Personalized probiotic strategy considering bowel habits: impacts on gut microbiota composition and alleviation of gastrointestinal symptoms via Consti-Biome and Sensi-Biome.

Personalized probiotic regimens, taking into account individual characteristics such as stool patterns, have the potential to alleviate gastrointestinal disorders and improve gut health while avoiding the variability exhibited among individuals by conventional probiotics. This study aimed to explore the efficacy of personalized probiotic interventions in managing distinct stool patterns (constipation and diarrhea) by investigating their impact on the gut microbiome and gastrointestinal symptoms using a prospective, randomized, double-blind, placebo-controlled clinical trial design. This research leverages the multi-strain probiotic formulas, Consti-Biome and Sensi-Biome, which have previously demonstrated efficacy in alleviating constipation and diarrhea symptoms, respectively. Improvement in clinical symptoms improvement and compositional changes in the gut microbiome were analyzed in participants with predominant constipation or diarrhea symptoms. Results indicate that tailored probiotics could improve constipation and diarrhea by promoting Erysipelotrichaceae and Lactobacillaceae, producers of short-chain fatty acids, and regulating inflammation and pain-associated taxa. These findings suggest the potential of tailored probiotic prescriptions and emphasize the need for personalized therapeutic approaches for digestive disorders. Clinical trial registration: https://cris.nih.go.kr/cris/index/index.do, identifier KCT0009111.

Multistrain Probiotics Alleviate Diarrhea by Modulating Microbiome-Derived Metabolites and Serotonin Pathway.

Diarrhea, a common gastrointestinal symptom in health problems, is highly associated with gut dysbiosis. The purpose of this study is to demonstrate the effect of multistrain probiotics (Sensi-Biome) on diarrhea from the perspective of the microbiome-neuron axis. Sensi-Biome (Lactiplantibacillus plantarum, Bifidobacterium animalis subsp. lactis, Lactobacillus acidophilus, Streptococcus thermophilus, Bifidobacterium bifidum, and Lactococcus lactis) was administered in a 4% acetic acid-induced diarrhea rat model at concentrations of 1 × 108 (G1), 1 × 109 (G2), and 1 × 1010 CFU/0.5 mL (G3). Diarrhea-related parameters, inflammation-related cytokines, and stool microbiota analysis by 16S rRNA were evaluated. A targeted and untargeted metabolomics approach was used to analyze the cecum samples using liquid chromatography and orbitrap mass spectrometry. The stool moisture content (p < 0.001), intestinal movement rate (p < 0.05), and pH (p < 0.05) were significantly recovered in G3. Serotonin levels were decreased in the multistrain probiotics groups. The inflammatory cytokines, serotonin, and tryptophan hydroxylase expression were improved in the Sensi-Biome groups. At the phylum level, Sensi-Biome showed the highest relative abundance of Firmicutes. Short-chain fatty acids including butyrate, iso-butyrate, propionate, and iso-valeric acid were significantly modified in the Sensi-Biome groups. Equol and oleamide were significantly improved in the multistrain probiotics groups. In conclusion, Sensi-Biome effectively controls diarrhea by modulating metabolites and the serotonin pathway.

Multi-strain probiotics alleviate loperamide-induced constipation by adjusting the microbiome, serotonin, and short-chain fatty acids in rats.

