Characterization of peptides released from frozen-then-aged beef after digestion in an in vitro infant gastrointestinal model.

This study investigated whether the freezing-then-aging treatment of beef affects protein digestibility and release of potentially bioactive peptides using an in vitro infant digestion model. After 28 days of storage, aged-only (AO) and frozen-then-aged (FA) beef exhibited higher α-amino group contents in the 10% trichloroacetic acid-soluble fraction compared to day 0 (P < 0.05). Following in vitro digestion in the infant model, FA showed higher contents of α-amino groups and smaller proteins (<3 and 1 kDa) than day 0 and AO (P < 0.05). Relative contributions of myofibrillar, sarcoplasmic, and stromal proteins to the bioactive peptides released from AO and FA differed from those of day 0. In addition, FA exhibited a higher proportion of potential bioactive peptide sequences. Overall, freezing-then-aging treatment can enhance the potential health benefits of beef to be used as a protein source for complementary foods.

Validation of Signal Intensity Gradient from TOF-MRA for Wall Shear Stress by Phase-Contrast MR.

To validate the correlation between the signal intensity gradient (SIG) from time-of-flight magnetic resonance angiography (TOF-MRA) and wall shear stress (WSS) determined by phase contrast magnetic resonance (PC-MR), we conducted both experimental and human studies. In the experimental study, we measured WSS in four tubes of different sizes with variable flow rates using PC-MR and TOF-MRA. The flow rates of water in the experimental study ranged from 0.06 to 12.75 mL/s, resulting in PC-WSS values between 0.1 and 1.6 dyne/cm2. The correlation between PC-WSS and SIG was statistically significant, showing a coefficient of 0.86 (P < 0.001, R2 = 0.75). The line fit provided the conversion equation as Y = 1.6287X - 1.1563 (Y = PC-WSS, X = SIG). For the human study, 28 subjects underwent TOF-MRA and PC-MR examinations of carotid and vertebral arteries. Arterial PC-WSS and SIG were determined in the same segment for each subject. The arterial PC-WSS ranged from 1.9 to 21.0 dyne/cm2. Both carotid and vertebral arteries showed significant correlations between PC-WSS and SIG, with coefficients of 0.85, 0.86, 0.91, and 0.81 in the right and left carotid and vertebral arteries, respectively. Our results show that SIG from TOF-MRA and SIG-WSS derived from the conversion equation provide concurrent in vivo hemodynamic information on arterial shear stress. This study was registered on ClinicalTrials.gov with the identifier NCT04585971 on October 14, 2020.

Heat-induced gelation of egg white proteins depending on heating temperature: Insights into protein structure and digestive behaviors in the elderly in vitro digestion model.

This study investigated the effects of heating temperature of egg white gels (EWGs) on the digestive characteristics by heating egg white (EW) to reach 75 °C (EWG-75) and 95 °C (EWG-95). The gel protein structure showed a decrease in the maximum tryptophan fluorescence intensity and a significant increase in the surface hydrophobicity of EWGs compared to EW (P < 0.05). The total and reactive free sulfhydryl groups were higher in the EWGs than in the EW (P < 0.05). While the proportions of α-helical and ß-sheet structures remained similar in EW and EWG-75 (P > 0.05), EWG-95 exhibited a notable decrease in α-helix content (P < 0.05) and an increase in ß-sheet content (P < 0.05). Furthermore, EWG-95 displayed higher hardness and cohesiveness than EWG-75 (P < 0.05). In the adult and elderly in vitro digestion models, EWG-95 exhibited the highest protein digestibility (50.44 % and 54.65 % in the models of elderly and adult subjects, respectively) after GI digestion (P < 0.05), followed by EWG-75 and EW. The electrophoretogram of the digesta revealed more intense protein bands in the elderly digestion model, particularly in the gastric digesta of EW, indicating slower digestion compared to the adult model. Therefore, EW should be appropriately heated before consumption, especially for elderly individuals, to facilitate efficient protein digestion and absorption.

Recent strategies for improving the quality of meat products.

