Genetic Variants That Modify the Neuroendocrine Regulation of Foraging Behavior in C. elegans.

The molecular mechanisms underlying diversity in animal behavior are not well understood. A major experimental challenge is determining the contribution of genetic variants that affect neuronal gene expression to differences in behavioral traits. The neuroendocrine TGF-beta ligand, DAF-7, regulates diverse behavioral responses of Caenorhabditis elegans to bacterial food and pathogens. The dynamic neuron-specific expression of daf-7 is modulated by environmental and endogenous bacteria-derived cues. Here, we investigated natural variation in the expression of daf-7 from the ASJ pair of chemosensory neurons and identified common variants in gap-2, encoding a GTPase-Activating Protein homologous to mammalian SynGAP proteins, which modify daf-7 expression cell-non-autonomously and promote exploratory foraging behavior in a DAF-7-dependent manner. Our data connect natural variation in neuron-specific gene expression to differences in behavior and suggest that genetic variation in neuroendocrine signaling pathways mediating host-microbe interactions may give rise to diversity in animal behavior.

Robust unenhanced peripheral magnetic resonance angiography using single-slab 3D chemical-shift-encoded GRASE.

Objective.To develop a novel, unenhanced magnetic resonance angiography (MRA) exploiting cardiac-gated, single-slab 3D chemical-shift-encoded gradient- and spin-echo (GRASE) imaging for robust background suppression.Approach.The proposed single-slab 3D GRASE employs variable-flip-angles (VFA) in the refocusing radio-frequency (RF) pulse train to promote sensitivity to blood flow as well as imaging encoding efficiency. Phase encoding blips are inserted between adjacent lobes of the switching readout gradients such that chemical shift-induced phase information is encoded into different locations in k-space. Based on the assumption that most background signals in the angiogram come from the fatty tissues, the proposed method directly separates angiograms from fatty background tissue signals from highly incomplete measurements by solving a constrained optimization problem with sparsity prior. Numerical simulations and experiments were performed to validate the effectiveness of the proposed method in healthy volunteers as compared with conventional fresh blood imaging (FBI).Main results.Compared with conventional FBI, the proposed method yields clearer delineation of small branching arteries and robust fatty background suppression without apparent loss of signals.Significance.We have successfully demonstrated the feasibility of the proposed, single-slab 3D VFA GRASE with chemical-shift-encoded reconstruction for the generation of robust unenhanced peripheral MRA.

A prospective patient registry to monitor safety, effectiveness, and utilisation of bedaquiline in patients with multidrug-resistant tuberculosis in South Korea.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) represents a major public health concern, with an ongoing need for new effective treatments. Bedaquiline is an oral diarylquinoline that has shown encouraging treatment success and culture conversion rates in MDR-TB. METHODS: A South Korean patient registry was set up across 19 centres between 2016 and 2018 for the prospective collection of data from patients with MDR-TB who received either a bedaquiline-containing or a non-bedaquiline-containing regimen. Treatment was at the physician's discretion (bedaquiline use requiring approval by special committee) and was based on patient characteristics, disease status, and local treatment guidelines. RESULTS: The safety population included 172 patients (88 bedaquiline and 84 non-bedaquiline). The mean (standard deviation, SD) duration of follow-up was 24.3 (9.5) months. Mean (SD) durations of treatment were 5.4 (1.8) months in bedaquiline-treated patients and 15.7 (6.7) months in the non-bedaquiline group. Treatment success (cured and treatment completed according to WHO 2013 treatment outcome definitions) was achieved by 56.3% of bedaquiline-treated and 45.2% of non-bedaquiline-treated patients. Sputum culture conversion rates were 90.4% and 83.7% with and without bedaquiline, respectively. Diarrhoea and nausea were the most frequently reported treatment-emergent adverse events (TEAEs) in the bedaquiline group (27.3% [24/88] and 22.7% [20/88], respectively). The most frequent bedaquiline-related TEAEs were prolonged QT interval (10.2%; 9/88), and diarrhoea and nausea (9.1% each; 8/88). QT interval prolongation was reported in 19.3% (17/88) of bedaquiline-treated and 2.4% (2/84) of non-bedaquiline-treated patients, but bedaquiline was not discontinued for any patient for this reason. There were 13 (14.7%) and three (3.6%) deaths in the bedaquiline-treated and non-bedaquiline groups, respectively. Review of fatal cases revealed no unexpected safety findings, and no deaths were bedaquiline-related. The most common cause of death was worsening cancer (three patients). Patients in the bedaquiline group tended to have poorer baseline risk profiles than non-bedaquiline patients and were more likely to have relapsed or already failed second-line treatment. Interpretation of mortality data was complicated by high rates of loss to follow-up in both groups. CONCLUSIONS: The South Korean registry findings support previous risk/benefit observations and the continued use of bedaquiline as part of combination therapy in patients with MDR-TB.