Constipation is one of the most common gastrointestinal (GI) disorders worldwide. The use of probiotics to improve constipation is well known. In this study, the effect on loperamide-induced constipation by intragastric administration of probiotics Consti-Biome mixed with SynBalance® SmilinGut (Lactobacillus plantarum PBS067, Lactobacillus rhamnosus LRH020, Bifidobacterium animalis subsp. lactis BL050; Roelmi HPC), L. plantarum UALp-05 (Chr. Hansen), Lactobacillus acidophilus DDS-1 (Chr. Hansen), and Streptococcus thermophilus CKDB027 (Chong Kun Dang Bio) to rats was evaluated. To induce constipation, 5 mg/kg loperamide was intraperitoneally administered twice a day for 7 days to all groups except the normal control group. After inducing constipation, Dulcolax-S tablets and multi-strain probiotics Consti-Biome were orally administered once a day for 14 days. The probiotics were administered 0.5 mL at concentrations of 2 × 108 CFU/mL (G1), 2 × 109 CFU/mL (G2), and 2 × 1010 CFU/mL (G3). Compared to the loperamide administration group (LOP), the multi-strain probiotics not only significantly increased the number of fecal pellets but also improved the GI transit rate. The mRNA expression levels of serotonin- and mucin-related genes in the colons that were treated with the probiotics were also significantly increased compared to levels in the LOP group. In addition, an increase in serotonin was observed in the colon. The cecum metabolites showed a different pattern between the probiotics-treated groups and the LOP group, and an increase in short-chain fatty acids was observed in the probiotic-treated groups. The abundances of the phylum Verrucomicrobia, the family Erysipelotrichaceae and the genus Akkermansia were increased in fecal samples of the probiotic-treated groups. Therefore, the multi-strain probiotics used in this experiment were thought to help alleviate LOP-induced constipation by altering the levels of short-chain fatty acids, serotonin, and mucin through improvement in the intestinal microflora.

Clinical and Lifestyle Determinants of Continuous Glucose Monitoring Metrics in Insulin-Treated Patients with Type 2 Diabetes Mellitus

Background@#There was limited evidence to evaluate the association between lifestyle habits and continuous glucose monitoring (CGM) metrics. Thus, we aimed to depict the behavioral and metabolic determinants of CGM metrics in insulin-treated patients with type 2 diabetes mellitus (T2DM). @*Methods@#This is a prospective observational study. We analyzed data from 122 insulin-treated patients with T2DM. Participants wore Dexcom G6 and Fitbit, and diet information was identified for 10 days. Multivariate-adjusted logistic regression analysis was performed for the simultaneous achievement of CGM-based targets, defined by the percentage of time in terms of hyper, hypoglycemia and glycemic variability (GV). Intake of macronutrients and fiber, step counts, sleep, postprandial C-peptide-to-glucose ratio (PCGR), information about glucose lowering medications and metabolic factors were added to the analyses. Additionally, we evaluated the impact of the distribution of energy and macronutrient during a day, and snack consumption on CGM metrics. @*Results@#Logistic regression analysis revealed that female, participants with high PCGR, low glycosylated hemoglobin (HbA1c) and daytime step count had a higher probability of achieving all targets based on CGM (odds ratios [95% confidence intervals] which were 0.24 [0.09 to 0.65], 1.34 [1.03 to 1.25], 0.95 [0.9 to 0.99], and 1.15 [1.03 to 1.29], respectively). And participants who ate snacks showed a shorter period of hyperglycemia and less GV compared to those without. @*Conclusion@#We confirmed that residual insulin secretion, daytime step count, HbA1c, and women were the most relevant determinants of adequate glycemic control in insulin-treated patients with T2DM. In addition, individuals with snack consumption were exposed to lower times of hyperglycemia and GV.

Spontaneous Deltoid Tear in Cuff Tear Arthropathy and Its Effect on the Outcome of Reverse Total Shoulder Arthroplasty: A Comparison Using Propensity Score Matching

Background@#Deltoid function critically influences the results of reverse total shoulder arthroplasty (RTSA), and spontaneous deltoid attrition tears are frequently detected in cuff tear arthropathy (CTA) patients; however, the clinical impacts of these tears on RTSA outcomes are undetermined. Our aim was to determine the effect of spontaneous deltoid attrition tears on postoperative outcomes after RTSA without an additional deltoid procedure. @*Methods@#Seventy-two patients who underwent RTSA for CTA with preoperative magnetic resonance imaging (MRI) and a minimum clinical follow-up of 1 year (mean, 32 months) were retrospectively reviewed in the study. Patients with a history of previous shoulder surgery or injury were excluded. The presence and location of deltoid attrition tears were determined in preoperative MRI. Propensity score matching (1:1) was performed to construct tear and no-tear groups. Finally, 21 patients, matched with respect to age, sex, hand dominance, symptom duration, medical comorbidity (obesity, diabetes mellitus, and coronary artery disease), Hamada grade, and implant type, were assigned to each group. Clinical outcomes (functional scores, isometric power, and range of motion) in the two groups were compared. @*Results@#Deltoid attrition tears were detected in 21 of the 72 enrolled cases (29.1%). Anterolateral deltoid was the most frequent location and no tear was detected in the posterior deltoid. The tear rate increased with disease severity (Hamada G2, 4.8%; G3, 23.8%; > G4, 71.4%). No pre- or postoperative clinical variables differed significantly between the tear and no tear groups. @*Conclusions@#Deltoid attrition tears were detected in 29% of CTA patients who underwent RTSA. The most common site was the anterolateral region and tear prevalence tended to increase with CTA progression. However, RTSA was found to provide satisfactory outcomes regardless of the presence of a deltoid attrition tear.

