Associations of 2 Established Methods of Measuring Gait Speed and Sit-To-Stand Performance with Frailty and Life-Space Mobility in Community-Dwelling Older Adults.

OBJECTIVES: The 4-m gait speed (4mGS) and 10-m gait speed (10mGS) tests and the 30-second sit-to-stand (30sSTS) and 5-times sit-to-stand (5xSTS) tests are commonly used and advocated in consensus recommendations. We compared these tests on their predictive and clinical value concerning the risk of prefrailty/frailty and restricted life-space mobility (RLSM). DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: A sample of 1235 community-dwelling adults (mean ± SD, 68 ± 7 years) participated in this prospective cohort study. METHODS: At baseline assessment, participants completed a survey and functional assessment, from which gait speed, sit-to-stand performance, self-reported mobility limitation, 40-item Frailty Index, and Life Space Assessment were measured. Participants with a 40-item Frailty Index >0.15 and a Life Space Assessment <60 points were classified as having prefrailty/frailty and RLSM, respectively. At 1-year follow-up assessment, prefrailty/frailty and RLSM were evaluated. RESULTS: Correlations between gait speed and sit-to-stand measures were high (ρ values >0.80). In multivariable ordinal models, these measures added incremental prognostic value beyond a base model comprising demographics and self-reported mobility limitation variables in predicting baseline and 1-year outcomes. Between 10mGS and 4mGS, models with 10mGS had higher concordance indices (differences, 0.005-0.009), and these differences translated to generally greater net benefit in decision curve analyses. Between 30sSTS and 5xSTS measures, no one measure consistently outperformed the other, with small net benefit differences between measures (<0.2%). CONCLUSIONS AND IMPLICATIONS: In community-dwelling older adults, gait speed and sit-to-stand measures meaningfully predicted prefrailty/frailty and RLSM. 10mGS provided more robust prognostic information than the 4mGS, whereas 5xSTS and 30sSTS measures showed near equivalence of performance. These findings could guide the choice of functional measures in clinical and research settings.

Below-knee amputation with an ultrasonic scalpel: evaluation of early postoperative clinical outcomes.

OBJECTIVE: Despite the development of microscopic reconstructive techniques for lower limb salvage, major limb amputation is still required for critical, unsalvageable lower leg wounds, with steadily increasing estimates of major limb amputations. In this study, the authors highlight a surgical technique for below-knee (BK) amputation using an ultrasonic scalpel, and evaluate its safety and effectiveness compared with the conventional method of using surgical blades. METHOD: A retrospective chart review was conducted at the Department of Plastic and Reconstructive Surgery, St. Vincent's Hospital, Republic of Korea, on patients who underwent BK amputation between October 2012 and January 2021. Patients were assigned to two groups: amputation using classical methods, such as surgical blades and electrocautery (group A); and amputation using an ultrasonic scalpel (group B). Numerous perioperative factors, such as operation time, intraoperative blood loss, postoperative complications and recovery time were examined. The present study adhered to the STROBE guidelines. RESULTS: A total of 41 patients (16 in group A and 25 in group B) were included in this study. Operation time was significantly shorter in group B (p=0.001) and intraoperative blood loss was lower (p=0.011). Wound healing time did not vary between groups. CONCLUSION: In this study, the use of an ultrasonic scalpel for lower limb amputation was effective in reducing operation time and blood loss, which may be helpful in improving outcomes for patients with comorbidities.

The early life microbiome of giant grouper (Epinephelus lanceolatus) larvae in a commercial hatchery is influenced by microorganisms in feed.

