Evidence of the existence of multiple modules for the stroke-caused flexion synergy from Fugl-Meyer assessment scores.

Stroke-caused synergies may result from the preferential use of the reticulospinal tract (RST) due to damage to the corticospinal tract. The RST branches multiple motoneuron pools across the arm together resulting in gross motor control or abnormal synergies, and accordingly, the controllability of individual muscles decreases. However, it is not clear whether muscles involuntarily activated by abnormal synergy vary depending on the muscles voluntarily activated when motor commands descend through the RST. Studies showed that abnormal synergies may originate from the merging and reweighting of synergies in individuals without neurological deficits. This leads to a hypothesis that those abnormal synergies are still selectively excited depending on the context. In this study, we test this hypothesis, leveraging the Fugl-Meyer assessment that could characterize the neuroanatomical architecture in individuals with a wide range of impairments. We examine the ability to perform an out-of-synergy movement with the flexion synergy caused by either shoulder or elbow loading. The results reveal that about 14% [8/57, 95% confidence interval (5.0%, 23.1%)] of the participants with severe impairment (total Fugl-Meyer score <29) in the chronic phase (6 months after stroke) are able to keep the elbow extended during shoulder loading and keep the shoulder at neutral during elbow loading. Those participants underwent a different course of neural reorganization, which enhanced abnormal synergies in comparison with individuals with mild impairment (P < 0.05). These results provide evidence that separate routes and synergy modules to motoneuron pools across the arm might exist even if the motor command is mediated possibly via the RST.NEW & NOTEWORTHY We demonstrate that abnormal synergies are still selectively excited depending on the context.

Correlations in abnormal synergies between the upper and lower extremities across various phases of stroke.

The flexion synergy and extension synergy are a representative consequence of a stroke and appear in the upper extremity and the lower extremity. Since the ipsilesional corticospinal tract (CST) is the most influential neural pathway for both extremities in motor execution, damage by a stroke to this tract could lead to similar motor pathological features (e.g., abnormal synergies) in both extremities. However, less attention has been paid to the interlimb correlations in the flexion synergy and extension synergy across different recovery phases of a stroke. We used results of the Fugl-Meyer assessment (FMA) to characterize those correlations in a total of 512 participants with hemiparesis after stroke from the acute phase to 1 year. The FMA provides indirect indicators of the degrees of the flexion synergy and extension synergy after stroke. We found that, generally, strong interlimb correlations (r > 0.65 with all P values < 0.0001) between the flexion synergy and extension synergy appeared in the acute-to-subacute phase (<90 days). However, the correlations of the lower-extremity extension synergy with the upper-extremity flexion synergy and extension synergy decreased (down to r = 0.38) 360 days after stroke (P < 0.05). These results suggest that the preferential use of alternative neural pathways after damage by a stroke to the CST enhances the interlimb correlations between the flexion synergy and extension synergy. At the same time, the results imply that the recovery of CST integrity or/and the fragmentation (remodeling) of the alternative neural substrates in the chronic phase may contribute to diversity in neural pathways in motor execution, eventually leading to reduced interlimb correlations.NEW & NOTEWORTHY For the first time, this article addresses the asynchronous relationships in the strengths of flexion and extension synergy expressions between the paretic upper extremity and lower extremity across various phases of stroke.

CRISPR/Cas12a Collateral Cleavage-Driven Transcription Amplification for Direct Nucleic Acid Detection.

The clustered regularly interspaced short palindromic repeat/Cas (CRISPR/Cas) system is a powerful tool for nucleic acid detection owing to specific recognition as well as cis- and trans-cleavage capabilities. However, the sensitivity of CRISPR/Cas-based diagnostic approaches is determined by nucleic acid preamplification, which has several limitations. Here, we present a method for direct nucleic acid detection without preamplification, by combining the CRISPR/Cas12a system with signal enhancement based on light-up RNA aptamer transcription. We first designed two DNA templates to transcribe the light-up RNA aptamer and kleptamer (Kb) RNA: the first DNA template encodes a Broccoli RNA aptamer for fluorescence signal generation, and the Kb DNA template comprises a dsDNA T7 promoter sequence and an ssDNA sequence that encodes an antisense strand for the Broccoli RNA aptamer. Hepatitis B virus (HBV) target recognition activates a CRISPR/Cas12a complex, leading to the catalytic cleavage of the ssDNA sequence. Transcription of the added Broccoli DNA template can then produce several Broccoli RNA aptamer transcripts for fluorescence enhancement. The proposed strategy exhibited excellent sensitivity and specificity with 22.4 fM detection limit, good accuracy, and stability for determining the target HBV dsDNA in human serum samples. Overall, this newly designed signal enhancement strategy can be employed as a universal sensing platform for ultrasensitive nucleic acid detection.