Hypersensitivity reactions to ibuprofen and acetaminophen: A report of case with literature review

The higher the use of nonsteroidal anti-inflammatory drugs (NSAIDs), the more reports of adverse drug reactions, especially in children than in adults. As patients with fever take several NSAIDs alternatively, suspected symptoms allergic to drugs with different chemical structures are also experienced in the clinical field. This is because it appears not only through immunological mechanisms but also through cross-intolerant reactions. Therefore, when hypersensitivity to one or more NSAIDs is present, it is important to distinguish between the 2 mechanisms for future treatment planning. Although it is difficult to distinguish between the 2 mechanisms by clinical history, drug provocation test with aspirin is helpful in diagnosis. A 4-year-old patient who had urticaria/angioedema and shortness of breath after taking ibuprofen and acetaminophen visited Kangwon National University Hospital for a treatment plan using antipyretics and/or analgegics forward. We propose a diagnosis and treatment protocol for such patients with a brief literature review.

Characteristics and Treatment Outcomes of Transition among Patients with Inflammatory Bowel Disease

Purpose@#This study aimed to assess disease characteristics and outcomes of transition in patient care among adolescent patients with inflammatory bowel disease (IBD). @*Materials and Methods@#Data from patients younger than 18 years who were diagnosed with IBD (Crohn’s disease, ulcerative colitis, or intestinal Behçet’s disease) were investigated. We categorized the patients into two groups: transition IBD group (Group A, diagnosed in pediatric care followed by transfer to/attendance in adult IBD care) and non-transition group (Group B, diagnosed and followed up in pediatric care or adult IBD care without transfer). @*Results@#Data from a total of 242 patients [Group A (n=29, 12.0%), Group B (n=213, 88.0%)] were analyzed. A significantly higher number of patients was diagnosed at an earlier age in Group A than in Group B (p<0.001). Group A patients had more severe disease in terms of number of disease flare ups (p=0.011) and frequency of bowel-related complications (p<0.001). Multiple linear regression analysis showed that Group B patients had more medical non-compliance than Group A patients (β=2.31, p=0.018). After transition, IBD-related admission frequency, emergency admission frequency, disease flare frequency, and medical non-compliance were significantly improved. @*Conclusion@#The transition IBD group had more severe disease. Medical non-compliance was lower in the transition IBD group.Clinical outcomes improved after transition.

High-Intensity Focused Ultrasound Therapy Versus Coblation for the Treatment of Inferior Turbinate Hypertrophy: A Clinical Trial

Objectives@#. To compare the efficacy and safety of high-intensity focused ultrasound (HIFU) therapy with coblation for the treatment of inferior turbinate hypertrophy (ITH). @*Methods@#. In this randomized controlled clinical trial, 20 patients underwent inferior turbinate surgery, which consisted of either HIFU or coblation therapy. Efficacy, safety, and tolerability were evaluated by subjective symptom scores, acoustic rhinometry, and nasal endoscopy. @*Results@#. The modified nasal obstruction symptom evaluation (NOSE) score and nasal obstruction visual analog scale (NO-VAS) significantly decreased in both groups 12 weeks postoperatively. The between-group differences in the evaluation scores were not statistically significant. On nasal endoscopy, the HIFU patients showed improvements in mucosal swelling sooner than the patients undergoing coblation therapy. Nasal crusting significantly increased in the patients undergoing coblation compared to the patients undergoing HIFU therapy until postoperative week 4. Mucosal preservation was superior in the HIFU patients. Although HIFU was less painful than coblation therapy during the procedure, the difference was not significant (4.9 vs. 6.3, P=0.143). The difference in global satisfaction between the two groups was not statistically significant, although satisfaction was slightly higher among the HIFU patients than among the coblation patients (4.6 vs. 4.1, P=0.393). @*Conclusion@#. HIFU provided results similar to those of coblation therapy for patients with nasal obstruction due to ITH, but HIFU therapy caused less discomfort during the procedure. HIFU therapy appears to be a good noninvasive alternative to the current surgical modalities for ITH.

