Baseline capillaroscopy provides no evidence of microvascular changes to predict long-COVID syndrome.

BACKGROUND: Long-COVID refers to a variety of symptoms that continue for at least 4 weeks following the onset of acute COVID-19 infection. "Microclots/microvasculopathy" is a potential cutting-edge theory. Nailfold capillaroscopy is a non-invasive method used to assess microvascularity. In this study, we aimed to compare baseline characteristics and capillaroscopic findings of patients with and without long-COVID syndrome. METHODS: Baseline clinical characteristics of 53 patients who tested positive for SARS-CoV-2 were recorded. At the time of COVID-19 diagnosis, patients underwent nailfold capillaroscopy. One year later, patients were rescreened for long-COVID symptoms. Comparisons were made between patients with and without long-COVID syndrome in terms of their baseline characteristics and capillaroscopic findings. RESULTS: There were 35 individuals (66%) with long-COVID syndrome. The most common symptoms related to long-COVID were fatigue (43.4%), myalgia (34%), arthralgia (20.8%), dyspnea (20.8%). In total, 22 patients (41.5%) had abnormal capillaroscopy findings. Like other baseline characteristics, the proportion of patients with abnormal capillaroscopic findings (40% vs 44%, p=0.76) was similar between patients with and without long-COVID syndrome. CONCLUSION: Microvasculopathy and microthrombotic vascular damage are among the strongest hypotheses discussed in this regard. Our results may suggest that factors, rather than baseline microvasculopathy, may drive pathophysiological mechanism underlying the poorly understood long-COVID syndrome (Tab. 2, Ref. 35).

Size-Based Sorting of Emulsion Droplets in Microfluidic Channels Patterned with Laser-Ablated Guiding Tracks.

We demonstrate an autonomous, high-throughput mechanism for sorting of emulsion droplets with different sizes concurrently flowing in a microfluidic Hele-Shaw channel. The aqueous droplets of varying radii suspended in olive oil are separated into different streamlines across the channel upon interaction with a shallow (depth ∼ 700 nm) inclined guiding track ablated into the polydimethylsiloxane-coated surface of the channel with focused femtosecond laser pulses. Specifically, the observed differences in the droplet trajectories along the guiding track arise due to the different scaling of the confinement force attracting the droplets into the track, fluid drag, and wall friction, with the droplet radius. In addition, the distance traveled by the droplets along the track also depends on the track width, with wider tracks providing more stable droplet guiding for any given droplet size. We systematically study the influence of the droplet size and velocity on the trajectory of the droplets in the channel and analyze the sensitivity of size-based droplet sorting for varying flow conditions. The droplet guiding and sorting experiments are complemented by modeling of the droplet motion in the channel flow using computational fluid dynamics simulations and a previously developed model of droplet guiding. Finally, we demonstrate a complete separation of droplets produced by fusion of two independent droplet streams at the inlet of the Hele-Shaw channel from unfused daughter droplets. The presented droplet sorting technique can find applications in the development of analytical and preparative microfluidic protocols.

Enhanced Dissolution of Liquid Microdroplets in the Extensional Creeping Flow of a Hydrodynamic Trap.

A novel noncontact technique based on hydrodynamic trapping is presented to study the dissolution of freely suspended liquid microdroplets into a second immiscible phase in a simple extensional creeping flow. Benzyl benzoate (BB) and n-decanol microdroplets are individually trapped at the stagnation point of a planar extensional flow, and dissolution of single microdroplets into an aqueous solution containing surfactant is characterized at different flow rates. The experimental dissolution curves are compared to two models: (i) the Epstein-Plesset (EP) model which considers only diffusive mass transfer, and (ii) the Zhang-Yang-Mao (ZYM) model which considers both diffusive and convective mass transfer in the presence of extensional creeping flow. The EP model significantly underpredicts the experimentally determined dissolution rates for all experiments. In contrast, very good agreement is observed between the experimental dissolution curves and the ZYM model when the saturation concentration of the microdroplet liquid (cs) is used as the only fitting parameter. Experiments with BB microdroplets at low surfactant concentration (10 µM) reveal cs values very similar to that reported in the literature. In contrast, experiments with BB and n-decanol microdroplets at 10 mM surfactant concentration, higher than the critical micelle concentration (CMC) of 5 mM, show further enhancements in microdroplet dissolution rates due to micellar solubilization. The presented method accurately tests the dissolution of single microdroplets into a second immiscible phase in extensional creeping flow and has potential for applications such as separation processes, food dispersion, and drug development/design.