Uvaol ameliorates lipid deposition in hyperlipidemic hepatocytes by suppressing protein-tyrosine phosphatase 1B/ER stress signaling.

Uvaol (UV), a pentacyclic triterpene found in olives and virgin olive oil, is known for its anti-inflammatory and antioxidant effects in various disease models. While olive oil is reported to reduce obesity and insulin resistance, the specific impact of UV on liver lipid metabolism and its molecular mechanisms are not fully understood. In this study, hepatic lipid accumulation was measured using oil red O staining, and protein expression levels in liver cells were assessed via Western blot analysis. Apoptosis was evaluated through cell viability and caspase 3 activity assays. UV treatment reduced lipid accumulation, fatty acid uptake, apoptosis, and ER stress in palmitate-treated liver cells. Additionally, UV enhanced fatty acid oxidation. Mechanistically, increased SIRT6 expression and autophagy were observed in UV-treated cells. SIRT6-targeted siRNA or 3-methyladenine blocked the effects of UV in hyperlipidemic cells. In conclusion, UV improves SIRT6/autophagy signaling, reducing lipid deposition and apoptosis in liver cells under high lipid conditions. This in vitro study provides strong evidence for potential therapeutic strategies for hepatic steatosis.

Olaparib enhances sensitization of BRCA-proficient breast cancer cells to x-rays and protons.

PURPOSE: This study aimed to compare the radiosensitizing effect of the PARP inhibitor, Olaparib, between proton and X-rays irradiations in BRCA-proficient breast cancer (BC) cells. METHODS: Two BRCA-proficient BC cell lines, MDA-MB-231 and T47D BC, were used. Cell proliferation was assessed using the CCK-8 assay, and radiosensitivity was determined through the clonogenic survival assay. Flow cytometry was employed to analyze cell cycle distribution and apoptosis. The kinetics of DNA damage repair were evaluated using γH2AX immunofluorescence imaging and the comet assay. Tumor spheroid assays were conducted to test radiosensitivity in a three-dimensional culture condition. RESULTS: Olaparib sensitized both MDA-MB-231 and T47D cells to proton and X-ray irradiation in the clonogenic assay. MDA-MB-231 cells exhibited a higher dose enhancement factor for Olaparib than T47D cells. Olaparib increased radiation-induced G2/M cell cycle arrest and apoptosis specifically in MDA-MB-231 cells. γH2AX immunostaining and the comet assay showed Olaparib augmented radiation-induced DNA damage and apoptosis. The enhancement effect of Olaparib was more pronounced in proton irradiation than in X-ray irradiation, particularly in MDA-MB-231 cells than T47D cells. Both radiation and Olaparib dose-dependently inhibited spheroid growth in both cell lines. The synergy scores demonstrated that Olaparib interacted more strongly with protons than X-rays. The addition of an ATR inhibitor further enhanced Olaparib-induced proton radiosensitization in MDA-MB-231 cells. CONCLUSION: This study found that Olaparib enhanced radiation efficacy in BRCA-proficient breast cancer cells, with a more pronounced effect observed with proton irradiation compared to X-ray irradiation. Combining Olaparib with an ATR inhibitor increased the radiosensitizing effect of protons.

Suboptimal performance of LI-RADS v2018 on gadoxetic acid-enhanced MRI for detecting hepatocellular carcinoma in liver transplant candidates.

