Role of Potassium-competitive Acid Blockers in the Treatment of Gastric Acid-related Disorders

Owing to their superior pharmacokinetic and pharmacodynamic profiles, potassium-competitive acid blockers (P-CABs) score over proton pump inhibitors (PPIs) in the treatment of gastric acid-related disorders and may provide clinical benefit in the management of these conditions. Previous studies have compared P-CABs with PPIs for treatment of gastric acid-related disorders, and current data show that P-CABs are non-inferior to PPIs in the treatment of erosive esophagitis and as maintenance therapy. P-CABs are useful for effective healing and as maintenance medications in patients with severe esophagitis. These drugs also aid with healing of peptic ulcers and artificial ulcers secondary to gastric endoscopic submucosal dissection (ESD). Few studies have discussed prevention of delayed ulcer bleeding after gastric ESD and ulcers associated with long-term nonsteroidal anti-inflammatory drug administration. Well-controlled, large-scale prospective studies are warranted in future to compare P-CABs with PPIs

Accelerating and Supersonic Density Fluctuations in Coronal Hole Plumes: Signature of Nascent Solar Winds

Slow magnetoacoustic waves in a static background provide a seismological tool to probe the solar atmosphere in the analytic frame. By analyzing the spatiotemporal variation of the electron number density of plume structure in coronal holes above the limb for a given temperature, we find that the density perturbations accelerate with supersonic speeds in the distance range from 1.02 to 1.23 solar radii. We interpret them as slow magnetoacoustic waves propagating at about the sound speed with accelerating subsonic flows. The average sonic height of the subsonic flows is calculated to be 1.27 solar radii. The mass flux of the subsonic flows is estimated to be 44.1$\%$ relative to the global solar wind. Hence, the subsonic flow is likely to be the nascent solar wind. In other words, the evolution of the nascent solar wind in plumes at the low corona is quantified for the first time from imaging observations. Based on the interpretation, propagating density perturbations present in plumes could be used as a seismological probe of the gradually accelerating solar wind.Comment: Accepted for publication in ApJL, 11 pages, 5 figure

Actin Cytoskeleton and Golgi Involvement in Barley stripe mosaic virus Movement and Cell Wall Localization of Triple Gene Block Proteins.

Barley stripe mosaic virus (BSMV) induces massive actin filament thickening at the infection front of infected Nicotiana benthamiana leaves. To determine the mechanisms leading to actin remodeling, fluorescent protein fusions of the BSMV triple gene block (TGB) proteins were coexpressed in cells with the actin marker DsRed: Talin. TGB ectopic expression experiments revealed that TGB3 is a major elicitor of filament thickening, that TGB2 resulted in formation of intermediate DsRed:Talin filaments, and that TGB1 alone had no obvious effects on actin filament structure. Latrunculin B (LatB) treatments retarded BSMV cell-to-cell movement, disrupted actin filament organization, and dramatically decreased the proportion of paired TGB3 foci appearing at the cell wall (CW). BSMV infection of transgenic plants tagged with GFP-KDEL exhibited membrane proliferation and vesicle formation that were especially evident around the nucleus. Similar membrane proliferation occurred in plants expressing TGB2 and/or TGB3, and DsRed: Talin fluorescence in these plants colocalized with the ER vesicles. TGB3 also associated with the Golgi apparatus and overlapped with cortical vesicles appearing at the cell periphery. Brefeldin A treatments disrupted Golgi and also altered vesicles at the CW, but failed to interfere with TGB CW localization. Our results indicate that actin cytoskeleton interactions are important in BSMV cell-to-cell movement and for CW localization of TGB3

Proizvodnja antikomplementnih egzopolisaharida submerznim uzgojem gljive Flammulina velutipes