Processed meat products play a vital role in our daily dietary intake due to their rich protein content and the inherent convenience they offer. However, they often contain synthetic additives and ingredients that may pose health risks when taken excessively. This review explores strategies to improve meat product quality, focusing on three key approaches: substituting synthetic additives, reducing the ingredients potentially harmful when overconsumed like salt and animal fat, and boosting nutritional value. To replace synthetic additives, natural sources like celery and beet powders, as well as atmospheric cold plasma treatment, have been considered. However, for phosphates, the use of organic alternatives is limited due to the low phosphate content in natural substances. Thus, dietary fiber has been used to replicate phosphate functions by enhancing water retention and emulsion stability in meat products. Reducing the excessive salt and animal fat has garnered attention. Plant polysaccharides interact with water, fat, and proteins, improving gel formation and water retention, and enabling the development of low-salt and low-fat products. Replacing saturated fats with vegetable oils is also an option, but it requires techniques like Pickering emulsion or encapsulation to maintain product quality. These strategies aim to reduce or replace synthetic additives and ingredients that can potentially harm health. Dietary fiber offers numerous health benefits, including gut health improvement, calorie reduction, and blood glucose and lipid level regulation. Natural plant extracts not only enhance oxidative stability but also reduce potential carcinogens as antioxidants. Controlling protein and lipid bioavailability is also considered, especially for specific consumer groups like infants, the elderly, and individuals engaged in physical training with dietary management. Future research should explore the full potential of dietary fiber, encompassing synthetic additive substitution, salt and animal fat reduction, and nutritional enhancement. Additionally, optimal sources and dosages of polysaccharides should be determined, considering their distinct properties in interactions with water, proteins, and fats. This holistic approach holds promise for improving meat product quality with minimal processing.

Cerebral artery signal intensity gradient from Time-of-Flight Magnetic Resonance Angiography and clinical outcome in lenticulostriate infarction: a retrospective cohort study.

Purpose: Lenticulostriate infarction requires further research of arterial hemodynamic factors, as the disease is diagnosed in the absence of major arterial stenosis or cardioembolism. Methods: In this multicenter retrospective cohort study, we included patients who were hospitalized for lenticulostriate infarction from January 2015 to March 2021 at three stroke centers in South Korea. We obtained hemodynamic information on cerebral arteries using signal intensity gradient (SIG), an in-vivo approximated wall shear stress (WSS) derived from Time-of-Flight Magnetic Resonance Angiography (TOF-MRA). A favorable outcome was defined as a modified Rankin Scale of 0 to 2 at hospital discharge. Results: A total of 294 patients were included, of whom 146 (49.7%) had an unfavorable outcome. The unfavorable outcome group showed significantly lower SIG in both middle cerebral arteries (MCAs) than the favorable group (5.2 ± 1.2 SI/mm vs. 5.9 ± 1.2, p < 0.001), and similar findings were observed in other cerebral arteries. The SIGs in both MCAs were independently associated with favorable outcome, with an odds ratio of 1.42 (95% confidence interval, 1.11-1.80; p = 0.005) for the right MCA and 1.49 (95% CI, 1.15-1.93; p = 0.003) for the left MCA, after adjusting for potential confounders. Similar findings were observed in other cerebral artery SIGs. Conclusion: Cerebral artery SIG from TOF-MRA was significantly associated with short-term functional outcomes in patients with lenticulostriate infarction. Further studies are needed to investigate the temporal relationships of SIG in patients with cerebral infarction.

Geometric versus Hemodynamic Indexes for Rupture-Destined Aneurysms: A Retrospective Cohort and a Repeated-Measures Study.

INTRODUCTION: A proper stratification of intracranial aneurysms is critical in identifying rupture-destined aneurysms and unruptured intracranial aneurysms. We aimed to determine the utility of geometric and hemodynamic indexes in differentiating two types of aneurysms and to examine the characteristics of natural evolutionary changes of unruptured aneurysms. METHODS: Rupture-destined aneurysm refers to an aneurysm that undergoes subsequent aneurysmal subarachnoid hemorrhage (SAH). On the other hand, an unruptured intracranial aneurysm is characterized by an aneurysm that does not experience rupture during serial time-of-flight magnetic resonance angiography (TOF-MRA). In addition to geometric indexes, signal intensity gradient (SIG), an in vivo approximated wall shear stress from TOF-MRA, was measured in aneurysms. The difference between the maximum and minimum values of SIG in an aneurysm compared to parent arterial values was designated as the delta-SIG ratio. RESULTS: This study analyzed 20 rupture-destined aneurysms in 20 patients and 45 unruptured intracranial aneurysms in 41 patients with follow-up TOF-MRA. While geometric indexes did not show differences between the two groups, the delta-SIG ratio was higher in the rupture-destined aneurysms (1.5 ± 0.6 vs. 1.1 ± 0.3, p = 0.032). The delta-SIG ratio showed a higher area under the receiver operating characteristic curve for SAH than the size ratio (0.72 [95% CI, 0.58-0.87] vs. 0.56 [95% CI, 0.41-0.72], p = 0.033). The longitudinal re-examination of TOF-MRA in the unruptured intracranial aneurysms revealed evidence of aneurysmal growth, while concurrently exhibiting hemodynamic stability. CONCLUSION: The delta-SIG ratio showed higher discriminatory results between the two groups compared to geometric indexes. Aneurysmal rupture risk should be assessed by considering both geometric and hemodynamic information. This study was registered on ClinicalTrials.gov (NCT05450939).