Automated Detection of Surgical Implants on Plain Knee Radiographs Using a Deep Learning Algorithm.

Background and Objectives: The number of patients who undergo multiple operations on a knee is increasing. The objective of this study was to develop a deep learning algorithm that could detect 17 different surgical implants on plain knee radiographs. Materials and Methods: An internal dataset consisted of 5206 plain knee antero-posterior X-rays from a single, tertiary institute for model development. An external set contained 238 X-rays from another tertiary institute. A total of 17 different types of implants including total knee arthroplasty, unicompartmental knee arthroplasty, plate, and screw were labeled. The internal dataset was approximately split into a train set, a validation set, and an internal test set at a ratio of 7:1:2. You Only look Once (YOLO) was selected as the detection network. Model performances with the validation set, internal test set, and external test set were compared. Results: Total accuracy, total sensitivity, total specificity value of the validation set, internal test set, and external test set were (0.978, 0.768, 0.999), (0.953, 0.810, 0.990), and (0.956, 0.493, 0.975), respectively. Means ± standard deviations (SDs) of diagonal components of confusion matrix for these three subsets were 0.858 ± 0.242, 0.852 ± 0.182, and 0.576 ± 0.312, respectively. True positive rate of total knee arthroplasty, the most dominant class of the dataset, was higher than 0.99 with internal subsets and 0.96 with an external test set. Conclusion: Implant identification on plain knee radiographs could be automated using a deep learning technique. The detection algorithm dealt with overlapping cases while maintaining high accuracy on total knee arthroplasty. This could be applied in future research that analyzes X-ray images with deep learning, which would help prompt decision-making in clinics.

Generalized self-calibrating simultaneous multi-slice MR image reconstruction from 3D Fourier encoding perspective.

This work introduces a novel, k-space based one-step solution for simultaneous multi-slice MR image reconstruction from 3D Fourier encoding perspective. With undersampled SMS imaging, image reconstruction suffers from both inter-slice leakages and in-plane aliasing artifacts. Aliasing separation becomes further challenging in the presence of discrepancies between calibration and imaging. To address them, in this work a measured SMS 3D k-space with additional calibrating signals is decomposed into SMS imaging and self-calibrating data sets. Extended controlled aliasing is performed by upsampling the measured data in the kz-direction. A slice-specific null space operator is then learned using extended self-calibration exploiting target slices and additional in-plane-shifted images. Inter-slice leakages and in-plane aliasing artifacts are jointly resolved in a single step by solving a constrained optimization problem in which null space reconstruction consistency is balanced with a Hankel-structured low rank prior while data fidelity in 3D Fourier space is enforced. Retrospective and prospective studies are performed to validate the effectiveness of the proposed method in various regions including knee and L-spine.

Microwave-Assisted Dendropanax morbifera Extract for Cosmetic Applications.

Recently, utilizing natural bioactive compounds for active ingredients in cosmetics has become a growing worldwide trend. More and more studies aim to identify the sources of herbal ingredients for applications in the pharmaceutical and cosmetic fields. Additionally, in order to optimize the safety of natural ingredients, choosing an environmentally friendly extraction method also plays an important role. In this work, an eco-friendly extraction technique for Dendropanax morbifera using microwave treatment and microwave-assisted Dendropanax morbifera extract (MA-DME) was investigated. The results indicate that higher yields of MA-DME were obtained than with conventional methods and that D. morbifera's antioxidant properties were enhanced. Moreover, we found that MA-DME exhibited extraordinary antioxidant, anti-aging, and skin-whitening activities. We suggest MA-DME as a potential cosmeceutical ingredient than could be utilized for comprehensive protection of human skin.

