A dual-action niclosamide-based prodrug that targets cancer stem cells and inhibits TNBC metastasis.

Chemotherapy typically destroys the tumor mass but rarely eradicates the cancer stem cells (CSCs) that can drive metastatic recurrence. A key current challenge is finding ways to eradicate CSCs and suppress their characteristics. Here, we report a prodrug, Nic-A, created by combining a carbonic anhydrase IX (CAIX) inhibitor, acetazolamide, with a signal transducer and transcriptional activator 3 (STAT3) inhibitor, niclosamide. Nic-A was designed to target triple-negative breast cancer (TNBC) CSCs and was found to inhibit both proliferating TNBC cells and CSCs via STAT3 dysregulation and suppression of CSC-like properties. Its use leads to a decrease in aldehyde dehydrogenase 1 activity, CD44high/CD24low stem-like subpopulations, and tumor spheroid-forming ability. TNBC xenograft tumors treated with Nic-A exhibited decreased angiogenesis and tumor growth, as well as decreased Ki-67 expression and increased apoptosis. In addition, distant metastases were suppressed in TNBC allografts derived from a CSC-enriched population. This study thus highlights a potential strategy for addressing CSC-based cancer recurrence.

Ebastine impairs metastatic spread in triple-negative breast cancer by targeting focal adhesion kinase.

We sought to investigate the utility of ebastine (EBA), a second-generation antihistamine with potent anti-metastatic properties, in the context of breast cancer stem cell (BCSC)-suppression in triple-negative breast cancer (TNBC). EBA binds to the tyrosine kinase domain of focal adhesion kinase (FAK), blocking phosphorylation at the Y397 and Y576/577 residues. FAK-mediated JAK2/STAT3 and MEK/ERK signaling was attenuated after EBA challenge in vitro and in vivo. EBA treatment induced apoptosis and a sharp decline in the expression of the BCSC markers ALDH1, CD44 and CD49f, suggesting that EBA targets BCSC-like cell populations while reducing tumor bulk. EBA administration significantly impeded BCSC-enriched tumor burden, angiogenesis and distant metastasis while reducing MMP-2/-9 levels in circulating blood in vivo. Our findings suggest that EBA may represent an effective therapeutic for the simultaneous targeting of JAK2/STAT3 and MEK/ERK for the treatment of molecularly heterogeneous TNBC with divergent profiles. Further investigation of EBA as an anti-metastatic agent for the treatment of TNBC is warranted.

Cutting Off H+ Leaks on the Inner Mitochondrial Membrane: A Proton Modulation Approach to Selectively Eradicate Cancer Stem Cells.

Cancer stem cells (CSCs) are associated with the invasion and metastatic relapse of various cancers. However, current cancer therapies are limited to targeting the bulk of primary tumor cells while remaining the CSCs untouched. Here, we report a new proton (H+) modulation approach to selectively eradicate CSCs via cutting off the H+ leaks on the inner mitochondrial membrane (IMM). Based on the fruit extract of Gardenia jasminoides, a multimodal molecule channel blocker with high biosafety, namely, Bo-Mt-Ge, is developed. Importantly, in this study, we successfully identify that mitochondrial uncoupling protein UCP2 is closely correlated with the stemness of CSCs, which may offer a new perspective for selective CSC drug discovery. Mechanistic studies show that Bo-Mt-Ge can specifically inhibit the UCP2 activities, decrease the H+ influx in the matrix, regulate the electrochemical gradient, and deplete the endogenous GSH, which synergistically constitute a unique MoA to active apoptotic CSC death. Intriguingly, Bo-Mt-Ge also counteracts the therapeutic resistance via a two-pronged tactic: drug efflux pump P-glycoprotein downregulation and antiapoptotic factor (e.g., Bcl-2) inhibition. With these merits, Bo-Mt-Ge proved to be one of the safest and most efficacious anti-CSC agents, with ca. 100-fold more potent than genipin alone in vitro and in vivo. This study offers new insights and promising solutions for future CSC therapies in the clinic.

Validation of resonance Raman spectroscopy-measured skin carotenoid status as a biomarker for fruit and vegetable intake in Korean adults.