Total Knee Replacement After Arthroscopic Meniscectomy in Knee Osteoarthritis: A Nationwide Population-Based Cohort Study

Background@#Recent studies raise concerns that arthroscopic meniscectomy (AM) for degenerative tear may be detrimental to the maintenance of the joint structure. This study was performed to examine the rate of total knee replacement (TKR) among patients with knee osteoarthritis (OA) who underwent AM for meniscal tears and compare this rate with those who did not. @*Methods@#A retrospective cohort study was conducted using the National Health Insurance Database of South Korea. Among knee OA patients aged 50–79, those who were treated with AM due to meniscal damage from 2007 to 2009 were selected as the AM group while those not treated with AM despite the presence of meniscal damage were selected as control group. Both were matched based on a propensity score and followed-up until the earliest occurrence of:TKR, death, or 10 years. Cox proportional hazards models were used to compare the outcome. @*Results@#A total of 36,974 patients were included in AM groups and non-AM group after 1:1 matching. TKR occurred in 9.62% and 7.64% in AM and non-AM groups with the average duration after meniscectomy of 5.88 ± 2.77 and 5.50 ± 2.94 years, respectively. After adjustment for baseline confounders, the TKR rate in the AM group was calculated to be 25% higher than that in the non-AM group (subdistribution hazard ratio, 1.25; 95% confidence interval, 1.16–1.34). The mortality rate was 5.20%, which did not significantly differ between groups. @*Conclusion@#OA patients who underwent AM for the meniscal injury had higher incidence of TKR up to 10 years of follow-up than the non-operated group. The greater TKR utilization observed in patients undergoing AM merits caution when treating OA patients with meniscal injury.

Sleep Duration and the Risk of Type 2 Diabetes: A Community-Based Cohort Study with a 16-Year Follow-up

Background@#We aimed to investigate the moderating effects of obesity, age, and sex on the association between sleep duration and the development of diabetes in Asians. @*Methods@#We analyzed data from a cohort of the Korean Genome and Epidemiology Study conducted from 2001 to 2020. After excluding shift workers and those with diabetes at baseline, 7,407 participants were stratified into three groups according to sleep duration: ≤5 hoursight, >5 to 7 hoursight (reference), and >7 hoursight. The Cox proportional hazards analyses were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for incident type 2 diabetes mellitus (T2DM). Subgroup analyses were performed according to obesity, age, and sex. @*Results@#During 16 years of follow-up, 2,024 cases of T2DM were identified. Individuals who slept ≤5 hight had a higher risk of incident diabetes than the reference group (HR, 1.17; 95% CI, 1.02 to 1.33). The subgroup analysis observed a valid interaction with sleep duration only for obesity. A higher risk of T2DM was observed in the ≤5 hoursight group in non-obese individuals, men, and those aged 7 hoursight group in obese individuals (HRs were 1.34 [95% CI, 1.11 to 1.61], 1.22 [95% CI, 1 to 1.49], and 1.18 [95% CI, 1.01 to 1.39], respectively). @*Conclusion@#This study confirmed the effect of sleep deprivation on the risk of T2DM throughout the 16-year follow-up period. This impact was confined to non-obese or young individuals and men. We observed a significant interaction between sleep duration and obesity.

In Situ Scanning Electron Microscopy Analysis of the Interfacial Failure of Oxide Scales on Stainless Steels and Its Effect on Sticking during Hot Rolling.