SNR-Enhanced, Rapid Electrical Conductivity Mapping Using Echo-Shifted MRI.

Magnetic resonance electrical impedance tomography (MREIT) permits high-spatial resolution electrical conductivity mapping of biological tissues, and its quantification accuracy hinges on the signal-to-noise ratio (SNR) of the current-induced magnetic flux density (Bz). The purpose of this work was to achieve Bz SNR-enhanced rapid conductivity imaging by developing an echo-shifted steady-state incoherent imaging-based MREIT technique. In the proposed pulse sequence, the free-induction-decay signal is shifted in time over multiple imaging slices, and as a result is exposed to a plurality of injecting current pulses before forming an echo. Thus, the proposed multi-slice echo-shifting strategy allows a high SNR for Bz for a given number of current injections. However, with increasing the time of echo formation, the Bz SNR will also be compromised by T2*-related signal loss. Hence, numerical simulations were performed to evaluate the relationship between the echo-shifting and the Bz SNR, and subsequently to determine the optimal imaging parameters. Experimental studies were conducted to evaluate the effectiveness of the proposed method over conventional spin-echo-based MREIT. Compared with the reference spin-echo MREIT, the proposed echo-shifting-based method improves the efficiency in both data acquisition and current injection while retaining the accuracy of conductivity quantification. The results suggest the feasibility of the proposed MREIT method as a practical means for conductivity mapping.

FID-calibrated simultaneous multi-slice fast spin echo with long trains of hard pulses.

Objective. To develop a novel, free-induction-decay (FID)-calibrated single-shot simultaneous multi-slice fast spin echo (SMS-FSE) with very long hard pulse trains for high encoding efficiency and low energy deposition.Approach. The proposed single-shot SMS-FSE employs a mixed pulse configuration in which a long excitation pulse that is spatially multi-band (MB) selective is used in conjunction with short spatially nonselective refocusing pulses. To alleviate energy deposition to tissues while reducing signal modulation along the echo train, variable low flip angles with signal prescription are utilized in the refocusing pulse train. A time-efficient FID calibration and correction method is introduced before aliased voxels in the slice direction are resolved. Simulations and experiments are performed to demonstrate the feasibility of the proposed method as an alternative to conventional HASTE for generatingT2-weighted images.Main results. Compared with conventional HASTE, the proposed method enhances imaging speed effectively by an MB factor up to 5 without apparent loss of image contrast while successfully eliminating FID artifacts.Significance. We successfully demonstrated the feasibility of the proposed method as an encoding- and energy-efficient alternative to conventional HASTE for generation ofT2-weighted contrast.

Joint Reconstruction of Vascular Structure and Function Maps in Dynamic Contrast Enhanced MRI Using Vascular Heterogeneity Priors.

This work introduces a novel, joint reconstruction of vascular structure and microvascular function maps directly from highly undersampled data in k - t space using vascular heterogeneity priors for high-definition, dynamic contrast-enhanced (DCE) MRI. In DCE MRI, arteries and veins are characterized by rapid, high uptake and wash-out of contrast agents (CA). On the other hand, depending on CA uptake and wash-out signal patterns, capillary tissues can be categorized into highly perfused, moderately perfused, and necrotic regions. Given the above considerations, macrovascular maps are generated as a prior to differentiate penalties on arteries relative to capillary tissues during image reconstruction. Furthermore, as a microvascular prior, contrast dynamics in capillary regions are represented in a low dimensional space using a finite number of basic vectors that reflect actual tissue-specific signal patterns. Both vascular structure and microvascular function maps are jointly estimated by solving a constrained optimization problem in which the above vascular heterogeneity priors are represented by spatially weighted nonnegative matrix factorization. Retrospective and prospective experiments are performed to validate the effectiveness of the proposed method in generating well-defined vascular structure and microvascular function maps for patients with brain tumor at high reduction factors.

