Gene Transfer Using Micellar Nanovectors Inhibits Choroidal Neovascularization In Vivo

PURPOSE: Age-related macular degeneration caused by choroidal neovascularization (CNV) remains difficult to be treated despite the recent advent of several treatment options. In this study, we investigated the in vivo angiogenic control by intravenous injection of polyion complex (PIC) micelle encapsulating plasmid DNA (pDNA) using a mice CNV model. METHODS: The transfection efficiency of the PIC micelle was investigated using the laser-induced CNV in eight-week-old male C57 BJ/6 mice. Firstly, each mouse received intravenous injection of micelle encapsulating pDNA of Yellow Fluorescent Protein (pYFP) on days 1,3 and 5. The expression of YFP was analyzed using fluorescein microscopy and western blotting analysis. In the next experiments, each mouse received intravenous injection of micelle encapsulating pDNA of soluble Fms-like tyrosine kinase-1 (psFlt-1) 1,3 and 5 days after the induction of CNV and the CNV lesion was analyzed by choroidal flatmounts on day 7. RESULTS: Fluorescein microscopy and western blotting analysis revealed that the expression of YFP was confirmed in the CNV area after injection of the PIC micelle, but the expression was not detected neither in mice that received naked pDNA nor those without CNV. Furthermore, the CNV area in the mice that received intravenous injection of the psFlt-1-encapsulated PIC micelle was significantly reduced by 65% compared to that in control mice (p<0.01). CONCLUSIONS: Transfection of sFlt-1 with the PIC micelle by intravenous injection to mice CNV models showed significant inhibition of CNV. The current results revealed the significant potential of nonviral gene therapy for regulation of CNV using the PIC micelle encapsulating pDNA

The intraductal approach to the breast: raison d'être

Opportunities for the detection, prediction, and treatment of breast cancer exist at three biological levels: systemically via the blood, at the whole organ level, and within the individual ductal lobular structures of the breast. This review covers the evaluation of approaches targeted to the ductal lobular units, where breast cancer begins. Studies to date suggest the presence of 5 to 12 independent ductal lobular systems per breast, each harboring complex cellular fluids contributed by local and systemic processes. New techniques for accessing and interrogating these systems offer the potential to gauge the microenvironment of the breast and distill biological risk profiles

Grading variability of urothelial carcinoma: experience from a single academic medical center

INTRODUCTION: Tumor grade plays a critical role in the management of papillary non-invasive urothelial carcinoma (UC). Since grading of UC relies on morphologic criteria, variability in interpretation exists among pathologists. The objective of this study was to examine inter-observer variability in the grading of papillary non-invasive UC at a single academic medical center. MATERIALS AND METHODS: One general pathologist and two genitourinary pathologists were blinded to patient identity and graded 98 consecutive UC specimens using the 1973 and 2004 classification systems. Kappa statistics (kappa) were used to measure inter-observer reproducibility to account for agreement expected purely by chance. By convention, varkappa values from 0.21-0.4 represent fair , from 0.41-0.6 represent moderate , and \u3e 0.6 represent substantial agreement. RESULTS: Raw percentage agreement among all three pathologists was only 26% using the 1973 system and 47% using the 2004 system. When measured by kappa, overall agreement was only fair for both systems and while higher for the 2004 system than the 1973, this was not significant (: 0.38 versus 0.26, respectively). There were no significant differences in agreement when comparing the specialists agreement between themselves with agreement between each specialist and the generalist (varkappa: 0.31-0.37 versus varkappa: 0.18-0.46). CONCLUSIONS: The current grading system continues to demonstrate challenges in reproducibility among general and specialized pathologists. The degree of variability has significant implications on management decisions for non-invasive UC. Our findings underscore the need to identify molecular markers that can provide a more objective and reliable risk stratification system to guide patient management

Energetic Analysis of Low Global Warming Potential Refrigerants as Substitutes for R410A and R134a in Ground-Source Heat Pumps

The European building sector is responsible for approximately 40% of total energy consumption and for 36% of greenhouse gas emissions. Identifying technological solutions capable of reducing energy consumption and greenhouse gas emissions is one of the main objectives of the European Commission. Ground source heat pumps (GSHPs) are of particular interest for this purpose, promising a considerable reduction in greenhouse gas emissions of HVAC systems. This paper reports the results of the energetic analysis carried out within the EU research project GEO4CIVHIC about the performance of geothermal heat pumps working with low-GWP refrigerants as alternatives for R134a and R410A. The work has been carried out through computer simulations based on base and regenerative reverse cycles. Several heat sink and heat source temperature conditions have been considered in order to evaluate the GSHPs’ performance in the whole range of real conditions that can be found in Europe. Particular attention has been paid to the evaluation of compression isentropic efficiency and its influence on the overall cycle performance when dealing with steady-state heat pump simulations. To do so, five different scenarios of isentropic efficiency calculation have been studied and discussed

Energetic and exergetic analysis of low global warming potential refrigerants as substitutes for R410A in ground source heat pumps

In the European Union (EU), buildings are responsible for about 40% of the total final energy consumption, and 36% of the European global CO2 emissions. The European Commission released directives to push for the enhancement of the buildings energy performance and identified, beside the retrofit of the current building stock, Heating, Ventilation, and Air Conditioning (HVAC) systems as the other main way to increase renewable energy sharing and overall building energy efficiency. For this purpose, Ground Source Heat Pumps (GSHPs) represent one of the most interesting technologies to provide energy for heating, cooling, and domestic water production in residential applications, ensuring a significant reduction (e.g., up to 44% compared with air-source heat pumps) of energy consumption and the corresponding emissions. At present, GSHPs mainly employ the refrigerant R410A as the working fluid, which has a Global Warming Potential (GWP) of 2087. However, following the EU Regulation No. 517/2014 on fluorinated greenhouse gases, this high GWP refrigerant will have to be substituted for residential applications in the next years. Thus, to increase the sustainability of GSHPs, it is necessary to identify short time alternative fluids with lower GWP, before finding medium-long term solutions characterized by very low GWP. This is one of the tasks of the UE project "Most Easy, Efficient, and Low-Cost Geothermal Systems for Retrofitting Civil and Historical Buildings" (acronym GEO4CIVHIC). Here, a thorough thermodynamic analysis, based on both energy and exergy analysis, will be presented to perform a comparison between different fluids as substitutes for R410A, considered as the benchmark for GSHP applications. These fluids have been selected considering their lower flammability with respect to hydrocarbons (mainly R290), that is one of the main concerns for the companies. A parametric analysis has been performed, for a reversible GSHP cycle, at various heat source and sink conditions, with the aim to identify the fluid giving the best energetic performance and to evaluate the distribution of the irreversibilities along the cycle. Considering all these factors, R454B turned out to be the most suitable fluid to use in a ground source heat pump, working at given conditions. Special attention has been paid to the compression phase and the heat transfer in evaporator and condenser