Effect of modification methods on the physical properties and immunomodulatory activity of particulate ß-glucan.

ß-Glucan is an immunoenhancing agent whose biological activities are linked to molecular structure. On that basis, the polysaccharide can be physiochemically modified to produce valuable functional materials. This study investigated the physical properties and immunostimulatory activity of modified ß-glucan. Alkali-treated ß-glucan had a distinct shape and smaller particle size than untreated ß-glucan. The reduced particle size was conducive to the stability of the suspension because the ß-glucan appeared to be completely dissolved by this treatment, forming an amorphous mass. Furthermore, alkali treatment improved the immunostimulating activity of ß-glucan, whereas exposure of macrophages to heat-treated ß-glucan decreased their immune activity. ß-Glucan with reduced particle size by wet-grinding also displayed immunomodulatory activities. These results suggested that the particle size of ß-glucan is a key factor in ß-glucan-induced immune responses of macrophages. Thus, the modification of the ß-glucan particle size provides new opportunities for developing immunoenhancing nutraceuticals or pharmacological therapies in the future.

Check-all-that-apply (CATA)- and rate-all-that-apply (RATA)-based sensometric assessment of germinated-wheat beverages.

Sensometrics assesses sensory perspectives in consumer research using statistics and various methodologies. This study evaluated consumer responses to hot and cold germinated-wheat beverages in check-all-that-apply (CATA) and rate-all-that-apply (RATA) assessments using sensometric statistical approaches, including Cochran's Q test, penalty-lift analysis, and multiple factor analysis. Hot beverages (HB) were prepared by infusion using different amounts of germinated wheat (HB_1: 0.8 g/100 mL, HB_2: 2 g/100 mL, and HB_3: 4 g/100 mL), while cold beverages (CB) were made using cooled boiled germinated wheat with varying concentrations (CB_1: 25 g/L, CB_2: 50 g/L, and CB_3: 75 g/L). Results of the CATA study suggested that consumers preferred HB_1 and CB_1 because they expressed the sensory characteristics associated with liking, including "barley tea flavor", "neat taste", and "nutty taste", while "bitterish taste", "stuffy taste", and "astringent taste" were undesirable attributes. "Browning index", "barley tea odor", and "nutty taste" showed significant differences (p < 0.05) in both favorable and unfavorable rating scores. Overall, CB_1 elicited a clear taste and odor with fewer negative emotions. These findings demonstrate the usefulness of the sensometric approach combined with CATA and RATA analyses to obtain more easily interpretable results on the sensory perception of consumers to new food products. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05884-z.

Mitochondrial uncoupling proteins protect human airway epithelial ciliated cells from oxidative damage.

Apical cilia on epithelial cells defend the lung by propelling pathogens and particulates out of the respiratory airways. Ciliated cells produce ATP that powers cilia beating by densely grouping mitochondria just beneath the apical membrane. However, this efficient localization comes at a cost because electrons leaked during oxidative phosphorylation react with molecular oxygen to form superoxide, and thus, the cluster of mitochondria creates a hotspot for oxidant production. The relatively high oxygen concentration overlying airway epithelia further intensifies the risk of generating superoxide. Thus, airway ciliated cells face a unique challenge of producing harmful levels of oxidants. However, surprisingly, highly ciliated epithelia produce less reactive oxygen species (ROS) than epithelia with few ciliated cells. Compared to other airway cell types, ciliated cells express high levels of mitochondrial uncoupling proteins, UCP2 and UCP5. These proteins decrease mitochondrial protonmotive force and thereby reduce production of ROS. As a result, lipid peroxidation, a marker of oxidant injury, decreases. However, mitochondrial uncoupling proteins exact a price for decreasing oxidant production; they decrease the fraction of mitochondrial respiration that generates ATP. These findings indicate that ciliated cells sacrifice mitochondrial efficiency in exchange for safety from damaging oxidation. Employing uncoupling proteins to prevent oxidant production, instead of relying solely on antioxidants to decrease postproduction oxidant levels, may offer an advantage for targeting a local area of intense ROS generation.

Neuroimaging Approach: Effects of Hot and Cold Germinated Wheat Beverages on Electroencephalographic (EEG) Activity of the Human Brain.