OBJECTIVES: To evaluate the diagnostic performance for hepatocellular carcinoma (HCC) detection of the Liver Imaging Reporting and Data System (LI-RADS) version 2018 on gadoxetic acid-enhanced MRI, comparing liver transplant candidates (LT group) with patients who underwent surgical resection (SR group), and to determine significant clinical factors for diagnostic performance of LI-RADS v2018. METHODS: Patients who underwent gadoxetic acid-enhanced MRI and subsequent SR or LT for HCC were retrospectively included between January 2019 and December 2020. The sensitivity and specificity of LI-RADS LR-5 for HCC were compared between the two groups using generalized estimating equations. The accuracy of patient allocation according to the Milan criteria was calculated for the LT group. Univariable and multivariable logistic regression analyses were performed to determine significant clinical factors associated with the sensitivity of LI-RADS. RESULTS: Of the 281 patients, 237 were assigned to the SR group, and 44 were assigned to the LT group. The LT group showed significantly lower per-patient (48.5% vs. 79.6%, p < .001) and per-lesion sensitivity (31.0% vs. 75.9%, p < .001) than the SR group, whereas no significant difference in both per-patient (100.0% vs. 91.7%, p > .99) and per-lesion specificities (100.0% vs. 94.1%, p > .99). The accuracy of patient allocation was 50.0%. Sensitivity was significantly lower in patients with a smaller lesion size (p < .001), a larger lesion number (p = .002), and a higher Child-Pugh score (p = .009). CONCLUSION: LI-RADS v2018 on gadoxetic acid-enhanced MRI might be insufficient in liver transplant candidates and other diagnostic imaging tests should be considered in patients with these significant clinical factors. CLINICAL RELEVANCE STATEMENT: In liver transplant candidates with a smaller lesion size, a larger lesion number, and a higher Child-Pugh score, imaging tests other than gadoxetic acid-enhanced MRI may be clinically useful to determine the transplant eligibility. KEY POINTS: • The sensitivity of the Liver Imaging Reporting and Data System (LI-RADS) was lower in liver transplant candidates than in those who underwent surgical resection. • With the use of gadoxetic acid-enhanced MRI, the accuracy of patient allocation for liver transplantation on the basis of the Milan criteria was suboptimal. • The sensitivity of LI-RADS v2018 was significantly associated with lesion size, lesion number, and Child-Pugh classification.

LI-RADS threshold growth based on tumor growth rate can improve the diagnosis of hepatocellular carcinoma ≤ 3.0 cm.

OBJECTIVE: Despite the revision of threshold growth (TG) in the Liver Imaging Reporting and Data System (LI-RADS) version 2018, the appropriate time period between the two examinations for TG has not been determined. We compared the accuracy of LI-RADS with TG based on tumor growth rate for the diagnosis of hepatocellular carcinoma (HCC) with that of LI-RADS v2018 based on the original TG. METHODS: Patients who underwent preoperative MRI for focal solid lesions (≤ 3.0 cm) were retrospectively evaluated. Three readers measured the size of each lesion on prior CT/MRI and index MRI, with tumor growth rate defined as the percent change in lesion size per month. In addition to the original TG (≥ 50% size increase within ≤ 6 months), the modified TG based on tumor growth rates ≥ 10%/month (TG-10%), ≥ 20%/month (TG-20%), and ≥ 30%/month (TG-30%) were evaluated. The accuracies of these evaluation methods for LI-RADS category 5 HCC were compared using generalized estimation equations. RESULTS: A total of 508 lesions from 370 patients were evaluated. Compared with LI-RADS v2018 with the original TG, the accuracy of LI-RADS with TG-10% was significantly higher (85.0% vs. 80.7%, p < .001), whereas the accuracies of LI-RADS with TG-20% (81.3% vs. 80.7%, p = .404) and TG-30% (79.3% vs. 80.7%, p = .052) were not significant. The sensitivity of LI-RADS with TG-10% was higher than that of LI-RADS v2018 (79.0% vs. 72.5%, p < .001), whereas their specificities were not significantly different (96.6% vs. 96.6%, p > .999). CONCLUSION: TG-10% improved the sensitivity of LI-RADS by detecting additional hepatocellular carcinomas underestimated due to short-term follow-up. CLINICAL RELEVANCE STATEMENT: Threshold growth based on tumor growth rate can be clinically useful in the diagnosis of hepatocellular carcinoma, by improving the sensitivity of LI-RADS. KEY POINTS: • The diagnostic accuracy of Liver Imaging Reporting and Data System (LI-RADS) v2018 was not significantly affected by the time interval between prior and index assessments of threshold growth. • In the 334 hepatocellular carcinomas, the frequency of threshold growth was significantly higher using tumor growth rate ≥ 10%/month (TG-10%) than original threshold growth (53.3% vs. 18.0%, p < .001). • Compared with LI-RADS v2018 with the original threshold growth, LI-RADS with TG-10% had significantly higher accuracy (85.0% vs. 80.7%, p < .001) and sensitivity (79.0% vs. 72.5%, p < .001) but a similar specificity (96.6% vs. 96.6%, p > .999).

