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Metformin is widely used drugs in the treatment of type 2 diabetes mellitus. However, the mechanisms of action are complex and are still not fully understood yet. Metformin has a dose-dependent blood sugar-lowering effect. The most common adverse reactions of metformin are gastrointestinal symptoms, and women tend to be more experienced than men. A positive correlation between the administration of duration and the daily dose of metformin and the risk of vitamin B12 deficiency is confirmed. Novel glucose-lowering mechanism through the activation of AMP-activated protein kinase and alteration of gut microbiota composition is identified. In addition, metformin has immunomodulatory properties in various mechanisms, including anti-inflammatory actions, and so forth. Metformin improves insulin sensitivity, which may reduce the risk of tumor growth in certain cancers. The antiviral effects of metformin may occur through several mechanisms, including blocking angiotensin converting enzyme 2 receptor, and so forth. These potential mechanisms of metformin are promising in various clinical settings, such as inflammatory diseases, autoimmune diseases, cancer, and coronavirus disease 2019.

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Background: The importance of primary care physicians (PCPs) in managing metabolic dysfunction-associated steatotic liver disease (MASLD) has increased. This study aimed to assess the effectiveness of an online educational program on MASLD among physicians. Methods: In total, 869 physicians (72 physicians at referral centers and 797 PCPs) participated in this study. They completed an initial survey regarding their clinical practices for patients with MASLD, followed by a second online survey 8 weeks after receiving a series of seven weekly sets of educational materials on MASLD. Results: In the baseline survey, most PCPs did not routinely evaluate the stage of hepatic fibrosis in MASLD; they typically initiated assessments based on elevated liver enzyme levels. Only a limited number of PCPs used vibration-controlled transient elastography. The main hurdles in managing MASLD were "the absence of a fee for patient education" for PCPs and "short consultation time" for referral-center physicians. In the follow-up survey, the percentage of liver fibrosis assessments using noninvasive tests increased from 7.0 to 11.2%. Additionally, evaluations for cardiovascular disease increased from 3.9 to 8.2%, and the risk of ischemic stroke increased from 13.7 to 16.9%. The percentage of immediate referrals of patients to specialists after an MASLD diagnosis decreased from 15.4 to 12.3%. Conclusion: The discrepancies in management strategies and viewpoints regarding MASLD between PCPs and referral-center physicians can hinder efforts to mitigate the disease burden. Increasing awareness among PCPs regarding MASLD through a 7-week education program led to a reduction in unnecessary referral rates and an increase in cardiovascular evaluations.

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Although the associations between a patient's body mass index (BMI) and metabolic diseases, as well as their breath test results, have been studied, the relationship between breath hydrogen/methane levels and metabolic diseases needs to be further clarified. We aimed to investigate how the composition of exhaled breath gases relates to metabolic disorders, such as diabetes mellitus, dyslipidemia, hypertension, and nonalcoholic fatty liver disease (NAFLD), and their key risk factors. An analysis was performed using the medical records, including the lactulose breath test (LBT) data of patients who visited the Ajou University Medical Center, Suwon, Republic of Korea, between January 2016 and December 2021. The patients were grouped according to four different criteria for LBT hydrogen and methane levels. Of 441 patients, 325 (72.1%) had positive results for methane only (hydrogen < 20 parts per million [ppm] and methane ⩾ 3 ppm). BMIs and NAFLD prevalence were higher in patients with only methane positivity than in patients with hydrogen and methane positivity (hydrogen ⩾ 20 ppm and methane ⩾ 3 ppm). According to a multivariate analysis, the odds ratio of only methane positivity was 2.002 (95% confidence interval [CI]: 1.244-3.221,P= 0.004) for NAFLD. Our results demonstrate that breath methane positivity is related to NAFLD and suggest that increased methane gas on the breath tests has the potential to be an easily measurable biomarker for NAFLD diagnosis.