Fish health, growth and disease is intricately linked to its associated microbiome. Understanding the influence, source and ultimately managing the microbiome, particularly for vulnerable early life-stages, has been identified as one of the key requirements to improving farmed fish production. One tropical fish species of aquaculture importance farmed throughout the Asia-Pacific region is the giant grouper (Epinephelus lanceolatus). Variability in the health and survival of E. lanceolatus larvae is partially dependent on exposure to and development of its early microbiome. Here, we examined the development in the microbiome of commercially reared giant grouper larvae, its surrounding environment, and that from live food sources to understand the type of bacterial species larvae are exposed to, and where some of the sources of bacteria may originate. We show that species richness and microbial diversity of the larval microbiome significantly increased in the first 4 days after hatching, with the community composition continuing to shift over the initial 10 days in the hatchery facility. The dominant larval bacterial taxa appeared to be predominantly derived from live cultured microalgae and rotifer feeds and included Marixanthomonas, Candidatus Hepatincola, Meridianimaribacter and Vibrio. In contrast, a commercial probiotic added as part of the hatchery's operating procedure failed to establish in the larvae microbiome. Microbial source tracking indicated that feed was the largest influence on the composition of the giant grouper larvae microbiome (up to 55.9%), supporting attempts to modulate fish microbiomes in commercial hatcheries through improved diets. The marked abundances of Vibrio (up to 21.7% of 16S rRNA gene copies in larvae) highlights a need for rigorous quality control of feed material.

Analysis of dimer and trimer complexes of the non-amyloidogenic rat islet amyloid polypeptide 21-37 by electrospray ionization-tandem mass spectrometry.

The dimer and trimer structures of the non-amyloidogenic rat islet amyloid polypeptide 21-37 peptide, formed in an H2O/CH3OH (1% CH3COOH) solution were investigated using electrospray ionization-tandem mass spectrometry (ESI-MS/MS). The dissociation of monomers, dimers, and trimers was investigated by MS/MS using collision-induced dissociation. The peptide bond dissociation between L7 and P8 was mainly observed in the tandem mass spectra of the monomers and oligomers, regardless of the parent ion charge state. The fragment ions were observed as a series of bu (u = 3-4, 6-7, 12) or yn (n = 10-11, 13-14) in the [Mono + 2H]2+ (=[monomer + 2H]2+) tandem mass spectrum. MS/MS analysis of the [Di + 3H]3+ (=[dimer + 3H]3+) complex indicated that [Di + 3H]3+ comprised [Mono + H]1+ and [Mono + 2H]2+ subunits. During covalent bond dissociation of the [Di + 3H]3+ complex, a fragmentation pattern was observed in the form of {mono + (fragment ion of [Mono + 2H]2+)}, resulting from the collision energy dissociation of the [Mono + 2H]2+ peptide. The [(C-terminal)-(C-terminal)] interaction geometry was proposed for the [Di + 3H]3+ complex based on the observation of [y10 + yn]2+ (n = 10-11, 13-16) fragment ions in the [Di + 3H]3+ tandem mass spectrum. MS/MS analysis of the [Tri + 4H]4+ (=[trimer + 4H]4+) complex indicated that [Tri + 4H]4+ comprised [Mono + H]1+ and [Di + 3H]3+ subunits. The (monomer-[Di + 3H]3+)4+ complex geometry was assumed to be stable based on the presence of {mono + (fragment ion of [Di + 3H]3+)} ions in the tandem mass spectrum of the [Tri + 4H]4+ complex. The two [Mono + (y10 + y10)]2+ and [Mono + (Mono + y10)]3+ fragment ions also supported the (monomer-[Di + 3H]3+)4+ complex geometries of the [Tri + 4H]4+ complex. The [(C-terminal)-(C-terminal)] interaction geometry of the [Di + 3H]3+ subunit is thought to be conserved in the [Tri + 4H]4+ complex geometries.

Pharmacological inhibition of USP14 delays proteostasis-associated aging in a proteasome-dependent but foxo-independent manner.

