Diffusion Mapping with Diffractive Optical Elements for Periodically Patterned Photobleaching.

Fourier transform-fluorescence recovery after photobleaching (FT-FRAP) using a diffractive optical element (DOE) is shown to support distance-dependent diffusion analysis in biologically relevant media. Integration of DOEs enables patterning of a dot array for parallel acquisition of point-bleach FRAP measurements at multiple locations across the field of view. In homogeneous media, the spatial harmonics of the dot array analyzed in the spatial Fourier transform domain yield diffusion recovery curves evaluated over specific well-defined distances. Relative distances for diffusive recovery in the spatial Fourier transform domain are directly connected to the 2D (h,k) Miller indices of the corresponding lattice lines. The distribution of the photobleach power across the entire field of view using a multidot array pattern greatly increases the overall signal power in the spatial FT-domain for signal-to-noise improvements. Derivations are presented for the mathematical underpinnings of FT-FRAP performed with 2D periodicity in the photobleach patterns. Retrofitting of FT-FRAP into instrumentation for high-throughput FRAP analysis (Formulatrix) supports automated analysis of robotically prepared 96-well plates for precise quantification of molecular mobility. Figures of merit are evaluated for FT-FRAP in analysis for both slow diffusion of fluorescent dyes in glassy polymer matrices spanning several days and model proteins and monoclonal antibodies within aqueous solutions recovering in matters of seconds.

Periodic Photobleaching with Structured Illumination for Diffusion Imaging.

The use of periodically structured illumination coupled with spatial Fourier-transform fluorescence recovery after photobleaching (FT-FRAP) was shown to support diffusivity mapping within segmented domains of arbitrary shape. Periodic "comb-bleach" patterning of the excitation beam during photobleaching encoded spatial maps of diffusion onto harmonic peaks in the spatial Fourier transform. Diffusion manifests as a simple exponential decay of a given harmonic, improving the signal to noise ratio and simplifying mathematical analysis. Image segmentation prior to Fourier transformation was shown to support pooling for signal to noise enhancement for regions of arbitrary shape expected to exhibit similar diffusivity within a domain. Following proof-of-concept analyses based on simulations with known ground-truth maps, diffusion imaging by FT-FRAP was used to map spatially-resolved diffusion differences within phase-separated domains of model amorphous solid dispersion spin-cast thin films. Notably, multi-harmonic analysis by FT-FRAP was able to definitively discriminate and quantify the roles of internal diffusion and exchange to higher mobility interfacial layers in modeling the recovery kinetics within thin amorphous/amorphous phase-separated domains, with interfacial diffusion playing a critical role in recovery. These results have direct implications for the design of amorphous systems for stable storage and efficacious delivery of therapeutic molecules.

Readmission Risk Factors and Heart Failure With Preserved Ejection Fraction.

CONTEXT: Cases of heart failure with preserved ejection fraction (HFpEF) exacerbations continue to affect patients' quality of life and cause significant financial burden on our healthcare system. OBJECTIVE: To identify risk factors for readmission in patients discharged with a diagnosis of HFpEF. METHODS: Electronic health records of patients over 18 years of age with a primary diagnosis of HFpEF treated between August 1, 2017 and March 1, 2018 in a community hospital were retrospectively reviewed. The study population included patients with HFpEF greater than 40% who were screened but did not qualify for the ongoing CONNECT- HF trial being conducted by Duke Clinical Research. To be included, subjects had to fall into 1 of 2 classifications (NYHA Class II-IV or ACC/AHA Stage B-D) and have a life expectancy greater than 6 months. Patients were excluded if they had terminal illness other than HF, a prior heart transplant or were on a transplant list, a current or planned placement of a left ventricular assist device, chronic kidney disease requiring hemodialysis, inability to use mobile applications, or inability to participate in longitudinal follow up. Readmission rate was analyzed at 30 and 90 days along with patients' demographics and associated comorbidities, including peripheral vascular disease, anemia, pulmonary hypertension, arrythmia, and valvular heart disease. Patients were risk stratified using the LACE index readmission score and the Charlson comorbidity index. RESULTS: Of the 492 cases of HFpEF identified during the 7-month study period, 212 patients were included. The majority of patients were women (126; 59.4%), had a median body mass index above 30 kg/m2 (123; 58%), and had pulmonary hypertension (94; 44.3%), anemia (146; 68.8%), and arrhythmia (101, 47.6%). Forty-five (21.2%) patients were readmitted for HFpEF within 90 days of initial discharge; 32 of those (71.1%) were readmitted within 30 days of initial discharge. Patients with higher LACE and Charlson comorbidity index scores were more likely to be readmitted within 90 days. Peripheral vascular disease (P=.002), tricuspid regurgitation (P=.001), pulmonary hypertension (P=.049), and anemia (P=.029) were risk factors associated with readmissions. Use of ACEi/ARBs (P=.017) was associated with fewer readmissions. CONCLUSION: Anemia, peripheral vascular disease, pulmonary hypertension, and valvular heart disease are not only postulated mechanisms of HFpEF, but also important risk factors for readmission. These study findings affirm the need for continued research of the pathophysiology and associated comorbidities of the HFpEF population to improve quality of life and lower healthcare costs.

