Rethinking an Algorithm: The Utility of the Techinicium 99 m Labeled Red Cell (RBC) Scanning for Lower Gastrointestinal Bleeding (LGIB)

Purpose: Technetium 99 m (99 m Tc) labeled scan is often done to localize bleeding to facilitate treatment. No level 1 or 2 data supports this approach. The aim of this study was to determine the correlation between site of bleeding by nuclear scan and findings at surgery, angiogram or colonoscopy. Methods: Records of patients admitted to Cooper University Hospital from January 2001-December 2005 with LGIB who had 99mTc scan were analyzed. Results: 164 of 170 patients were eligible to be evaluated. There were 45 positive (27.5%) and 119 negative scans (72.5%). 21 of 45 patients with positive scans had angiography. 7 patients (33.3%) had positive and 14 (66.6%) negative angiograms. In 6 patients (85.7%) with (+) angiograms, there was correlation on the area of bleed as seen on the 99 m Tc scan (p = 0.125). 20 patients, in the positive scan group, required surgery. In 15 (75%) the findings at surgery correlated with the scan result (p = 0.04). 31 patients (68.8%) with positive scan had colonoscopy. There was correlation in 27 patients (87.0%) (p < 0.001). The patients with (+) scan received a total of 372 (8.2 per patient) transfusions of packed red blood cells (PRBC) compared to 333 (2.7 per patients) transfusions in patients with (–) scans. Surgeons documented in 7 patients that the result of scan influenced surgery. Patients with (+) and (–) scans had similar rates of colonoscopy (73.35% vs 76.4%), hospital length of stay (14.3 vs 12.10 days), while mortality rate was (8.8% vs 6.72%) respectively, Conclusion: 99 m Tc scan has low yield in the evaluation of LGIB. However when positive, they tend to correlate with findings at angiogram, surgery and colonoscopy.

Systematic development of ionizable lipid nanoparticles for placental mRNA delivery using a design of experiments approach

Ionizable lipid nanoparticles(LNPs)have gained attention as mRNA delivery platforms for vaccination against COVID-19 and for protein replacement therapies.LNPs enhance mRNA stability,circulation time,cellular uptake,and preferential delivery to specific tissues compared to mRNA with no carrier platform.However,LNPs are only in the beginning stages of development for safe and effective mRNA delivery to the placenta to treat placental dysfunction.Here,we develop LNPs that enable high levels of mRNA delivery to trophoblasts in vitro and to the placenta in vivo with no toxicity.We conducted a Design of Experiments to explore how LNP composition,including the type and molar ratio of each lipid component,drives trophoblast and placental delivery.Our data revealed that utilizing C12-200 as the ionizable lipid and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine(DOPE)as the phospholipid in the LNP design yields high transfection efficiency in vitro.Analysis of lipid molar composition as a design parameter in LNPs displayed a strong correlation between apparent pKa and poly(ethylene)glycol(PEG)content,as a reduction in PEG molar amount increases apparent pKa.Further,we present one LNP platform that exhibits the highest delivery of placental growth factor mRNA to the placenta in pregnant mice,resulting in synthesis and secretion of a potentially therapeutic protein.Lastly,our high-performing LNPs have no toxicity to both the pregnant mice and fetuses.Our results demonstrate the feasibility of LNPs as a platform for mRNA delivery to the placenta,and our top LNP formulations may provide a therapeutic platform to treat diseases that originate from placental dysfunction during pregnancy.

In vitro evaluation of 3D printed polycaprolactone scaffolds with angle-ply architecture for annulus fibrosus tissue engineering

Tissue engineering of the annulus fibrosus(AF)is currently being investigated as a treatment for intervertebral disc degeneration,a condition frequently associated with low back pain.The objective of this work was to use 3D printing to generate a novel scaffold for AF repair that mimics the structural and biomechanical properties of the native tissue.Multi-layer scaffolds were fabricated by depositing polycaprolactone struts in opposing angular orientations,replicating the angle-ply arrangement of the native AF tissue.Scaffolds were printed with varied strut diameter and spacing.The constructs were characterized morphologically and by static and dynamic mechanical analyses.Scaffold surfaces were etched with unidirectional grooves and the influence on bovine AF cell metabolic activity,alignment,morphology and protein expression was studied in vitro.Overall,the axial compressive and circumferential tensile properties of the scaffolds were found to be in a similar range to the native AF tissue.Confocal microscopy images indicated that cells were able to attach and spread on the smooth polycaprolactone scaffolds,but the surface texture induced cellular alignment and proliferation.Furthermore,immunofluorescence analysis demonstrated the aligned deposition of collagen type I,aggrecan and the AF-specific protein marker tenomodulin on the etched scaffolds.Overall,results demonstrated the potential for using the scaffolds as a template for AF regeneration.

一种含有分散型粘度指数改进剂组分的润滑油

美国Lubrizol公司6，639，034专利报道了1种润滑油分散型粘度指数改进剂组分，此专利包括含氮的聚合物作为润滑油的分散型的粘度指数改进剂组分，还有有关它的工艺和制备方法。