Blood carotenoid concentration measurement is considered the gold standard for fruit and vegetable (F&V) intake estimation; however, this method is invasive and expensive. Recently, skin carotenoid status (SCS) measured by optical sensors has been evaluated as a promising parameter for F&V intake estimation. In this cross-sectional study, we aimed to validate the utility of resonance Raman spectroscopy (RRS)-assessed SCS as a biomarker of F&V intake in Korean adults. We used data from 108 participants aged 20-69 years who completed SCS measurements, blood collection and 3-d dietary recordings. Serum carotenoid concentrations were quantified using HPLC, and dietary carotenoid and F&V intakes were estimated via 3-d dietary records using a carotenoid database for common Korean foods. The correlations of the SCS with serum carotenoid concentrations, dietary carotenoid intake and F&V intake were examined to assess SCS validity. SCS was positively correlated with total serum carotenoid concentration (r = 0·52, 95 % CI = 0·36, 0·64, P < 0·001), serum ß-carotene concentration (r = 0·60, 95 % CI = 0·47, 0·71, P < 0·001), total carotenoid intake (r = 0·20, 95 % CI = 0·01, 0·37, P = 0·04), ß-carotene intake (r = 0·30, 95 % CI = 0·11, 0·46, P = 0·002) and F&V intake (r = 0·40, 95 % CI = 0·23, 0·55, P < 0·001). These results suggest that SCS can be a valid biomarker of F&V intake in Korean adults.

Molecular mechanisms underlying the vulnerability of Pacific abalone (Haliotis discus hannai) to Vibrio harveyi infection at higher water temperature.

Climate change is one of the most important threats to farmed abalone worldwide. Although abalone is more susceptible to vibriosis at higher water temperatures, the molecular mode of action underlying this has not been fully elucidated. Therefore, this study aimed to address the high susceptibility of Halitotis discus hannai to V. harveyi infection using abalone hemocytes exposed to low and high temperatures. Abalone hemocytes were divided into four groups, 20C, 20 V, 25C, and 25 V, depending on co-culture with (V)/without (C) V. harveyi (MOI = 12.8) and incubation temperature (20 °C or 25 °C). After 3 h of incubation, hemocyte viability and phagocytic activity were measured, and RNA sequencing was performed using Illumina Novaseq. The expression of several virulence-related genes in V. harveyi was analyzed using real-time PCR. The viability of hemocytes was significantly decreased in the 25 V group compared to cells in the other groups, whereas phagocytic activity at 25 °C was significantly higher than at 20 °C. Although a number of immune-associated genes were commonly upregulated in abalone hemocyte exposed to V. harveyi, regardless of temperature, pathways and genes regarding pro-inflammatory responses (interleukin-17 and tumor necrosis factor) and apoptosis were significantly overexpressed in the 25 V group compared to the 25C group. Notably, in the apoptosis pathway, genes encoding executor caspases (casp3 and casp7) and pro-apoptotic factor, bax were significantly up-regulated only in the 25 V group, while the apoptosis inhibitor, bcl2L1 was significantly up-regulated only in the 20 V group compared to the control group at the respective temperatures. The co-culture of V. harveyi with abalone hemocytes at 25 °C up-regulated several virulence-related genes involved in quorum sensing (luxS), antioxidant activity (katA, katB, and sodC), motility (flgI), and adherence/invasion (ompU) compared to those at 20 °C. Therefore, our results showed that H. discus hannai hemocytes exposed to V. harveyi at 25 °C were highly stressed by vigorously activated inflammatory responses and that the bacterial pathogen overexpressed several virulence-related genes at the high temperature tested. The transcriptomic profile of both abalone hemocytes and V. harveyi in the present study provide insight into differential host-pathogen interactions depending on the temperature conditions and the molecular backgrounds related to increased abalone vulnerability upon global warming.

Deciphering Functional Connectivity Differences Between Motor Imagery and Execution of Target-Oriented Grasping.