An Easy-to-Fabricate Microfluidic Shallow Trench Induced Three-Dimensional Cell Culturing and Imaging (STICI3D) Platform.

Compared to the established monolayer approach of two-dimensional cell cultures, three-dimensional (3D) cultures more closely resemble in vivo models; that is, the cells interact and form clusters mimicking their organization in native tissue. Therefore, the cellular microenvironment of these 3D cultures proves to be more clinically relevant. In this study, we present a novel easy-to-fabricate microfluidic shallow trench induced 3D cell culturing and imaging (STICI3D) platform, suitable for rapid fabrication as well as mass manufacturing. Our design consists of a shallow trench, within which various hydrogels can be formed in situ via capillary action, between and fully in contact with two side channels that allow cell seeding and media replenishment, as well as forming concentration gradients of various molecules. Compared to a micropillar-based burst valve design, which requires sophisticated microfabrication facilities, our capillary-based STICI3D can be fabricated using molds prepared with simple adhesive tapes and razors alone. The simple design supports the easy applicability of mass-production methods such as hot embossing and injection molding as well. To optimize the STICI3D design, we investigated the effect of individual design parameters such as corner radii, trench height, and surface wettability under various inlet pressures on the confinement of a hydrogel solution within the shallow trench using Computational Fluid Dynamics simulations supported with experimental validation. We identified ideal design values that improved the robustness of hydrogel confinement and reduced the effect of end-user dependent factors such as hydrogel solution loading pressure. Finally, we demonstrated cultures of human mesenchymal stem cells and human umbilical cord endothelial cells in the STICI3D to show that it supports 3D cell cultures and enables precise control of cellular microenvironment and real-time microscopic imaging. The easy-to-fabricate and highly adaptable nature of the STICI3D platform makes it suitable for researchers interested in fabricating custom polydimethylsiloxane devices as well as those who are in need of ready-to-use plastic platforms. As such, STICI3Ds can be used in imaging cell-cell interactions, angiogenesis, semiquantitative analysis of drug response in cells, and measurement of transport through cell sheet barriers.

Magnetic resonance and fluorescence imaging of doxorubicin-loaded nanoparticles using a novel in vivo model.

We report here the in vivo combined-modality imaging of multifunctional drug delivery nanoparticles. These dextran core-based stealth liposomal nanoparticles (nanosomes) contained doxorubicin, iron oxide for magnetic resonance imaging (MRI) contrast, and BODIPY for fluorescence. The particles were long-lived in vivo because of surface decoration with polyethylene glycol and the incorporation of acetylated lipids that were ultraviolet cross-linked for physical stability. We developed a rodent dorsal skinfold window chamber that facilitated both MRI and non-invasive optical imaging of nanoparticle accumulation in the same tumors. Chamber tumors were genetically labeled with DsRed-2, which enabled co-localization of the MR images, the red fluorescence of the tumor, and the blue fluorescence of the nanoparticles. The nanoparticle design and MR imaging developed with the window chamber were then extended to orthotopic pancreatic tumors expressing DsRed-2. The tumors were MR-imaged using iron oxide-dextran liposomes and by fluorescence to demonstrate the deep imaging capability of these nanoparticles.

A micropillar-based microfluidic viscometer for Newtonian and non-Newtonian fluids.