Radiofrequency ablation of subcapsular versus nonsubcapsular hepatocellular carcinomas ≤ 3 cm: analysis of long-term outcomes from two large-volume liver centers.

OBJECTIVES: To compare the safety and efficacy of RFA for single HCCs ≤ 3 cm in subcapsular versus nonsubcapsular locations using a propensity score matched analysis. MATERIALS AND METHODS: This retrospective study included patients with solitary HCCs ≤ 3 cm in size who underwent percutaneous RFA from 2005 to 2015 as initial treatment at two large-volume liver centers. Patients were divided into two groups, consisting of those with subcapsular and nonsubcapsular tumor locations. Complications, local tumor progression (LTP), and overall survival (OS) were compared in these two groups before and after propensity score matching (PSM). RESULTS: The study population consisted of 964 patients (712 men [74%]) of mean age 58.3 years. Of these 964 patients, 561 (58%) had nonsubcapsular and 403 (42%) had subcapsular HCCs. PSM generated 402 pairs of patients. Major complication rate was low, but significantly higher in the subcapscular group (p = 0.047). Rates of technical effectiveness in these two groups were 99% and 98%, respectively (p = 0.315). However, during follow-up, cumulative 1-, 3-, 5-, and 10-year LTP and OS rates did significantly differ in both entire and PSM cohorts, resulting in the latter 8%, 15%, 20%, and 26% in the nonsubcapsular group vs. 13%, 24%, 30%, and 31% in the subcapsular group (p = 0.015), and 99%, 91%, 80%, and 59% vs. 98%, 85%, 73%, and 50% in the two groups (p = 0.004), respectively. CONCLUSION: Rates of major complications, LTP, and OS differed significantly following first-line RFA treatment of single HCCs ≤ 3 cm in favor of the nonsubcapsular locations. CLINICAL RELEVANCE STATEMENT: This large-scale study provides evidence that radiofrequency ablation for small (≤ 3 cm) hepatocellular carcinomas is safer and more effective in nonsubcapsular location than in subcapsular location. KEY POINTS: • There exist conflicting outcomes on the effectiveness of RFA for early HCC depending on tumor location. • Rate of local tumor progression was significantly higher in the subcapsular hepatocellular carcinomas. • Overall survival rate was significantly poorer in the subcapsular hepatocellular carcinomas.

Chemoembolization versus radiofrequency ablation for single small (≤ 3 cm) hepatocellular carcinoma: a propensity score matching analysis.

OBJECTIVES: To compare the efficacy of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for patients with single small (≤ 3 cm) hepatocellular carcinoma (HCC) and preserved liver function (Child-Pugh class A). MATERIALS AND METHODS: The clinical features of treatment-naïve patients who underwent TACE and RFA as first-line treatment were balanced through propensity score matching (PSM). The primary endpoint was overall survival (OS), and the secondary endpoints were local tumor recurrence (LTR) and recurrence-free survival (RFS). RESULTS: The analysis included 440 patients who received TACE, and 430 patients who received RFA. After PSM adjustment (323 pairs), the 5- and 10-year OS rates were 81% and 61%, respectively, in patients who underwent RFA, and 77% and 51%, respectively, for patients who underwent TACE (p = 0.021). Subgroup analyses showed that OS, LTR, and RFS were homogeneously better in the RFA group. CONCLUSION: RFA was associated with better survival outcomes than TACE in patients with single small HCC and preserved liver function. CLINICAL RELEVANCE STATEMENT: This large-scale comparative study provides evidence that radiofrequency ablation has a better overall survival rate than chemoembolization for small (≤ 3 cm) hepatocellular carcinomas. KEY POINTS: • The relative effectiveness of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for early HCC is unclear. • Overall survival rate was significantly higher in the RFA group. • The effects of RFA on overall survival, local tumor recurrence, and recurrence-free survival were homogeneously better in all subgroups.

Improvement in functional motor scores in patients with non-ambulatory spinal muscle atrophy during Nusinersen treatment in South Korea: a single center study.

