Exoskeleton Usability Questionnaire: a preliminary evaluation questionnaire for the lower limb industrial exoskeletons.

Exoskeleton robots are a promising solution to reduce musculoskeletal disorders (MSDs) in different work environments, but a specific usability scale for evaluating them is lacking. This study aimed to develop and verify a preliminary Exoskeleton Usability Questionnaire (EUQ) for the lower limb exoskeletons by creating a draft survey questionnaire from existing questions in prior studies. An experiment was conducted with 20 participants who performed a specific task while wearing three lower limb robots and provided subjective feedback using the developed questionnaire. Data were analysed using exploratory and confirmatory factor analysis (CFA), resulting in a usability evaluation questionnaire for exoskeleton robots clustered into four main factors: mobility, adjustability, handling and safety. This study's findings are expected to be useful in evaluating the usability of the lower limb exoskeletons in both general production sites and agricultural work, which can aid in reducing the prevalence of lower limb MSDs.Practitioner Summary: This study developed a preliminary subjective usability evaluation questionnaire for exoskeleton robots. The questionnaire is clustered into four main factors: mobility, adjustability, handling and safety. These findings provide a valuable tool for assessing exoskeleton usability, potentially reducing musculoskeletal disorders (MSDs) in various work environments.

Deubiquitinating enzyme YOD1 deubiquitinates and destabilizes α-synuclein.

α-synuclein is one of the proteins involved in degenerative neuronal diseases such as Parkinson's disease (PD) or Lewy body dementia (LBD). The pathogenesis is imparted by the abnormal accumulation of α-synuclein resulting in the formation of a Lewy body (LB) and exerting neurotoxicity via an unknown mechanism. Regulation of α-synuclein is achieved by the ubiquitin-proteasome system (UPS), which influences protein homeostasis via inducing proteasome-dependent degradation by attaching a small molecule (ubiquitin) to the substrate. Deubiquitinating enzymes (DUBs) control the UPS by cleaving the peptide or isopeptide bond between ubiquitin and its substrate proteins. In a previous study, we found that YOD1 deubiquitinates and regulates the cellular function of neural precursor cell expressed developmentally down-regulated protein 4 (NEDD4), an E3 ligase that induces α-synuclein degradation. We hypothesized that YOD1 acts as a DUB involved in a modulated pathway of α-synuclein. In the current study, we found that YOD1 directly interacts with α-synuclein and deubiquitinates K6-, K11-, K29-, K33-, and K63-linked polyubiquitin chains on α-synuclein. Furthermore, YOD1 destabilizes α-synuclein protein stability by upregulating NEDD4. Collectively, this suggests the possibility that YOD1 is potentially a new regulator in the NEDD4-α-synuclein pathway.

Synergistic effect of YOD1 and USP21 on the Hippo signaling pathway.

BACKGROUND: Deubiquitinating enzymes (DUBs) comprise a family of proteases responsible for cleaving the peptide or isopeptide bond between ubiquitin and its substrate proteins. Ubiquitin is essential for regulating diverse cellular functions by attaching to target proteins. The Hippo signaling pathway plays a crucial role in controlling tissue size, cell proliferation, and apoptosis. In a previous study, we discovered that YOD1 regulates the Hippo signaling pathway by deubiquitinating the neural precursor cell expressed developmentally down-regulated protein 4 (NEDD4), an E3 ligase of large tumor suppressor kinase 1 (LATS1). Here, our aim was to investigate potential substrates of YOD1 implicated in the Hippo signaling pathway. METHODS: We employed various bioinformatics tools (BioGRID, STRING, and Cytoscape) to identify novel potential substrates of YOD1. Furthermore, we used western blotting, co-immunoprecipitation (co-IP), glutathione S-transferase (GST) pull-down, immunocytochemistry (ICC) assays to investigate cellular interactions. To evaluate cell proliferation, we performed cell counting kit-8 (CCK-8), wound healing, colony forming, and flow cytometry assays using A549, HEK293T, and HeLa cells. Additionally, we assessed the expression levels of YAP and p-YAP in A549, HEK293T, and HeLa cells through western blotting. RESULTS: Our investigations revealed that YOD1 interacts with ubiquitin-specific proteases 21 (USP21), a DUB involved in the Hippo signaling pathway, and deubiquitinates the microtubule-affinity regulating kinase (MARK). Intriguingly, YOD1 and USP21 mutually deubiquitinate each other; while YOD1 regulates the protein stability of USP21, USP21 does not exert a regulatory effect on YOD1. Moreover, we observed the synergistic effect of YOD1 and USP21 on cell proliferation through the modulation of the Hippo signaling pathway. CONCLUSIONS: Our study revealed multiple cellular interactions between YOD1 and USP21. Moreover, our findings suggest that the combined activities of YOD1 and USP21 synergistically influence cell proliferation in A549 cells by regulating the Hippo signaling pathway.