Anomalous Diffusion Characterization by Fourier Transform-FRAP with Patterned Illumination.

Fourier transform fluorescence recovery after photobleaching (FT-FRAP) with patterned illumination is theorized and demonstrated for quantitatively evaluating normal and anomalous diffusion. Diffusion characterization is routinely performed to assess mobility in cell biology, pharmacology, and food science. Conventional FRAP is noninvasive, has low sample volume requirements, and can rapidly measure diffusion over distances of a few micrometers. However, conventional point-bleach measurements are complicated by signal-to-noise limitations, the need for precise knowledge of the photobleach beam profile, potential for bias due to sample heterogeneity, and poor compatibility with multiphoton excitation because of local heating. In FT-FRAP with patterned illumination, the time-dependent fluorescence recovery signal is concentrated to puncta in the spatial Fourier domain, with substantial improvements in signal-to-noise, mathematical simplicity, representative sampling, and multiphoton compatibility. A custom nonlinear optical beam-scanning microscope enabled patterned illumination for photobleaching through two-photon excitation. Measurements in the spatial Fourier domain removed dependence on the photobleach profile, suppressing bias from imprecise knowledge of the point spread function. For normal diffusion, the fluorescence recovery produced a simple single-exponential decay in the spatial Fourier domain, in excellent agreement with theoretical predictions. Simultaneous measurement of diffusion at multiple length scales was enabled through analysis of multiple spatial harmonics of the photobleaching pattern. Anomalous diffusion was characterized by FT-FRAP through a nonlinear fit to multiple spatial harmonics of the fluorescence recovery. Constraining the fit to describe diffusion over multiple length scales resulted in higher confidence in the recovered fitting parameters. Additionally, phase analysis in FT-FRAP was shown to inform on flow/sample translation.

A novel interventional approach to upper extremity swelling.

This case report describes a 57-year-old man who presented to the emergency department with right upper extremity swelling and redness. He was diagnosed with right upper extremity deep venous thrombosis extending from the brachial vein to the subclavian vein. The patient underwent successful mechanical thrombectomy with the ClotTriever system (Inari Medical, Irvine, Calif).

Slow-releasing permanganate ions from permanganate core-manganese oxide shell particles for the oxidative degradation of an algae odorant in water.

In this work, potassium permanganate particles (KMnO4) were modified with a manganese oxide (MnOx) shell comprising passages for the slow release of permanganate ions (MnO4-) in aquatic systems. The bare particle (KMnO4) and KMnO4 core-MnOx shell particles (CP-60) were characterized by attenuated total reflectance (ATR)-Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and X-ray photoelectron spectroscopy (XPS). The CP-60 were evaluated as a slow source of MnO4- for the oxidative treatment of pure and lake water containing dimethyl trisulfide (DMTS), a water odorant produced by cyanobacteria in many eutrophic waters. XPS and ATR-FTIR results confirmed the presence of MnOx surface shell (diameter ∼ 1 µm) on CP-60. SEM images revealed cracks on CP-60, which serve as outlets for MnO4-. Approximately 0.76 ±â€¯0.07 g KMnO4/g of CP-60 was released from the core of CP-60 after 120 min. The CP-60 degraded 88.9 ±â€¯2.5% and 70.8 ±â€¯6.3% of DMTS in pure water and lake water matrix within 120 min, respectively. The degradation was slightly more effective than the degradation using aqueous KMnO4 (74.2%) reported in literature. The release kinetics of the particles is consistent with a pseudo-first order equation with correlation coefficients of 0.99 and 0.97 in pure water and lake water matrix, respectively. The CP could serve as low cost slow-release particles for the degradation of micropollutants, even in cyanobacteria laden water. Notably, the in situ MnOx formed during the KMnO4 oxidation reaction can facilitate adsorption of organics and metal ions, improving water quality.