Aging is often accompanied by a decline in proteostasis, manifested as an increased propensity for misfolded protein aggregates, which are prevented by protein quality control systems, such as the ubiquitin-proteasome system (UPS) and macroautophagy/autophagy. Although the role of the UPS and autophagy in slowing age-induced proteostasis decline has been elucidated, limited information is available on how these pathways can be activated in a collaborative manner to delay proteostasis-associated aging. Here, we show that activation of the UPS via the pharmacological inhibition of USP14 (ubiquitin specific peptidase 14) using IU1 improves proteostasis and autophagy decline caused by aging or proteostatic stress in Drosophila and human cells. Treatment with IU1 not only alleviated the aggregation of polyubiquitinated proteins in aging Drosophila flight muscles but also extended the fly lifespan with enhanced locomotive activity via simultaneous activation of the UPS and autophagy. Interestingly, the effect of this drug disappeared when proteasomal activity was inhibited, but was evident upon proteostasis disruption by foxo mutation. Overall, our findings shed light on potential strategies to efficiently ameliorate age-associated pathologies associated with perturbed proteostasis.Abbreviations: AAAs: amino acid analogs; foxo: forkhead box, sub-group O; IFMs: indirect flight muscles; UPS: ubiquitin-proteasome system; USP14: ubiquitin specific peptidase 14.

Current trends in digital replantation-a narrative review.

Background and Objective: Digital replantation for traumatic amputation has become the standard of care with advances in microsurgical techniques and technology. While digital replantation has progressed significantly, there are still gaps in knowledge in many aspects. Some of the controversial topics in digital replantation include the indications and contraindications, anesthesia, number of vessel anastomoses, mechanism of injury, role of vein graft, distal fingertip replantation, and postoperative management. This article is a narrative review that discusses these controversies and current issues pertaining to digital replantation. Methods: PubMed, Web of Science, and Google scholar were searched using keywords relating to "digit replantation", "amputation", and "digital replant" with the following terms: "indications", "contraindications", "anaesthesia", "survival", "vessels", "mechanism of injury", "vein graft", "outcome", and "thrombophylaxis". Relevant articles pertaining to digital replantation and deemed by the authors as current or controversial were included. Key Content and Findings: The reported survival rates of digital replantation are high. With the advancement of microsurgical techniques and technology, the boundaries of digital replantation continue to be pushed. Various methods have been described recently to improve the success rates of difficult replants, such as strategies for venous outflow and vein grafting. However, there are still aspects of digital replantation that remain unanswered, such as the number of veins to anastomose and the thromboprophylaxis regime. Conclusions: The review delves into controversial aspects of digital replantation, including contraindications, anesthesia, and postoperative management. Indications and contraindications will continue to evolve alongside advancements in microsurgical techniques and anesthesia. It highlights key factors influencing survival rates, such as the number of repaired vessels and the mechanism of injury. Finally, the review consolidates strategies for managing challenging digital replantations.

Significance of physical factors on activities of daily living in patients with tetraplegia after spinal cord injury: a retrospective study.

BACKGROUND: Tetraplegia is a debilitating sequela of spinal cord injury (SCI). However, comprehensive approaches for determining the influence of various factors on activities of daily living (ADL) in patients with tetraplegia are limited. Therefore, this study aimed to determine the influence of physical factors on ADL in patients with tetraplegia after adjusting for demographic, SCI-related, and cognitive factors. METHODS: This retrospective cross-sectional study enrolled 201 patients with tetraplegia who underwent inpatient rehabilitation at the National Rehabilitation Center in South Korea between 2019 and 2021. Patients' mean age was 50.5 years (standard deviation, 16.3), and 170 (84.6%) were men. The Korean Spinal Cord Independence Measure III (K-SCIM III) was used as the main outcome measure to assess patients' ADL ability. Hierarchical multiple regression modeling was conducted with K-SCIM as the dependent variable to examine the level of functioning and relative influencing factors. RESULTS: Upper-extremity motor score (UEMS), upper-extremity spasticity and sitting balance scores were significant predictors of self-care; lower-extremity motor score (LEMS), musculoskeletal pain of shoulder, and sitting balance were significant predictors of respiratory and sphincter management; UEMS, LEMS, and sitting balance score were significant predictors of mobility; and UEMS, LEMS, musculoskeletal pain of shoulder, and sitting balance scores were significant predictors of the K-SCIM III total score after adjustment for demographic, SCI-related, and cognitive factors. CONCLUSIONS: Physical factors had the greatest impact on all subscores and the K-SCIM III total score. Upper- and lower-extremity muscle strength and sitting balance significantly affected functional ability across all subscores.