A Method for Accessing the Non-Slip Function of Socks in an Acute Maneuver.

The shoe upper hides the foot motion on the insole, so it has been challenging to measure the non-slip function of socks in a dynamic motor task. The study aimed to propose a method to estimate the non-slip function of socks in an acute maneuver. Participants performed a shuttle run task while wearing three types of socks with different frictional properties. The forces produced by foot movement on the upper during the task were measured by pressure sensors installed at the upper. A force platform was also used to measure the ground reaction force at the outsole and ground. Peak force and impulse values computed by using forces measured by the pressure sensors were significantly different between the sock conditions, while there were no such differences in those values computed by using ground reaction forces measured by a force platform. The results suggested that the non-slip function of socks could be quantified by measuring forces at the foot-upper interface. The method could be an affordable option to measure the non-slip function of socks with minimal effects from skin artifacts and shoe upper integrity.

A Novel Method to Measure the Static Coefficient of Friction for Socks.

Mechanical testers have commonly been used to measure the frictional properties of socks. However, the friction values may be susceptible to the level of stretchiness of tested fabrics or human variability. Thus, the aim of this study was to propose a novel method that enables friction measurement of socks in a sock-wearing condition with less human variability effects. Five socks with different frictional properties were chosen. Three experimental ramp tests were performed with an artificial structure shaped like the foot-ankle complex (last) and a ramp tester to quantify the static coefficient of friction (COF) at the foot against sock, at the sock against an insole, and the foot wearing socks against the insole, respectively. The angle where the last slipped while the ramp surface was gradually inclined was used to compute the static COF values for each sock. The reliability was 0.99, and COF values ranged from 0.271 to 0.861 at the foot-sock interface, 0.342 to 0.639 at the sock-insole interface, and 0.310 to 0.614 in the third test. Socks with different frictional properties were successfully distinguished each other. Thus, the suggested protocol could be a reliable option for measuring the static COF values in the tension similar with it found in a sock-waring condition with reduced effects of human variability.

Acute Myeloid Leukemia-Related Proteins Modified by Ubiquitin and Ubiquitin-like Proteins.

Acute myeloid leukemia (AML), the most common form of an acute leukemia, is a malignant disorder of stem cell precursors of the myeloid lineage. Ubiquitination is one of the post-translational modifications (PTMs), and the ubiquitin-like proteins (Ubls; SUMO, NEDD8, and ISG15) play a critical role in various cellular processes, including autophagy, cell-cycle control, DNA repair, signal transduction, and transcription. Also, the importance of Ubls in AML is increasing, with the growing research defining the effect of Ubls in AML. Numerous studies have actively reported that AML-related mutated proteins are linked to Ub and Ubls. The current review discusses the roles of proteins associated with protein ubiquitination, modifications by Ubls in AML, and substrates that can be applied for therapeutic targets in AML.

Role of p53 in transcriptional repression of SVCT2.