This study aimed to delineate overlapping and distinctive functional connectivity in visual motor imagery, kinesthetic motor imagery, and motor execution of target-oriented grasping action of the right hand. Functional magnetic resonance imaging data were obtained from 18 right-handed healthy individuals during each condition. Seed-based connectivity and multi-voxel pattern analyses were employed after selecting seed regions with the left primary motor cortex and supplementary motor area. There was equivalent seed-based connectivity during the three conditions in the bilateral frontoparietal and temporal areas. When the seed region was the left primary motor cortex, increased connectivity was observed in the left cuneus and superior frontal area during visual and kinesthetic motor imageries, respectively, compared with that during motor execution. Multi-voxel pattern analyses revealed that each condition was differentiated by spatially distributed connectivity patterns of the left primary motor cortex within the right cerebellum VI, cerebellum crus II, and left lingual area. When the seed region was the left supplementary motor area, the connectivity patterns within the right putamen, thalamus, cerebellar areas IV-V, and left superior parietal lobule were significantly classified above chance level across the three conditions. The present findings improve our understanding of the spatial representation of functional connectivity and its specific patterns among motor imagery and motor execution. The strength and fine-grained connectivity patterns of the brain areas can discriminate between motor imagery and motor execution.

Evaluation of a Commercial Device Based on Reflection Spectroscopy as an Alternative to Resonance Raman Spectroscopy in Measuring Skin Carotenoid Levels: Randomized Controlled Trial.

Resonance Raman spectroscopy (RRS) has been used as a reference method for measuring skin carotenoid levels (SCL), which indicate vegetable and fruit intake. However, RRS is not an easy-to-use method in SCL measurement due to its complicated implementation. In this study, a commercial spectrophotometer based on reflection spectroscopy (RS), which is relatively simple and inexpensive, was evaluated to confirm usability compared with RRS in measuring SCL. To investigate the agreement between RS and RRS, eighty participants were randomly assigned to a high-carotenoid diet group (21 mg/day of total carotenoids) or a control-carotenoid diet group (14 mg/day of total carotenoids) during a 6-week whole-diet intervention period and a 4-week tracking period. Strong correlations between the RS and RRS methods were observed at baseline (r = 0.944) and the entire period (r = 0.930). The rate of SCL increase was similar during the diet intervention; however, the initiation of the SCL decrease in RS was slower than in RRS during the tracking period. To confirm the agreement of RS and RRS from various perspectives, new visualization tools and indices were additionally applied and confirmed the similar response patterns of the two methods. The results indicate that the proposed RS method could be an alternative to RRS in SCL measurements.

ß-Escin overcomes trastuzumab resistance in HER2-positive breast cancer by targeting cancer stem-like features.

BACKGROUND: The emergence of de novo or intrinsic trastuzumab resistance is exceedingly high in breast cancer that is HER2 positive and correlates with an abundant cancer stem cell (CSC)-like population. We sought to examine the capacity of ß-escin, an anti-inflammatory drug, to address trastuzumab resistance in HER2-positive breast cancer cells. METHODS: The effect of ß-escin on trastuzumab-resistant and -sensitive cell lines in vitro was evaluated for apoptosis, expression of HER2 family members, and impact on CSC-like properties. An in vivo model of trastuzumab-resistant JIMT-1 was used to examine the efficacy and toxicity of ß-escin. RESULTS: ß-escin induced mitochondrial-mediated apoptosis accompanied by reactive oxygen species (ROS) production and increased active p18Bax fragmentation, leading to caspase-3/-7 activation. Attenuation of CSC-related features by ß-escin challenge was accompanied by marked reductions in CD44high/CD24low stem-like cells and aldehyde dehydrogenase 1 (ALDH1) activity as well as hindrance of mammosphere formation. ß-escin administration also significantly retarded tumor growth and angiogenesis in a trastuzumab-resistant JIMT-1 xenograft model via downregulation of CSC-associated markers and intracellular domain HER2. Importantly, ß-escin selectively inhibited malignant cells and was less toxic to normal mammary cells, and no toxic effects were found in liver and kidney function in animals. CONCLUSIONS: Taken together, our findings highlight ß-escin as a promising candidate for the treatment of trastuzumab-resistant HER2-positive breast cancers.

Discovery of a simplified deguelin analog as an HSP90 C-terminal inhibitor for HER2-positive breast cancer.

A series of O-substituted analogs of the C-ring-truncated scaffold of deguelin designed as heat shock protein 90 (HSP90) C-terminal inhibitors were investigated as novel antitumor agents against human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Among the synthesized compounds, compound 37 displayed significant inhibition in both trastuzumab-sensitive and trastuzumab-resistant breast cancer cells with little cytotoxicity to normal cells. Mechanistic studies of compound 37 carried out by HSP90α C-terminal inhibitor screening, the induction of the heat shock response and downregulation of HSP90 client proteins indicated that the antitumor activity of 37 in breast cancer cells could be attributed to the destabilization and inactivation of HSP90 client proteins by the binding of 37 to the C-terminal domain of HSP90. A molecular docking study of compound 37 with a HSP90 homology model indicated that its S-isomer fit well in the ATP binding site of the C-terminal domain, forming key interactions.