Whole-Neck Non-Contrast-Enhanced MR Angiography Using Velocity Selective Magnetization Preparation.

This study aimed to optimize velocity-selective magnetic resonance angiography (VS-MRA) protocols for whole-neck angiography and demonstrate its feasibility in healthy subjects with comparisons to clinical 3D time-of-flight (TOF) angiography. To help optimize VS-MRA protocols, 2D phase-contrast (PC) flow imaging and 3D B0 and B1 field mappings were performed on five healthy volunteers. Based on these measurements, a slab-selective (SS) inversion preparation was applied prior to a VS saturation preparation to further suppress venous blood, while the VS preparation pulse was designed with compensation for field offsets. VS-MRA and 3D TOF were performed on six healthy subjects, and relative contrast ratios (CRs) between artery and muscle signals were calculated for twenty arterial regions for comparisons. The pre-compensated VS pulse improved the visualization of the subclavian arteries and suppression of background tissues, which involved large B0 and B1 field errors. The combination of SS and VS preparations effectively suppressed venous blood. While the relative CR values were 0.78 ± 0.08 and 0.72 ± 0.10 for VS-MRA and 3D TOF, respectively, over the twenty segments, VS-MRA outperformed 3D TOF in visualizing arterial segments of a small size or with a horizontal orientation, such as subclavian, facial, and occipital arteries. The proposed neck VS-MRA with the field-error-compensated VS preparation combined with the SS preparation is feasible and superior to 3D TOF in visualizing small and/or horizontally oriented arterial segments.

Assessing the reproducibility of high temporal and spatial resolution dynamic contrast-enhanced magnetic resonance imaging in patients with gliomas.

Temporal and spatial resolution of dynamic contrast-enhanced MR imaging (DCE-MRI) is critical to reproducibility, and the reproducibility of high-resolution (HR) DCE-MRI was evaluated. Thirty consecutive patients suspected to have brain tumors were prospectively enrolled with written informed consent. All patients underwent both HR-DCE (voxel size, 1.1 × 1.1 × 1.1 mm3; scan interval, 1.6 s) and conventional DCE (C-DCE; voxel size, 1.25 × 1.25 × 3.0 mm3; scan interval, 4.0 s) MRI. Regions of interests (ROIs) for enhancing lesions were segmented twice in each patient with glioblastoma (n = 7) to calculate DCE parameters (Ktrans, Vp, and Ve). Intraclass correlation coefficients (ICCs) of DCE parameters were obtained. In patients with gliomas (n = 25), arterial input functions (AIFs) and DCE parameters derived from T2 hyperintense lesions were obtained, and DCE parameters were compared according to WHO grades. ICCs of HR-DCE parameters were good to excellent (0.84-0.95), and ICCs of C-DCE parameters were moderate to excellent (0.66-0.96). Maximal signal intensity and wash-in slope of AIFs from HR-DCE MRI were significantly greater than those from C-DCE MRI (31.85 vs. 7.09 and 2.14 vs. 0.63; p < 0.001). Both 95th percentile Ktrans and Ve from HR-DCE and C-DCE MRI could differentiate grade 4 from grade 2 and 3 gliomas (p < 0.05). In conclusion, HR-DCE parameters generally showed better reproducibility than C-DCE parameters, and HR-DCE MRI provided better quality of AIFs.

Clinical Implications of Neurological Comorbidities and Complications in ICU Patients with COVID-19.