Level Optimization of Beet Powder and Caramel Color for Beef Color Simulation in Meat Analogs before and after Cooking.

In this study, concentration levels of beet powder (BP) and caramel color (CC) were optimized to simulate beef color in meat analogs before and after cooking. The central composite design of response surface methodology (RSM) was used to set the levels of BP and CC, and the CIE L*, CIE a*, and CIE b* were selected as the responses for RSM. After optimization, myoglobin-free beef patties were prepared with three optimized levels of BP and CC. When raw, all the patties had the same color as natural beef; however, CIE L*, CIE a*, and CIE b* were statistically different from those of beef after cooking (p<0.05). Moreover, the use of BP and CC induced "browning" after the cooking process, with no excessive yellow color. Therefore, based on the overall desirability in the color optimization using RSM, the combination of BP (1.32%) and CC (1.08%) with the highest overall desirability can be used to simulate the color change of beef in meat analogs.

High-pressure processing of beef increased the in vitro protein digestibility in an infant digestion model.

Beef is an ideal protein source for use as a complementary food in infants. Considering the limited protein-digesting capacity of infants, it is required to enhance protein digestibility while minimizing the deterioration of beef quality. Thus, this study aimed to determine the effects of high-pressure processing (HPP) on the physicochemical properties and in vitro digestibility of beef proteins in an infant digestion model. HPP at 200 and 300 MPa decreased the tryptophan fluorescence intensity of the myosin and actin fractions relative to that at 0.1 MPa (P < 0.05). Compared to treatment at 0.1 and 100 MPa, HPP at 300 MPa decreased α-helix and ß-turn contents in the myosin and actin fractions (P < 0.05), whilst increasing the ß-sheet content (P < 0.05). Beef actomyosin content decreased (P < 0.05) during HPP at 200 and 300 MPa (c.f., 0.1 and 100 MPa). After in vitro digestion of beef, HPP at 200 and 300 MPa increased the α-amino group content and the abundance of proteins below 3 kDa in the digesta (P < 0.05). However, due to the considerable lipid oxidation at 300 MPa, HPP at 200 MPa is ideal for improving the protein digestibility of beef when incorporated into complementary foods for infants.

Strategies for modulating the lipid digestion of emulsions in the gastrointestinal tract.

The structural changes in emulsion products can be used to control the bioavailability of fatty acids and lipophilic compounds. After ingestion, lipid droplets undergo breakdown and structural changes as they pass through the gastrointestinal tract. The oil-water interface plays a critical role in modulating the digestive behavior of lipid droplets because changes in the interfacial layer control the adsorption of lipase and bile salts and determine the overall rate and extent of lipid digestion. Therefore, lipid digestibility can be tuned by selecting the appropriate types and levels of stabilizers. The stabilizer can change the lipase accessibility and exposure of lipid substrates, resulting in variable digestion rates. However, emulsified lipids are not only added to food matrixes but are also co-ingested from other dietary components. Therefore, overall consumption behaviors can affect the digestion rate and digestibility of emulsified lipids. Although designing an emulsion structure is challenging, controlling lipid digestion can improve the health benefits of products. Therefore, a thorough understanding of the process of emulsified lipid digestion is required to develop food products that enable specific physiological responses. The targeted or delayed release of lipophilic molecules and fatty acids through emulsion systems has significant applications in healthcare and pharmaceuticals.

Higher Protein Digestibility of Chicken Thigh than Breast Muscle in an In Vitro Elderly Digestion Model.

