Summary
Background
Proton pump inhibitors (PPIs) are widely used for the treatment of acid‐related diseases. Vonoprazan is a member of a new class of acid suppressants; potassium‐competitive acid ...blockers. Vonoprazan may thus be an alternative to PPIs.
Aim
To evaluate efficacy, rapidity and duration of acid‐inhibitory effects of vonoprazan vs. two control PPIs, esomeprazole and rabeprazole, in 20 healthy Japanese adult male volunteers with CYP2C19 extensive metaboliser genotype.
Methods
In this randomised, open‐label, two‐period cross‐over study, vonoprazan 20 mg and esomeprazole 20 mg (Study V vs. E) or rabeprazole 10 mg (Study V vs. R) were orally administered daily for 7 days. Primary pharmacodynamic endpoint was gastric pH over 24 h measured as percentage of time pH ≥3, ≥4 and ≥5 (pH holding time ratios; HTRs) and mean gastric pH.
Results
Acid‐inhibitory effect (pH4 HTR) of vonoprazan was significantly greater than that of esomeprazole or rabeprazole on both Days 1 and 7; Day 7 difference in pH4 HTR for vonoprazan vs. esomeprazole was 24.6% 95% confidence interval (CI): 16.2–33.1 and for vonoprazan vs. rabeprazole 28.8% 95% CI: 17.2–40.4. The Day 1 to Day 7 ratio of 24‐h pH4 HTRs was >0.8 for vonoprazan, compared with 0.370 for esomeprazole and 0.393 for rabeprazole. Vonoprazan was generally well tolerated. One vonoprazan subject withdrew due to a rash which resolved after discontinuation.
Conclusions
This study demonstrated a more rapid and sustained acid‐inhibitory effect of vonoprazan 20 mg vs. esomeprazole 20 mg or rabeprazole 10 mg. Therefore, vonoprazan may be a potentially new treatment for acid‐related diseases.
Background
Recurrent abdominal pain is a common and costly health‐care problem attributed, in part, to visceral hypersensitivity. Increasing evidence suggests that gut bacteria contribute to ...abdominal pain perception by modulating the microbiome‐gut‐brain axis. However, specific microbial signals remain poorly defined. γ‐aminobutyric acid (GABA) is a principal inhibitory neurotransmitter and a key regulator of abdominal and central pain perception from peripheral afferent neurons. Although gut bacteria are reported to produce GABA, it is not known whether the microbial‐derived neurotransmitter modulates abdominal pain.
Methods
To investigate the potential analgesic effects of microbial GABA, we performed daily oral administration of a specific Bifidobacterium strain (B. dentiumATCC 27678) in a rat fecal retention model of visceral hypersensitivity, and subsequently evaluated pain responses.
Key Results
We demonstrate that commensal Bifidobacterium dentium produces GABA via enzymatic decarboxylation of glutamate by GadB. Daily oral administration of this specific Bifidobacterium (but not a gadB deficient) strain modulated sensory neuron activity in a rat fecal retention model of visceral hypersensitivity.
Conclusions & Inferences
The functional significance of microbial‐derived GABA was demonstrated by gadB‐dependent desensitization of colonic afferents in a murine model of visceral hypersensitivity. Visceral pain modulation represents another potential health benefit attributed to bifidobacteria and other GABA‐producing species of the intestinal microbiome. Targeting GABAergic signals along this microbiome‐gut‐brain axis represents a new approach for the treatment of abdominal pain.
Increasing evidence suggests that gut bacteria contribute to abdominal pain perception by modulating the microbiome‐gut‐brain axis. Here, we demonstrate that commensal Bifidobacterium dentium produces GABA via enzymatic decarboxylation of glutamate by GadB. Daily oral administration of this specific Bifidobacterium (but not a gadB deficient) strain modulated sensory neuron activity in a rat fecal retention model of visceral hypersensitivity.
Diabetes is associated with an increased risk of fracture, although type 2 diabetes is often characterized by normal bone mineral density (BMD). Enzymatic and glycation-induced non-enzymatic ...cross-links play important roles in the expression of bone strength. The serum vitamin B6 concentration is lower in patients with diabetes than in healthy controls. The aim our study was to see if spontaneously diabetic WBN/Kob rats in the pre- and post-onset of diabetes would serve as a suitable model for studying the pathogenesis of the susceptibility to fracture in diabetes without the reduction of bone mineral density. Seventy male WBN/Kob rats were obtained at the ages of 1 to 18 months.
Seventy normal male Wistar rats were used as the non-diabetic, age-matched control. The contents of enzymatic cross-links (dihydroxylysinonorleucine, hydroxylysinonorleucine, lysinonorleucine, pyridinoline and deoxypyridinoline) and non-enzymatic cross-links (pentosidine) were determined in femoral bone. We also analyzed the serum concentration of vitamin B6 (pyridoxal and pyridoxamine), femoral BMD and a three-point bending test of the femur.
A low level of serum vitamin B6 was associated with a decrease in enzymatic crosslinking in bone during the subclinical diabetes stage. After the onset of diabetes, there was a steady decrease in enzymatic cross-links and a steep increase in pentosidine. Furthermore, impaired bone mechanical properties in the WBN/Kob rats despite the lack of reduction in BMD coincided with impaired enzymatic cross-link formation and increases in glycation-induced pentosidine.
These results indicate that the alteration of enzymatic and non-enzymatic crosslinking in bone could be important for explaining the variation of fracture susceptibility in diabetes.