Clinical implications of neurological problems during intensive care unit (ICU) care for coronavirus disease 2019 (COVID-19) patients are unknown. This study aimed to describe the clinical implications of preexisting neurological comorbidities and new-onset neurological complications in ICU patients with COVID-19. ICU patients who were isolated and treated for COVID-19 between 19 February 2020 and 3 May 2020, from one tertiary hospital and one government-designated branch hospital were included. Clinical data including previous neurological disorders were extracted from electronic medical records. All neurological complications were evaluated by neurointensivists. Multiple logistic regression analysis was performed to investigate independent factors in ICU mortality. The median age of 52 ICU patients with COVID-19 was 73 years. Nineteen (36.5%) patients had preexisting neurological comorbidities, and new-onset neurological complications occurred in 23 (44.2%) during ICU admission. Patients with preexisting neurological comorbidities required tracheostomy more frequently and more ventilator and ICU days than those without. Patients with new-onset neurological complications experienced more medical complications and had higher ICU severity score and ICU mortality rates. New-onset neurological complications remained an independent factor for ICU mortality. Many COVID-19 patients in the ICU have preexisting neurological comorbidities, making them at a high risk of new-onset neurological complications.

Single-shot pseudo-centric EPI for magnetization-prepared imaging.

PURPOSE: To implement a single-shot centric-reordered EPI (1sh-CenEPI), which reduces TE significantly, thus enabling to improve SNR for magnetization-prepared imaging. METHODS: We proposed a 1sh-CenEPI in which grouped oscillating readout gradients, phase-encoding blips within each group, and big phase-encoding jumps between two consecutive groups are incorporated to encode whole k-space from the center to the edges in a single shot. The concept was tested on phantoms and human brains at 3 T. In addition, the proposed reordering scheme was applied to pseudo-continuous arterial spin labeling for evaluating the efficiency of the centric reordering in magnetization-prepared imaging. RESULTS: The proposed 1sh-CenEPI reduced TE from 50 ms to 1.4 ms for gradient-echo EPI, and from 100 ms to 7 ms for spin-echo EPI, while the elongation of readout duration was below 10% of the whole readout duration in most cases. The 1sh-CenEPI images exhibited no distinct geometric distortion both in phantom and human brain, comparable to the conventional two-shot center-out EPI. In pseudo-continuous arterial spin labeling results, 3-fold temporal SNR increase and 2-fold spatial SNR increase in the perfusion-weighted images were achieved with 1sh-CenEPI compared with the conventional linear ordering, whereas the cerebral blood flow values were consistent with previous studies. CONCLUSION: The proposed 1sh-CenEPI significantly reduced TE while maintaining similar readout window and providing images comparable to the conventional linear and multishot center-out EPI images. It can be a qualified candidate as a new readout for various magnetization-prepared imaging techniques.

Rapid three-dimensional steady-state chemical exchange saturation transfer magnetic resonance imaging.

PURPOSE: To make clinically feasible whole-brain chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) by enhancing imaging efficiency. METHODS: A novel, whole-brain three-dimensional (3D) steady-state CEST MRI method was introduced by utilizing a time-efficient, fat-suppressed excitation followed by rapid, segmented 3D echo-planar-imaging with incoherent undersampling in k-ω space. Missing signals and CEST-specific spectral images were then jointly estimated directly from incomplete measurements using model-based reconstruction and robust spectral analysis. In vivo studies were performed at 3T both retrospectively (using a fully sampled reference) and prospectively to validate the effectiveness of the proposed method in patients with brain cancer. RESULTS: In retrospective studies, the proposed method exhibits superior accuracies to existing methods in estimating images, z-spectra, and APTw relative to the reference. In prospective patient studies, compared with existing methods, the proposed method is statistically significantly different in contrast-to-noise ratio of the APTw contrast between tumor and normal appearing white matter (NAWM) and amide proton transfer weighted contrast (p < 0.05) while not being significantly different in signal-to-noise ratio in an NAWM region. CONCLUSIONS: We successfully demonstrated that it is feasible to perform whole-brain CEST MRI roughly within 4 minutes for patients with brain cancer. It is expected that the proposed method widens clinical utilities of CEST MRI.

Immediate activation of chemosensory neuron gene expression by bacterial metabolites is selectively induced by distinct cyclic GMP-dependent pathways in Caenorhabditis elegans.