Neuroimaging studies using electroencephalography (EEG) have been crucial in uncovering brain activity in sensory perception, emotion regulation, and decision-making. Despite tea's global popularity, its temperature-related neural basis remains underexplored. This study investigated the effect of hot and cold germinated wheat beverages (HB and CB) in changes of brain waves using EEG. Four distinct approaches and topographical assessments were performed to gain deeper insights into the impact of EEG signals in the human brain. The four approaches showed different impacts of HB and CB intake, as all EEG spectral powers increased after drinking HB and decreased after consumption of CB. Significant increases in delta and theta waves were observed as a result of drinking HB, but significant decreases in alpha and beta waves were observed after drinking CB. The topographic maps illustrate the significant effects of HB more prominently than those of CB, displaying greater changes in delta, theta, and beta. These findings suggest the intake of HB is probably related to relaxation, calmness, mindfulness and concentration, while the intake of CB is related to alertness, attention, and working memory. Ultimately, the neuroscientific approaches provided in this study could advance consumer-based research on beverage consumption.

Phytochemical profiling of Symplocos tanakana Nakai and S. sawafutagi Nagam. leaf and identification of their antioxidant and anti-diabetic potential.

Symplocos sp. contains various phytochemicals and is used as a folk remedy for treatment of diseases such as enteritis, malaria, and leprosy. In this study, we discovered that 70% ethanol extracts of Symplocos sawafutagi Nagam. and S. tanakana Nakai leaves have antioxidant and anti-diabetic effects. The components in the extracts were profiled using high-performance liquid chromatography coupled to electrospray ionization and quadrupole time-of-flight mass spectrometry; quercetin-3-O-(6''-O-galloyl)-ß-d-galactopyranoside (6) and tellimagrandin II (7) were the main phenolic compounds. They acted as strong antioxidants with excellent radical scavenging activity and as inhibitors of non-enzymatic advanced glycation end-products (AGEs) formation. Mass fragmentation analysis demonstrated that compounds 6 and 7 could form mono- or di-methylglyoxal adducts via reaction with methylglyoxal, which is a reactive carbonyl intermediate and an important precursor of AGEs. In addition, compound 7 effectively inhibited the binding between AGE2 and receptor for AGEs as well as the activity of α-glucosidase. Enzyme kinetic study revealed that compound 7 acts as a competitive inhibitor of α-glucosidase, through interaction with the active site of the enzyme. Therefore, compounds 6 and 7, the major constituents of S. sawafutagi and S. tanakana leaves, are promising for developing drugs for preventing or treating diseases caused by aging and excessive sugar consumption.

The Multi-dimensional Assessment of Suicide Risk in Chronic illness-20 (MASC-20): Development and validation.

BACKGROUND: We developed and tested the psychometric properties of the Multi-dimensional assessment of suicide risk in chronic illness-20 (MASC-20), which assess suicidal behavior (SB), and its associated distress in chronic physical illness (CPI). METHODS: Items were developed by incorporating inputs from patient interviews, a review of existing instruments, and expert consultations. Pilot testing with 109 patients and field testing with 367 patients with renal, cardiovascular, and cerebrovascular diseases were conducted. We analyzed Time (T) 1 data to select items and T2 data to examine psychometric properties. RESULTS: Forty preliminary items were selected through pilot testing; 20 were finalized from field testing. Optimal internal consistency (α = 0.94) and test-retest reliability (Intra class correlation coefficient = 0.92) of the MASC-20 supported reliability. Good fit of the four-factor model (physical distress, psychological distress, social distress, and SB) from exploratory structural equation modeling demonstrated factorial validity. Its correlations with MINI suicidality (r = 0.59) and the Schedule of Attitudes Toward Hastened Death-abbreviated scores (r = 0.62) indicated convergent validity. Higher MASC-20 scores in patients with clinical levels of depression and anxiety and low health status demonstrated known-group validity. The MASC-20 distress score predicted SB beyond known SB risk factors, supporting incremental validity. A cutoff score of 16 was optimal for identifying suicide risk. The area under the curve was within a moderately accurate range. The sum of sensitivity and specificity (1.66) indicated diagnostic utility. LIMITATIONS: MASC-20's applicability to other patient populations and its sensitivity to change requires testing. CONCLUSIONS: The MASC-20 appears to be a reliable and valid tool for assessing SB in CPI.

A randomized controlled trial of postoperative rehabilitation using digital healthcare system after rotator cuff repair.

