Bile acids cause relaxation of the lower esophageal sphincter through G-protein-coupled bile acid receptors

AbstractObjectivesBile acids inhibit contraction of the gallbladder and intestine through the G-protein-coupled bile acid receptor (GPBAR). Perfusion of the esophagus with bile and acid (HCl) decreases lower esophageal sphincter (LES) pressure. The effects of bile acids on LES motility are not clear. The purpose of the present study was to investigate the effects of bile acids on LES motility in vitro.Materials and MethodsWe measured the relaxation of muscle strips isolated from guinea pig and rat LES caused by bile acids or the selective GPBAR agonist RG-239. Reverse transcription polymerase chain reaction (RT-PCR) was performed to determine GPBAR expression in rat LES.ResultsIn carbachol-contracted guinea pig LES strips, lithocholic acid (LCA), deoxycholic acid (DCA), chenodeoxycholic acid (CDCA), and cholic acid (CA) produced relaxation in a concentration-dependent manner. The relative potency was LCA ≥ DCA > CDCA > CA. RG-239 also induced concentration-dependent relaxation. This suggests that GPBAR mediates relaxation in guinea pig LES. DCA-induced LES relaxation was attenuated by the protein kinase A inhibitor KT 5720 but not by the protein kinase G inhibitor KT 5823 or the NO synthase inhibitor L-NNA. This suggests the involvement of cAMP. Separately, in endothelin-1-contracted rat LES strips, bile acids induced relaxation. The relative potency was LCA = DCA > CDCA > CA. RT-PCR revealed GPBAR expression in rat LES.ConclusionThese results demonstrate that bile acids cause relaxation of guinea pig and rat LES through GPBAR

Cysteinyl Leukotriene Receptor Type 1 (CysLT1) Mediates Contraction of the Guinea Pig Lower Esophageal Sphincter

AbstractObjectiveLeukotriene D4 (LTD4) causes contraction of the cat lower esophageal sphincter. The effects of leukotrienes in the guinea pig lower esophageal sphincter and the cysteinyl leukotriene receptor (CysLT) subtype that mediate this contraction are not known. The purpose of the present study was to characterize the CysLT receptors in the guinea pig lower esophageal sphincter.Materials and MethodsWe measured the contractions of transverse strips from the guinea pig lower esophageal sphincter caused by cysteinyl leukotrienes, LTC4, LTD4 and LTE4, and the dihydroxy leukotriene, LTB4. We also measured LTD4-induced contraction inhibited by CysLT receptor antagonists, tetrodotoxin and atropine.ResultsIn the guinea pig lower esophageal sphincter strips, LTC4, LTD4 and LTE4, but not LTB4, caused concentration-dependent contractions. The relative potencies for cysteinyl leukotrienes to cause contraction were LTD4 = LTC4 > LTE4. LTE4 was a partial agonist. The LTD4-induced contraction was inhibited by two selective CysLT1 receptor antagonists, montelukast and zafirlukast, and by the dual CysLT1 and CysLT2 receptor antagonist BAY u9773. The combination of both montelukast and BAY u9773 did not potentiate the inhibition caused by montelukast alone. These findings indicate that CysLT1 mediates the contraction in the lower esophageal sphincter. Furthermore, LTD4-induced contraction was not affected by tetrodotoxin or atropine, suggesting a direct effect.ConclusionThese results demonstrate that cysteinyl leukotrienes, but not the dihydroxy leukotriene LTB4, cause contraction of the guinea pig lower esophageal sphincter. The CysLT1 receptor mediates this contraction

Quantum mechanical Gaussian wavepackets of single relativistic particles

We study the evolutions of selected quasi-(1+1) dimensional wavepacket solutions to the Klein-Gordon equation for a relativistic charged particle in uniform motion or accelerated by a uniform electric field in Minkowski space. We explore how good the charge density of a Klein-Gordon wavepacket can be approximated by a Gaussian state with the single-particle interpretation. We find that the minimal initial width of a wavepacket for a good Gaussian approximation in position space is about the Compton wavelength of the particle divided by its Lorentz factor at the initial moment. Relativistic length contraction also manifests in the spreading of the wavepacket's charge density.Comment: 15 pages, 8 figure

Perceptions, Behavioral Expectations, and Implementation Timing for Response Actions in a Hurricane Emergency

This study examined the perceived attributes, behavioral expectations, and expected implementation timing of 11 organizational emergency response actions for hurricane emergencies. The perceived attributes of the hurricane response actions were characterized by two hazard-related attributes (effectiveness for person protection and property protection) and five resource-related attributes (financial costs, required knowledge/skill, required equipment, required time/effort, and required cooperation). A total of 155 introductory psychology students responded to a hypothetical scenario involving an approaching Category 4 hurricane. The data collected in this study explain previous findings of untimely protective action decision making. Specifically, these data reveal distinctly different patterns for the expected implementation of preparatory actions and evacuation recommendations. Participants used the hazard-related and resource-related attributes to differentiate among the response actions and the expected timing of implementation. Moreover, participants’ behavioral expectations and expected implementation timing for the response actions were most strongly correlated with those actions’ effectiveness for person protection. Finally, participants reported evacuation implementation times that were consistent with a phased evacuation strategy in which risk areas are evacuated in order of their proximity to the coast. However, the late initiation of evacuation in risk areas closest to the coast could lead to very late evacuation of risk areas farther inland