We analyzed the changes in various motor function scores over a four-year period in patients with non-ambulatory spinal muscular atrophy (SMA) during Nusinersen treatment. Patients underwent Hammersmith Infant Neurological Examination (HINE) or Hammersmith Functional Motor Scale Expanded (HFMSE) before treatment, and approximately every 4 months thereafter. Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) or Children's Hospital of Philadelphia - Adult Test of Neuromuscular Disorders (CHOP ATEND), Revised Upper Limb Module (RULM), and Motor Function Measure (MFM) were performed based on baseline functional status. Narrative interviews were conducted to explore post-treatment physical improvement regarding activities of daily living (ADLs) and fatigue after ADLs. Based on HFMSE results, 9 patients achieved minimum clinically important differences. Average rates of change (slopes) with corresponding 95% confidence intervals for all assessment tools were in a positive direction. CHOP-INTEND showed the most prominent improvement in children and adolescents followed by HFMSE. Improvements in CHOP-ATEND were most noticeable in adults. Improvements were accompanied by changes in ADLs as observed in the narrative interviews. It is necessary to consider various functional aspects to determine the effectiveness of Nusinersen therapy. The objective assessment of the therapeutic effect of Nusinersen in non-ambulatory SMA requires consideration of functional aspects and the related ADLs.

Jatrophihabitans cynanchi sp. nov., isolated from rhizosphere soil of Cynanchum wilfordii.

A novel actinobacterial strain, SB3-54T was isolated from rhizosphere soil of Cynanchum wilfodill, Jaecheon, Chungcheongbuk-do, Republic of Korea. Cells of strain SB3-54T were Gram-stain-positive, aerobic, rod-shaped, and flagellated which formed pale yellow colonies on Reasoner's 2A (R2A) agar. Growth occurred at 15-30 °C (optimum 25 °C), pH 5-8 (optimum pH 7), and 0-2.5% NaCl (optimum 0%). Phylogenetic and phylogenomic analyses showed that strain SB3-54T formed a separate lineage in the genus Jatrophihabitans with Jatrophihabitans telluris N237T. Strain SB3-54T was positive for catalase activity. Genomic analysis showed that SB3-54T has plant-beneficial function contributing (referred to as PBFC) genes such as root colonization and plant protection from oxidative stress. Furthermore, genome of SB3-54T contained gene clusters related to cytokinin biosynthesis, auxin response, tryptophan biosynthesis, siderophore biosynthesis and bacterial toxin-antitoxin systems. Strain SB3-54T contained iso-C16:0 as the major fatty acid and MK-9(H4) and MK-9(H6) as the predominant quinones. The organism had meso-diaminopimelic acid as the diagnostic diamino acid in the peptidoglycan. The major polar lipids were diphosphatidylglycerol, phosphatidylinositol polymannosides, two unidentified aminoglycophospholipids and three unidentified phospholipids. Based on phylogenetic, physiological and chemotaxonomic characteristics, strain SB3-54T represents a novel species of the genus Jatrophihabitans. The type strain is SB3-54T (= KCTC 49134T = NBRC 114108T).

Enhancement of Exfoliating Effects through the Novel Cosmetic Ingredient Mandelic acid_Carnitine Ion-Pairing Complex.

PURPOSE: This study aimed to develop a novel exfoliating material with high efficacy and low irritation by synthesizing the Mandelic acid_Carnitine ion pairing complex (M_C complex) and evaluating its exfoliating properties. Additionally, the study assessed the skin improvement effects of the M_C complex through clinical evaluations. METHODS: The M_C complex was synthesized in a 1:1 molar ratio of Mandelic acid and Carnitine. Structural characterization was performed using dynamic light scattering and Fourier-transform infrared spectroscopy. Exfoliating efficacy was evaluated on porcine skin, and clinical assessments were conducted on human subjects to measure various skin improvement parameters. RESULTS: The formation of the M_C complex was confirmed through particle size analysis, zeta-potential measurements, and FT-IR spectroscopy. The M_C complex demonstrated superior exfoliating efficacy compared to Mandelic acid alone, especially at pH 4.5. Clinical evaluations showed significant improvements in blackheads, whiteheads, pore volume, depth, density, count, and affected area, as well as skin texture. No adverse reactions were observed. CONCLUSION: The M_C complex exhibits high exfoliating efficacy and minimal irritation, making it a promising cosmetic ingredient for improving skin health. These findings support its potential as a low-irritation exfoliating material under mildly acidic conditions, contributing to overall skin health enhancement.

Prevalence and clinical characteristics of Sarcopenia in older adult patients with stable chronic obstructive pulmonary disease: a cross-sectional and follow-up study.