Dynamic gene expression in neurons shapes fundamental processes in the nervous systems of animals. However, how neuronal activation by different stimuli can lead to distinct transcriptional responses is not well understood. We have been studying how microbial metabolites modulate gene expression in chemosensory neurons of Caenorhabditis elegans. Considering the diverse environmental stimuli that can activate chemosensory neurons of C. elegans, we sought to understand how specific transcriptional responses can be generated in these neurons in response to distinct cues. We have focused on the mechanism of rapid (<6 min) and selective transcriptional induction of daf-7, a gene encoding a TGF-ß ligand, in the ASJ chemosensory neurons in response to the pathogenic bacterium Pseudomonas aeruginosa. DAF-7 is required for the protective behavioral avoidance of P. aeruginosa by C. elegans. Here, we define the involvement of two distinct cyclic GMP (cGMP)-dependent pathways that are required for daf-7 expression in the ASJ neuron pair in response to P. aeruginosa. We show that a calcium-independent pathway dependent on the cGMP-dependent protein kinase G (PKG) EGL-4, and a canonical calcium-dependent signaling pathway dependent on the activity of a cyclic nucleotide-gated channel subunit CNG-2, function in parallel to activate rapid, selective transcription of daf-7 in response to P. aeruginosa metabolites. Our data suggest that fast, selective early transcription of neuronal genes require PKG in shaping responses to distinct microbial stimuli in a pair of C. elegans chemosensory neurons.

Association of scar distribution with epicardial electrograms and surface ventricular tachycardia QRS duration in nonischemic cardiomyopathy.

INTRODUCTION: The association of late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) with epicardial and surface ventricular tachycardia (VT) electrogram features, in nonischemic cardiomyopathy (NICM), is unknown. We sought to define the association of LGE and viable wall thickness with epicardial electrogram features and exit site paced QRS duration in patients with NICM. METHODS: A total of 19 patients (age 53.5 ± 11.5 years) with NICM (ejection fraction 40.2 ± 13.2%) underwent CMR before VT ablation. LGE transmurality was quantified on CMR and coregistered with 2294 endocardial and 2724 epicardial map points. RESULTS: Both bipolar and unipolar voltage were associated with transmural signal intensity on CMR. Longer electrogram duration and fractionated potentials were associated with increased LGE transmurality, but late potentials or local abnormal ventricular activity were more prevalent in nontransmural versus transmural LGE regions (p < .05). Of all critical VT sites, 19% were located adjacent to regions with LGE but normal bipolar and unipolar voltage. Exit site QRS duration was affected by LGE transmurality and intramural scar location, but not by wall thickness, at the impulse origin. CONCLUSIONS: In patients with NICM and VT, LGE is associated with epicardial electrogram features and may predict critical VT sites. Additionally, exit site QRS duration is affected by LGE transmurality and intramural location at the impulse origin or exit.

Model-Based Chemical Exchange Saturation Transfer MRI for Robust z-Spectrum Analysis.

This paper introduces a novel, model-based chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI), in which asymmetric spectra of interest are directly estimated from complete or incomplete measurements by incorporating subspace-based spectral signal decomposition into the measurement model of CEST MRI for a robust z-spectrum analysis. Spectral signals are decomposed into symmetric and asymmetric components. The symmetric component, which varies smoothly, is delineated by the linear superposition of a finite set of vectors in a basis trained from the simulated (Lorentzian) signal vectors augmented with data-driven signal vectors, while the asymmetric component is to be inherently lower than or equal to zero due to saturation transfer phenomena. Spectral decomposition is performed directly on the measured spectral data by solving a constrained optimization problem that employs the linearized spectral decomposition model for the symmetric component and the weighted Frobenius norm regularization for the asymmetric component while utilizing additional spatial sparsity and low-rank priors. The simulations and in vivo experiments were performed to demonstrate the feasibility of the proposed method as a reliable molecular MRI.

Model-Based High-Definition Dynamic Contrast Enhanced MRI for Concurrent Estimation of Perfusion and Microvascular Permeability.