Effects of Automatic Abdominal Massage Device in Treatment of Chronic Constipation Patients: A Prospective Study.

BACKGROUND AND AIM: Manual abdominal massage has been shown to effectively treat slow-transit constipation, but it is labor-intensive. To offer an alternative treatment option for constipation, the Bamk-001 automatic abdominal massage device was developed. The aim of this study was to assess the effect of the Bamk-001 device on symptom profiles and colon transit time (CTT) in patients with chronic constipation. METHODS: Thirty-seven patients with chronic functional constipation diagnosed using the Rome IV criteria were enrolled prospectively from December 2018 to February 2019. All patients received device-assisted automatic abdominal massage for 15 min twice daily, once in the morning before breakfast and once at night, for 14 days. CTT was measured before and at the end of the study period. Slow-transit constipation and very-slow-transit constipation were defined as CTT ≥ 48 h and ≥ 72 h, respectively. Patients' symptom profiles regarding overall defecation satisfaction and device-related adverse events were analyzed. RESULTS: Among the 37 patients, the mean age was 40.1 ± 11.8, and 5.4% (n = 2) were men. The Bamk-001 device significantly improved CTT from 54.0 (33.6-75.6) to 28.8 (18.0-52.8) h (p = 0.001) in patients with chronic constipation. In subgroup analysis, CTT improved significantly from 54.0 (33.6-75.6) to 28.8 (18.0-52.8) h (p = 0.003) and from 88.2 (74.4-124.8) to 45.6 (27.3-74.1) h (p = 0.005) in the slow-transit and very-slow-transit constipation groups, respectively (p = 0.001). Moreover, all patient symptoms were alleviated after treatment. No serious adverse events were reported. CONCLUSION: The Bamk-001 automatic abdominal massage device showed significant care efficacy, including the improvement in CTT and symptom profiles in patients with slow-transit constipation. The use of an automatic abdominal massage device as an adjunct in the management of constipation is a potentially beneficial intervention for patients with slow-transit constipation.

Primary Ciliogenesis by 2-Isopropylmalic Acid Prevents PM2.5-Induced Inflammatory Response and MMP-1 Activation in Human Dermal Fibroblasts and a 3-D-Skin Model.

Particulate matters (PMs) increase oxidative stress and inflammatory response in different tissues. PMs disrupt the formation of primary cilia in various skin cells, including keratinocytes and melanocytes. In this study, we found that 2-isopropylmalic acid (2-IPMA) promoted primary ciliogenesis and restored the PM2.5-induced dysgenesis of primary cilia in dermal fibroblasts. Moreover, 2-IPMA inhibited the generation of excessive reactive oxygen species and the activation of stress kinase in PM2.5-treated dermal fibroblasts. Further, 2-IPMA inhibited the production of pro-inflammatory cytokines, including IL-6 and TNF-α, which were upregulated by PM2.5. However, the inhibition of primary ciliogenesis by IFT88 depletion reversed the downregulated cytokines by 2-IPMA. Moreover, we found that PM2.5 treatment increased the MMP-1 expression in dermal fibroblasts and a human 3-D-skin model. The reduced MMP-1 expression by 2-IPMA was further reversed by IFT88 depletion in PM2.5-treated dermal fibroblasts. These findings suggest that 2-IPMA ameliorates PM2.5-induced inflammation by promoting primary ciliogenesis in dermal fibroblasts.

A novel HSP90 inhibitor targeting the C-terminal domain attenuates trastuzumab resistance in HER2-positive breast cancer.