To cope with the continuous traffic growth, spectral efficiency needs to be enhanced. Ultra-dense WDM systems, where narrower guard-bands are inserted between wavelength-division-multiplexed (WDM) ...signals than those used in conventional dense WDM (DWDM) systems, are expected to offer higher spectral efficiency. However, such systems are hindered by the spectrum narrowing induced by wavelength selective switches (WSSs) at nodes. As a result, intersymbol interference (ISI) can be excessive. Linear digital filters widely used in typical digital coherent receivers can equalize the ISI. However, ISI equalization yields noise enhancement due to the interaction between ISI and amplifier noise. Sequence estimation can alleviate the impact of this interaction; however, to introduce sequence estimation into real systems, an ISI-imposing filter is needed because the adaptive filter used for polarization recovery automatically equalizes the ISI. Although the optimum ISI-imposing filter can be created with the proper spectrum model, its characteristics change frequently in real optical path networks. Therefore, we need to develop a demodulation framework that does not necessitate any spectrum models. In this letter, we propose a novel demodulation framework that uses a recurrent neural network (RNN) to simultaneously realize the ISI-imposing filter and sequence estimator. Extensive computer simulations show that our proposal increases the transmission distance in ultra-dense WDM networks.
In the hole-doped cuprates, a small number of carriers suppresses antiferromagnetism and induces superconductivity. In the electron-doped cuprates, on the other hand, superconductivity appears only ...in a narrow window of high-doped Ce concentration after reduction annealing, and strong antiferromagnetic correlation persists in the superconducting phase. Recently, Pr(1.3-x)La0.7Ce(x)CuO4 (PLCCO) bulk single crystals annealed by a protect annealing method showed a high critical temperature of around 27 K for small Ce content down to 0.05. Here, by angle-resolved photoemission spectroscopy measurements of PLCCO crystals, we observed a sharp quasi-particle peak on the entire Fermi surface without signature of an antiferromagnetic pseudogap unlike all the previous work, indicating a dramatic reduction of antiferromagnetic correlation length and/or of magnetic moments. The superconducting state was found to extend over a wide electron concentration range. The present results fundamentally challenge the long-standing picture on the electronic structure in the electron-doped regime.
Distinguishing autosomal‐dominant polycystic kidney disease (ADPKD) from other inherited renal cystic diseases in patients with adult polycystic kidney disease and no family history is critical for ...correct treatment and appropriate genetic counseling. However, for patients with no family history, there are no definitive imaging findings that provide an unequivocal ADPKD diagnosis. We analyzed 53 adult polycystic kidney disease patients with no family history. Comprehensive genetic testing was performed using capture‐based next‐generation sequencing for 69 genes currently known to cause hereditary renal cystic diseases including ADPKD. Through our analysis, 32 patients had PKD1 or PKD2 mutations. Additionally, 3 patients with disease‐causing mutations in NPHP4, PKHD1, and OFD1 were diagnosed with an inherited renal cystic disease other than ADPKD. In patients with PKD1 or PKD2 mutations, the prevalence of polycystic liver disease, defined as more than 20 liver cysts, was significantly higher (71.9% vs 33.3%, P = .006), total kidney volume was significantly increased (median, 1580.7 mL vs 791.0 mL, P = .027) and mean arterial pressure was significantly higher (median, 98 mm Hg vs 91 mm Hg, P = .012). The genetic screening approach and clinical features described here are potentially beneficial for optimal management of adult sporadic polycystic kidney disease patients.
Adult polycystic kidney disease patients with no family history (n = 53).
This study explores how current shipboard/onboard training arrangements vary among countries and what informs these differences. The study – employing qualitative and quantitative research approaches ...in the form of an online survey and in-depth semi-structured interviews – collected data on onboard training arrangements from 95 MET institutions from 44 countries. From the data analysis, onboard training arrangements were categorised into seven dominant types based on regional and institutional differences with respect to four elements: substitution by simulator training, integration into the academic programme, schedule, and type of ships used. The analysis further explored the different rationales for the diverse approaches to onboard training and the dominance of the approaches in different regions. Although not explicitly mentioned by research participants, a variety of learning theories can explain the reasons underpinning the choice of particular onboard training strategies and these are discussed. Given the fundamental differences in onboard training strategies identified in this study, future research should first examine the issues and difficulties that confront the implementation of onboard training and the factors/trends that actually and/or potentially influence such implementation. Secondly, future research should explore the development of a model that can comprehensively address the challenge of onboard training across countries and do so with current trends in mind, in particular, the increasing fidelity and abilities of simulation for seafarer education and training as well as developments in ship operation with increasing levels of automation.
An effective approach to realize high-efficiency photocatalysts is the stable formation of heterojunction composite and increasing the junction area. We report that a facile fabrication method was ...proposed to form a stable heterojunction composite of SnS
2
/g-C
3
N
4
, and a favorable coupling of SnS
2
and g-C
3
N
4
at the interfaces was aimed at maximizing the heterojunction area. The degradation of methylene blue (MB) dye under exposure to low-power visible LED was sufficiently enhanced by the synthesized SnS
2
/g-C
3
N
4
photocatalyst. From the experiments, the SnS
2
nanosheet/g-C
3
N
4
microsheet heterostructure exhibited a high apparent pseudo-first order rate constant
k
of 0.0274 min
−1
, four and two times higher than the
k
value of SnS
2
and g-C
3
N
4
, respectively. The cyclic experiments showed that the as-prepared heterojunctions exhibited good stability even without recovery treatment. X-ray photoelectron spectroscopy (XPS) analysis and MB adsorption curves explained the mechanism of the enhanced photocatalytic performance by increasing the 2D/2D heterojunction area. This study provides an efficient method for designing effective two-dimensional heterojunctions for photocatalytic applications.
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