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BackgroundSocial support and e-health literacy are closely related to individual health behaviors, while behavior is premised on decision-making. Few studies have identified the relationships among social support, e-health literacy, and behavioral decision-making, and the nature of these relationships among pregnant women with gestational diabetes remains unclear. Therefore, this study aimed to investigate relationships among social support, e-health literacy, and glycemic management behavioral decisions in pregnant women with gestational diabetes.MethodsUsing continuous sampling, an online cross-sectional survey was conducted among pregnant women with gestational diabetes who met the inclusion and exclusion criteria at four Class 3 hospitals in Fujian Province from October to December 2023. A structured questionnaire was used to collect data on general characteristics, socioeconomic status, social support, e-health literacy, and behavioral decision-making regarding glycemic management. Descriptive statistical analyses, correlation analyses, and mediation effects were used to assess associations.ResultsA total of 219 pregnant women with gestational diabetes participated, and 217 valid results were obtained. The level of glycemic management behavior decision-making in women with gestational diabetes was positively correlated with e-health literacy (r = 0.741, p

Techniques to expand human hematopoietic stem cells ex-vivo could be beneficial to the fields of clinical hematopoietic stem cell transplantation and gene therapy targeted at hematopoietic stem cells. NUP98-HOXA10HD is a relatively newly discovered fusion gene that in mouse transplant experiments has been shown to increase numbers of hematopoietic stem cells. We evaluated whether this fusion gene could be used to expand engrafting human primitive CD34+ cells in an immunodeficient mouse model. Gene transfer was achieved using a lentiviral based vector. The engraftment of mobilized peripheral blood human CD34+ cells grown in culture for one week after gene transfer was evaluated 3–4 months after transplant and found to be 2–3 fold higher in the NUP98-HOXA10HD groups as compared to controls. These data suggest an expansive effect at least at the short term human repopulating cell level. Further evaluation in long term repopulating models and investment in a NUP98-HOXA10HD protein seems worthy of consideration. Additionally, the results here provide strong impetus to utilize NUP98-HOXA10HD as a tool to search for underlying genes and pathways involved in hematopoietic stem cell expansion that can be enhanced and have an even more potent expansive effect. [ABSTRACT FROM AUTHOR]

The safety of lentiviral (LV) vectors for gene therapy of genetic hematopoietic diseases would be considerably enhanced by the identification of a non-viral promoter capable of driving therapeutic levels of transgene expression in the target cell. Here, we tested the efficacy of the murine phosphoglycerate kinase (mPgk) promoter in a self-inactivating (SIN) LV vector to express canine CD18 in animals with canine leukocyte adhesion deficiency (CLAD) and in human LAD-1 CD34+ cells in NSG mice. Despite high transduction levels and high levels of CD18 expression per cell in CLAD CD34+ cells in vitro using the mPgk vector to drive canine CD18 expression, only two of five CLAD animals treated with ex vivo gene therapy achieved therapeutic levels of CD18+ neutrophils in vivo. Similarly, despite high transduction efficiency and high levels of CD18 expression in human LAD-1 CD34+ cells in vitro, the mPgk-hCD18 promoter resulted in a low percentage of CD45+/CD18+ cells and low levels of CD18 expression per neutrophil, when the transduced cells were transplanted into NSG mice. In contrast, human LAD-1 CD34+ cells transduced with a LV vector containing the viral MND promoter (MND-hCD18) and injected into NSG mice displayed a high percentage of CD45+/CD18+ cells and high levels of CD18 expression per neutrophil. These studies demonstrated that the mPgk promoter does not direct sufficient CD18 expression in neutrophils to replace a viral promoter for gene therapy of children with LAD-1. [ABSTRACT FROM AUTHOR]

Patients with severe sickle cell disease (SCD) are candidates for gene therapy using autologous hematopoietic stem cells (HSCs), but concomitant multi-organ disease may contraindicate pretransplant conditioning with full myeloablation. We tested whether nonmyeloablative conditioning, a regimen used successfully for allogeneic bone marrow transplantation of adult SCD patients, allows engraftment of γ-globin gene-corrected cells to a therapeutic level in the Berkeley mouse model of SCD. Animals transplanted according to this regimen averaged 35% engraftment of transduced hematopoietic stem cells with an average vector copy < 2.0. Fetal hemoglobin (HbF) levels ranged from 20 to 44% of total hemoglobin and approximately two-thirds of circulating red blood cells expressed HbF detected by immunofluorescence (F-cells). Gene therapy treatment of SCD mice ameliorated anemia, reduced hyperleukocytosis, improved renal function, and reduced iron accumulation in liver, spleen, and kidneys. Thus, modest levels of chimerism with donor cells expressing high levels of HbF from an insulated γ-globin lentiviral vector can improve the pathology of SCD in mice, thereby illustrating a potentially safe and effective strategy for gene therapy in humans.

Hematopoietic cell gene therapy using retroviral vectors has achieved success in clinical trials. However, safety issues regarding vector insertional mutagenesis have emerged. In two different trials, vector insertion resulted in the transcriptional activation of proto-oncogenes. One strategy for potentially diminishing vector insertional mutagenesis is through the use of self-inactivating lentiviral vectors containing the 1.2-kb insulator element derived from the chicken beta-globin locus. However, use of this element can dramatically decrease both vector titer and transgene expression, thereby compromising its practical use. Here, we studied lentiviral vectors containing either the full-length 1.2-kb insulator or the smaller 0.25-kb core element in both orientations in the partially deleted long-terminal repeat. We show that use of the 0.25-kb core insulator rescued vector titer by alleviating a postentry block to reverse transcription associated with the 1.2-kb element. In addition, in an orientation-dependent manner, the 0.25-kb core element significantly increased transgene expression from an internal promoter due to improved transcriptional termination. This element also demonstrated barrier activity, reducing variability of expression due to position effects. As it is known that the 0.25-kb core insulator has enhancer-blocking activity, this particular insulated lentiviral vector design may be useful for clinical application.