Seven species of basidiomycetes have been investigated for anti-complementary activity in hot water extracts and ethanol soluble fractions. Since Flammulina velutipes had the most potent activity, culture conditions for its mycelial growth were optimized to increase the production efficiency of anti-complementary exopolysaccharides. The optimal medium composition was (in g/L): galactose 15, sodium nitrate 5, glutamic acid 3, KH2PO4 2.5 and MgSO4·7H2O 0.6. Optimal production of anti-complementary activity was achieved at pH=3.5–5.5 and 25 °C. With these optimal medium and culture conditions, mycelial dry mass was maximized at 3.17 mg/mL after 6 days of cultivation in a 5-liter stirred-tank bioreactor, without pH control. The anti-complementary activity of exopolysaccharides increased sharply after 4 days of cultivation, and showed a high level at 5–6 days of cultivation. A periodate-labile carbohydrate moiety played a leading role in the anti-complementary activity exhibited by exopolysaccharide produced from F. velutipes. Results of tests on the anti-complementary activity in the absence of Ca²+ and immunoelectrophoresis indicated that the mode of complement activation by exopolysaccharide from F. velutipes is via both the classical and alternative pathways and that the activation degree is almost the same in each pathway.Istražena je antikomplementna aktivnost spojeva ekstrahiranih vrućom vodom i etanolom iz sedam vrsta gljiva stapčara. Optimirani su uvjeti uzgoja micelija gljive s najvećom aktivnosti, Flammulina velutipes, radi povećanja proizvodnje antikomplementnih egzopolisaharida. Optimalni sastav podloge bio je (u g/L): galaktoza 15, natrijev nitrat 5, glutamična kiselina 3, KH2PO4 2,5 i MgSO4·7H2O 0,6. Optimalna proizvodnja postignuta je pri pH=3,5-5,5 i 25 ºC. Pri tim uvjetima proizvedena je maksimalna količina suhe tvari od 3,17 mg/L nakon 6 dana uzgoja u bioreaktoru s miješalicom zapremnine 5 L, bez kontrole pH-vrijednosti. Antikomplementna aktivnost egzopolisaharida naglo se povećala nakon 4 dana, te je bila visoka nakon 5-6 dana uzgoja. Šećerni je ostatak, podložan djelovanju perjodata, glavni razlog antikomplementne aktivnosti egzopolisaharida gljive F. velutipes. Rezultati testiranja takve aktivnosti u odsutnosti Ca²+ iona i imunoelektroforeza upućuju na to da se komplementi egzopolisaharida iz F. velutipes aktiviraju klasičnim i alternativnim putem te da je stupanj aktivacije skoro jednak za oba puta

Culture supernatant of adipose stem cells can ameliorate allergic airway inflammation via recruitment of CD4+CD25+Foxp3 T cells

SDS-PAGE of supernatant after ASC cultivation. Comparison of protein composition of con sup (concentrated medium for ASCs cultivation) and ASC sup (concentrated culture supernatant after ASC cultivation for 3 days) using SDS-PAGE. Thirty micrograms of each sample was loaded into an SDS-PAGE gel. After electrophoresis, the gel was stained by Coomassie Blue (M molecular marker, arrow indicated extra proteins compared to control). (PPT 370 kb

Comparison of different machine learning algorithms to estimate liquid level for bioreactor management

Estimating the liquid level in an anaerobic digester can be disturbed by its closedness, bubbles and scum formation, and the inhomogeneity of the digestate. In our previous study, a soft-sensor approach using seven pressure meters has been proposed as an alternative for real-time liquid level estimation. Here, machine learning techniques were used to improve the estimation accuracy and optimize the number of sensors required in this approach. Four algorithms, multiple linear regression (MLR), artificial neural network (ANN), random forest (RF), and support vector machine (SVM) with radial basis function kernel were compared for this purpose. All models outperformed the cubic model developed in the previous study, among which the ANN and RF models performed the best. Variable importance analysis suggested that the pressure readings from the top (in the headspace) were the most significant, while the other pressure meters showed varying significance levels depending on the model type. The sensor that experienced both headspace and liquid phases depending on the level variation incurred a higher error than other sensors. The results showed that the ML techniques can provide an effective tool to estimate digester liquid levels by optimizing the number of sensors and reducing the error rate