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Calcium and vitamin D deficiencies have been ongoing problems in Koreans due to a lack of food sources of calcium and vitamin D. Postmenopausal women aged 50 to 64 years (n = 25) were randomly assigned to consume three home meal replacements (HMRs)/week with (treatment) and without (control) eggshell powder and vitamin D for 6 months. Additionally, subjects who agreed to continue the study consumed the same three HMRs/week for an additional 6 months in this randomized double-blind study. We confirmed the high compliance of the study participants by analyzing carotenoids, the bioactive substances of HMRs, in the blood. The treatment group consumed an additional 261 mg/d of calcium and 10.3 µg/d of vitamin D from the HMRs, thus meeting the recommended intakes of calcium and vitamin D for Koreans. As a result of consuming fortified HMRs for 6 months, the decline in femoral neck bone density was significantly reduced in the treatment group (p = 0.035). This study indicates that inexpensive eggshell powder may be a good source of calcium for populations with low consumption of milk and dairy products. Additionally, functional HMRs fortified with eggshell powder and vitamin D can be a good dietary strategy for bone health.

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Herein, we present our experience using a single-stage peninsular-shaped lateral tongue flap (pLTF) to cover various intraoral defects and confirm the versatile utility and effective application of pLTF in intraoral defect reconstruction. This study included eight cases (six males and two females; average age 60.3 ± 16.9 years) of intraoral defect reconstruction performed by a single surgeon between August 2020 and May 2023 using the single-stage pLTF technique. Electronic medical records and photographs of the patients were collected and analyzed. The functional intraoral Glasgow scale (FIGS) was used to evaluate preoperative and postoperative tongue function. Defect sizes ranged from 3 cm × 3 cm to 4 cm × 6 cm. Notably, all defects were successfully covered with pLTFs, and the flap sizes ranged between 3 cm × 4.5 cm and 4.5 cm × 7.5 cm. The flaps completely survived without any postoperative complications. At follow-up (average, 9.87 ± 2.74 months), no patient had tumor recurrence or significant tongue functional deficits. The mean preoperative and postoperative FIGS were 14.75 ± 0.46 and 14.00 ± 0.92, respectively (p = 0.059). Thus, the single-stage pLTF technique is a good reconstructive modality for various small to moderate intraoral defect coverage in selected cases for personalized intraoral reconstruction.

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We aimed to demonstrate the effective application of keystone perforator island flap (KPIF) in scalp and forehead reconstruction by demonstrating the authors' experience with modified KPIF reconstruction for small- to moderate-sized scalp and forehead defects. Twelve patients who underwent modified KPIF reconstruction of the scalp and forehead from September 2020 to July 2022 were enrolled in this study. In addition, we retrospectively reviewed and evaluated the patient's medical records and clinical photographs. All defects (size range, 2 cm × 2 cm to 3 cm × 7 cm) were successfully covered using four modified KPIF techniques (hemi-KPIF, Sydney Melanoma Unit Modification KPIF, omega variation closure KPIF, and modified type II KPIF) with ancillary procedures (additional skin grafts and local flaps). All flaps (size range, 3.5 cm × 4 cm to 7 cm × 16 cm) fully survived, and only one patient developed marginal maceration that healed with conservative management. Furthermore, through the final scar evaluation with the patient satisfaction survey and Harris 4-stage scale, all patients were satisfied with their favorable outcomes at the average final follow-up period of 7.66 ± 2.14 months. The study showed that the KPIF technique with appropriate modifications is an excellent reconstructive modality for covering scalp and forehead defects.