This study investigated the protein digestibility of chicken breast and thigh in an in vitro digestion model to determine the better protein sources for the elderly in terms of bioavailability. For this purpose, the biochemical traits of raw muscles and the structural properties of myofibrillar proteins were monitored. The thigh had higher pH, 10% trichloroacetic acid-soluble α-amino groups, and protein carbonyl content than the breast (p<0.05). In the proximate composition, the thigh had higher crude fat and lower crude protein content than the breast (p<0.05). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of myofibrillar proteins showed noticeable differences in the band intensities of tropomyosin α-chain and myosin light chain-3 between the thigh and breast. The intrinsic tryptophan fluorescence intensity of myosin was lower in the thigh than in the breast (p<0.05). Moreover, circular dichroism spectroscopy of myosin revealed that the thigh had higher α-helical and lower ß-sheet structures than the breast (p<0.05). The cooked muscles were then chopped and digested in the elderly digestion model. The thigh had more α-amino groups than the breast after both gastric and gastrointestinal digestion (p<0.05). SDS-PAGE analysis of the gastric digesta showed that more bands remained in the digesta of the breast than that of the thigh. The content of proteins less than 3 kDa in the gastrointestinal digesta was also higher in the thigh than in the breast (p<0.05). These results reveal that chicken thigh with higher in vitro protein digestibility is a more appropriate protein source for the elderly than chicken breast.

Impact of an Education Program for Caregivers of Patients with Alzheimer's Disease on Treatment Discontinuation and Compliance in Korea.

BACKGROUND AND PURPOSE: Reportedly 30-50% of patients being treated for chronic illnesses do not adhere to their medication regimen. We assessed the impact of a nurse-led education program for caregivers of Korean de novo Alzheimer's disease patients who had newly been prescribed donepezil. METHODS: This multicenter study analyzed 93 participants in a caregiver education group and 92 participants in a caregiver no-education group. At every visit up to the end of the study (1 year), caregivers in the education group were given educational brochures regarding Alzheimer's disease and the efficacy and adverse events of donepezil treatment. The primary endpoint was the discontinuation rate of donepezil treatment during the 1-year observation period. The secondary endpoints included the effect of education on compliance with donepezil treatment assessed at each visit using a clinician rating scale (CRS) and visual analog scale (VAS), and changes from baseline in cognitive assessment tests. RESULTS: The donepezil discontinuation rates at 1 year were 5.38% (5/93) and 6.52% (6/92) in the caregiver education and no-education groups, respectively (p=0.742). No significant between-group differences in donepezil compliance rates on the CRS and VAS were observed, but significant changes were observed in some cognitive tests from baseline to the end of the study. CONCLUSIONS: Caregiver education had no significant effect on treatment discontinuation, but this may have been due to the low severity of cognitive impairment among the included population at baseline. In addition, the low discontinuation rates meant that no significant difference in treatment compliance was observed.

Discontinuation Rate of Newly Prescribed Donepezil in Alzheimer's Disease Patients in Asia.

BACKGROUND AND PURPOSE: The rate of donepezil discontinuation and the underlying reasons for discontinuation in Asian patients with Alzheimer's disease (AD) are currently unknown. We aimed to determine the treatment discontinuation rates in AD patients who had newly been prescribed donepezil in routine clinical practice in Asia. METHODS: This 1-year observational study involved 38 institutions in seven Asian countries, and it evaluated 398 participants aged 50-90 years with a diagnosis of probable AD and on newly prescribed donepezil monotherapy. The primary endpoint was the rate of donepezil discontinuation over 1 year. Secondary endpoints included the reason for discontinuation, treatment duration, changes in cognitive function over the 1-year study period, and compliance as assessed using a clinician rating scale (CRS) and visual analog scale (VAS). RESULTS: Donepezil was discontinued in 83 (20.9%) patients, most commonly due to an adverse event (43.4%). The mean treatment duration was 103.67 days in patients who discontinued. Among patients whose cognitive function was assessed at baseline and 1 year, there were no significant changes in scores on the Mini-Mental State Examination, Montreal Cognitive Assessment, and Trail-Making Test-Black and White scores, whereas the Clinical Dementia Rating score increased significantly (p<0.001). Treatment compliance at 1 year was 96.8% (306/316) on the CRS and 92.6±14.1% (mean±standard deviation) on the VAS. CONCLUSIONS: In patients on newly prescribed donepezil, the primary reason for discontinuation was an adverse event. Cognitive assessments revealed no significant worsening at 1 year, indicating that continuous donepezil treatment contributes to the maintenance of cognitive function.