BACKGROUND: The relationship between sarcopenia and chronic obstructive pulmonary disease (COPD) has been increasingly reported, and there is some overlap regarding their clinical features and pulmonary rehabilitation (PR) strategies. No Korean study has reported the actual prevalence of sarcopenia in patients with stable COPD who are recommended for pulmonary rehabilitation. This study evaluated the prevalence and clinical features of sarcopenia in older adult outpatients with stable COPD and the changes after 6 months. METHODS: In this cross-sectional and 6-month follow-up study, we recruited 63 males aged ≥ 65 diagnosed with stable COPD. Sarcopenia was diagnosed using the AWGS 2019 criteria, which included hand grip strength testing, bioelectrical impedance analysis, Short Physical Performance Battery administration, and Strength, Assistance with walking, Rising from a chair, Climbing stairs, and Falling screening tool administration. A 6-minute walk test (6 MWT) was conducted, forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), maximal inspiratory and expiratory pressures (MIP and MEP, respectively) and peak expiratory flow (PEF) were assessed, and patient-reported questionnaires were administered. RESULTS: At baseline, 14 (22%) patients were diagnosed with possible sarcopenia, and eight (12.6%) were diagnosed with sarcopenia. There were significant differences in the age; body mass index; Body mass index, airflow Obstruction, Dyspnea, and Exercise index; modified Medical Research Council dyspnea scores; and International Physical Activity Questionnaire scores between the normal and sarcopenia groups. Whole-body phase angle, MIP, MEP, PEF, and 6-minute walk distance (6 MWD) also showed significant differences. Over 6 months, the proportion of patients with a reduced FEV1 increased; however, the proportion of patients with sarcopenia did not increase. CONCLUSION: A relatively low prevalence of sarcopenia was observed in older adult outpatients with stable COPD. No significant change in the prevalence of sarcopenia was found during the 6-month follow-up period. TRIAL REGISTRATION: The study was registered with the Clinical Research Information Service (KCT0006720). Registration date: 30/07/2021.

Toxicology and safety study of L-tryptophan and its impurities for use in broiler feed.

L-tryptophan has been utilized as a feed additive in animal nutrition to improve growth performance, as well as a dietary supplement to alleviate various emotional symptoms in humans. Despite its benefits, concerns regarding its safety arose following the outbreak of eosinophilia-myalgia syndrome (EMS) among individuals who consumed L-tryptophan. The causative material of EMS was determined to be not L-tryptophan itself, but rather L-tryptophan impurities resulting from a specific manufacturing process. To investigate the effect of L-tryptophan and its impurities on humans who consume meat products derived from animals that were fed L-tryptophan and its impurities, an animal study involving broiler chickens was conducted. The animals in test groups were fed diet containing 0.065%-0.073% of L-tryptophan for 27 days. This study aimed to observe the occurrence of toxicological or EMS-related symptoms and analyze the residues of L-tryptophan impurities in meat products. The results indicated that there was no evidence of adverse effects associated with the test substance in the investigated parameters. Furthermore, most of the consumed EMS-causing L-tryptophan impurities did not remain in the meat of broiler chickens. Thus, this study demonstrated the safety of L-tryptophan and some of its impurities as a feed additive.

Toxicology and safety study of L-tryptophan and its impurities for use in swine.

L-tryptophan, an essential amino acid for physiological processes, metabolism, development, and growth of organisms, is widely utilized in animal nutrition and human health as a feed additive and nutritional supplement, respectively. Despite its known benefits, safety concerns have arisen due to an eosinophilia-myalgia syndrome (EMS) outbreak linked to L-tryptophan consumed by humans. Extensive research has established that the EMS outbreak was caused by an L-tryptophan product that contained certain impurities. Therefore, safety validations are imperative to endorse the use of L-tryptophan as a supplement or a feed additive. This study was conducted in tertiary hybrid [(Landrace × Yorkshire) × Duroc] pigs to assess general toxicity and potential risks for EMS-related symptoms associated with L-tryptophan used as a feed additive. Our investigation elucidated the relationship between L-tryptophan and EMS in swine. No mortalities or clinical signs were observed in any animals during the administration period, and the test substance did not induce toxic effects. Hematological analysis and histopathological examination revealed no changes in EMS-related parameters, such as eosinophil counts, lung lesions, skin lesions, or muscle atrophy. Furthermore, no test substance-related changes occurred in other general toxicological parameters. Through analyzing the tissues and organs of swine, most of the L-tryptophan impurities that may cause EMS were not retained. Based on these findings, we concluded that incorporating L-tryptophan and its impurities into the diet does not induce EMS in swine. Consequently, L-tryptophan may be used as a feed additive throughout all growth stages of swine without safety concerns.