Molecular signatures diversity unveiled through a comparative transcriptome analysis of longissimus dorsi and psoas major muscles in Hanwoo cattle.

This study investigates the transcriptome-level alterations that influence production traits and early fattening stage myogenesis in Hanwoo cattle, specifically focusing on the highly prized Longissimus dorsi (LD) and Psoas major (PM) skeletal muscles, which hold significant commercial value. We conducted RNA sequencing analysis on LD and PM muscles from 14 Hanwoo steers (n = 7, each group) at the age of 10 months, all fed the same diet. Our results unveiled a total of 374 and 206 up-regulated differentially expressed genes (DEGs) in LD and PM muscles, respectively, with statistical significance (p < 0.05) and a log2fold change ≥ 1. Genes governing muscle development processes, such as PAX3, MYL3, COL11A1, and MYL6B, were found to be expressed at higher levels in both tissues. Conversely, genes regulating lipid metabolism, including FABP3, FABP4, LEP, ADIPOQ, and PLIN1, exhibited higher expression in the PM muscle. Functional enrichment analysis revealed a tissue-specific response, as PM muscle showed increased lipid metabolism allied pathways, including the PPAR signaling pathway and regulation of lipolysis in adipocytes, while LD was characterized by growth and proliferative processes. Our findings validate the presence of a muscle-dependent transcription and co-expression pattern that elucidates the transcriptional landscape of bovine skeletal muscle.

Reliability and Validity of a Tablet-Based Neuropsychological Test (the Hellocog) for Screening Dementia.

OBJECTIVE: To address the gap in timely diagnosis of dementia due to limited screening tools, we investigated the validity and reliability of the Hellocog, computerized neuropsychological test based on tablets for screening dementia. The higher the probability score on the Hellocog, the higher the likelihood of dementia. METHODS: This study included 100 patients with dementia and 100 individuals with normal cognition who were aged 60 years or older and free of other major psychiatric, neurological, or medical conditions. They administered the Hellocog on a tablet under the supervision of a neuropsychologist. To determine test-retest reliability, 20 took the Hellocog again after 4 weeks. Diagnostic performance was assessed using the receiver operator characteristics (ROC) analysis. RESULTS: The Hellocog showed adequate internal consistency (Cronbach's alpha=0.69) and good test-retest reliability (intraclass correlation coefficient=0.86, p<0.001). Participants with dementia scored higher on the Hellocog than those with normal cognition (p<0.001), confirming its high criterion validity. Strong correlations with the Mini-Mental Status Examination (MMSE) score and the total score of the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery (CERAD-TS) highlight the concurrent validity of the Hellocog. The area under the ROC curve for dementia of the Hellocog was excellent (0.971) and comparable to that of the MMSE and CERAD-TS. The sensitivity and specificity for dementia were 0.945 and 0.872%, respectively, which were slightly better than those of the MMSE and CERAD-TS. CONCLUSION: Hellocog stands out as a valid and reliable tool for self-administered dementia screening, with promise for improving early detection of dementia.

Long-Term Pulmonary Function Postspinal Cord Injury.

OBJECTIVE: To investigate mean values of pulmonary function tests (PFT) at specific time points to assess long-term progression in patients with spinal cord injury (SCI). DESIGN: Retrospective cohort study from 1997-2022. SETTING: National rehabilitation hospital, providing scheduled admission for potential SCI-related issues. Follow-up assessments are recommended annually, guiding the observation period into consecutive 1-year intervals. PARTICIPANTS: This study included 1394 adult patients who were admitted at least twice to the National Rehabilitation Center between 1997 and 2022, selected from an initial pool of 1510. Overall, 116 patients were excluded owing to the absence of any PFT results. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Changes in PFT values over time, specifically assessing for a potential 2-phase pattern after injury. The hypothesis that PFT values would initially improve before declining was formulated based on existing literature. RESULTS: Significant changes in pulmonary function were noted among 1394 adults with SCI. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) initially increased within the first 1-2 years after injury but declined to below baseline levels after 6 years. Pronounced changes occurred between <1 year and 1-2 years after injury (FVC: Δ=4.89, SE=0.87, P<.001; FEV1: Δ=4.28, SE=1.09, P=.002) and 1-2 years to >6 years (FVC: Δ= -5.83, SE=0.94, P<.001; FEV1: Δ= -6.49, SE=1.18, P<.001). No significant changes in the FEV1/FVC ratio. Motor completeness was significantly associated with the increase and decline phase, showing a steeper increase and less decline compared with the motor-incomplete group. CONCLUSIONS: Pulmonary function in SCI initially increases but declines over time, falling below initial levels by 6 years. Further evaluation with more complete datasets is warranted to elucidate the factors influencing these changes.