A digital healthcare system based on augmented reality (AR) has promising uses for postoperative rehabilitation. We compare effectiveness of AR-based and conventional rehabilitation in patients after rotator cuff repair (RCR). This study randomly allocates 115 participants who underwent RCR to digital healthcare rehabilitation group (DR group) and conventional rehabilitation group (CR group). The DR group performs AR-based home exercises using UINCARE Home+, whereas the CR group performs brochure-based home exercises. The primary outcome is a change in the Simple Shoulder Test (SST) score between baseline and 12 weeks postoperatively. The secondary outcomes are the Disabilities of the Arm, Shoulder and Hand (DASH) score; Shoulder Pain And Disability Index (SPADI) score; EuroQoL 5-Dimension 5-Level (EQ5D5L) questionnaire score; pain; range of motion (ROM); muscle strength; and handgrip strength. The outcomes are measured at baseline, and at 6, 12, and 24 weeks postoperatively. The change in SST score between baseline and 12 weeks postoperatively is significantly greater in the DR group than in the CR group (p = 0.025). The SPADI, DASH, and EQ5D5L scores demonstrate group×time interactions (p = 0.001, = 0.04, and = 0.016, respectively). However, no significant differences over time are observed between the groups in terms of pain, ROM, muscle strength, and handgrip strength. The outcomes show significant improvement in both groups (all p < 0.001). No adverse events are reported during the interventions. AR-based rehabilitation shows better improvement in terms of shoulder function after RCR compared to conventional rehabilitation. Therefore, as an alternative to the conventional rehabilitation, the digital healthcare system is effective for postoperative rehabilitation.

Live Mycobacterium paragordonae induces heterologous immunity of natural killer cells by eliciting type I interferons from dendritic cells via STING-dependent sensing of cyclic-di-GMP.

Exploiting the heterologous effects of vaccines is a feasible strategy to combat different pathogens. These effects have been explained by enhanced immune responses of innate immune cells. Mycobacterium paragordonae is a rare nontuberculosis mycobacterium that has temperature-sensitive properties. Although natural killer (NK) cells exhibit heterologous immunity features, the cellular crosstalk between NK cells and dendritic cells (DCs) during live mycobacterial infection has remained elusive. We show that live but not dead M. paragordonae enhances heterologous immunity against unrelated pathogens in NK cells by IFN-ß of DCs in both mouse models and primary human immune cells. C-di-GMP from live M. paragordonae acted as a viability-associated pathogen-associated molecular pattern (Vita-PAMP), leading to STING-dependent type I IFN production in DCs via the IRE1α/XBP1s pathway. Also, increased cytosolic 2'3'-cGAMP by cGAS can induce type I IFN response in DCs by live M. paragordonae infection. We found that DC-derived IFN-ß plays a pivotal role in NK cell activation by live M. paragordonae infection, showing NK cell-mediated nonspecific protective effects against Candida albicans infection in a mouse model. Our findings indicate that the heterologous effect of live M. paragordonae vaccination is mediated by NK cells based on the crosstalk between DCs and NK cells.

MR evaluation of the posteromedial corner of the knee: association of posterior horn medial meniscus tear with posterior oblique ligament and distal semi-membranosus tendon tear.

OBJECTIVE: To assess if posterior oblique ligament and distal semi-membranosus tendon tears are associated with posterior horn medial meniscus tears on MRI. METHODS: From January 1, 2018 to December 31, 2019, 56 patients who met the inclusion criteria were enrolled in this study. Of the 56 patients, 43 patients who had a posterior horn of medial meniscus tear were included in the study group. A control group of 13 individuals was formed for comparison. Two radiologists reviewed the MR images and recorded the presence and grades of posterior oblique ligament and distal semi-membranosus tendon tears. We used the independent t-test and one-way ANOVA to compare the tear grades. Interobserver agreement was analyzed using a Cohen's κ coefficient (κ value) for categorical variables. RESULTS: The mean grades for the posterior oblique ligament and distal semi-membranosus tendon tears were significantly higher in the study group (all, p < 0.001). Interobserver agreement between the two readers was substantial in assessing the grade of posterior oblique ligament tear (κ = 0.653±0.087) and almost perfect in assessing the grade of distal semi-membranosus tendon tear (κ = 0.876±0.060). CONCLUSION: Posterior oblique ligament and distal semi-membranosus tendon tears are significantly associated with posterior horn of medial meniscus tear and medial meniscus posterior root tears, and the peel-back mechanism could be related to this association. ADVANCES IN KNOWLEDGE: Presenting this paper could adjust radiologist search patterns and potentially help orthopedists with management and pre-surgical planning for the posteromedial corner injury of the knee.