This work introduces a model-based, high-definition dynamic contrast enhanced (DCE) MRI for concurrent estimation of perfusion and microvascular permeability over the whole brain. A time series of reference-subtracted signals is decomposed into one component that reflects main contrast dynamics and the other one that includes residual contrast agents (CA) and background signals. The former is described by linear superposition of a finite number of basic vectors trained from an augmented set of data that consists of tracer-kinetic model driven signal vectors and patient-specific measured ones. Contrast dynamics is estimated by solving a constrained optimization problem that incorporates the linearized signal decomposition into the measurement model of DCE MRI and then combining the main component with the background-suppressed, residual CA signals. To the best of our knowledge, this is the first work that prospectively enables rapid temporal sampling with 1.5 s (3 ∼ 4 times higher than clinical routines) while simultaneously achieving high isotropic spatial resolution with 1.0 mm3 (4 ∼ 6 times higher than routines), enhancing estimation of both patient-specific inputs and outputs for quantification of microvascular functions. Simulations and experiments are performed to demonstrate the effectiveness of the proposed method in patients with brain cancer.

Status of international normalized ratio control and treatment patterns in patients with nonvalvular atrial fibrillation taking vitamin K antagonist with or without antiplatelet therapy: Results from KORAFII registry.

BACKGROUND: Studies have shown that the concomitant use of a vitamin K antagonist (VKA) and an antiplatelet (APL) drug increased the bleeding risk and was less effective at preventing ischemic events. This study aimed to investigate the control status of international normalized ratio (INR) and the discontinuation rate of a VKA in patients taking VKA plus an APL drug compared with those taking a VKA alone. METHODS: Data were extracted from the KORean Atrial Fibrillation Investigation II registry, a multicenter noninterventional prospective observational study. Nonvalvular atrial fibrillation (NVAF) patients with CHADS 2 scores ≥ 1 who newly started (within 3 months) a VKA were enrolled and followed up for 1 year. RESULTS: A total of 866 NVAF patients (mean age, 67.7 years; 60.3% men) without a bleeding history were divided into the VKA+APL (n = 229) and VKA alone (n = 637) groups. During follow-up, mean INR level was lower in the VKA+APL group than in the VKA alone group (1.7 ± 0.8 vs 1.9 ± 0.9, P = 0.0005). INR levels were poorly controlled in both groups (66.1% and 64.7%, respectively). Patients in the VKA+APL group more frequently discontinued VKA than patients in the VKA alone group (28.8% vs 24.2%, P = 0.045). Major causes of VKA discontinuation were uncontrolled INR level and patient dissatisfaction or concerns. CONCLUSIONS: The conditions of NVAF patients were inadequately controlled with VKA with or without an APL. These findings suggest that other antithrombotic treatment options are warranted in NVAF patients to achieve INR control.

Biocompatibility evaluation of bioprinted decellularized collagen sheet implanted in vivo cornea using swept-source optical coherence tomography.

Corneal transplantation by full-thickness penetrating keratoplasty with human donor tissue is a widely accepted treatment for damaged or diseased corneas. Although corneal transplantation has a high success rate, a shortage of high-quality donor tissue is a considerable limitation. Therefore, bioengineered corneas could be an effective solution for this limitation, and a decellularized extracellular matrix comprises a promising scaffold for their fabrication. In this study, three-dimensional bioprinted decellularized collagen sheets were implanted into the stromal layer of the cornea of five rabbits. We performed in vivo noninvasive monitoring of the rabbit corneas using swept-source optical coherence tomography (OCT) after implanting the collagen sheets. Anterior segment OCT images and averaged amplitude-scans were acquired biweekly to monitor corneal thickness after implantation for 1 month. The averaged cornea thickness in the control images was 430.3 ± 5.9 µm, while the averaged thickness after corneal implantation was 598.5 ± 11.8 µm and 564.5 ± 12.5 µm at 2 and 4 weeks, respectively. The corneal thickness reduction of 34 µm confirmed the biocompatibility through the image analysis of the depth-intensity profile base. Moreover, hematoxylin and eosin staining supported the biocompatibility evaluation of the bioprinted decellularized collagen sheet implantation. Hence, the developed bioprinted decellularized collagen sheets could become an alternative solution to human corneal donor tissue, and the proposed image analysis procedure could be beneficial to confirm the success of the surgery.