Despite various strategies to address sticking failure in stainless steels (STSs), difficulties in understanding its fundamental mechanisms hinder precise solutions during STS fabrication. This study investigated the effect of chromium (Cr) content on the microstructures and failure modes of oxide scales under a tensile load, simulating the hot-rolling process. The dynamic, real-time behavior of crack initiation, propagation, and interfacial delamination in the oxide scales under tension was analyzed using an in situ scanning electron microscopy (SEM) tensile test. With a high Cr content, iron (Fe) oxide and chromium(III) oxide (Cr2O3) form a layered structure, which is delaminated along the interfaces between the thin Cr2O3 layer and the bulk after perpendicular cracking. The saturated crack densities obtained from in situ SEM provide interfacial strength, while the elastic modulus and hardness obtained from nanoindentation provide vertical fracture strength. In combination with an ex situ elemental image analysis, the in situ SEM results reveal three different failure modes of the four different STSs. The results confirm that sticking failure is more likely to occur as the Cr content increases.

Metastable hexagonal close-packed palladium hydride in liquid cell TEM.

Metastable phases-kinetically favoured structures-are ubiquitous in nature1,2. Rather than forming thermodynamically stable ground-state structures, crystals grown from high-energy precursors often initially adopt metastable structures depending on the initial conditions, such as temperature, pressure or crystal size1,3,4. As the crystals grow further, they typically undergo a series of transformations from metastable phases to lower-energy and ultimately energetically stable phases1,3,4. Metastable phases sometimes exhibit superior physicochemical properties and, hence, the discovery and synthesis of new metastable phases are promising avenues for innovations in materials science1,5. However, the search for metastable materials has mainly been heuristic, performed on the basis of experiences, intuition or even speculative predictions, namely 'rules of thumb'. This limitation necessitates the advent of a new paradigm to discover new metastable phases based on rational design. Such a design rule is embodied in the discovery of a metastable hexagonal close-packed (hcp) palladium hydride (PdHx) synthesized in a liquid cell transmission electron microscope. The metastable hcp structure is stabilized through a unique interplay between the precursor concentrations in the solution: a sufficient supply of hydrogen (H) favours the hcp structure on the subnanometre scale, and an insufficient supply of Pd inhibits further growth and subsequent transition towards the thermodynamically stable face-centred cubic structure. These findings provide thermodynamic insights into metastability engineering strategies that can be deployed to discover new metastable phases.

Identification of Stem Cell Related Gene Expression from the Osteosarcoma Cell Core Side

Osteosarcoma is the most frequent primary malignant bone tumor with higher incidences in children and adolescents. Despite clinical evolutions, patients with osteosacoma have had a poor prognosis. There has been increasing evidence that cancer is a stem cell disease. This study sought to isolate and characterize cancer stem cells from human osteosarcoma with relevant literature reviews. Here we show that the emerging evidence suggests osteosarcoma should be regarded as a differentiation disease such as stem cell disease. Two human osteosarcoma cell lines were cultured in non-adherent culture conditions as sarcospheres. Sarcospheres were observed using histomorphology and alkaline phosphatase (ALP) staining. Expression of the embryonic stem cell marker was analyzed with use of reverse transcriptase-PCR. Sarcospheres could be reproduced consistently throughout multiple passages and produced adherent osteosarcoma cell cultures. Expression of stem cell-associated genes such as those encoding Nanog, octamer-binding transcription factor 3/4, sex determining region Y box 2 , c-Myc and ALP indicated pluripotent stem-like cells. These results support the extension of the cancer stem cell theory to include osteosarcoma. Understanding the cancer stem cell derived from human osteosarcoma could lead to the evolution of diagnosis and treatment for osteosarcoma patients.