Intra-individual comparison of lumbar spine CT, abdomen-pelvis contrast enhanced CT, and low-dose chest CT for bone density measurement.

BACKGROUND: Dual-energy X-ray absorptiometry (DXA) is the reference standard for the measurement of bone mineral density (BMD) and subsequent diagnosis of osteoporosis. Since various computed tomography (CT) protocols are scanned for various indications, we can incidentally measure BMD using CT. Previous studies have revealed a correlation between BMD and Hounsfield unit (HU) values obtained with different CT protocols. PURPOSE: To compare the diagnostic value of CT protocols (lumbar spine CT [LSCT], abdomen-pelvis contrast-enhanced CT [APCT], and low-dose chest CT [LDCT]) for osteoporosis. MATERIAL AND METHODS: We retrospectively included 17 patients (6 men, 11 women; mean age=68 years) who had undergone all four imaging studies within six months, during 2011-2021. HU values were manually measured at the center of the L1 vertebra by a radiology resident. Pearson correlation test was performed between HU values and BMD of L1 vertebra. The diagnostic performance of each CT protocol was assessed with receiver operating characteristic (ROC) analysis. Intra-individual concordance of the four tests to diagnose osteoporosis was analyzed by tabulating. RESULTS: The mean HU values were 104.4 ± 47.2 HU with LSCT, 149.0 ± 56.9 HU with APCT, and 114.3 ± 60.0 HU with LDCT. HU values from each protocol were positively correlated (r = 0.676-0.735; P < 0.005) with BMD. LDCT had the highest diagnostic performance (area under the ROC curve [AUC] = 0.701) and APCT the lowest (AUC = 0.569). APCT was discordant with the other protocols for diagnosing osteoporosis. CONCLUSION: LDCT had the highest diagnostic performance for osteoporosis with predetermined cutoff value. APCT requires the increase of cutoff value for osteoporosis diagnosis.

Validation of a Lymphedema Index Score Based on Noncontrast Magnetic Resonance Lymphangiography: Correlation with Clinical Staging and Indocyanine Green Lymphangiography.

Background: A standardized lymphedema grading system is a prerequisite for accurately and objectively evaluating its severity, both preoperatively and postoperatively. The purpose of this study was to establish a clinically feasible noncontrast magnetic resonance lymphangiography (NMRL) protocol and a standardized scoring system for the evaluation of lymphedema. Methods and Results: From January 2020 to February 2021, 39 patients who had been clinically diagnosed with lymphedema and had undergone NMRL were included. The severity and circumferential extent of lymphedema were assessed using magnetic resonance imaging, and a combined index was devised as the sum of the product of the severity and extent scores determined at four different levels. A magnetic resonance imaging (MRI) stage was allocated based on the combined index score, its correlation with clinical indices was analyzed. The MR and clinical staging showed a percentage agreement of 85.9% and a kappa coefficient of 0.641, indicating moderate agreement (p < 0.001). Both the interlimb volume and interlimb impedance ratios differed significantly between groups (p < 0.001 for both). The correlation analysis revealed a significant correlation between the combined index score and the inter-limb volume ratio (r = 0.70, p < 0.001) and inter-limb impedance ratio at both 1 kHz (r = 0.71, p < 0.001) and 5 kHz (r = 0.71, p < 0.001). The interobserver agreement was moderate for the severity score, extent score, and combined score. Conclusion: The proposed standardized scoring system for evaluating lymphedema based on NMRL can reproducibly determine the severity and extent of lymphedema in both the upper and lower extremities, and correlates strongly with established clinical measures.

Successful full-term delivery after out-of-hospital cardiac arrest during the second trimester of pregnancy: a case report.

Out-of-hospital cardiac arrest in pregnancy is extremely rare. In this case report, a 43-year-old female patient at 24.0 weeks of gestation collapsed outside her home after cardiac arrest. The paramedics performed cardiopulmonary resuscitation with defibrillation for ventricular fibrillation. Spontaneous circulation was achieved after 19 minutes. The fetus was stable during postarrest care. The patient exhibited high blood pressure with seizure-like symptoms for 2 days afterwards, which resolved with magnesium sulfate. She gradually recovered and returned to her daily activities while on treatment with beta blockers for cardiomyopathy and premature ventricular contractions until delivery. At 37.2 weeks of gestation, she underwent elective Cesarean section under spinal anesthesia. The baby weighed 2.55 kg and did not present with any complications. Here, we report a case of successful full-term delivery in a patient who underwent cardiopulmonary resuscitation for sudden cardiac arrest during the second trimester of pregnancy.

