UNASSIGNED: Overprescribing of acid suppressants is a common phenomenon in human and small animal patients, leading to potential deleterious gastrointestinal (GI) and non-GI consequences. The impact of consensus statements on veterinary prescribing habits in clinical practice have not been fully evaluated. This study aimed to compare the prescribing habits of the proton pump inhibitor (PPI), omeprazole, in dogs in an academic veterinary teaching hospital before and after the publication of the American College of Veterinary Internal Medicine (ACVIM) consensus statement on rational use of gastrointestinal protectants.
UNASSIGNED: Evaluation of the prescribing habits of omeprazole in dogs during the years 2017 and 2021 was retrospectively compared. These years were selected to reflect a 12-month period prior to and following the publication of the consensus statement. One hundred dogs from each year were randomly selected. Dose, frequency of administration, duration of treatment, concurrent prescription of more than one gastroprotectant and indications for prescribing omeprazole were analyzed.
UNASSIGNED: A significant increase in the cases that received omeprazole q12h (p < 0.0001) or that underwent a tapering dose after ≥4 week-therapy (p > 0.0001) was detected after the publication of the 2018 ACVIM consensus statement. Considering the indications, there was also a significant increase in the appropriate prescription of omeprazole in the second compared to the first period of study (p < 0.0001). Fifteen of 16 clinicians (94%) involved in the prescription of omeprazole indicated that their reading of the consensus statement had changed their clinical practice regarding PPI administration in dogs.
UNASSIGNED: These results support the beneficial impact of the ACVIM consensus statement on the judicious prescribing of omeprazole in an academic veterinary hospital. These results should not be extrapolated to first-opinion veterinary practices, and further efforts should be made to ensure that PPIs are prescribed prudently with a clear indication and regular review of the appropriateness of continued administration to minimize possible risks and adverse drug interactions.

Adherent-invasive Escherichia coli (AIEC) strain LF82, isolated from patients with Crohn\'s disease, invades gut epithelial cells, and replicates in macrophages contributing to chronic inflammation. In this study, we found that RstAB contributing to the colonization of LF82 in a mouse model of chronic colitis by promoting bacterial replication in macrophages. By comparing the transcriptomes of rstAB mutant- and wild-type when infected macrophages, 83 significant differentially expressed genes in LF82 were identified. And we identified two possible RstA target genes (csgD and asr) among the differentially expressed genes. The electrophoretic mobility shift assay and quantitative real-time PCR confirmed that RstA binds to the promoters of csgD and asr and activates their expression. csgD deletion attenuated LF82 intracellular biofilm formation, and asr deletion reduced acid tolerance compared with the wild-type. Acidic pH was shown by quantitative real-time PCR to be the signal sensed by RstAB to activate the expression of csgD and asr. We uncovered a signal transduction pathway whereby LF82, in response to the acidic environment within macrophages, activates transcription of the csgD to promote biofilm formation, and activates transcription of the asr to promote acid tolerance, promoting its replication within macrophages and colonization of the intestine. This finding deepens our understanding of the LF82 replication regulation mechanism in macrophages and offers new perspectives for further studies on AIEC virulence mechanisms.