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Synbiotics, including probiotics and prebiotics, are useful for patients with functional bowel disorders. However, which synbiotics are beneficial for patients with which diseases, especially those with functional diarrhea (FDr) with high fecal calprotectin levels, is currently unknown. FDr is an extension of irritable bowel syndrome with diarrhea (IBS-D). Although fewer studies have been conducted on FDr compared to IBS-D, its importance is increasing as its prevalence increases. The aim of this study was to evaluate the effects of a synbiotic containing a mixture of Lactobacillus and Bifidobacterium and its substrate, fructooligosaccharide, on bowel symptoms, fecal calprotectin levels, fecal microbiota, and safety in FDr patients with high fecal calprotectin levels. Forty patients were randomly assigned to either a synbiotic group or a placebo group. A total of 20 subjects in the synbiotic group and 19 subjects in the placebo group completed the study (8 weeks). Changes in FDr symptoms, fecal calprotectin levels, and gut microbiota were assessed during the intervention period. At 4 and 8 weeks, the number of bowel movements tended to increase in the synbiotic group, with a significant increase in the number of formed stools rather than loose stools (p < 0.05). Bowel movement satisfaction was significantly increased in the synbiotic group, but not in the placebo group. Intestinal flora analysis revealed that Lactobacillales at the order level was increased only in the synbiotic group at the end of the intervention. In contrast, at week 8 of the intervention, log-transformed fecal calprotectin levels were significantly decreased in the synbiotic group, although the change was not significantly different from that of the placebo group. These findings suggest that the intake of a multi-strain-containing synbiotic for 8 weeks could improve gut symptoms and the intestinal microenvironment of FDr patients with high fecal calprotectin levels.

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Micro-inflammation in the gut, assessed by fecal calprotectin (FC), is considered a component of the pathogenesis of functional diarrhea (FD). Since probiotics may suppress micro-inflammation in the intestine by competing with harmful bacteria, we hypothesized that they would reduce the ratio of loose stool symptoms and gut inflammation in patients with FD. We conducted a double-blind, placebo-controlled trial to assess the clinical and laboratory effects of Lactobacillus plantarum CJLP243 in FD patients with elevated FC levels for two months. Twenty-four patients diagnosed with FD with elevated FC levels were randomly assigned to either a probiotic group or a placebo group. After 2 months, 10 patients in the probiotic group and 12 patients in the placebo group completed the study, and FD symptoms, FC values, and intestinal flora were re-evaluated in these subjects. The percentage of subjects who had adequate FD relief (decrease in loose stool frequency) in the probiotic group was significantly increased after two months compared with the baseline. In addition, the probiotic group showed a statistically significant decrease in log-transformed FC values compared with the pre-treatment group, whereas the placebo group showed no difference before and after the intervention. Furthermore, the levels of Leuconostoc genus organisms in the gut microbiota composition in the probiotic group increased significantly after the end of the study compared with the baseline values. In this preliminary exploratory research, we found that two months of Lactiplantibacillus plantarum CJLP243 treatment resulted in FD symptom improvement, reduced FC values, and increased Leuconostoc levels, suggesting that the intake of Lactiplantibacillus plantarum was helpful in those patients. These findings need to be validated via further clinical studies.

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Numerous mobile robots in various forms specialize in either ground or aerial locomotion, whereas very few robots can perform complex locomotion tasks beyond simple walking and flying. We present the design and control of a multimodal locomotion robotic platform called LEONARDO, which bridges the gap between two different locomotion regimes of flying and walking using synchronized control of distributed electric thrusters and a pair of multijoint legs. By combining two distinct locomotion mechanisms, LEONARDO achieves complex maneuvers that require delicate balancing, such as walking on a slackline and skateboarding, which are challenging for existing bipedal robots. LEONARDO also demonstrates agile walking motions, interlaced with flying maneuvers to overcome obstacles using synchronized control of propellers and leg joints. The mechanical design and synchronized control strategy achieve a unique multimodal locomotion capability that could potentially enable robotic missions and operations that would be difficult for single-modal locomotion robots.