SVCT2, Sodium-dependent Vitamin C Transporter 2, uniquely transports ascorbic acid (also known as vitamin C and ascorbate) into all types of cells. Vitamin C is an essential nutrient that must be obtained through the diet and plasma levels are tightly regulated by transporter activity. Vitamin C plays an important role in antioxidant defenses and is a cofactor for many enzymes that enable hormone synthesis, oxygen sensing, collagen synthesis and epigenetic pathways. Although SVCT2 has various functions, regulation of its expression/activity remains poorly understood. We found a p53-binding site, within the SVCT2 promoter, using a transcription factor binding-site prediction tool. In this study, we show that p53 can directly repress SVCT2 transcription by binding a proximal- (~-185 to -171 bp) and a distal- (~-1800 to -1787 bp) p53-responsive element (PRE), Chromatin immunoprecipitation assays showed that PRE-bound p53 interacts with the corepressor-histone deacetylase 3 (HDAC3), resulting in deacetylation of histones Ac-H4, at the proximal promoter, resulting in transcriptional silencing of SVCT2. Overall, our data suggests that p53 is a potent transcriptional repressor of SVCT2, a critical transporter of diet-derived ascorbic acid, across the plasma membranes of numerous essential tissue cell types.

Chemosensitivity to HM90822, a novel synthetic IAP antagonist, is determined by p-AKT-inducible XIAP phosphorylation in human pancreatic cancer cells.

Inhibitor of apoptosis proteins (IAPs) are overexpressed in the majority of cancers and prevent apoptosis by inhibiting caspases. IAPs have therefore attracted considerable attention as potential targets for anticancer therapy. Here, we demonstrated that HM90822 (abbreviated HM822; a new synthetic IAP antagonist) induced apoptotic cell death via proteasome-dependent degradation of BIR2/3 domain-containing IAPs in human pancreatic cancer cells. HM822 inhibited the expression of XIAP and cIAP1/2 proteins in Panc-1 and BxPC-3 cells, which are sensitive to HM822. HM822 also induced IAP ubiquitination and promoted proteasome-dependent IAP degradation. However, cells expressing phospho-XIAP (Ser87) and AKT exhibited resistance to HM822. In other words, the overexpression of AKT-CA (constitutive active form for AKT) or AKT-WT induced resistance to HM822. In addition, in Panc-1 xenograft and orthotopic mouse models, we revealed that tumor growth was suppressed by the administration of HM822. Taken together, these results suggest that HM822 induces apoptosis through ubiquitin/proteasome-dependent degradation of BIR3 domain-containing IAPs. These findings suggest that phospho-XIAP and phospho-AKT may be used as biomarkers for predicting the efficacy of HM822 in pancreatic cancer patients.

Targeting ß-catenin overcomes MEK inhibition resistance in colon cancer with KRAS and PIK3CA mutations.

BACKGROUND: Mitogen-activated protein kinases (MEK 1/2) are central components of the RAS signalling pathway and are attractive targets for cancer therapy. These agents continue to be investigated in KRAS mutant colon cancer but are met with significant resistance. Clinical investigations have demonstrated that these strategies are not well tolerated by patients. METHODS: We investigated a biomarker of response for MEK inhibition in KRAS mutant colon cancers by LC-MS/MS analysis. We tested the MEK inhibitor in PIK3CA wild(wt) and mutant(mt) colon cancer cells. In addition, we tested the combinational effects of MEK and TNKS inhibitor in vitro and in vivo. RESULTS: We identified ß-catenin, a key mediator of the WNT pathway, in response to MEK inhibitor. MEK inhibition led to a decrease in ß-catenin in PIK3CA wt colon cancer cells but not in mt. Tumour regression was promoted by combination of MEK inhibition and NVP-TNS656, which targets the WNT pathway. Furthermore, inhibition of MEK promoted tumour regression in colon cancer patient-derived xenograft models expressing PIK3CA wt. CONCLUSIONS: We propose that inhibition of the WNT pathway, particularly ß-catenin, may bypass resistance to MEK inhibition in human PIK3CA mt colon cancer. Therefore, we suggest that ß-catenin is a potential predictive marker of MEK inhibitor resistance.

Automated non-contact measurement of the spine curvature at the sagittal plane using a deep neural network.