Association of Basic Psychological Need Fulfillment and School Happiness with Obesity Levels and Intensity of Physical Activity during Physical Education Classes in South Korean Adolescents.

This study examined the relationship between basic psychological need fulfillment (BPNF) and school happiness in relation to the intensity of physical activity exhibited by adolescents during physical education (PE) classes and their obesity levels. We measured BPNF and school happiness using a questionnaire administered to 600 junior high school students. After exclusion, 532 questionnaires were analyzed. A 3D accelerometer (GT3X model) from Actigraph and the body mass index were used to measure physical activity intensity and obesity, respectively. The findings of this study indicate that BPNF and school happiness were significantly associated with physical activity intensity. Specifically, students who engaged in high-intensity physical activity exhibited higher levels of BPNF and school happiness. Additionally, BPNF and school happiness were not significantly related to obesity, whereas a significant relationship was observed between BPNF, school happiness, and the interaction between physical activity intensity and obesity level. This finding implies that adolescents with higher physical activity intensity and lower obesity reported higher levels of BPNF and school happiness. These findings suggest that physical activity intensity during PE classes significantly influences emotional development. Therefore, incorporating moderate-to-vigorous physical activity into PE may serve as a strategy for promoting emotional development in adolescents.

Comparative Analysis of Coumarin Profiles in Different Parts of Peucedanum japonicum and Their Aldo-Keto Reductase Inhibitory Activities.

Peucedanum japonicum (Umbelliferae) is widely distributed throughout Southeast Asian countries. The root of this plant is used in traditional medicine to treat colds and pain, whereas the young leaves are considered an edible vegetable. In this study, the differences in coumarin profiles for different parts of P. japonicum including the flowers, roots, leaves, and stems were compared using ultra-performance liquid chromatography time-of-flight mass spectrometry. Twenty-eight compounds were tentatively identified, including three compounds found in the genus Peucedanum for the first time. Principal component analysis using the data set of the measured mass values and intensities of the compounds exhibited distinct clustering of the flower, leaf, stem, and root samples. In addition, their anticancer activities were screened using an Aldo-keto reductase (AKR)1C1 assay on A549 human non-small-cell lung cancer cells and the flower extract inhibited AKR1C1 activity. Based on these results, seven compounds were selected as potential markers to distinguish between the flower part versus the root, stem, and leaf parts using an orthogonal partial least-squares discriminant analysis. This study is the first to provide information on the comparison of coumarin profiles from different parts of P. japonicum as well as their AKR1C1 inhibitory activities. Taken together, the flowers of P. japonicum offer a new use related to the efficacy of overcoming anticancer drug resistance, and may be a promising source for the isolation of active lead compounds.

Comparative Flavor Profile of Roasted Germinated Wheat (Triticum aestivum L.) Beverages Served Hot and Cold Using Electronic Sensors Combined with Chemometric Statistical Analysis.

In order to fulfill the objective of the comparative flavor profiling of hot and cold serving, different concentrations of hot (hot infusion) and cold (boiled and cold serving) roasted-steamed-germinated wheat beverages were prepared in order to explore the comparative profile of the amino acids, volatiles, taste, total flavonoid content (TFC), total phenolic content (TPC), and antioxidant capacities, including 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity (DPPH) and the Trolox equivalent antioxidant activity (TEAC). The instrumental analysis was performed using electronic sensors (an electric nose and an electric tongue), high-performance liquid chromatography, and spectrophotometry, and the statistical assessment was conducted using univariate (correlation pattern and heatmap) and multivariate (clustering and principal component analysis) analyses. The cold beverages at the highest concentration showed the highest values of TFC, TPC, DPPH, and TEAC, showing 32.31 ± 1.13 µg CE/100 mL, 202.37 ± 20.94 µg GAE/100 mL, 68.43 ± 3.41 µM TE/100 mL, and 126.66 ± 4.00 mM TE/100 mL, respectively. The correlation analysis revealed a remarkable correlation between the taste and the flavor compounds. The clustering analysis and the PCA clearly divided the key metabolites, which were attributed to the different tastes in the hot and cold beverages. This study clearly demonstrates the impact of different temperatures on the aroma metabolites, the taste, and the characteristics of wheat beverages.