Impact of vancomycin-induced changes in the intestinal microbiota on the pharmacokinetics of simvastatin

The pharmacokinetic (PK) properties of drugs are affected in several ways by interactions with microbiota. The aim of this study was to investigate the effects of oral vancomycin on the gut microbiota and, consequently, on the PKs of simvastatin. An open-label, single arm, sequential crossover study was conducted in six healthy Korean male subjects. After 6 days on a control diet, simvastatin 40 mg was orally administered to the subjects before and after 1 week of oral vancomycin treatment. Blood samples for PK analysis and fecal samples for metagenomic and metabolomic analyses were collected. After vancomycin treatment, the richness of microbiota considerably decreased, and the composition was altered. In particular, the relative abundance of Bacteroidetes decreased, whereas that of proteobacteria increased. In addition, changes in fecal metabolites, including D-glucuronic acid, were observed. However, systemic exposure of simvastatin was not changed whereas that of hydroxysimvastatin showed a tendency to increase. The relationship between the change of PKs of simvastatin and the change of gut microbiota and fecal metabolites were not clearly observed

Changes in the gut microbiome influence the hypoglycemic effect of metformin through the altered metabolism of branched-chain and nonessential amino acids

AIMS: Although metformin has been reported to affect the gut microbiome, the mechanism has not been fully determined. We explained the potential underlying mechanisms of metformin through a multiomics approach. METHODS: An open-label and single-arm clinical trial involving 20 healthy Korean was conducted. Serum glucose and insulin concentrations were measured, and stool samples were collected to analyze the microbiome. Untargeted metabolomic profiling of plasma, urine, and stool samples was performed by GC-TOF-MS. Network analysis was applied to infer the mechanism of the hypoglycemic effect of metformin. RESULTS: The relative abundances of Escherichia, Romboutsia, Intestinibacter, and Clostridium were changed by metformin treatment. Additionally, the relative abundances of metabolites, including carbohydrates, amino acids, and fatty acids, were changed. These changes were correlated with energy metabolism, gluconeogenesis, and branched-chain amino acid metabolism, which are major metabolic pathways related to the hypoglycemic effect. CONCLUSIONS: We observed that specific changes in metabolites may affect hypoglycemic effects through both pathways related to AMPK activation and microbial changes. Energy metabolism was mainly related to hypoglycemic effects. In particular, branched-chain amino acid metabolism and gluconeogenesis were related to microbial metabolites. Our results will help uncover the potential underlying mechanisms of metformin through AMPK and the microbiome

A Narrow Internal Auditory Canal with Duplication in a Patient with Congenital Sensorineural Hearing Loss

A narrow internal auditory canal (IAC) with duplication is a rare anomaly of the temporal bone. It is associated with congenital sensorineural hearing loss. Aplasia or hypoplasia of the vestibulocochlear nerve may cause the hearing loss. We present an unusual case of an isolated narrow IAC with duplication that was detected by a CT scan. In this case, the IAC was divided by a bony septum into an empty stenotic inferoposterior portion and a large anterosuperior portion containing the facial nerve that was clearly delineated on MRI

Optical repumping of triplet PP-states enhances magneto-optical trapping of ytterbium atoms

Radiative decay from the excited $^1P_1$ state to metastable $^3P_2$ and $^3P_0$ states is expected to limit attainable trapped atomic population in a magneto-optic trap of ytterbium (Yb) atoms. In experiments we have carried out with optical repumping of $^3P_{0,2}$ states to $^3P_1$, we observe enhancement of trapped atoms yield in the excited $^1P_1$ state. The individual decay rate to each metastable state is measured and the results show an excellent agreement with the theoretical values.Comment: 5 pages, 5 figure