BACKGROUND: Non-radiographical techniques have been suggested to measure the spine curvature at the sagittal plane. However, a neural network has not been used to measure the curvature. METHODS: A single video camera captured images of a standing posture at the sagittal plane from twenty healthy males. Six marker positions along the spine's contour in each image were identified for measuring inclination, thoracic kyphosis, and lumbar lordosis angles. We estimated three inflection points around the neck, hip, and between the neck and hip, followed by identifying two adjacent marker positions per inflection point to compute its tangent. The angular deviation of each tangent line from the horizontal was computed to measure inclination angles. Thoracic kyphosis and lumbar lordosis angles were computed by the angular difference between the two adjacent tangents. A deep neural network was trained with 500,000 iterations using the labeled images from 18 participants (388 and 44 images for training and test set) and then evaluated using the unseen images (2 participants, 48 images; evaluation set). FINDINGS: The mean total training and test errors were <2 pixels (∼ 0.6 cm). The total error in the evaluation set was qualitatively comparable (∼ 3 pixels = âˆ¼ 0.9 cm), suggesting the model performance was maintained in the unseen data. The angle values between labeled and network-predicted marker positions were similar in the evaluation set. INTERPRETATION: The network training with a relatively small number of images was successful based on the small error values observed in the evaluation set. The model may be an affordable, automated, and non-contact measurement tool for the human spine curvature.

The efficacy and safety of MARS-PD: Meridian activation remedy system for Parkinson's disease-A single-center, assessor and statistician-blinded, parallel-group randomized, controlled trial protocol.

BACKGROUND: Parkinson's disease (PD) patients face a substantial unmet need for disease-modifying interventions. Potential approaches such as exercise and acupuncture have been investigated to slow PD progression. To address this unmet need, we developed a novel therapeutic approach that integrates acupuncture and exercise: the Meridian Activation Remedy System for PD patients (MARS-PD). Building upon promising outcomes observed in our preliminary pilot study, where MARS-PD exhibited a large clinically important difference on the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS Part III), we embark on a randomized controlled trial with the primary objective of examining the efficacy, safety, and economic impact of MARS-PD. METHODS: In this single-center, assessor and statistician-blinded, parallel-group randomized controlled trial, we aim to investigate the clinical efficacy of MARS-PD through 16 interventions administered over 8 weeks in 88 PD patients. Participants will be randomly assigned to the experimental (n = 44) or control (n = 44) groups. The experimental group will receive MARS-PD intervention alongside standard care, while the control group will solely receive standard care. The intervention period spans 8 weeks, followed by a 12-week post-intervention follow-up. The primary endpoint is the change in MDS-UPDRS Part III score from baseline to the conclusion of the 8-week intervention. Secondary outcomes encompass various assessments, including MDS-UPDRS, International Physical Activity Questionnaire Short Form, Parkinson Self Questionnaire, Parkinson's Disease Sleep Scale, Timed Up and Go test, GAITRite metrics, Functional Near-Infrared Spectroscopy measurements, smart band outcomes, gut microbiome analysis results, and iris connective tissue texture. DISCUSSION: Previous studies by the authors have indicated MARS-PD's safety and benefits for PD patients. Building upon this foundation, our current study aims to provide a more comprehensive and detailed confirmation of the efficacy of MARS-PD. TRIAL REGISTRATION: cris.nih.go.kr KCT0006646 -First posted on 7 October 2021; ClinicalTrials.gov NCT05621772 -First posted on 11 November 2022.

Effectiveness and Safety of Meridian Activation Remedy System for Alleviating Motor Symptoms in Parkinson's Disease: an Observational Study.