How Do Perceptions of Risk Communicator Attributes Affect Emergency Response? An Examination of a Water Contamination Emergency in Boston, USA

A water main break that contaminated the Boston area\u27s water distribution system prompted a four-day “boil water” order. To understand risk communication during this incident, 600 randomly sampled residents were mailed questionnaires, yielding 110 valid responses. This article describes how perceptions of different social stakeholders influenced whether respondents complied with the Protective Action Recommendation—PAR (i.e., drank boiled water), took alternative protective actions (i.e., drank bottled water or/and self-chlorinated water), or ignored the threat (i.e., continued to drink untreated tap water). Respondents perceived technical authorities (i.e., water utility, public health, and emergency management) to be higher on three social influence attributes (hazard expertize, trustworthiness, and protection responsibility) than public (i.e., news media, elected officials) and private (i.e., self/family, peers, and personal physicians) intermediate sources. Furthermore, respondents were most likely to comply with the PAR if they perceived authorities and public intermediates to be high on all three attributes and if they had larger households and lower income. Contrarily, they were more likely to take alternative actions if they were younger and had higher levels of income, risk perception, and emergency preparedness. These results underscore the need for technical authorities to develop credibility with their potential audiences before a crisis occurs

Quantum correlation generation capability of experimental processes

Einstein-Podolsky-Rosen (EPR) steering and Bell nonlocality illustrate two different kinds of correlations predicted by quantum mechanics. They not only motivate the exploration of the foundation of quantum mechanics, but also serve as important resources for quantum-information processing in the presence of untrusted measurement apparatuses. Herein, we introduce a method for characterizing the creation of EPR steering and Bell nonlocality for dynamical processes in experiments. We show that the capability of an experimental process to create quantum correlations can be quantified and identified simply by preparing separable states as test inputs of the process and then performing local measurements on single qubits of the corresponding outputs. This finding enables the construction of objective benchmarks for the two-qubit controlled operations used to perform universal quantum computation. We demonstrate this utility by examining the experimental capability of creating quantum correlations with the controlled-phase operations on the IBM Quantum Experience and Amazon Braket Rigetti superconducting quantum computers. The results show that our method provides a useful diagnostic tool for evaluating the primitive operations of nonclassical correlation creation in noisy intermediate scale quantum devices.Comment: 5 figures, 3 appendice

Early utilization of hypertonic peritoneal dialysate and subsequent risks of non-traumatic amputation among peritoneal dialysis patients: a nationwide retrospective longitudinal study

BACKGROUND: The hemodialysis (HD) population has a particularly high incidence of amputation, which is likely associated with decreased tissue oxygenation during HD. However, information about the risk factors leading to amputation in peritoneal dialysis (PD) patients is limited. Here, we have investigated the association between the use of hypertonic peritoneal dialysate (HPD) and subsequent amputation in PD patients. METHODS: Based on the data from the Taiwan National Health Insurance research database, this observational cohort study enrolled 203 PD patients who had received HPD early during treatment and had not undergone amputation and 296 PD controls who had not undergone amputation. Subjects were followed through until the end of 2009 and the event rates of new non-traumatic amputation were compared between groups. RESULTS: The incidence of amputation was 3 times higher for the HPD cohort than for the comparison cohort (23.68 vs. 8.01 per 1000 person-years). The hazard ratio (HR) for this group, estimated using a multivariable Cox model, was 2.48 (95% confidence interval [CI] = 1.06–5.79). The HR for patients with both diabetes and early adoption of HPD increased to 44.34 (95% CI = 5.51-357.03), compared to non-HPD non-diabetic PD controls. CONCLUSION: Early utilization of HPD in PD patients is associated with increasing risk of amputation; this risk considerably increases for those with concomitant diabetes

Automatic B cell lymphoma detection using flow cytometry data

Background: Flow cytometry has been widely used for the diagnosis of various hematopoietic diseases. Although there have been advances in the number of biomarkers that can be analyzed simultaneously and technologies that enable fast performance, the diagnostic data are still interpreted by a manual gating strategy. The process is labor-intensive, time-consuming, and subject to human error. Results: We used 80 sets of flow cytometry data from 44 healthy donors, 21 patients with chronic lymphocytic leukemia (CLL), and 15 patients with follicular lymphoma (FL). Approximately 15% of data from each group were used to build the profiles. Our approach was able to successfully identify 36/37 healthy donor cases, 18/18 CLL cases, and 12/13 FL cases. Conclusions: This proof-of-concept study demonstrated that an automated diagnosis of CLL and FL can be obtained by examining the cell capture rates of a test case using the computational method based on the multi-profile detection algorithm. The testing phase of our system is efficient and can facilitate diagnosis of B-lymphocyte neoplasms