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Emerging data suggest that an increase in serum alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) as biomarkers of oxidative stress are associated with increased risk of impaired fasting glucose (IFG). The present study was an investigation of whether an increase in serum ALT and GGT had a combined effect on increasing IFG risk through cross-sectional and longitudinal studies. In the cross-sectional study, data were analyzed from 9937 subjects without diabetes who underwent health check-ups between 1999 and 2001 (baseline data). In the longitudinal study, 6390 subjects were analyzed who had been rechecked between 2009 and 2014, excluding IFG patients from baseline data. In cross-sectional analysis, adjusted odds ratio (OR) of IFG in the fourth quartile of both ALT and GGT was 1.829 (95% confidence interval [CI] 1.545-2.164) compared with the reference group (1st and 2nd quartiles of ALT and GGT). In longitudinal analysis, IFG probability increased gradually with an increase in the circulating levels of ALT and GGT. Adjusted hazard ratios for developing IFG in the fourth quartile of both ALT and GGT was 1.625 (95% CI 1.263-2.091) compared with the reference group (1st and 2nd quartiles). Increased serum ALT and GGT levels are well associated with IFG after potential confounders are adjusted for, and elevated ALT and GGT at the same time can have a combined effect in predicting the development of IFG.

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The contingent valuation method (CVM) is used to measure non-market value. However, the CVM evaluates values using the subjective survey responses of consumers. Therefore, to analyze non-market value, we improve an integrated analysis module, which is divided into the following three parts: (1) a dose-response function that describes the relationship between noise exposure and annoyance, (2) the calculation of willingness to pay to reduce the noise level from the spike model in the CVM analysis, and (3) the calculation of the non-market value-related benefits by linking steps 1 and 2 above. We use the proposed integrated analysis module to analyze the value of noise reduction in South Korea. From this integrated analysis module, we find that a 1 dB reduction in living noise generated from a construction site has a value from 4578 KRW (USD$3.94) to 5794 KRW (USD$4.99) and that this value varies depending on the noise exposure level. The integrated analysis module can thus be used to improve noise policies in South Korea.

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Metabolic syndrome is well known to increase the risk of cardiovascular diseases. We have reported that phytochemicals rich black rice with giant embryo reduced fat mass and metabolic disorders in an animal model. However, such effects have not been evaluated in humans. Subjects with metabolic syndrome (n = 49, 38 male, 44.3 ± 6.1 years) were randomly assigned into two groups and ingested roasted black-rice with giant embryo (BR, n = 26, 20 male) or white-rice (WR, n = 23, 18 male) powders mixed with water for breakfast for three months. Subjects were evaluated for various metabolic parameters before and after intervention. All parameters were not significantly different between groups before starting the intervention. After three months of consumption of either BR or WR, changes of body weight in BR vs WR groups (-1.54 kg vs -1.29 kg, p = 0.649) as well as waist circumference (-1.63 cm vs -1.02 cm, p = 0.365) were not significantly different between groups. However, changes in highly-sensitive C reactive proteins in BR vs WR groups (-0.110 mg/dl vs 0.017 mg/dl, p = 0.003) had significant differences. Three months of meal replacement with BR had a significant reduction of highly-sensitive C reactive protein compared to those with WR in adults with metabolic syndrome.