Background: Parkinson's disease (PD) lacks disease-modifying drugs or sustainable interventions, creating an unmet treatment need. Investigating complementary and alternative medicines aims to improve PD patients' quality of life by alleviating symptoms and delaying the course of the disease. Objectives: In this single-center, prospective, observational, single-arm study, we aimed to assess the effectiveness and safety of acupuncture combined with exercise therapy and the Meridian Activation Remedy System (MARS). Methods: From March to October 2021, 13 PD patients with Hoehn and Yahr stages 1 to 3 were recruited. For 8 weeks, MARS intervention was carried out twice a week. T-statistics were used to evaluate functional near-infrared spectroscopy (fNIRS) and GAITRite outcomes. All of the remaining outcome variables were evaluated using the Wilcoxon signed-rank test. Results: The MARS intervention significantly reduced PD patients' Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDSUPDRS) Part III score (from 20.0 ± 11.8 to 8.8 ± 5.5, p = 0.003), 10-meter walk test speed (from 9.5 ± 1.8 to 8.7 ± 1.3 seconds, p = 0.040), and timed up and go time (from 9.8 ± 1.8 to 8.9 ± 1.4 seconds, p = 0.040). Moreover, the MDS-UPDRS Part II, fNIRS hemodynamics, 360-degree turn test, fall efficacy scale, and Parkinson's Disease Questionnaire 39 scores improved but not significantly. All participants completed the 8-week intervention without any adverse reactions. Conclusion: An 8-week MARS intervention improved motor symptoms in PD patients. In particular, improvements in UPDRS Part III scores exhibited large clinically important differences. The findings are encouraging, and a randomized controlled trial will be conducted to determine the efficacy and cost-effectiveness of MARS intervention.

IN-1233-eluting covered metallic stent to prevent hyperplasia: experimental study in a rabbit esophageal model.

PURPOSE: To investigate the efficacy of an IN-1233-eluting covered stent in preventing tissue hyperplasia in a rabbit esophageal model. MATERIALS AND METHODS: The local animal research committee approved all experiments. Esophageal stents were placed in 40 male New Zealand rabbits (weight range, 2.8-3.2 kg). The drug group (D) received IN-1233-eluting covered stents (n = 20); the control group (C) received polyurethane-covered stents (n = 20). Drug loading of IN-1233-eluting covered stent was 10%. Four study groups were formed: C and D animals sacrificed at 4 (D4, C4) and 8 (D8, C8) weeks after stent placement (n = 10). Esophagography was used to assess the percentage of diameter stenosis. Histologic findings of the drug and control stents were compared. The Mann-Whitney U test was used to evaluate differences. RESULTS: The mean percentage ± standard deviation of diameter stenosis was significantly lower in D groups than in C groups at both 4 (C4 = 36.15% ± 12.63, D4 = 7.83% ± 8.12 [P < .001]) and 8 (C8 = 50.21% ± 20.43, D8 = 27.78% ± 14.40 [P = .019]) weeks. Percentage of granulation tissue area (C4 = 33.07% ± 19.11, D4 = 21.59% ± 18.22 [P = .028]; C8 = 44.70% ± 21.71, D8 = 31.97% ± 22.54 [P = .131]), number of epithelial layers (C4 = 4.77 ± 1.55, D4 = 3.37 ± 1.73 [P = .002]; C8 = 5.50 ± 1.38, D8 = 4.50 ± 1.63 [P = .057]), and thickness of submucosal fibrosis (C4 = 2.42 mm ± 1.08, D4 = 1.62 mm ± 0.77 [P = .006]; C8 = 2.89 mm ± 1.00, D8 = 2.07 mm ± 0.71 [P = .007]) were lower in D than in C groups. Inflammatory cell infiltration was significantly higher in D than in C groups (C4 = 2.63 ± 0.81, D4 = 3.33 ± 1.09 [P = .032]; C8 = 2.20 ± 0.81, D8 = 3.00 ± 0.95 [P = .012]). CONCLUSION: The use of an IN-1233-eluting covered stents decreased tissue hyperplasia secondary to stent placement in a rabbit esophageal model.

Evaluation of the Efficacy of a Lift-Assist Device Regarding Caregiver Posture and Muscle Load for Transferring Tasks.

The aim of this study was to confirm the effect of a lift-assist device when performing a patient-lifting task. Ten working caregivers participated in this experiment, and lifting patients from bed to wheelchair (B2C) and wheelchair to bed (C2B) was performed for manual care (MC) and lift-assist device (robot) care (RC). EMG sensors and IMU motion sensors were attached as indicators of the assistive device's effectiveness. EMG was attached to the right side of eight muscles (UT, MD, TB, BB, ES, RF, VA, and TA), and flexion/extension angles of the neck, shoulder, back, and knee were collected using motion sensors. As a result of the analysis, both B2C and C2B showed higher muscle activities in MC than RC. When using a lift-assist device to lift patients, the RC method showed reductions in muscle activities compared to MC. As a result of the work-posture analysis, both the task type and the task phase exhibited pronounced reductions in shoulder, back, and knee ROM (range of motion) compared to those of MC. Therefore, based on the findings of this study, a lift-assist device is recommended for reducing the physical workloads of caregivers while performing patient-lifting tasks.