Trastuzumab resistance in HER2-positive breast cancer is associated with a poorer prognosis. HSP90 is thought to play a major role in such resistance, but N-terminal inhibitors of this target have had little success. We sought to investigate the utility of NCT-547, a novel, rationally-designed C-terminal HSP90 inhibitor in the context of overcoming trastuzumab resistance. NCT-547 treatment significantly induced apoptosis without triggering the heat shock response (HSR), accompanied by caspase-3/- 7 activation in both trastuzumab-sensitive and -resistant cells. NCT-547 effectively promoted the degradation of full-length HER2 and truncated p95HER2, while also attenuating hetero-dimerization of HER2 family members. The impairment of cancer stem-like traits was observed with reductions in ALDH1 activity, the CD24low/CD44high subpopulation, and mammosphere formation in vitro and in vivo. NCT-547 was an effective inhibitor of tumor growth and angiogenesis, and no toxic outcomes were found in initial hepatic and renal analysis. Our findings suggest that NCT-547 may have applications in addressing trastuzumab resistance in HER2-positive breast cancer.

Discovery of novel anti-breast cancer agents derived from deguelin as inhibitors of heat shock protein 90 (HSP90).

A series of O-substituted analogues of the B,C-ring truncated scaffold of deguelin were designed as C-terminal inhibitors of heat shock protein 90 (HSP90) and investigated as novel antiproliferative agents against HER2-positive breast cancer. Among the synthesized compounds, compound 80 exhibited significant inhibition in both trastuzumab-sensitive and trastuzumab-resistant breast cancer cells, whereas compound 80 did not show any cytotoxicity in normal cells. Compound 80 markedly downregulated the expression of the major client proteins of HSP90 in both cell types, indicating that the cytotoxicity of 80 in breast cancer cells is attributed to the destabilization and inactivation of HSP90 client proteins and that HSP90 inhibition represents a promising strategy to overcome trastuzumab resistance. A molecular docking study of 80 with the homology model of a HSP90 homodimer showed that 80 fit nicely in the C-terminal domain with a higher electrostatic complementary score than that of ATP.

Efficacy of repeat forward-view examination of the right-sided colon during colonoscopy: A prospective randomized controlled trial.

BACKGROUND AND AIM: Generally, colonoscopy is less effective for detecting colorectal adenomas in the right-sided colon compared with the distal colon. Repeat forward-view (RF) examination of the right-sided colon has been suggested to increase the adenoma detection rate (ADR). However, studies investigating the efficacy of RF examination are lacking. Thus, the aim of this study was to determine whether RF examination in the right-sided colon enhances right-sided ADR. METHODS: We performed a prospective, randomized controlled trial, including asymptomatic subjects who underwent screening colonoscopy. Subjects were randomized to the RF group, in which the right-sided colon was examined twice in the forward view, or to the standard forward-view (SF) group, in which the right-sided colon was examined once in the forward view. The primary outcome was the right-sided ADR on RF examination of the right-sided colon. RESULTS: A total of 640 subjects completed the study protocol (RF group, n = 320; SF group, n = 320). The right-sided ADR in the RF group was significantly higher than that in the SF group (17.5% vs 11.9%, respectively; P = 0.044). In the RF group, an additional 31 adenomas were found, resulting in an increased detection rate of adenomas of 38.3% compared with the first forward view. The ADR of the whole colon was similar between the groups. CONCLUSIONS: In our prospective randomized controlled trial, RF examination of the right-sided colon, which can be easily performed in clinical practice, was associated with an increased rate of detection of right-sided ADR.

Effect of work-related factors on the prevalence of peptic ulcer disease among Korean workers: a nationwide population-based study.

BACKGROUND: Working environment such as psychosocial factors impacts the health of workers. However, few studies have assessed the association of work-related factors with the prevalence of peptic ulcer disease (PUD) in large population based study. METHODS: After exclusion of military personnel, 16,099 wage workers (20 ≤ age ≤ 65 years) from the Fourth Korea National Health and Nutrition Examination Survey (2008-2011) were included in this study. Job status was defined as the place of employment of longest duration. To evaluate the working environment, we used a comprehensive work-stressor measure. Univariate and multivariable regression analyses were performed to assess the effect of occupation type on the prevalence of PUD. RESULTS: Among the subjects, 5540, 3398, and 7161 were white-, pink-, and blue-collar workers, respectively. The prevalence of PUD was highest among blue-collar workers (n = 336, 7.1%), followed by pink-collar (n = 116, 5.1%) and white-collar (n = 180, 4.9%) workers. In the multivariable analysis, work type and uncomfortable gestures were independently associated with the risk of PUD. Compared with office workers, operators in industrial plants and machine operators had a significantly higher prevalence of PUD (odds ratio, 1.9; 95% confidence interval, 1.1-3.3) after adjusting for age, socioeconomic factors, sex, smoking, alcohol consumption, daily exercise, sleep duration, and working conditions. DISCUSSION: In conclusion, work-related factors, particularly blue-collar work and uncomfortable job gestures, are independently associated with the risk of PUD. Therefore, it is important to monitor the development of PUD in workers exposed to these factors.