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The autonomic nervous system (ANS) maintains homeostasis in the gastrointestinal tract, including immunity, inflammation and motility, through the brain-gut axis. To date, the associations between ANS function and inflammatory bowel disease (IBD) have been controversial and inconclusive in human studies. PubMed, Cochrane Library, and Embase were searched through February 2020 for articles reporting these association between heart rate variability (HRV), an indirect measure of ANS activity, and IBD. The standardized mean differences and 95% confidence intervals (CIs) were calculated. Ten eligible studies involving 273 ulcerative colitis patients, 167 Crohn's disease patients and 208 healthy controls were included. The values of the total power (SMD = -0.83, 95% CI = -1.44, -0.21), high frequency (SMD = -0.79, 95% CI = -1.20, -0.38), RR interval (SMD = -0.66, 95% CI = -1.04, -0.27), standard deviation of the RR intervals (SMD = -1.00, 95% CI = -1.73, -0.27), percentage of RR intervals with a greater than 50-millisecond variation (SMD = -0.82, 95% CI = -1.33, -0.30) and the square root of the mean squared differences in successive RR intervals (SMD = -0.71, 95% CI = -1.15, -0.26) of the IBD patients were lower than those of the healthy controls, and moderate to large effect sizes were observed in all HRV indices, except for low frequency (SMD = -0.41, 95% CI = 0.95, 0.13). IBD was strongly associated with an overall decrease in HRV, indicating substantially decreased ANS activity. Furthermore, the parasympathetic nerve displayed a stronger inverse association with ANS activity than the sympathetic nerve, indicating ANS dysfunction in patients with IBD.

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Metal catalysts are generally supported on hard inorganic materials because of their high thermochemical stabilities. Here, we support Pd catalysts on a thermochemically stable but "soft" engineering plastic, polyphenylene sulfide (PPS), for acetylene partial hydrogenation. Near the glass transition temperature (~353 K), the mobile PPS chains cover the entire surface of Pd particles via strong metal-polymer interactions. The Pd-PPS interface enables H2 activation only in the presence of acetylene that has a strong binding affinity to Pd and thus can disturb the Pd-PPS interface. Once acetylene is hydrogenated to weakly binding ethylene, re-adsorption of PPS on the Pd surface repels ethylene before it is further hydrogenated to ethane. The Pd-PPS interaction enables selective partial hydrogenation of acetylene to ethylene even in an ethylene-rich stream and suppresses catalyst deactivation due to coke formation. The results manifest the unique possibility of harnessing dynamic metal-polymer interaction for designing chemoselective and long-lived catalysts.

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Functional dyspepsia (FD) is associated with small intestinal bacterial overgrowth (SIBO). Several animal studies have reported that ursodeoxycholic acid (UDCA) has antibacterial and anti-inflammatory effects in the intestine. We hypothesized that UDCA may be effective against dyspeptic symptoms and SIBO in patients with FD. We conducted this randomized controlled trial to investigate the effects of UDCA in FD patients with SIBO. Twenty-four patients diagnosed with FD and SIBO based on lactulose breath test (LBT) were randomly assigned to either a UDCA treatment group or an untreated group. The treatment group received 100 mg of UDCA three times per day for two months; the untreated group was monitored for two months without intervention. After two months in both groups, we reevaluated LBT and FD symptoms using the Nepean dyspepsia index-K. FD symptoms in the UDCA-treated group were significantly reduced after two months compared with baseline and FD symptom scores between the UDCA-treated and untreated groups showed statistically significant differences after two months. In addition, the total methane gas levels for 90 minutes in LBT were significantly decreased after two months compared with baseline in the UDCA-treated group. In this preliminary exploratory study, we found that two months of UDCA treatment resulted in FD symptom improvement and reduced methane values during 90 minutes on the LBT, suggesting that methane-producing SIBO were associated with symptoms of dyspepsia and that UDCA was helpful in these patients. These findings need to be validated via large-scale controlled and well-designed studies.

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High levels of serum alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) are associated with increased diabetes risk. In the present study, we investigated the combined effects of ALT and GGT on the development of diabetes in a Korean population. A total of 9405 individuals (4020 women and 5385 men) without diabetes were enrolled in this study. From the baseline health screening to the follow-up examination, the development of diabetes, based on changes in ALT and GGT quartile levels, was analyzed. In addition, we analyzed the quartiles of ALT and GGT together to determine any synergistic effect from the fourth quartile of ALT and GGT on the development of diabetes. The development of diabetes gradually increased with an increase in the circulating levels of ALT and GGT. For the fourth quartile ALT and GGT, the hazard ratios of diabetes compared with the first quartile were 1.892 (95% confidence interval [CI]: 1.26-2.83, P = .002) and 3.526 (95% CI: 2.12-5.85, P < .001) after adjusting for confounders, respectively. Hazard ratios of diabetes after combining both fourth quartiles of ALT and GGT were 3.663 (95% CI: 2.42-5.52, P < .001), as compared with the first and second quartiles. Serum ALT and GGT levels are well associated with diabetes in Koreans after adjusting for confounders, and a combination of ALT and GGT levels can have a synergy in predicting the development of diabetes.