Association of Carotid Artery Endothelial Signal Intensity Gradient with Unilateral Large Artery Ischemic Stroke.

BACKGROUND: Common carotid artery (CCA) and internal carotid artery (ICA) are aligned linearly, but their hemodynamic role in ischemic stroke has not been studied in depth. OBJECTIVES: We aimed to investigate whether CCA and ICA endothelial shear stress (ESS) could be associated with the ischemic stroke of large artery atherosclerosis (LAA). METHODS: We enrolled consecutive patients with unilateral ischemic stroke of LAA and healthy controls aged >60 years in the stroke center of Jeonbuk National University Hospital. All patients and controls were examined with carotid artery time-of-flight magnetic resonance angiography, and their endothelial signal intensity gradients (SIGs) were determined, as a measure of ESS. The effect of right or left unilateral stroke on the association between carotid artery endothelial SIG and ischemic stroke of LAA was assessed. RESULTS: In total, the results from 132 patients with ischemic stroke of LAA and 121 controls were analyzed. ICA endothelial SIG showed significant and independent associations with the same-sided unilateral ischemic stroke of LAA, even after adjusting for the potential confounders including carotid stenosis, whereas CCA endothelial SIG showed a significant association with the presence of the ischemic stroke of LAA. CONCLUSION: Although CCA and ICA are located with continuity, the hemodynamics and their roles in large artery ischemic stroke should be considered separately. Further studies are needed to delineate the pathophysiologic roles of ESS in CCA and ICA for large artery ischemic stroke.

Clinical Factors Associated with the Risk of Intracranial Aneurysm Rupture in Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND: The occurrence of intracranial aneurysms is higher in patients with autosomal dominant polycystic kidney disease (ADPKD) than in the healthy population. However, research concerning the factors related to the risk of intracranial aneurysm rupture in patients with ADPKD is still insufficient. OBJECTIVES: The aim of the study was to investigate the prevalence of intracranial aneurysms and aneurysmal subarachnoid hemorrhage (SAH) and to analyze the systemic factors associated with high-risk aneurysms in patients with ADPKD. METHODS: We screened patients who underwent cerebral angiography between January 2007 and May 2017 in the ADPKD registry. Patients were examined for the presence of intracranial aneurysms and subsequently reclassified into 3 groups based on the risk of aneurysmal rupture: the aneurysm-negative (group 1), low-risk aneurysm (group 2), or high-risk aneurysm (group 3). Various systemic factors were compared, and independent factors associated with high-risk aneurysms were analyzed. RESULTS: Among the 926 patients, 148 (16.0%) had intracranial aneurysms and 11 (1.2%) had previous aneurysmal SAH. Patients with intracranial aneurysms were further classified into group 2 (low-risk aneurysms, 15.5%) or group 3 (high-risk aneurysms, 84.5%). Age (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.01-1.05, p = 0.004), female sex (OR 3.13, 95% CI 1.94-5.0 6, p < 0.001), dolichoectasia (OR 8.57, 95% CI 1.53-48.17, p = 0.015), and mitral inflow deceleration time (DT) (OR 1.01, 95% CI 1.00-1.01, p = 0.046) were independently associated with high-risk aneurysms, whereas hypercholesterolemia (OR 0.46, 95% CI 0.29-0.72, p = 0.001) was negatively associated. CONCLUSION: In the present study among patients with ADPKD, the prevalence of intracranial aneurysms and aneurysmal SAH was 16 and 1.2%, respectively. Age, female sex, dolichoectasia, and mitral inflow DT were positively associated with high-risk aneurysms, whereas hypercholesterolemia was negatively associated. A subsequent large-scaled longitudinal study is needed to define the plausibility of the clinical parameters.

Impact of Endothelial Shear Stress on the Bilateral Progression of Unilateral Moyamoya Disease.