Postoperative distress and influencing factors in patients with pancreatobiliary cancer.

This study aimed to investigate distress levels, using the distress thermometer (DT), and the factors associated with distress in postoperative patients with pancreatobiliary cancer. This study retrospectively investigated 155 patients who underwent surgery for pancreatobiliary cancer between December 1, 2019 and September 30, 2021. The DT and problem list were used to measure distress. Descriptive statistics, t-test, and multivariate logistic regression analysis were used to analyze the data. Of the 155 patients, 16.8% (n = 26) and 83.2% (n = 129) were in the mild-distress and moderate-to-severe distress groups, respectively. The average DT score was 6.21; that for the mild-distress and moderate-to-severe distress groups was 2.46 and 6.97, respectively. More patients in the moderate-to-severe distress group reported having problems of "sadness" (χ2 = 4.538, P < 0.05), "indigestion" (χ2 = 10.128, P < 0.001), "eating" (χ2 = 6.147, P < 0.013), and "getting around" (χ2 = 4.275, P < 0.039) than in the mild-distress group. In addition, occupation status (odds ratio [OR] = 0.342, 95% confidence interval [CI] = 0.133-0.879, P = 0.026) and indigestion (OR = 5.897, 95% CI = 1.647-21.111, P = 0.006) were independent risk factors for the presence of severe distress. Patients with pancreatobiliary cancer demonstrated elevated levels of psychological distress. Healthcare providers should therefore be vigilant when evaluating patients for distress and providing appropriate referrals, particularly those who are unemployed or have indigestion.

Characteristics of chronic enteropathy associated with SLCO2A1 gene (CEAS) in children, a unique type of monogenic very early-onset inflammatory bowel disease.

BACKGROUND:  Chronic enteropathy associated with SLCO2A1 gene (CEAS) is a unique type of inflammatory bowel disease. CEAS is monogenic disease and is thought to develop from childhood, but studies on pediatric CEAS are scarce. We analyzed characteristics of pediatric CEAS. METHODS: Eleven patients diagnosed with CEAS at Seoul National University Children's Hospital were identified and analyzed. Clinical data of patients were collected. Sanger sequencing of SLCO2A1 was performed on all patients. RESULTS: Patients were diagnosed at a median age of 16.0 years (IQR 11.0 ~ 20.0), and the median age at symptoms onset was only 4.0 years (IQR 2.5 ~ 6.0). Growth delay was observed at the time of diagnosis. Patients showed multiple ulcers or strictures in the small intestine, while the esophagus and colon were unaffected in any patients. Almost half of the patients underwent small intestine resection. The major laboratory features of pediatric CEAS include iron deficiency anemia (IDA), hypoalbuminemia, and near-normal levels of C-reactive protein (CRP). Two novel mutations of SLCO2A1 were identified. The most prevalent symptoms were abdominal pain and pale face. None of the immunomodulatory drugs showed a significant effect on CEAS. CONCLUSIONS: Pediatric CEAS typically develop from very young age, suggesting it as one type of monogenic very early onset inflammatory bowel disease. CEAS can cause growth delay in children but there is no effective treatment currently. We recommend screening for SLCO2A1 mutations to pediatric patients with chronic IDA from a young age and small intestine ulcers without elevation of CRP levels.

Development and Validation of a Low-Cost Drilling Model.