Sestrin2 Regulates Beneficial β3-Adrenergic Receptor-Mediated Effects Observed in Inguinal White Adipose Tissue and Soleus Muscle

Sestrin2, a well-known adenosine monophosphate-activated protein kinase (AMPK) regulator, plays a protective role against metabolic stress. The β3-adrenergic receptor (β3AR) induces fat browning and inhibits muscle atrophy in an AMPK-dependent manner. However, no prior research has examined the relationship of sestrin2 with β3AR in body composition changes. In this study, CL 316,243 (CL), a β3AR agonist, was administered to wild-type and sestrin2-knockout (KO) mice for 2 weeks, and fat and muscle tissues were harvested. CL induced AMPK phosphorylation, expression of brown-fat markers, and mitochondrial biogenesis, which resulted in the reduction of lipid droplet size in inguinal white adipose tissue (iWAT). These effects were not observed in sestrin2-KO mice. In CL-treated soleus muscle, sestrin2-KO was related to decreased myogenic gene expression and increased levels of muscle atrophy-related molecules. Our results suggest that sestrin2 is associated with beneficial β3AR-mediated changes in body composition, especially in iWAT and in the soleus.

Predicting Aspiration Using the Functions of Production and Quality of Voice in Dysphagic Patients / 대한연하장애학회지

Objective@#This study aims to identify the usefulness of voice function in early screening for dysphagia. We sought to evaluate if screening tests through the functions of production and quality of voice were correlated with aspiration in dysphagic patients. @*Methods@#This study involved 55 participants who were referred to videofluoroscopic swallowing study (VFSS) for suspected dysphagia. Blinded examiners rated the voice production function (MVI, MPT) using a portable instrument and evaluated the quality of voice (jitter, shimmer, NHR) using Visi-pitch. Swallowing functions were also evaluated by utilizing the penetration-aspiration scale (PAS), American Speech-Language-Hearing Association (ASHA), National Outcome Measurement System (NOMS) swallowing scale and VDS. The patients were divided into two groups, the penetration group, and the aspiration group according to the PAS score. The difference in variables was analyzed using the Mann-Whitney U test between the two groups. The relationship between voice parameters and swallow-related parameters was determined using the Spearman correlation coefficient. In addition, the cut-off, sensitivity, and specificity of meaningful variables in silent aspiration were analyzed using the ROC curve analysis. @*Results@#The functions of production and quality of voice were found to be significantly different between the penetration and aspiration groups (P＜.000). The PAS score was correlated with all parameters of the functions of production and quality of voice (P＜.001). VDS was correlated with MVI, ASHA was correlated with MVI, and Shimmer (P＜.001). The meaningful variables for silent aspiration were jitter and shimmer. @*Conclusion@#Through a clinical screening test, it may be possible to predict the difference between penetration and aspiration through the functions of production and quality of voice.

Preoperative Meniscus: Pitfalls and Traps to Avoid

To accurately interpret knee MRI, it is important not only to know the basic meniscal anatomy but also to distinguish it from that under pathological conditions. Thus, it would be helpful to know the normal meniscus variants (false positives) that could be mistaken for meniscal tears, and tears that could easily be missed and incorrectly diagnosed as normal (false negatives).False positives include synovial recesses, meniscal flounce, the relationship between the popliteus tendon and lateral meniscus, transverse ligament, the anterior root of the meniscus, and meniscofemoral ligament. False negatives include focal radial tears, flap tears, posterior root tears, meniscocapsular separation, and discoid meniscal tears. In this pictorial essay, we reviewed the imaging data obtained in the aforementioned cases.

The Effect of COVID–19 on Pediatric Intussusception: A Retrospective Study of a Single Center in South Korea with 10–Year Experience

Purpose@#To evaluate the effect of the emergence of coronavirus disease-19 (COVID-19) on pediatric intussusception. @*Materials and Methods@#Patients (< 18 years) who were diagnosed with intussusception and received enema reduction from 2011 to 2020 were included. We reviewed the demographics, yearly/monthly/seasonal incidence of intussusception, method and failure rate of enema reduction, recurrence rate of intussusception, surgical record, and pathologic report. Subsequently, we investigated the differences in mean age, failure rate of enema reduction, and recurrence rate of intussusception between the cases in 2020 and those in the period from 2011 to 2019. @*Results@#A total of 859 enema reductions were performed during the past decade, more in males and in the age < 1 year (mean age, 22.2 months). The yearly incidence was highest in 2014 and lowest in 2020, and the monthly incidence was highest on December and September. The cases in 2020 (n = 27) had a lower mean age (18.1 months vs. 22.8 months), higher failure rate of enema reduction (7.4% vs. 2.4%), and higher recurrence rate of intussusception (14.8% vs 7.3%) compared with those that occurred between 2011 and 2019 (n = 832). However, these results did not show statistical significance (p = 0.07, p = 0.15, p = 0.14, respectively). @*Conclusion@#With the emergence of COVID-19, the number of enema reductions was remarkably decreased with a lower mean age, higher failure rate, and higher recurrence rate.