暂无摘要。

BACKGROUND: Caustic ingestions are relatively uncommon, but remain a significant source of morbidity. Patients with caustic injury often undergo an urgent EGD, although it is not clear if an EGD is routinely needed in an asymptomatic patient. The study has two primary objectives; 1) to determine the utility of routine EGD in asymptomatic suicidal caustic ingestions; 2) to determine if asymptomatic unintentional acidic ingestions can be managed with observation alone, similar to basic ingestions.
METHODS: This retrospective study, which took place at 14 hospitals in three countries evaluated all patients who presented with a caustic ingestion between 2014-2020. The presence of symptoms and esophageal injury, demographic information, pH of ingested substance, reason for the ingestion, and outcome were recorded.
RESULTS: 409 patients were identified; 203 (46.9%) were male. The median (IQR) age was 18 (4-31) years; overall range 10 months to 78 years. Suicidal ingestions accounted for 155 (37.9%) of cases. Dysphagia or dysphonia were more likely in those with significant esophageal injury compared to those without (59.3% vs. 12.6% respectively; OR 10.1; 95% CI 4.43-23.1). Among 27 patients with significant esophageal injury, 48% were found in suicidal patients, compared with 51.9% in non-suicidal patients (p = NS). On multivariate regression, there was no difference in the rate of significant esophageal injury among suicidal vs. non suicidal patients (aOR 1.55; p = 0.45, 95% CI 0.45-5.33). Most ingestions involved basic substances (332/409; 81.2%). Unknown or mixed ingestions accounted for 25 (6.11%) of the ingestions. Significant esophageal burns were found in 6/52 (11.5%) of acid ingestions, compared with 21/332 (6.3%) of basic ingestions. Of the 42 cases of acidic ingestions without dysphagia or odynophagia, 2 (4.8%; 0.58-16.1%) had significant esophageal burns, compared with 9 (3.2%; 95% CI 1.4-5.9%) of the 284 basic ingestions; p = 0.64). On multivariate logistic regression, patients with acidic ingestions were not more likely to experience a significant burn (aOR 1.7; p = 0.11, 95% CI 0.9-3.1) compared to those with basic ingestions. No patient with significant esophageal burns was asymptomatic.
CONCLUSIONS: In this study, there was no statistical differences in the rates of significant burns between acidic and basic caustic ingestions. There were no significant esophageal injuries noted among asymptomatic patients.

The purpose of this review and commentary was to provide an historical and evidence-based account of organic acids and the biochemical and organic chemistry evidence for why cells do not produce metabolites that are acids. The scientific study of acids has a long history dating to the 16th and 17th centuries, and the definition of an acid was proposed in 1884 as a molecule that when in an aqueous solution releases a hydrogen ion (H+). There are three common ionizable functional groups for molecules classified as acids: 1) the carboxyl group, 2) the phosphoryl group and 3) the amine group. The propensity by which a cation will associate or dissociate with a negatively charged atom is quantified by the equilibrium constant (Keq) of the dissociation constant (Kd) of the ionization (Keq ​= ​Kd), which for lactic acid (HLa) vs. lactate (La-) is expressed as: Keq=Kd=[H+][La-][HLa]= 4 677.351 4 (ionic strength ​= ​0.01 Mol⋅L-1, T ​= ​25 ​°C). The negative log10 of the dissociation pKd reveals the pH at which half of the molecules are ionized, which for HLa ​= ​3.67. Thus, knowing the pKd and the pH of the solution at question will reveal the extent of the ionization vs. acidification of molecules that are classified as acids.

The kidney plays a crucial role in acid-base homeostasis. In the distal nephron, α-intercalated cells contribute to urinary acid (H+) secretion and β-intercalated cells accomplish urinary base (HCO3-) secretion. β-intercalated cells regulate the acid base status through modulation of the apical Cl-/HCO3- exchanger pendrin (SLC26A4) activity. In this review, we summarize and discuss our current knowledge of the physiological role of the renal transporter AE4 (SLC4A9). The AE4, as cation-dependent Cl-/HCO3- exchanger, is exclusively expressed in the basolateral membrane of β-intercalated cells and is essential for the sensing of metabolic acid-base disturbances in mice, but not for renal sodium reabsorption and plasma volume control. Potential intracellular signaling pathways are discussed that might link basolateral acid-base sensing through the AE4 to apical pendrin activity.

It is a challenge to characterize the acid properties of microporous materials in either experiments or theory. This study presents the crystal structure, acid site, acid strength, proton siting, and IR spectra of HSAPO-34 from the SCAN + rVV10 method. The results indicate: the crystal structures of various acid sites of HSAPO-34 deviate from the space group of R3¯; the acid strength inferred from the DPE value likely decreases with the proton binding sites at O(2), O(4), O(1),and O(3), contrary to the stability order in view of the internal energy; the calculated ensemble-averaged DPE is about 1525 kJ/mol at 673.15 K; and the proton siting and the proton distribution are distinctly influenced by the temperature: at low temperatures, the proton is predominantly located at O(3), while it prefers O(2) at high temperatures, and the proton at O(4) assumedly has the least distribution at 273.15-773.15 K. In line with the neutron diffraction experiment, a correction factor of 0.979 is needed to correct for the calculated hydroxyl stretching vibration (ν(O-H)) of HSAPO-34. It seems that the SCAN meta-GGA method, compensating for some drawbacks of the GGA method, could provide satisfying results regarding the acid properties of HSAPO-34.