Efficacy of passive upper-limb exoskeletons in reducing musculoskeletal load associated with overhead tasks.

Overhead work can pose substantial musculoskeletal stress in many industrial settings. This study aimed to evaluate the efficacy of passive upper-limb exoskeletons in reducing muscular activity and subjective discomfort ratings. In a repeated-measures laboratory experiment, 20 healthy male participants performed 10-min drilling tasks with and without two passive upper-limb exoskeletons (VEX and Airframe). During the tasks, muscle activity in eight muscles (upper limb - upper trapezius, middle deltoid, biceps brachii, triceps brachii; low back - erector spinae; lower limb - rectus femoris, biceps femoris, tibialis anterior) was collected using electromyography as a physical exertion measure. Subjective discomfort rating in six body parts was measured using the Borg's CR-10 scale. The results showed that muscle activity (especially in the upper-limb muscles) was significantly decreased by 29.3-58.1% with both exoskeletons compared to no exoskeleton condition. The subjective discomfort ratings showed limited differences between the conditions. These findings indicate that passive upper-limb exoskeletons may have potential as an effective intervention to reduce muscular loading and physical exertion during overhead work.

Effects of electrical muscle stimulation on core muscle activation and physical performance in non-athletic adults: A randomized controlled trial.

BACKGROUND: Electrical muscle stimulation (EMS) activates muscles through electrical currents, resulting in involuntary muscle contractions. This study aimed to evaluate the immediate clinical effects of superimposing EMS on strength training compared with conventional exercise in healthy non-athletic adults. METHODS: This study was a randomised, controlled, parallel-group trial conducted at a single centre. Forty-one healthy young volunteers were recruited and randomised into two groups: strengthening with superimposed EMS (S+E) and strengthening (S) groups. All participants underwent the 30 minutes of strength training program, three times a week for 8 weeks, consisting of core muscle exercises. Additionally, the S+E group received EMS during training, which stimulated the bilateral abdominal, gluteus, and hip adductor muscles. As the primary outcome measure, we evaluated the changes in muscle thickness, including the abdominal, gluteal, and hip adductor muscles, using ultrasound. Muscle thickness was measured in both resting and contracted states. For secondary outcomes, physical performance (Functional Movement System score, McGill's core stability test, and hip muscle power) and body composition analysis were evaluated. All assessments were performed at the beginning and end of the intervention. RESULTS: 39 participants (S+E group = 20, S group = 19) completed the study. The clinical characteristics and baseline functional status of each group did not differ significantly between the groups. After completion of the training, the S+E group showed more efficient contraction in most of the evaluated muscles. The resting muscle thickness did not differ significantly between the groups; however, the contracted muscle thickness in the S+E group was higher than that in the S group (p < 0.05). Physical performance and body composition were not significantly different between the two groups. No intervention-related complications were reported during the study. CONCLUSION: EMS seems to be a safe and reasonable modality for improving physical fitness in healthy individuals.

A passive upper-limb exoskeleton reduced muscular loading during augmented reality interactions.

The aim of this study was to evaluate a passive upper-limb exoskeleton as an ergonomic control to reduce the musculoskeletal load in the shoulders associated with augmented reality (AR) interactions. In a repeated-measures laboratory study, each of the 20 participants performed a series of AR tasks with and without a commercially-available upper-limb exoskeleton. During the AR tasks, muscle activity (anterior, middle, posterior deltoid, and upper trapezius), shoulder joint postures/moment, and self-reported discomfort were collected. The results showed that the exoskeleton significantly reduced muscle activity in the upper trapezius and deltoid muscle groups and self-reported discomfort. However, the shoulder postures and task performance measures were not affected by the exoskeleton during the AR interactions. Given the significant decrease in muscle activity and discomfort without compromising task performance, a passive exoskeleton can be an effective ergonomic control measure to reduce the risks of developing musculoskeletal discomfort or injuries in the shoulder regions.