GPR40 Agonism Modulates Inflammatory Reactions in Vascular Endothelial Cells

Endothelial dysfunction is strongly linked with inflammatory responses, which can impact cardiovascular disease. Recently, G protein-coupled receptor 40 (GPR40) has been investigated as a modulator of metabolic stress; however, the function of GPR40 in vascular endothelial cells has not been reported. We analyzed whether treatment of GPR40-specific agonists modulated the inflammatory responses in human umbilical vein endothelial cells (HUVECs). Treatment with LY2922470, a GPR40 agonist, significantly reduced lipopolysaccharide (LPS)-mediated nuclear factor-kappa B (NF-κB) phosphorylation and movement into the nucleus from the cytosol. However, treatment with another GPR40 agonist, TAK875, did not inhibit LPS-induced NF-κB activation. LPS treatment induced expression of adhesion molecules vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) and attachment of THP-1 cells to HUVECs, which were all decreased by LY2922470 but not TAK875. Our results showed that ligand-dependent agonism of GPR40 is a promising therapeutic target for overcoming inflammatory reactions in the endothelium.

Design of V-Substituted TiFe-Based Alloy for Target Pressure Range and Easy Activation.

Titanium iron (TiFe) alloy is a room-temperature hydrogen-storage material, and it absorbs hydrogen via a two-step process to form TiFeH and then TiFeH2. The effect of V addition in TiFe alloy was recently elucidated. The V substitution for Ti sublattice lowers P2/P1 ratio, where P1 and P2 are the equilibrium plateau pressure for TiFe/TiFeH and TiFeH/TiFeH2, respectively, and thus restricts the two-step hydrogenation within a narrow pressure range. The focus of the present investigation was to optimize the V content such that maximum usable storage capacity can be achieved for the target pressure range: 1 MPa for absorption and 0.1 MPa for desorption. The effect of V substitution at selective Ti or Fe sublattices was closely analyzed, and the alloy composition Ti46Fe47.5V6.5 displayed the best performance with ca. 1.5 wt.% of usable capacity within the target pressure range. At the same time, another issue in TiFe-based alloys, which is a difficulty in activation at room temperature, was solved by Ce addition. It was shown that 3 wt.% Ce dispersion in TiFe alloy imparted to it easy room-temperature (RT) activation properties.

Association Between Visit-to-Visit Fasting Plasma Glucose Variability and Osteoporotic Fractures in Nondiabetic Subjects.

CONTEXT: Although long-term glucose variability has been reported to be a risk factor associated with osteoporosis, there have been no previous studies between the relationship of glucose variability and fractures in people without diabetes. OBJECTIVE: We assessed visit-to-visit variations in fasting plasma glucose (FPG) as a prognostic factor in predicting osteoporotic fractures in individuals without diabetes. METHODS: Using a nationwide cohort database, we examined the impact of FPG on the development of osteoporotic fractures in men and women (aged ≥50 years). The primary outcomes were the number of total fractures and vertebral fractures. FPG variability was measured using standard deviation (FPG-SD), coefficient of variation (FPG-CV), and variability independent of the mean (FPG-VIM). RESULTS: Of the 92 929 participants, 5262 (5.7%) developed osteoporotic fractures during the mean follow-up of 8.4 years. Individuals in the highest quartile of FPG-SD showed an 11% and 16% increase in risk of total and vertebral fractures, respectively, compared with those in the lowest quartile after adjustment for mean FPG and other risk factors. Analyses using FPG-CV and FPG-VIM demonstrated similar results. Subgroup analyses and sensitivity analyses to explore potential heterogeneity showed consistent results. CONCLUSION: FPG variability may be a novel risk factor for osteoporotic fractures independent of risk factors in the general population without diabetes.