Background and Purpose- In unilateral moyamoya disease, altered endothelial shear stress on the intact-side terminal internal carotid artery might trigger the progression to bilateral disease. We analyzed the endothelial shear stress parameters of the normally appearing terminal internal carotid artery in unilateral moyamoya disease and its association with the progression to bilateral disease. Methods- This retrospective cohort study included patients diagnosed with unilateral moyamoya disease by cerebral angiography and followed-up with regular magnetic resonance imaging/magnetic resonance angiography evaluations for >1 year. Endothelial shear stress parameters acquired were mean and maximum signal intensity gradients (SIG) and SIG SD at the vessel boundary in time-of-flight sequences in initial brain magnetic resonance imaging/magnetic resonance angiography. Contralateral disease progression defined as the detection of newly developed vessel steno-occlusion with an magnetic resonance angiography steno-occlusive stage of ≥2, in the previously intact side of the brain on follow-up magnetic resonance imaging/magnetic resonance angiography evaluation. Results- Among 146 patients (66 males [45.2%] and 80 females [54.8%]; 76 pediatric [52.1%]), contralateral disease progression was detected in 43 patients (29.5%) after a mean follow-up of 4.3±2.4 years. Multivariate analysis showed that SIG SD was significantly associated with this progression (odds ratio, 13.001 [95% CI, 1.764-95.794], P=0.012). In receiver operating characteristic curve analysis, SIG SD predicted the contralateral progression with area under the curve values of 0.803 (95% CI, 0.726-0.880, P<0.001). The regression model was reproduced in the external cohort of 31 patients. Conclusions- Increased spatial variability of the endothelial shear stress around the normally appearing terminal internal carotid artery, as measured by SIG SD in time-of-flight sequences, may predict the contralateral progression of unilateral moyamoya disease.

FusionPro, a Versatile Proteogenomic Tool for Identification of Novel Fusion Transcripts and Their Potential Translation Products in Cancer Cells.

Fusion proteoforms are translation products derived from gene fusion. Although very rare, the fusion proteoforms play important roles in biomedical science. For example, fusion proteoforms influence the development of tumors by serving as cancer markers or cell cycle regulators. Although numerous studies have reported bioinformatics tools that can predict fusion transcripts, few proteogenomic tools are available that can predict and identify proteoforms. In this study, we develop a versatile proteogenomic tool "FusionPro," which facilitates the identification of fusion transcripts and their potential translatable peptides. FusionPro provides an independent gene fusion prediction module and can build sequence databases for annotated fusion proteoforms. FusionPro shows greater sensitivity than the available fusion finders when analyzing simulated or real RNA sequencing data sets. We use FusionPro to identify 18 fusion junction peptides and three potential fusion-derived peptides by MS/MS-based analysis of leukemia cell lines (Jurkat and K562) and ovarian cancer tissues from the Clinical Proteomic Tumor Analysis Consortium. Among the identified fusion proteins, we molecularly validate two fusion junction isoforms and a translation product of FAM133B:CDK6. Moreover, sequence analysis suggests that the fusion protein participates in the cell cycle progression. In addition, our prediction results indicate that fusion transcripts often have multiple fusion junctions and that these fusion junctions tend to be distributed in a nonrandom pattern at both the chromosome and gene levels. Thus, FusionPro allows users to detect various types of fusion translation products using a transcriptome-informed approach and to gain a comprehensive understanding of the formation and biological roles of fusion proteoforms.

Effect of warfarin versus aspirin on blood viscosity in cardioembolic stroke with atrial fibrillation: a prospective clinical trial.

BACKGROUND: Warfarin is evidence-based therapy for the prevention of cardioembolic stroke, but has not been studied for its effects on whole blood viscosity (WBV). This study investigated the effect of warfarin versus aspirin on WBV in patients presenting with non-valvular atrial fibrillation (NVAF) and acute cardioembolic stroke. METHODS: We enrolled patients with acute cerebral infarction, aged 56-90 years who had NVAF, CHADS2 score ≥ 2, presenting with mild-to-moderate stroke (National Institute of Health Stroke Scale (NIHSS) score < 20 and modified Rankin Scale (2mRS) score < 4) in a single center. The patients were alternately assigned to warfarin or aspirin groups. Post-treatment WBV was assessed after international normalized ratio (INR) reached target range [2, 3] for patients in the warfarin group, and 5 days after baseline in the aspirin group. RESULTS: Total 67 patients were included, and 56 completed this study (33 warfarin and 23 aspirin). Compared to baseline values, warfarin reduced post-treatment BV at all shear rates. The BV reductions greater than 1 cP measured at shear rates of 300, 150, 5, and 1 s- 1 were independently and significantly associated with warfarin treatment compared to aspirin after adjusting for age, sex, CHA2DS2-VASc scores, and baseline hematocrit. CONCLUSIONS: Warfarin confers greater reductions in BV than aspirin in patients with acute cardioembolic stroke. BV could be a useful method to estimate thrombotic risk in patients receiving warfarin. TRIAL REGISTRATION: KCT0001291 , Date of Registration: 2014-12-01.