NRF2 Knockdown Resensitizes 5-Fluorouracil-Resistant Pancreatic Cancer Cells by Suppressing HO-1 and ABCG2 Expression.

Chemoresistance is a leading cause of morbidity and mortality in patients with pancreatic cancer and remains an obstacle to successful treatment. The antioxidant transcription factor nuclear factor (erythroid-derived 2)-related factor 2 (NRF2), which plays important roles in tumor angiogenesis and invasiveness, is upregulated in pancreatic ductal adenocarcinoma (PDAC), where it correlates with poor survival. Here, we investigated the role of NRF2 in two 5-Fluourouracil-resistant (5-FUR) PDAC cell lines: BxPC-3 and CFPAC-1. Levels of NRF2 and antioxidants, such as heme oxygenase 1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1), and superoxide dismutase 2 (SOD2), were higher in the chemoresistant cells than in their chemosensitive counterparts. Expression of epithelial mesenchymal transition (EMT) markers, stemness markers, including Nanog, Oct4, and CD133, and that of the drug transporter ATP binding cassette, subfamily G, member A2 (ABCG2) was also upregulated in 5-FUR PDAC cells. NRF2 knockdown reversed 5-FU resistance of PDAC cells via suppression of ABCG2 and HO-1. In summary, these data indicate that NRF2 is a potential target for resensitizing 5-FUR PDAC cells to 5-FU to improve treatment outcomes in patients with pancreatic cancer.

The Efficacy, Safety, and Convenience of a New Device for Flushing Intravenous Catheters (Baro Flush™): A Prospective Study.

Background and Objectives: An effective flushing technique is essential to reduce intravenous (IV)-related complications and improve patient care. New technology should contribute to such improvements, while reducing costs and increasing care efficiency. This study evaluated the efficacy, safety, and convenience of a new flushing technique using a Baro Flush™ controller. Materials and Methods: We evaluated the efficacy and safety of Baro Flush™ by measuring the infusion flushing volume and pressure in vitro. Afterwards, we prospectively enrolled 3000 patients with flushing and assigned 1500 patients with a new technique for flushing and 1500 with a conventional flushing method, which was performed by 48 registered nurses (RNs) at the Gil Medical Center in June 2018. The efficacy, safety, and convenience of the new flushing method were evaluated though a questionnaire survey. Results: The average flushing pressure was 12.5 ± 0.6 psi (86.18 ± 4.14 kPa) with 1.2 ± 0.2 mL per flush, as recommended by the Centers for Disease Control and Prevention based on 85 experiments. No IV-catheter-related complications were reported by the RNs during the study. More than 80% of the RNs reported that the new flushing method was easier to learn, improved care efficacy, and was more convenient than conventional flushing. Conclusions: The new flushing method using a Baro Flush™ controller showed improved efficacy, safety, and convenience compared with the conventional flushing method, and no IV-catheter-related complications occurred, including occlusion and inflammation. The new flushing method promises to reduce IV-catheter-related complications and shows improved efficacy, safety, and convenience.

Sarcopenia is Independently Associated with an Increased Risk of Peptic Ulcer Disease: A Nationwide Population-Based Study.

Background and objective: Although obesity is associated with an increased risk of peptic ulcer disease (PUD), no study has evaluated the association of PUD with sarcopenia. The aim of this study was to evaluate the association of sarcopenia and obesity with PUD. Material and Methods: Data from the Korean National Health and Nutrition Examination Survey (KNHANES) IV and V for 2007-2012 were used. PUD history, dietary, alcohol consumption, smoking, physical activity patterns, and other socioeconomic factors were analyzed. Sarcopenia index (appendicular skeletal muscle mass (kg) ÷ body mass index (kg/m2)) and body fat mass were determined by dual-energy X-ray absorptiometry. Univariate and multivariate analyses were performed to evaluate the association of sarcopenia with the prevalence of PUD. Results: The 7092 patients were divided into the sarcopenic obesity (SO, n = 870), sarcopenic non-obesity (n = 2676), non-sarcopenic obesity (NSO, n = 2698), and non-sarcopenic non-obesity (NSNO, n = 848) groups. The prevalence of PUD in these groups was 70 (7.9%), 170 (7.4%), 169 (6.3%), and 47 (3.8%), respectively (p < 0.001). A crude analysis revealed that the prevalence of PUD was 2.2-fold higher in the SO group than in the NSNO group (odds ratio (OR), 2.2; 95% confidence interval (CI), 1.5-3.2), the significance of which remained after adjustment for age, sex, body mass index, and HOMA-IR (homeostatic model assessment insulin resistance) score (OR, 1.9; 95% CI, 1.3-2.7). Conclusion: In conclusion, in this nationally representative cohort, the combination of muscle and fat mass, as well as obesity, was associated with an increased risk of PUD.