In this study, a novel viscosity measurement technique based on measuring the deflection of flexible (poly) dimethylsiloxane (PDMS) micropillars is presented. The experimental results show a nonlinear relationship between fluid viscosity and the deflection of micropillars due to viscoelastic properties of PDMS. A calibration curve, demonstrating this nonlinear relationship, is generated, and used to determine the viscosity of an unknown fluid. Using our method, viscosity measurements for Newtonian fluids (glycerol/water solutions) can be performed within 2-100 cP at shear rates γ = 60.5-398.4 s-1. We also measured viscosity of human whole blood samples (non-Newtonian fluid) yielding 2.7-5.1 cP at shear rates γ = 120-345.1 s-1, which compares well with measurements using conventional rotational viscometers (3.6-5.7 cP). With a sensitivity better than 0.5 cP, this method has the potential to be used as a portable microfluidic viscometer for real-time rheological studies.

Microfluidic cell sorter with integrated piezoelectric actuator.

We demonstrate a low-power (<0.1 mW), low-voltage (<10 V(p-p)) on-chip piezoelectrically actuated micro-sorter that can deflect single particles and cells at high-speed. With rhodamine in the stream, switching of flow between channels can be visualized at high actuation frequency (micro1.7 kHz). The magnitude of the cell deflection can be precisely controlled by the magnitude and waveform of input voltage. Both simulation and experimental results indicate that the drag force imposed on the suspended particle/cell by the instantaneous fluid displacement can alter the trajectory of the particle/cell of any size, shape, and density of interest in a controlled manner. The open-loop E. Coli cell deflection experiment demonstrates that the sorting mechanism can produce a throughput of at least 330 cells/s, with a promise of a significantly higher throughput for an optimized design. To achieve close-loop sorting operation, fluorescence detection, real-time signal processing, and field-programmable-gate-array (FPGA) implementation of the control algorithms were developed to perform automated sorting of fluorescent beads. The preliminary results show error-free sorting at a sorting efficiency of micro 70%. Since the piezoelectric actuator has an intrinsic response time of 0.1-1 ms and the sorting can be performed under high flowrate (particle speed of micro 1-10 cm/s), the system can achieve a throughput of >1,000 particles/s with high purity.

Technology Advancements in Blood Coagulation Measurements for Point-of-Care Diagnostic Testing.

In recent years, blood coagulation monitoring has become crucial to diagnosing causes of hemorrhages, developing anticoagulant drugs, assessing bleeding risk in extensive surgery procedures and dialysis, and investigating the efficacy of hemostatic therapies. In this regard, advanced technologies such as microfluidics, fluorescent microscopy, electrochemical sensing, photoacoustic detection, and micro/nano electromechanical systems (MEMS/NEMS) have been employed to develop highly accurate, robust, and cost-effective point of care (POC) devices. These devices measure electrochemical, optical, and mechanical parameters of clotting blood. Which can be correlated to light transmission/scattering, electrical impedance, and viscoelastic properties. In this regard, this paper discusses the working principles of blood coagulation monitoring, physical and sensing parameters in different technologies. In addition, we discussed the recent progress in developing nanomaterials for blood coagulation detection and treatments which opens up new area of controlling and monitoring of coagulation at the same time in the future. Moreover, commercial products, future trends/challenges in blood coagulation monitoring including novel anticoagulant therapies, multiplexed sensing platforms, and the application of artificial intelligence in diagnosis and monitoring have been included.

Solid State Sensor for Simultaneous Measurement of Total Alkalinity and pH of Seawater.

A novel design is demonstrated for a solid state, reagent-less sensor capable of rapid and simultaneous measurement of pH and Total Alkalinity (AT) using ion sensitive field effect transistor (ISFET) technology to provide a simplified means of characterization of the aqueous carbon dioxide system through measurement of two "master variables": pH and AT. ISFET-based pH sensors that achieve 0.001 precision are widely used in various oceanographic applications. A modified ISFET is demonstrated to perform a nanoliter-scale acid-base titration of AT in under 40 s. This method of measuring AT, a Coulometric Diffusion Titration, involves electrolytic generation of titrant, H+, through the electrolysis of water on the surface of the chip via a microfabricated electrode eliminating the requirement of external reagents. Characterization has been performed in seawater as well as titrating individual components (i.e., OH-, HCO3-, CO32-, B(OH)4-, PO43-) of seawater AT. The seawater measurements are consistent with the design in reaching the benchmark goal of 0.5% precision in AT over the range of seawater AT of ∼2200-2500 µmol kg-1 which demonstrates great potential for autonomous sensing.