ASV-ID, a Proteogenomic Workflow To Predict Candidate Protein Isoforms on the Basis of Transcript Evidence.

One of the goals of the Chromosome-Centric Human Proteome Project (C-HPP) is to map and characterize the functions of protein isoforms produced by alternative splicing of genes. However, identifying alternative splice variants (ASVs) via mass spectrometry remains a major challenge, because ASVs usually contain highly homologous peptide sequences. A routine protein sequence analysis suggests that more than half of the investigated proteins do not generate two or more uniquely mapping peptides that would enable their isoforms to be distinguished. Here, we develop a new proteogenomics method, named "ASV-ID" (alternative splicing variants identification), which enables identification of ASVs by using a cell type-specific protein sequence database that is supported by RNA-Seq data. Using this workflow, we identify 1935 distinct proteins under highly stringent conditions. In fact, transcript evidence on these 841 proteins helps us distinguish them from other isoforms, despite the fact that these proteins are not predicted to make 2 or more uniquely mapping peptides. We also demonstrate that ASV-ID enables detection of 19 differently expressed isoforms present in several cell lines. Thus, a new workflow using ASV-ID has the potential to map yet-to-be-identified difficult protein isoforms in a simple and robust way.

Microbubble signal and trial of org in acute stroke treatment (TOAST) classification in ischemic stroke.

PURPOSE: Right-to-left shunt (RLS) through a patent foramen ovale (PFO) is likely associated with ischemic stroke. Many studies have attempted to demonstrate the association between RLS and ischemic stroke. However, information on the association between the degree of RLS and the subtypes of ischemic stroke categorized by the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification is lacking. METHOD: This was a retrospective study involving 508 patients with ischemic stroke who underwent a transcranial Doppler (TCD) microbubble test between 2013 and 2015. The degree of RLS was divided into 4 grades according to the microbubble signal (MBS) as follows: no MBS, grade 1; MBS < 20, grade 2; MBS > 20, grade 3; curtain sign, grade 4. The degree of RLS and the type of ischemic stroke as classified by TOAST were analyzed and compared with other clinical information and laboratory findings. RESULTS: The higher RLS grade was associated with the cardioembolism (CE) and stroke of undetermined etiology (SUE), and the microbubble signals were inversely related with small vessel disease (SVD). An MBS higher than grade 3 showed a 2.95-fold higher association with SUE than large artery atherosclerosis (LAA), while grade 4 MBS revealed an approximately 8-fold higher association with SUE than LAA. CONCLUSION: RLS identified by the TCD microbubble test was significantly and independently associated with cryptogenic ischemic stroke (negative evaluation). Subsequent studies are needed to determine the biologic relationship between RLS and ischemic stroke, particularly the cryptogenic subtype of ischemic stroke.

Direct Assessment of Wall Shear Stress by Signal Intensity Gradient from Time-of-Flight Magnetic Resonance Angiography.

The aim of the study was to calculate the arterial wall signal intensity gradient (SIG) from time-of-flight MR angiography (TOF-MRA) and represent arterial wall shear stress. We developed a new algorithm that uses signal intensity (SI) of a TOF-MRA to directly calculate the signal intensity gradient (SIG). The results from our phantom study showed that the TOF-MRA SIG could be used to distinguish the magnitude of blood flow rate as high (mean SIG ± SD, 2.2 ± 0.4 SI/mm for 12.5 ± 2.3 L/min) and low (0.9 ± 0.3 SI/mm for 8.5 ± 2.6 L/min) in vessels (p < 0.001). Additionally, we found that the TOF-MRA SIG values were highly correlated with various flow rates (ß = 0.96, p < 0.001). Remarkably, the correlation coefficient between the WSS obtained from the computational fluid dynamics (CFD) analysis and the TOF-MRA SIG was greater than 0.8 in each section at the carotid artery (p < 0.001 for all ß values). This new technique using TOF-MRA could enable the rapid calculation of the TOF-MRA SIG and thereby the WSS. Thus, the TOF-MRA SIG can provide clinicians with an accurate and efficient screening method for making rapid decisions on the risk of vascular disease for a patient in clinical practice.