Factors to improve odds of success following medial opening-wedge high tibial osteotomy: a machine learning analysis.

BACKGROUND: Although high tibial osteotomy (HTO) is an established treatment option for medial compartment osteoarthritis, predictive factors for HTO treatment success remain unclear. This study aimed to identify informative variables associated with HTO treatment success and to develop and internally validate machine learning algorithms to predict which patients will achieve HTO treatment success for medial compartmental osteoarthritis. METHODS: This study retrospectively reviewed patients who underwent medial opening-wedge HTO (MOWHTO) at our center between March 2010 and December 2015. The primary outcomes were a lack of conversion to total knee arthroplasty (TKA) and achievement of a minimal clinically important difference of improvement in the Knee Injury and Osteoarthritis Outcome Score (KOOS) at a minimum of five years postoperatively. Recursive feature selection was used to identify the combination of variables from an initial pool of 25 features that optimized model performance. Five machine learning algorithms (XGBoost, multilayer perception, support vector machine, elastic-net penalized logistic regression, and random forest) were trained using five-fold cross-validation three times and applied to an independent test set of patients. The performance of the model was evaluated by the area under the receiver operating characteristic curve (AUC). RESULTS: A total of 231 patients were included, and 200 patients (86.6%) achieved treatment success at the mean of 9 years of follow-up. A combination of seven variables optimized algorithm performance, and the following specific cutoffs increased the likelihood of MOWHTO treatment success: body mass index (BMI) ≤ 26.8 kg/m2, preoperative KOOS for pain ≤ 46.0, preoperative KOOS for quality of life ≤ 33.0, preoperative International Knee Documentation Committee score ≤ 42.0, preoperative Short-Form 36 questionnaire (SF-36) score > 42.25, three-month postoperative hip-knee-ankle angle > 1.0°, and three-month postoperative medial proximal tibial angle (MPTA) > 91.5° and ≤ 94.7°. The random forest model demonstrated the best performance (F1 score: 0.93; AUC: 0.81) and was transformed into an online application as an educational tool to demonstrate the capabilities of machine learning. CONCLUSIONS: The random forest machine learning algorithm best predicted MOWHTO treatment success. Patients with a lower BMI, poor clinical status, slight valgus overcorrection, and postoperative MPTA < 94.7 more frequently achieved a greater likelihood of treatment success. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Associations between body mass index and interface pressure after 3 h loading in healthy adults.

AIM OF THE STUDY: The purpose of this study was to determine the associations between body mass index and interface pressure after 3 h loading in healthy adults and to establish a foundation for the development of interventions tailored to body mass index. MATERIAL AND METHODS: A secondary data analysis based on a clinical trial involving 75 adults was conducted. Data were analyzed using descriptive statistics, repeated measure ANOVA, and ANCOVA. The statistics program IBM SPSS Statistics 27.0 was used for data analysis. RESULTS: Loading caused a significant increase in average pressure in the obesity group compared to the underweight group. There was a significant increase in risk area ratio calculated based on 30 mmHg and 45 mmHg in both obesity and overweight groups compared to the underweight group. On both support surfaces, average pressure, peak pressure, and risk area ratio were higher in the obese group compared to the normal weight group. However, these differences were not statistically significant. CONCLUSION: Given the emphasized risk of pressure injuries, long-term observation of body mass index-specific changes in interface pressure can provide crucial evidence for pressure injury prevention nursing. The results of this study suggest the need to implement pressure injury prevention interventions that consider the pressure characteristics according to BMI.

Factors associated with intention to use care robots among people with physical disabilities.

BACKGROUND: As the disabled population ages and the demand for care increases, Socially, the need for care robots is emerging but, perceptions of care robots among care recipients is unknown. PURPOSE: To determine the level of intention to use care robots among care recipients and identify predictors of intention to use care robots. METHODS: A cross-sectional survey was conducted using a convenience sample of 163 persons with disabilities from January to March 2022 at the Veterans Health Service Medical Center. DISCUSSION: Overall, 64.42% of respondents intended to use care robots. Predictors included perceived behavioral control, participants' perceptions of the caregiver's burden, attitude toward robot use, subjective norms, and age. CONCLUSION: These findings suggest that individuals who are community-dwelling desire the use care robots to maintain their independence and may provide useful insignt for the introduction various care robots in acute care and long-term care settings.