The effect of ursodeoxycholic acid treatment on epidermal growth factor in patients with bile reflux gastritis.

BACKGROUND/AIMS: Study was performed to evaluate the effect of ursodeoxychlic acid treatment on epidermal growth factor, which is secreted in response to mucosal injury and is also a factor in the protection and healing of gastric mucosal injury in patients with bile reflux gastritis following cholecystectomy. METHODS: Thirty-one dyspeptic patients who had previously undergone cholecystectomy were included in the study. Upper gastrointestinal endoscopy was performed before and after a six week ursodeoxychlic acid treatment period and a biopsy was taken. Endoscopic biopsy materials were stained with epidermal growth factor (Zymed, supersensitive) immunohistochemical monoclonal kit. RESULTS: The results of endoscopic examination prior to treatment were as follows: 24 cases (77%) had reflux gastritis, five cases (16%) antral gastritis, two cases (6.5%) diffuse gastritis and all cases had enterogastric reflux. In all but one case, epidermal growth factor was found to be positive at varning degrees. After ursodeoxychlic acid treatment, complete healing was observed at endoscopy in nine cases (29%) and partial healing at varning degrees was observed in all others. The degree of positivity of epidermal growth factor reduced significantly (p<0.001). CONCLUSIONS: A decrease in the degree of epidermal growth factor positivity was observed following ursodeoxychlic acid treatment. This can be explained by the decrease in epidermal growth factor release due to healing of mucosal injury following treatment. Further investigations are needed to clarify whether ursodeoxychlic acid has a direct effect on epidermal growth factor.

Enhancing magnetic resonance imaging tumor detection with fluorescence intensity and lifetime imaging.

Early detection is important for many solid cancers but the images provided by ultrasound, magnetic resonance imaging (MRI), and computed tomography applied alone or together, are often not sufficient for decisive early screening ∕ diagnosis. We demonstrate that MRI augmented with fluorescence intensity (FI) substantially improves detection. Early stage murine pancreatic tumors that could not be identified by blinded, skilled observers using MRI alone, were easily identified with MRI along with FI images acquired with photomultiplier tube detection and offset laser scanning. Moreover, we show that fluorescence lifetime (FLT) imaging enables positive identification of the labeling fluorophore and discriminates it from surrounding tissue autofluorescence. Our data suggest combined-modality imaging with MRI, FI, and FLT can be used to screen and diagnose early tumors.

[Effect of propranolol on renal hemodynamics in patients with cirrhosis: assessment with Doppler US]. / Siroz hastalarinda propranololün renal hemodinamik etkileri: Doppler US ile degerlendirme.

PURPOSE: To determine the renal resistive index profile in cirrhotic patients before and after propranolol treatment and assess the effects of propranolol on renal hemodynamics. MATERIALS AND METHODS: Thirty-six patients with cirrhosis and ascites (decompensated group), 39 patients with cirrhosis but no ascites (compensated group) and 25 patients with normal renal and hepatic functions (control group) were studied. All had normal blood urea nitrogen and serum creatinine levels. The renal resistive index was calculated in all patients before and after oral propranolol treatment. RESULTS: Resistive index was significantly higher in the decompensated group (p<0.05) than in other groups. After propranolol treatment, resistive indices decreased in the compensated patients (p<0.05) but increased in the decompensated group (p<0.05). There was a slight but statistically insignificant increase in the control group. CONCLUSION: In patients with cirrhosis renal failure is a significant risk factor for liver transplantation. In these patients, Doppler sonography provides early detection of renal dysfunction even before renal function tests are abnormal. Doppler sonography is a useful noninvasive method to evaluate the effects of drugs on renal hemodynamics.