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Soft spherical tensegrity robots are novel steerable mobile robotic platforms that are compliant, lightweight, and robust. The geometry of these robots is suitable for rolling locomotion, and they achieve this motion by properly deforming their structures using carefully chosen actuation strategies. The objective of this work is to consolidate and add to our research to date on methods for realizing rolling locomotion of spherical tensegrity robots. To predict the deformation of tensegrity structures when their member forces are varied, we introduce a modified version of the dynamic relaxation technique and apply it to our tensegrity robots. In addition, we present two techniques to find desirable deformations and actuation strategies that would result in robust rolling locomotion of the robots. The first one relies on the greedy search that can quickly find solutions, and the second one uses a multigeneration Monte Carlo method that can find suboptimal solutions with a higher quality. The methods are illustrated and validated both in simulation and with our hardware robots, which show that our methods are viable means of realizing robust and steerable rolling locomotion of spherical tensegrity robots.

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: This study was performed to investigate the changes in gene expression in periodontal ligament (PDL) cells following mechanical stimulus through RNA sequencing. In this study, premolars extracted for orthodontic treatment were used. To stimulate the PDL cells, an orthodontic force of 100× g was applied to the premolar (experimental group; n = 11), whereas the tooth on the other side was left untreated (control group; n = 11). After the PDL cells were isolated from the extracted teeth, gene set enrichment analysis (GSEA), differentially expressed gene (DEG) analysis, and real-time PCR were performed to compare the two groups. GSEA demonstrated that gene sets related to the cell cycle pathway were upregulated in PDL. Thirteen upregulated and twenty downregulated genes were found through DEG analysis. Real-time PCR results confirmed that five upregulated genes (CC2D1B, CPNE3, OPHN1, TANGO2, and UAP-1) and six downregulated genes (MYOM2, PPM1F, PCDP1, ATP2A1, GPR171, and RP1-34H18.1-1) were consistent with RNA sequencing results. We suggest that, from among these eleven genes, two upregulated genes, CPNE3 and OPHN1, and one downregulated gene, PPM1F, play an important role in PDL regeneration in humans when orthodontic force is applied.

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Hydrogen formed by small intestinal bacterial overgrowth in patients with non-constipated irritable bowel syndrome has an inverse relationship with obesity. However, the effect of eradicating small intestinal hydrogen-producing bacterial overgrowth on the body weight of these patients has not yet been reported. The aim of this study was to investigate body weight changes after eradicating small intestinal bacterial overgrowth with rifaximin treatment in patients with non-constipated irritable bowel syndrome.We reviewed the charts of patients with non-constipated irritable bowel syndrome who showed abdominal symptoms with documented lactulose hydrogen breath test results in order to diagnose small intestinal bacterial overgrowth. A total of 153 patients were enrolled in the study and divided into quartiles according to body mass index (BMI) and body weight.In the lowest body weight quartile, the BMI and body weight were significantly increased (0.4 kg/m, P = .038; 0.6 kg, P = .010, respectively) in patients with negative lactulose hydrogen breath tests after rifaximin treatment. However, there was no significant change in body weight in the other quartiles. Despite treatment with rifaximin for 12 weeks, there was no change in BMI or body weight in any group of patients with consistently positive lactulose hydrogen breath tests.Eradication of hydrogen formed by small intestinal bacterial overgrowth does not cause clinically significant changes in body weight.

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