Comparison of outcomes of continuation/discontinuation of 5-aminosalicylic acid after initiation of anti-tumor necrosis factor-alpha therapy in patients with inflammatory bowel disease.

BACKGROUND: Few maintenance therapeutic options are available for inflammatory bowel disease (IBD). Data on the effects of continuing 5-aminosalicylic acid (5-ASA) treatment in patients who commence on biologics as maintenance treatment remain scarce. We evaluated IBD patient outcomes after continuation/discontinuation of 5-ASA when biologics were administered as maintenance treatment. METHODS: We retrospectively reviewed the clinical, laboratory, and imaging data of patients diagnosed with IBD (ulcerative colitis (UC), 763; Crohn's disease (CD), 537) in the Gil Medical Center (GMC) from February 2005 to June 2018. We divided patients administered with biologics as maintenance treatment into those who did and did not continue on 5-ASA and compared the efficacies of the two treatment options using the log-rank test and Cox proportional hazards models. RESULTS: Of 1300 total IBD patients, 128 (UC, 63; CD, 65) were prescribed biologics as induction and maintenance treatments. The median follow-up period was 109.5 weeks. All cases were divided into those who did or did not combine 5-ASA with biologics as maintenance treatments. Kaplan-Meier analysis showed that the event-free survival (exacerbation of disease activity) of UC patients treated with biologics and 5-ASA (n = 42) was not significantly lower than that of those taking biologics alone (n = 21) (log rank test, P = 0.68). The same was true of CD patients (n = 42, biologics and 5-ASA; n = 23, biologics only) (log rank test, P = 0.87). CONCLUSIONS: Continuation of 5-ASA after initiation of anti-tumor necrosis factor-alpha agents did not improve prognosis in Korean IBD patients compared with that of those who discontinued 5-ASA during maintenance treatment, particularly in patients who experienced more than two disease aggravations.

Vision-aided brain-machine interface training system for robotic arm control and clinical application on two patients with cervical spinal cord injury.

BACKGROUND: While spontaneous robotic arm control using motor imagery has been reported, most previous successful cases have used invasive approaches with advantages in spatial resolution. However, still many researchers continue to investigate methods for robotic arm control with noninvasive neural signal. Most of noninvasive control of robotic arm utilizes P300, steady state visually evoked potential, N2pc, and mental tasks differentiation. Even though these approaches demonstrated successful accuracy, they are limited in time efficiency and user intuition, and mostly require visual stimulation. Ultimately, velocity vector construction using electroencephalography activated by motion-related motor imagery can be considered as a substitution. In this study, a vision-aided brain-machine interface training system for robotic arm control is proposed and developed. METHODS: The proposed system uses a Microsoft Kinect to detect and estimates the 3D positions of the possible target objects. The predicted velocity vector for robot arm input is compensated using the artificial potential to follow an intended one among the possible targets. Two participants with cervical spinal cord injury trained with the system to explore its possible effects. RESULTS: In a situation with four possible targets, the proposed system significantly improved the distance error to the intended target compared to the unintended ones (p < 0.0001). Functional magnetic resonance imaging after five sessions of observation-based training with the developed system showed brain activation patterns with tendency of focusing to ipsilateral primary motor and sensory cortex, posterior parietal cortex, and contralateral cerebellum. However, shared control with blending parameter α less than 1 was not successful and success rate for touching an instructed target was less than the chance level (= 50%). CONCLUSIONS: The pilot clinical study utilizing the training system suggested potential beneficial effects in characterizing the brain activation patterns.