (DCR). And to evaluate the efficacy of combining intraoperative mitomycin C and TABP for endoscopic DCR., Methods: A total of 198 eyes of 148 patients who underwent endoscopic DCR for acquired nasolacrimal duct obstruction were retrospectively analysed. The patients were randomly divided into three groups: Group A included patients treated without intraoperative mitomycin C but with TABP, Group B included patients treated without triamcinolone but with intraoperative mitomycin C and normal saline-impregnated nasal packing, and Group C included patients treated with intraoperative mitomycin C and TABP., Results: The results revealed no significant difference in the overall success rates between Groups A (86.8%) and B (89.2%; P =0.377). However, Group C (97.5%) showed a significantly higher overall success rate than Groups A and B. The incidence of granulomas was significantly lower in group C (5%) than in Groups A (20.8%) and B (15.2%; P =0.009). Other complications, such as crust, synechiae, and revision surgery, did not differ significantly among the three groups., Conclusion: The combination of intraoperative mitomycin C and TABP effectively prevents granulomas and enhances surgical success rate. Additionally, there is no statistically significant difference observed between the use of mitomycin C or TABP alone., Competing Interests: Conflicts of Interest: Kim SY, None; Chambers CB, None; Ahn JH, None., (International Journal of Ophthalmology Press.)