Predictors of Burden for First-Ever Stroke Survivor's Long-Term Caregivers: A Study of KOSCO.

Long-term changes in caregiver burden should be clarified considering that extended post-stroke disability can increase caregiver stress. We assessed long-term changes in caregiver burden severity and its predictors. This study was a retrospective analysis of the Korean Stroke Cohort for Functioning and Rehabilitation. Patients with an acute first-ever stroke were enrolled from August 2012 to May 2015. Data were collected at 6 months and 6 years after stroke onset. The caregiver burden was measured with a subjective caregiver burden questionnaire based on the Korean version of the Caregiver Burden Inventory. The caregivers' characteristics and patients' clinical and functional status were also examined at each follow-up. A high caregiver burden, which suggests a risk of burnout, was reported by 37.9% and 51.7% of caregivers at 6 months and 6 years post-stroke, respectively. Both the caregiver burden total score and proportion of caregivers at risk of burnout did not decrease between 6 months and 6 years. The patients' disability (OR = 11.60; 95% CI 1.58-85.08; p = 0.016), caregivers' self-rated stress (OR = 0.03; 95% CI 0.00-0.47; p = 0.013), and caregivers' quality of life (OR = 0.76; 95% CI 0.59-0.99; p = 0.042) were burden predictors at 6 months. At 6 years, only the patients' disability (OR = 5.88; 95% CI 2.19-15.82; p < 0.001) and caregivers' psychosocial stress (OR = 1.26; 95% CI 1.10-1.44; p = 0.001) showed significance. Nearly half of the caregivers were at risk of burnout, which lasted for 6 years after stroke onset. The patients' disability and caregivers' stress were burden predictors in both subacute and chronic phases of stroke. The findings suggest that consistent interventions, such as emotional support or counseling on stress relief strategies for caregivers of stroke survivors, may reduce caregiver burden. Further research is needed to establish specific strategies appropriate for Korean caregivers to alleviate their burden in caring for stroke patients.

Value of threshold growth as a major diagnostic feature of hepatocellular carcinoma in LI-RADS.

BACKGROUND & AIMS: The Liver Reporting and Data System (LI-RADS) version 2018 simplified the definition of threshold growth to '≥50% size increase in a mass in ≤6 months'. However, the diagnostic value of threshold growth for hepatocellular carcinoma (HCC) remained unclear. We evaluated the value of threshold growth, as defined by LI-RADS v2018, in diagnosing HCCs. METHODS: Patients who underwent preoperative gadoxetate disodium-enhanced MRI because of the presence of LI-RADS category 2, 3, or 4 rather than category 5 on prior CT/MRI between January 2017 and December 2020 were retrospectively evaluated. Pathologic or clinical diagnoses were used as reference standards. Imaging features were evaluated by three readers according to LI-RADS v2018. The frequency and diagnostic odds ratio of threshold growth were calculated. The diagnostic performance of LI-RADS category 5 was separately evaluated when threshold growth was and was not considered a major feature, and results were compared using generalized estimation equations. Subgroups of patients who underwent CT/MRI during the previous 3-6 months were analyzed. RESULTS: Analysis of 340 observations in 243 patients found that the frequency of threshold growth was 18.8% and it gradually increased over time. Threshold growth was significantly associated with HCC (diagnostic odds ratio 5.2; 95% CI 2.1-12.7; p <0.001). Use of threshold growth as a major feature significantly increased sensitivity in both the overall (66.4% vs. 57.3%, p <0.001) and subgroup (73.4% vs. 58.2%, p <0.001) cohorts, but had no effect on specificity in either the overall (97.5% vs. 98.3%, p = 0.319) or subgroup (95.9% vs. 98.0%, p = 0.323) cohorts. CONCLUSION: The revised threshold growth of LI-RADS v2018 was significantly associated with HCC. Use of threshold growth as a major diagnostic feature of HCC can improve the sensitivity of LI-RADS v2018. IMPACT AND IMPLICATIONS: We found that the revised threshold growth in the Liver Imaging Reporting and Data System version 2018 (LI-RADS v2018) was a significant predictor of hepatocellular carcinoma (HCC). The use of threshold growth as a major imaging feature of HCC significantly increased the sensitivity of LI-RADS v2018, especially small HCCs (≤3.0 cm), compared with its non-use. Because these small HCCs are eligible for curative treatments, the additional detection of small HCCs is clinically meaningful.