Transcription factor RORα enforces stability of the Th17 cell effector program by binding to a Rorc cis-regulatory element.

T helper 17 (Th17) cells regulate mucosal barrier defenses but also promote multiple autoinflammatory diseases. Although many molecular determinants of Th17 cell differentiation have been elucidated, the transcriptional programs that sustain Th17 cells in vivo remain obscure. The transcription factor RORγt is critical for Th17 cell differentiation; however, it is not clear whether the closely related RORα, which is co-expressed in Th17 cells, has a distinct role. Here, we demonstrated that although dispensable for Th17 cell differentiation, RORα was necessary for optimal Th17 responses in peripheral tissues. The absence of RORα in T cells led to reductions in both RORγt expression and effector function among Th17 cells. Cooperative binding of RORα and RORγt to a previously unidentified Rorc cis-regulatory element was essential for Th17 lineage maintenance in vivo. These data point to a non-redundant role of RORα in Th17 lineage maintenance via reinforcement of the RORγt transcriptional program.

Rates of rare copy number variants in different circumstances among patients with genetic developmental and epileptic encephalopathy.

BACKGROUND: Most patients with developmental and epileptic encephalopathy (DEE) have genetic etiology, which has been uncovered with different methods. Although chromosomal microarray analysis (CMA) has been broadly used in patients with DEE, data is still limited. METHODS: Among 560 children (<18 years) who underwent CMA in our hospital between January 2013 and June 2021, 146 patients with developmental delay and recurrent seizures were screened. Patients with major brain abnormalities, metabolic abnormalities, and specific syndromes were excluded. The rate of rare copy number variants (CNVs) was estimated in total and according to seizure-onset age, relation to first seizure with the diagnosis of developmental delay, epilepsy syndromes, and organ anomalies. RESULTS: Among the 110 patients enrolled, the rate of rare CNVs was 16.4%, varying by seizure-onset age: 33.3% in three neonates, 21.2% in 33 infants, 13.3% in 45 early childhood patients, 5.3% in 19 late childhood patients, and 30.0% in 10 adolescents. In relation to the first seizure with the diagnosis of developmental delay, the rates were 3.7%, 22.2%, and 12.5% in "before", "after", and "concurrent" subclasses, respectively. The rates of rare CNVs were 16.7% in "other predominantly focal or multifocal epilepsy", 28.6% in "other predominantly generalized epilepsy (PGE)", and 15.4% in West syndrome. The rates were 27.8% in minor brain anomalies, 37.5% in facial dysmorphism, and 22.2%, 20.0%, and 57.1% in endocrine, genitourinary and cardiovascular anomalies, respectively. CONCLUSION: The rate of rare CNVs in patients with genetic DEE was 16.4% in total, which was higher in seizures occurring below the infantile period or after the diagnosis of developmental delay, in PGE, and in the presence of facial dysmorphism or cardiovascular anomalies.

Features of non-traumatic spinal cord infarction on MRI: Changes over time.

BACKGROUND AND PURPOSE: Spinal cord infarction (SCI) is difficult to diagnosis using MRI findings. We aimed to suggest the optimal timing of MRI studies for diagnosing SCI. MATERIALS AND METHODS: This retrospective study was approved by our institutional review board. The requirement for informed consent was waived. MRI scans of SCI patients diagnosed between January 2015 and August 2019 were enrolled in the SCI group and subdivided according to the interval between symptom onset and time of MRI scan (A, within 6 h; B, 6-12 hours; C, 12-24 hours; D, 24-72 hours; E, 3-7 days). Three radiologists analyzed the T2WI scans and evaluated the confidence level of diagnosing SCI using a five-point Likert scale: 1, certainly not; 2, probably not; 3, equivocal; 4, probably yes; 5, certainly yes. Scores of 4 and 5 were defined as "T2WI-positive SCI" and scores of 1-3 were defined as "T2WI-negative SCI". RESULTS: The SCI group included 58 MRI scans of 34 patients (mean age, 60.6 ± 14.0 years; 18 women). The T2WI positivity rate was 72.4% (42/58). In contrast to the other subgroups, subgroup A included fewer cases of T2WI-positive SCI (1/4, 25%) than T2WI-negative SCI. A confidence score of 5 was the most common in subgroup D (4/27, 14.8%). Among the 12 patients who underwent MRI studies more than twice, confidence scores increased with time. CONCLUSION: In patients with suspected SCI showing equivocal initial MRI findings, follow-up MRI studies are helpful, especially when performed between 24 and 72 hours after symptom onset.

