Methylene blue dose-dependently induces cutaneous inflammation and heat hyperalgesia in a novel rat model.

Methylene blue (MB) has been shown to reduce mortality and morbidity in vasoplegic patients after cardiac surgery. Though MB is considered to be safe, extravasation of MB leading to cutaneous toxicity has been reported. In this study, we sought to characterize MB-induced cutaneous toxicity and investigate the underlying mechanisms. To induce MB-induced cutaneous toxicity, we injected 64 adult male Sprague-Dawley rates with 200 µL saline (vehicle) or 1%, 0.1%, or 0.01% MB in the plantar hind paws. Paw swelling, skin histologic changes, and heat and mechanical hyperalgesia were measured. Injection of 1%, but not 0.1% or 0.01% MB, produced significant paw swelling compared to saline. Injection of 1% MB produced heat hyperalgesia but not mechanical hyperalgesia. Pain behaviors were unchanged following injections of 0.1% or 0.01% MB. Global transcriptomic analysis by RNAseq identified 117 differentially expressed genes (111 upregulated, 6 downregulated). Ingenuity Pathway Analysis showed an increased quantity of leukocytes, increased lipids, and decreased apoptosis of myeloid cells and phagocytes with activation of IL-1ß and Fos as the two major regulatory hubs. qPCR showed a 16-fold increase in IL-6 mRNA. Thus, using a novel rat model of MB-induced cutaneous toxicity, we show that infiltration of 1% MB into cutaneous tissue causes a dose-dependent pro-inflammatory response, highlighting potential roles of IL-6, IL-1ß, and Fos. Thus, anesthesiologists should administer dilute MB intravenously through peripheral venous catheters. Higher concentrations of MB (1%) should be administered through a central venous catheter to minimize the risk of cutaneous toxicity.

Ionizable lipid nanoparticles for in utero mRNA delivery.

Clinical advances enable the prenatal diagnosis of genetic diseases that are candidates for gene and enzyme therapies such as messenger RNA (mRNA)-mediated protein replacement. Prenatal mRNA therapies can treat disease before the onset of irreversible pathology with high therapeutic efficacy and safety due to the small fetal size, immature immune system, and abundance of progenitor cells. However, the development of nonviral platforms for prenatal delivery is nascent. We developed a library of ionizable lipid nanoparticles (LNPs) for in utero mRNA delivery to mouse fetuses. We screened LNPs for luciferase mRNA delivery and identified formulations that accumulate within fetal livers, lungs, and intestines with higher efficiency and safety compared to benchmark delivery systems, DLin-MC3-DMA and jetPEI. We demonstrate that LNPs can deliver mRNAs to induce hepatic production of therapeutic secreted proteins. These LNPs may provide a platform for in utero mRNA delivery for protein replacement and gene editing.

Highly sensitive and spatially resolved polyvinyl alcohol/acrylamide photopolymer for real-time holographic applications.

By employing low molecular-weight polyvinyl alcohol (PVA) as binder, the spatial resolution of a red-sensitive PVA/acrylamide based photopolymer are improved from 1000 lines/mm to 3000 lines/mm. By increasing the ambient temperature during the holographic recording, the photosensitivity of photopolymer is also increased about 5 times. The optimized photopolymer system has high capacity such as high photosensitivity (8 mJ/cm(2)), high spatial resolution (over 3000 lines/mm) and high diffraction efficiency (over 94%). To our knowledge, its holographic recording performance is the best of ever reported PVA/acrylamide based photopolymer systems. It has good application prospects in real-time holographic interferometry, holographic storage and holographic display.

Nonprescribed antimicrobial drugs in Latino community, South Carolina.

We investigated in a sample of Latinos the practices of antimicrobial drug importation and use of nonprescribed antimicrobial drugs. In interviews conducted with 219 adults, we assessed health beliefs and past and present behaviors consistent with acquiring antimicrobial drugs without a prescription in the United States. Many (30.6%) believed that antimicrobial drugs should be available in the United States without a prescription. Furthermore, 16.4% had transported nonprescribed antimicrobial drugs into the United States, and 19.2% had acquired antimicrobial agents in the United States without a prescription. A stepwise logistic regression analysis showed that the best predictors of having acquired nonprescribed antimicrobial drugs in the United States were beliefs and behavior consistent with limited regulations on such drugs. Many persons within the Latino community self-medicate with antimicrobial drugs obtained without a prescription both inside and outside the United States, which adds to the reservoir of antimicrobial drugs in the United States.

Influence of atmospheric and system parameters on multiple scattering in spaceborne backscatter lidar measurements.

We have simulated backscatter signals of spaceborne lidar systems with the help of a Monte Carlo model. Calculations were performed for various combinations of system parameters. As typical examples of atmospheric observation targets, two kinds of cirrus cloud and two kinds of aerosol were considered. Both total multiple scattering and the significance of individual higher scattering orders are discussed. For all cases, an approximate multiple scattering factor F was calculated that can be used to correct the single-scattering lidar equation to account also for multiple scattering.

Acousto-optic differential optical absorption spectroscopy for atmospheric measurement of nitrogen dioxide in Hong Kong.

Measurement of the atmospheric concentration of nitrogen dioxide (NO(2)) pollutant was demonstrated by differential optical absorption spectroscopy (DOAS) using a visible acousto-optic tunable filter. In a traditional spectral scanning DOAS system for atmospheric concentration monitoring, a highly stable light source is required. When the light intensity fluctuates during scanning, the concentration retrieval will be inaccurate. In order to reduce the error due to intensity fluctuations, a modified DOAS system has been developed by introducing a broadband light intensity monitoring channel. Using the measured intensity of the broadband channel as the intensity of the light source, the spectrum can be de-biased and the residual intensity variation will primarily result from atmospheric extinction. In addition, by employing the lock-in detection technique, the background light interference is also removed in the modified DOAS system. The atmospheric NO(2) concentration measurement was performed at the campus of City University of Hong Kong, and the results were compared with the concentration reported from a nearby monitoring station in Sham Shui Po, operated by the Hong Kong Environmental Protection Department.

Scattering matrix of infrared radiation by ice finite circular cylinders.

Scattering matrix characteristics of polydisperse, randomly oriented, small ice crystals modeled by finite circular cylinders with various ratios of the length to diameter (L/D) ratio are calculated by use of the exact T-matrix approach, with emphasis on the thermal infrared spectral region that extends from the atmospheric short-wave IR window to the far-IR wavelengths to as large as 30 microm. The observed ice crystal size distribution and the well-known power-law distribution are considered. The results of the extensive calculations show that the characteristics of scattering matrix elements of small ice circular cylinders depend strongly on wavelengths and refractive indices, particle size distributions, and the L/D ratios. The applicability of the power-law distribution and particle shapes for light scattering calculations for small ice crystals is discussed. The effects of the effective variance of size distribution on light scattering characteristics are addressed. It seems from the behavior of scattering matrix elements of small ice crystals that the combination of 25 and 3.979 microm has some advantages and potential applications for remote sensing of cirrus and other ice clouds.