The apricot (Prunus armeniaca L.) is a fruit that belongs to the Rosaceae family; it has a unique flavor and is of important economic and nutritional value. The composition and content of soluble sugars and organic acids in fruit are key factors in determining the flavor quality. However, the molecular mechanism of sugar and acid accumulation in apricots remains unclear. We measured sucrose, fructose, glucose, sorbitol, starch, malate, citric acid, titratable acid, and pH, and investigated the transcriptome profiles of three apricots (the high-sugar cultivar \'Shushanggan\', common-sugar cultivar \'Sungold\', and low-sugar cultivar \'F43\') at three distinct developmental phases. The findings indicated that \'Shushanggan\' accumulates a greater amount of sucrose, glucose, fructose, and sorbitol, and less citric acid and titratable acid, resulting in a better flavor; \'Sungold\' mainly accumulates more sucrose and less citric acid and starch for the second flavor; and \'F43\' mainly accumulates more titratable acid, citric acid, and starch for a lesser degree of sweetness. We investigated the DEGs associated with the starch and sucrose metabolism pathways, citrate cycle pathway, glycolysis pathway, and a handful of sugar transporter proteins, which were considered to be important regulators of sugar and acid accumulation. Additionally, an analysis of the co-expression network of weighted genes unveiled a robust correlation between the brown module and sucrose, glucose, and fructose, with VIP being identified as a hub gene that interacted with four sugar transporter proteins (SLC35B3, SLC32A, SLC2A8, and SLC2A13), as well as three structural genes for sugar and acid metabolism (MUR3, E3.2.1.67, and CSLD). Furthermore, we found some lncRNAs and miRNAs that regulate these genes. Our findings provide clues to the functional genes related to sugar metabolism, and lay the foundation for the selection and cultivation of high-sugar apricots in the future.

Living organisms rely on pH levels for a multitude of crucial biological processes, such as the digestion of food and the facilitation of enzymatic reactions. Among these organisms, animals, including insects, possess specialized taste organs that enable them to discern between acidic and alkaline substances present in their food sources. This ability is vital, as the pH of these compounds directly influences both the nutritional value and the overall health impact of the ingested substances. In response to the various chemical properties of naturally occurring compounds, insects have evolved peripheral taste organs. These sensory structures play a pivotal role in identifying and distinguishing between nourishing and potentially harmful foods. In this concise review, we aim to provide an in-depth examination of the molecular mechanisms governing pH-dependent taste responses, encompassing both acidic and alkaline stimuli, within the peripheral taste organs of the fruit fly, Drosophila melanogaster, drawing insights from a comprehensive analysis of existing research articles.

The purpose of this study was to investigate the effects of puffing, acid, and high hydrostatic pressure (HHP) treatments on the ginsenoside profile and antioxidant capacity of mountain-cultivated Panax ginseng (MCPG) before and after treatments. Puffing and HHP treatments decreased extraction yield and increased crude saponin content. The combination of puffing and HHP treatment showed significantly higher crude saponin content than each single treatment. Puffing treatment showed the highest ginsenoside conversion compared with HHP and acid treatments. Significant ginsenoside conversion was not observed in HHP treatment but was in acid treatment. When the puffing and acid treatments were combined, Rg3 and compound K content (1.31 mg and 10.25 mg) was significantly higher than that of the control (0.13 mg and 0.16 mg) and acid treatment (0.27 mg and 0.76 mg). No synergistic effect was observed between acid and HHP treatments. In the case of functional properties, the puffing treatment showed a significant increase in TFC (29.6%), TPC (1072%), and DPPH radical scavenging capacity (2132.9%) compared to the control, while acid and HHP combined treatments did not significantly increase; therefore, the synergistic effects of HHP/puffing and acid/puffing treatments were observed in crude saponin content and ginsenoside conversion, respectively. Consequently, puffing combined with acid or HHP treatments may provide new ways to produce high-value-added MCPG with a higher content of Rg3 and compound K or crude saponin compared to untreated MCPG.