A spatio-temporal analysis of groundwater level changes in relation to urban growth and groundwater recharge potential for Waukesha County, Wisconsin

The main objective of this study was to spatially and temporally analyze groundwater level changes using geographic information systems and spatial analysis with respect to urban development, groundwater water withdrawal, and groundwater recharge potential. The study focused on Waukesha County in southeastern Wisconsin, where urban development has been accelerating while groundwater has been declining during the last several decades. We analyzed data about groundwater withdrawal, groundwater level, land use/land cover, and precipitation utilizing correlation analysis, Geographically Weighted Regression (GWR), land-use change analysis, and map overlay. As a result, we found that (1) Urban areas increased faster in areas with high recharge potential than in areas with low or moderate recharge potential, (2) The effect of urban growth on groundwater level is highly variable by time and space, and (3) The changes in groundwater level are strongly related to the spatial distribution of groundwater withdrawal. The study pinpoints the need to consider the spatial unevenness of groundwater withdrawal in understanding the changes in groundwater level and groundwater recharge potential for better managing groundwater resources

The Influence of Preoperative Bladder Outlet Obstruction on Continence and Satisfaction in Patients with Stress Urinary Incontinence after Midurethral Sling

Purpose We studied the influence of preoperative bladder outlet obstruction (BOO) on postoperative continence rates and patient satisfaction after the midurethral sling procedure. Methods A total of 159 women who underwent the midurethral sling procedure were evaluated. Using the Blaivas-Groutz nomogram, we assigned the patients were assigned to Group I (n=37, no obstruction), Group II (n=89, mild obstruction), or Group III (n=33, moderate to severe obstruction). Continence rates, patient satisfaction, urinary sensation scale and uroflowmetry were evaluated postoperatively. Results There were no significant differences in continence rates, satisfaction, or postoperative maximal flow rate between the 3 groups. Postoperative urgency was improved after surgery in Groups I and II (P<0.05) but not in Group III. Conclusions BOO does not seem to be a risk factor for failure after the midurethral sling procedure. However, BOO may be considered as a potential factor for persistent storage symptoms after the midurethral sling

Characterization of Fabry mice treated with recombinant adeno-associated virus 2/8-mediated gene transfer

<p>Abstract</p> <p>Background</p> <p>Enzyme replacement therapy (ERT) with α-galactosidase A (α-Gal A) is currently the most effective therapeutic strategy for patients with Fabry disease, a lysosomal storage disease. However, ERT has limitations of a short half-life, requirement for frequent administration, and limited efficacy for patients with renal failure. Therefore, we investigated the efficacy of recombinant adeno-associated virus (rAAV) vector-mediated gene therapy for a Fabry disease mouse model and compared it with that of ERT.</p> <p>Methods</p> <p>A pseudotyped rAAV2/8 vector encoding α-Gal A cDNA (rAAV2/8-hAGA) was prepared and injected into 18-week-old male Fabry mice through the tail vein. The α-Gal A expression level and globotriaosylceramide (Gb3) levels in the Fabry mice were examined and compared with Fabry mice with ERT. Immunohistochemical and ultrastructural studies were conducted.</p> <p>Results</p> <p>Treatment of Fabry mice with rAAV2/8-hAGA resulted in the clearance of accumulated Gb3 in tissues such as liver, spleen, kidney, heart, and brain with concomitant elevation of α-Gal A enzyme activity. Enzyme activity was elevated for up to 60 weeks. In addition, expression of the α-Gal A protein was identified in the presence of rAAV2/8-hAGA at 6, 12, and 24 weeks after treatment. α-Gal A activity was significantly higher in the mice treated with rAAV2/8-hAGA than in Fabry mice that received ERT. Along with higher α-Gal A activity in the kidney of the Fabry mice treated with gene therapy, immunohistochemical studies showed more α-Gal A expression in the proximal tubules and glomerulus, and less Gb3 deposition in Fabry mice treated with this gene therapy than in mice given ERT. The α-gal A gene transfer significantly reduced the accumulation of Gb3 in the tubules and podocytes of the kidney. Electron microscopic analysis of the kidneys of Fabry mice also showed that gene therapy was more effective than ERT.</p> <p>Conclusions</p> <p>The rAAV2/8-hAGA mediated α-Gal A gene therapy provided improved efficiency over ERT in the Fabry disease mouse model. Furthermore, rAAV2/8-hAGA-mediated expression showed a greater effect in the kidney than ERT.</p

Controlled release of human growth hormone fused with a human hybrid Fc fragment through a nanoporous polymer membrane

Nanotechnology has been applied to the development of more effective and compatible drug delivery systems for therapeutic proteins. Human growth hormone (hGH) was fused with a hybrid Fc fragment containing partial Fc domains of human IgD and IgG(4) to produce a long-acting fusion protein. The fusion protein, hGH-hyFc, resulted in the increase of the hydrodynamic diameter (ca. 11 nm) compared with the diameter (ca. 5 nm) of the recombinant hGH. A diblock copolymer membrane with nanopores (average diameter of 14.3 nm) exhibited a constant release rate of hGH-hyFc. The hGH-hyFc protein released in a controlled manner for one month was found to trigger the phosphorylation of Janus kinase 2 (JAK2) in human B lymphocyte and to exhibit an almost identical circular dichroism spectrum to that of the original hGH-hyFc, suggesting that the released fusion protein should maintain the functional and structural integrity of hGH. Thus, the nanoporous release device could be a potential delivery system for the long-term controlled release of therapeutic proteins fused with the hybrid Fc fragment.X111313sciescopu

Production of Transgenic Cloned Miniature Pigs with Membrane-bound Human Fas Ligand (FasL) by Somatic Cell Nuclear Transfer

Cell-mediated xenograft rejection, including NK cells and CD8+ CTL, is a major obstacle in successful pig-to-human xenotransplantation. Human CD8+ CTL and NK cells display high cytotoxicity for pig cells, mediated at least in part by the Fas/FasL pathway. To prevent cell-mediated xenocytotoxicity, a membrane-bound form of human FasL (mFasL) was generated as an inhibitor for CTL and NK cell cytotoxicity that could not be cleaved by metalloproteinase to produce putative soluble FasL. We produced two healthy transgenic pigs harboring the mFasL gene via somatic cell nuclear transfer (SCNT). In a cytotoxicity assay using transgenic clonal cell lines and transgenic pig ear cells, the rate of CD8+ CTL-mediated cytotoxicity was significantly reduced in transgenic pig&#x27;s ear cells compared with that in normal minipig fetal fibroblasts. Our data indicate that grafts of transgenic pigs expressing membrane-bound human FasL control the cellular immune response to xenografts, creating a window of opportunity to facilitate xenograft survival