Cloud-based digital healthcare development for precision medical hospital information system.

Aim: This study aims to develop a cloud-based digital healthcare system for precision medical hospital information systems (P-HIS). Methods: In 2020, international standardization of P-HIS clinical terms and codes was performed. In 2021, South Korea's first tertiary hospital cloud was established and implemented successfully. Results: P-HIS was applied at Korea's first tertiary general hospital. Common data model-compatible precision medicine/medical service solutions were developed for medical support. Ultrahigh-quality medical data for precision medicine were acquired and built using big data. Joint global commercialization and dissemination/spreading were achieved using the P-HIS consortium and global common data model-based observational medical outcome partnership network. Conclusion: To provide personalized precision medical services in the future, establishing and using big medical data is essential.

Characteristics of insulin resistance in Korean adults from the perspective of circadian and metabolic sensing genes.

BACKGROUND: The biological clock allows an organism to anticipate periodic environmental changes and adjust its physiology and behavior accordingly. OBJECTIVE: This retrospective cross-sectional study examined circadian gene polymorphisms and clinical characteristics associated with insulin resistance (IR). METHODS: We analyzed data from 1,404 Korean adults aged 30 to 55 with no history of cancer and cardio-cerebrovascular disease. The population was classified according to sex and homeostasis model assessment of insulin resistance (HOMA-IR) values. Demographics, anthropometric and clinical characteristics, and single nucleotide polymorphisms (SNPs) were analyzed with respect to sex, age, and HOMA-IR values. We used association rule mining to identify sets of SNPs from circadian and metabolic sensing genes that may be associated with IR. RESULTS: Among the subjects, 15.0% of 960 women and 24.3% of 444 men had HOMA-IR values above 2. Most of the parameters differed significantly between men and women, as well as between the groups with high and low insulin sensitivity. Body fat mass of the trunk, which was significantly higher in insulin-resistant groups, had a higher correlation with high sensitivity C-reactive protein and hemoglobin levels in women, and alanine aminotransferase and aspartate aminotransferase levels in men. Homozygous minor allele genotype sets of SNPs rs17031578 and rs228669 in the PER3 gene could be more frequently found among women with HOMA-IR values above 2 (p = .014). CONCLUSION: Oxidative stress enhanced by adiposity and iron overload, which may also be linked to NRF2 and PER3-related pathways, is related to IR in adulthood. However, due to the small population size in this study, more research is needed.

Safety evaluation of self-expanding metallic biliary stents eluting gemcitabine in a porcine model.

BACKGROUND AND AIM: Palliative biliary decompression by metal stent is the treatment of choice for unresectable malignant biliary obstruction; however, conventional stents provide only mechanical palliation and exert no anti-tumor effects. Gemcitabine (GEM) has been reported to be more effective in unresectable pancreatic cancer and biliary cancer compared with other chemotherapeutic drugs. We evaluated the safety of a GEM-eluting stent by analyzing histologic responses of the porcine bile duct. METHODS: Stents containing GEM (0%, 10%, 15%, and 20% [w/v]) were surgically inserted into bile ducts of pigs (each group, n = 2). The animals were euthanized after 4 weeks, and the stented bile duct segment underwent gross and microscopic examination. Laboratory assay was performed for aspartate transaminase (AST), alanine transaminase (ALT), total bilirubin, and gamma-glutamyl transferase (γ-GTP). RESULTS: Moderate to severe inflammation was observed in the bile ducts in contact with stents containing 15 and 20% GEM, compared with no inflammation with 0% GEM and mild inflammation with 10% GEM. Fibrous reactions observed in the submucosal layer did not differ among groups. Transmural necrosis and perforations were not observed in any animal. No abnormal laboratory test findings were directly caused by GEM. CONCLUSION: Our newly developed GEM eluting stents can be used safely in normal bile ducts. Our results indicated that 10% GEM produced mild histologic changes in the stented segment and adjacent tissue; this concentration may be appropriate for clinical application.