Background: Simulation models enable learners to have repeated practise at their own time, to master the psycho-motor and sensory acuity aspects of surgery and build their confidence in the procedure. The study aims to develop and evaluate the feasibility of a low-cost drilling model to train surgeons in the drilling task. The model targets three aspects of drilling - (1) Reduce plunge depth, (2) Ability to differentiate between bone and medullary canal and (3) Increase accuracy drilling in various angles. Methods: This cross-sectional study was conducted after obtaining ethics approval. We invited Consultants in the field of Orthopaedic or Hand Surgery to form the 'expert' group, and the 'novice' group consisted of participants who had no prior experience in bone drilling. We developed a drilling simulator model made from a polyvinyl chloride (PVC) pipe filled with liquid silicone. This model cost less than US$5. An electric Bosch drill (model GBM 10 RE) with a 1.4 mm K-wire 10 cm in length (6.5 cm outside the drill) was used for drilling. The main outcomes of the study were time taken for drilling, plunge depth, ability to penetrate the far cortex and accuracy. Results: Thirty-one participants were recruited into the study, of which 15 were experts and 16 were novices. The experts performed significantly better for plunge depth (t = -3.65, p = 0.0003) and accuracy (t = -2.07, p = 0.04). The experts required 20% less time to complete the drilling tasks, but it was not statistically significant (t = -0.79, p = 0.43). Conclusions: The low-cost drilling model could be useful in training Residents in the drilling task. It will allow Residents to practise independently at their own time and assess their own performance.

Fabrication of porous poly(L-lactide-co-ε-caprolactone) micropowder for microbubble effect and ultrasound-mediated drug delivery.

Biodegradable elastic poly(L-lactide-co-ε-caprolactone) (PLCL) copolymer (50:50, lactide:caprolactone molar ratio) was synthesized and porous PLCL micropowders was fabricated by a simple method involving rapid cooling of 0.1, 0.5, and 1% (wt/vol) PLCL/dioxane spray into liquid nitrogen. The physicochemical properties of the porous PLCL micropowders were examined by measuring their pore size, pore morphology, and microbead size using a scanning electron microscopy (SEM) and dye and temozolomide (TMZ)-release testing under ultrasound. Human U-87MG, glioblastoma (GBM) cell culture tests were performed to evaluate cell cytotoxicity by released drug from PLCL micropowders. In this study, the porous PLCL micropowders prepared from 1 wt%/vol% PLCL solutions showed a highly porous structure, satisfactory mechanical properties, and optimal drug release efficiency compared with those produced from 0.1 or 0.5 wt%/vol% solutions. The results of the accumulated release test with the results of the absorbance of the dye initially applied, it was confirmed that more than 80% of the added dye was trapped inside the micropowder, and clearly GBM cytotoxicity effect could be observed by the released TMZ. The drug release system using micropowders and ultrasound can be applied as a drug supply system for various diseases such as brain tumors with low drug permeability.

Salvage of failed proximal interphalangeal arthroplasty with vascularised toe joint transfer: Report of two cases.

Failed implants of the proximal interphalangeal joint may result in bone and soft tissue deficits and joint instability with limited reliable options for reconstruction besides an arthrodesis procedure. The purpose of this report is to illustrate the use of vascularized second toe joint for salvage of failed, multi-operated proximal interphalangeal joint in two active patients. Pre-existing scars are used to define the approach and choice of donor site. Flow through anastomosis was performed on the finger digital artery. At final follow-up, the transplanted joints achieved 80-90 degrees of motion and the patients were able to return to their desired level of activities. The procedure is a good alternative for the fit patient wanting to achieve a stable finger with preservation of motion in catastrophic failure of prosthetic proximal interphalangeal joint arthroplasty.

Comparative Antioxidant Potentials and Quantitative Phenolic Compounds Profiles among the Flowers and Leaves from Various Chrysanthemum morifolium Cultivars.