Phytoestrogen Coumestrol Selectively Inhibits Monoamine Oxidase-A and Amyloid ß Self-Aggregation.

Pueraria lobata leaves contain a variety of phytoestrogens, including flavonoids, isoflavonoids, and coumestan derivatives. In this study, we aimed to identify the active ingredients of P. lobata leaves and to elucidate their function in monoamine oxidase (MAO) activation and Aß self-aggregation using in vitro and in silico approaches. To the best of our knowledge, this is the first study to elucidate coumestrol as a selective and competitive MAO-A inhibitor. We identified that coumestrol, a coumestan-derivative, exhibited a selective inhibitory effect against MAO-A (IC50 = 1.99 ± 0.68 µM), a key target protein for depression. In a kinetics analysis with 0.5 µg MAO-A, 40-160 µM substrate, and 25 °C reaction conditions, coumestrol acts as a competitive MAO-A inhibitor with an inhibition constant of 1.32 µM. During an in silico molecular docking analysis, coumestrol formed hydrogen bonds with FAD and pi-pi bonds with hydrophobic residues at the active site of the enzyme. Moreover, based on thioflavin-T-based fluorometric assays, we elucidated that coumestrol effectively prevented self-aggregation of amyloid beta (Aß), which induces an inflammatory response in the central nervous system (CNS) and is a major cause of Alzheimer's disease (AD). Therefore, coumestrol could be used as a CNS drug to prevent diseases such as depression and AD by the inhibition of MAO-A and Aß self-aggregation.

Oculomics for sarcopenia prediction: a machine learning approach toward predictive, preventive, and personalized medicine.

Aims: Sarcopenia is characterized by a gradual loss of skeletal muscle mass and strength with increased adverse outcomes. Recently, large-scale epidemiological studies have demonstrated a relationship between several chronic disorders and ocular pathological conditions using an oculomics approach. We hypothesized that sarcopenia can be predicted through eye examinations, without invasive tests or radiologic evaluations in the context of predictive, preventive, and personalized medicine (PPPM/3PM). Methods: We analyzed data from the Korean National Health and Nutrition Examination Survey (KNHANES). The training set (80%, randomly selected from 2008 to 2010) data were used to construct the machine learning models. Internal (20%, randomly selected from 2008 to 2010) and external (from the KNHANES 2011) validation sets were used to assess the ability to predict sarcopenia. We included 8092 participants in the final dataset. Machine learning models (XGBoost) were trained on ophthalmological examinations and demographic factors to detect sarcopenia. Results: In the exploratory analysis, decreased levator function (odds ratio [OR], 1.41; P value <0.001), cataracts (OR, 1.31; P value = 0.013), and age-related macular degeneration (OR, 1.38; P value = 0.026) were associated with an increased risk of sarcopenia in men. In women, an increased risk of sarcopenia was associated with blepharoptosis (OR, 1.23; P value = 0.038) and cataracts (OR, 1.29; P value = 0.010). The XGBoost technique showed areas under the receiver operating characteristic curves (AUCs) of 0.746 and 0.762 in men and women, respectively. The external validation achieved AUCs of 0.751 and 0.785 for men and women, respectively. For practical and fast hands-on experience with the predictive model for practitioners who may be willing to test the whole idea of sarcopenia prediction based on oculomics data, we developed a simple web-based calculator application (https://knhanesoculomics.github.io/sarcopenia) to predict the risk of sarcopenia and facilitate screening, based on the model established in this study. Conclusion: Sarcopenia is treatable before the vicious cycle of sarcopenia-related deterioration begins. Therefore, early identification of individuals at a high risk of sarcopenia is essential in the context of PPPM. Our oculomics-based approach provides an effective strategy for sarcopenia prediction. The proposed method shows promise in significantly increasing the number of patients diagnosed with sarcopenia, potentially facilitating earlier intervention. Through patient oculometric monitoring, various pathological factors related to sarcopenia can be simultaneously analyzed, and doctors can provide personalized medical services according to each cause. Further studies are needed to confirm whether such a prediction algorithm can be used in real-world clinical settings to improve the diagnosis of sarcopenia. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-022-00292-3.