Chrysanthemum morifolium is a valuable plant that contains a wide range of phytochemical compounds and exhibits various biological activities. Ethanol extracts from both the leaves and flowers of 17 different cultivars of C. morifolium were tested for antioxidant activities using the 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) assays and were quantitatively analyzed for 12 phenolic compounds using high-performance liquid chromatography with diode-array detection. We found that the 'Ford' and 'Raina' cultivars demonstrated strong antioxidant abilities and high phenolic compound contents compared to other cultivars, while the flowers of 'Cielo' and the leaves of 'White Cap' exhibited low antioxidant capacity in both assays. The 'Cielo' cultivar also displayed the lowest compound contents. Additionally, in most samples, 3,5-dicaffeoylquinic acid and 4,5-dicaffeoylquinic acid stood out as high-content compounds in the extracts. This study provides foundational knowledge that can be used for selecting appropriate C. morifolium cultivars for further research. Moreover, the 'Ford' and 'Raina' cultivars, containing high amounts of bioactive compounds and showing superior antioxidant ability, could be applied to produce health-beneficial products.

Pro-inflammatory enzyme inhibition of lipoxygenases by flavonoid rich extract from Artemisia vulgaris.

The peroxyl radicals generated by the activity of lipoxygenases (LOX) are mediators to trigger inflammatory diseases. Therefore, it is important to investigate potent LOX inhibitor for modulating the occurrence and resolving inflammatory processes. Artemisa vulgaris, is a herbal plant that is known for flavonoids, potentially inhibiting lipid peroxidation and scavenging radicals. The objectives of the present study were to obtain flavonoids rich extract from A. vulgaris, and determine the inhibitory mode of the extract against LOX. The flavonoids rich extract was optimized in an ultrasound assisted extraction using ionic liquids as extraction solvent. The results found that the optimum conditions; ratio of solid-to-liquid (1:10) and 30 min of extraction time could produce the high yield (10.14 %) and flavonoid content (5.30 mg QE/g). The LOX activity was demonstrated to follow a mixed mode of inhibition in the presence of the flavonoid rich extract as an inhibitor. The Michaelis-Menten constant (Km) was increased from 0.283 µM to 0.435 µM, whereas the maximum velocity was reduced from 0.22 µM/min to 0.058 µM/min in the inhibition. The flavonoids rich extract is likely to be a natural potent non-competitive inhibitor which may bind to free LOX or substrate-bound LOX.

PARVB and HSD17B13 variants are associated with nonalcoholic fatty liver disease in children.

BACKGROUND AND AIM: The aim of this study was to investigate the comprehensive genetic effects of exploratory variants of LYPLAL1, GCKR, HSD17B13, TRIB1, APOC3, MBOAT7, and PARVB on pediatric nonalcoholic fatty liver disease in addition to the previously reported variants of TM6SF2, PNPLA3, and SAMM50 in Korean children. METHODS: A prospective case-control study was conducted involving 309 patients diagnosed using ultrasound and 339 controls. Anthropometric measurements, liver function tests, and metabolic marker analysis were conducted, and fibrosis scores were calculated. Transient elastography was performed in 69 some patients with nonalcoholic fatty liver disease. TaqMan allelic discrimination assays were used for genotyping. The genetic risk scores were calculated using significant variants, namely, HSD17B13, PARVB, PNPLA3, SAMM50, and TM6SF2, to evaluate the additive effect. RESULTS: Risk allele carriers of the PARVB variant showed significantly higher levels of aminotransferases, gamma-glutamyl transferase, alkaline phosphatase, pediatric nonalcoholic fatty liver disease fibrosis score, and aspartate aminotransferase/platelet ratio index. Individuals with a homozygous variant of HSD17B13 showed significantly lower levels of aminotransferase, gamma-glutamyl transferase, liver stiffness measurement, and aspartate aminotransferase/platelet ratio index than those with other genotypes. These parameters did not significantly differ among other variants of LYPLAL1, GCKR, TRIB1, APOC3, and MBOAT7. The genetic risk scores was identified as an independent risk factor for nonalcoholic fatty liver disease and had a positive association with severity. CONCLUSION: HSD17B13 has protective effects on the severity of pediatric nonalcoholic fatty liver disease. Variants of HSD17B13, PARVB, PNPLA3, SAMM50, and TM6SF2 had an additive effect on nonalcoholic fatty liver disease.