When is proton pump inhibitor use appropriate?

Proton pump inhibitor (PPI) therapy is commonly used outside of Food and Drug Administration indication for a broad range of conditions such as extra-esophageal reflux and PPI-responsive esophageal eosinophilia. While this may be appropriate in some scenarios, it has also resulted in widespread inappropriate PPI use. At the same time, data suggesting adverse effects of long-term PPI therapy are multiplying, albeit mainly from low quality studies. The systematic review by Scarpignato et al. (BMC Med 14:179, 2016) addresses this dilemma with a comprehensive analysis of the risks and benefits of PPI use. The authors concluded that, while PPIs are highly efficacious in erosive acid-peptic disorders, efficacy is not equaled in other conditions. In some instances, they found no supportive evidence of benefit. With respect to side effects, they indicated that the questionable harms associated with PPI therapy do not outweigh the benefits afforded by appropriate PPI use. However, inappropriate PPI use results in increased healthcare costs and unnecessary exposure to potential adverse effects. Ideally, PPI therapy should be personalized, based on indication, effectiveness, patient preference, and risk assessment.Please see related article: http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-016-0718-z

The Neurobiological Correlates of Savoring

Personality traits pertaining to positive emotion may be a key factor in deriving vitality from our lives. Positive affectivity refers to one\u27s disposition to experience intense and frequent episodes of positive affect, while savoring capacity refer to one\u27s ability to regulate positive affect. Both traits have been positively associated with happiness, self-esteem, prosocial behaviors, improved health outcomes, as well as attenuated depressive symptomatology and neuroticism. The late positive potential (LPP) is an electroencephalography (EEG) component that is theorized to index a visual cortical/amygdala pathway that is involved in evaluating the affective salience of stimuli. LPP is sensitive to the emotional content of stimuli, as well as how these stimuli are appraised. Research examining the neural time course of affective processing has long utilized the International Affective Picture System (IAPS). The Open Affective Standardized Image Set (OASIS) is an up-to-date and open access stimulus set that may improve upon some shortcomings of the IAPS. Thus, the present study evaluated the following hypotheses: a) enhanced LPP is evoked by positive and negative compared to neutral OASIS images, b) participants\u27 LPP evoked by passively watching positive images will vary based on levels of positive affectivity and c) participants\u27 LPP in response to increasing emotional intensity to positive images will vary based on levels of savoring capacity. As predicted, results showed enhanced LPP in response to positive and negative OASIS stimuli, indicating that the OASIS may be an advantageous replacement stimulus set for the IAPS in future psychophysiological research. However, in the present study, positive affectivity and savoring capacity did not moderate the relationship between passively viewing positive images/increasing emotional intensity in response to positive images and LPP activity. The present study brings much needed attention to positive emotion and its neurobiological correlates. This work is critical to developing neuroscience-informed clinical interventions for those with psychological and physiological disorders, as well as uncovering the biological implementations of well-being

Individual Differences and Neural Correlates of Emotion Reactivity and Regulation: Potential Intervention Targets in Depression

Depression, Electroencephalography, Emotion reactivity, Emotion regulatio

A fully resolved active musculo-mechanical model for esophageal transport

Esophageal transport is a physiological process that mechanically transports an ingested food bolus from the pharynx to the stomach via the esophagus, a multi-layered muscular tube. This process involves interactions between the bolus, the esophagus, and the neurally coordinated activation of the esophageal muscles. In this work, we use an immersed boundary (IB) approach to simulate peristaltic transport in the esophagus. The bolus is treated as a viscous fluid that is actively transported by the muscular esophagus, which is modeled as an actively contracting, fiber-reinforced tube. A simplified version of our model is verified by comparison to an analytic solution to the tube dilation problem. Three different complex models of the multi-layered esophagus, which differ in their activation patterns and the layouts of the mucosal layers, are then extensively tested. To our knowledge, these simulations are the first of their kind to incorporate the bolus, the multi-layered esophagus tube, and muscle activation into an integrated model. Consistent with experimental observations, our simulations capture the pressure peak generated by the muscle activation pulse that travels along the bolus tail. These fully resolved simulations provide new insights into roles of the mucosal layers during bolus transport. In addition, the information on pressure and the kinematics of the esophageal wall due to the coordination of muscle activation is provided, which may help relate clinical data from manometry and ultrasound images to the underlying esophageal motor function

Savoring the moment: A link between affectivity and depression

Objective: Positive affectivity (PA; disposition to experience positive moods) and negative affectivity (NA; disposition to experience negative moods) may be risk factors for depression. Low PA may impair positive emotion regulation (savoring), potentially exacerbating depression. Understanding the mechanisms in which temporal domains of savoring influence the relationship between affectivity and depression may help advance depression treatments.Method: 1,618 participants (1,243 females; 70.0% Caucasian, 19.1% Asian, 4.5% African American, 0.9% Pacific Islander, 0.7% American Indian or Alaskan Native, 4.9% Biracial) ages 17 - 40 (M = 18.99, SD = 1.33) completed questionnaires. An exploratory path analysis was run with PA and NA as exogenous variables, savoring domains as mediators, and depression the outcome.Results: PA and NA were associated with depression and all three savoring temporal domains. Momentary savoring distinctly mediated the relationship between both PA and NA and depression.Limitations: The data are self-report and cross-sectional, precluding causal inference. Post-hoc power analysis indicated that the present study was underpowered. The use of a college sample primarily comprised of Caucasian women limits generalizability.Conclusions: Affectivity was associated with the temporal domains of savoring and indirectly associated with depression via momentary savoring. All temporal domains of savoring may bolster PA and mitigate NA. Momentary savoring may reduce depression symptoms in individuals with low PA and high NA

A continuum mechanics-based musculo-mechanical model for esophageal transport

In this work, we extend our previous esophageal transport model using an immersed boundary (IB) method with discrete fiber-based structural model, to one using a continuum mechanics-based model that is approximated based on finite elements (IB-FE). To deal with the leakage of flow when the Lagrangian mesh becomes coarser than the fluid mesh, we employ adaptive interaction quadrature points to deal with Lagrangian-Eulerian interaction equations based on a previous work (Griffith and Luo [1]). In particular, we introduce a new anisotropic adaptive interaction quadrature rule. The new rule permits us to vary the interaction quadrature points not only at each time-step and element but also at different orientations per element. This helps to avoid the leakage issue without sacrificing the computational efficiency and accuracy in dealing with the interaction equations. For the material model, we extend our previous fiber-based model to a continuum-based model. We present formulations for general fiber-reinforced material models in the IB-FE framework. The new material model can handle non-linear elasticity and fiber-matrix interactions, and thus permits us to consider more realistic material behavior of biological tissues. To validate our method, we first study a case in which a three-dimensional short tube is dilated. Results on the pressure-displacement relationship and the stress distribution matches very well with those obtained from the implicit FE method. We remark that in our IB-FE case, the three-dimensional tube undergoes a very large deformation and the Lagrangian mesh-size becomes about 6 times of Eulerian mesh-size in the circumferential orientation. To validate the performance of the method in handling fiber-matrix material models, we perform a second study on dilating a long fiber-reinforced tube. Errors are small when we compare numerical solutions with analytical solutions. The technique is then applied to the problem of esophageal transport. We use two fiber-reinforced models for the esophageal tissue: a bi-linear model and an exponential model. We present three cases on esophageal transport that differ in the material model and the muscle fiber architecture. The overall transport features are consistent with those observed from the previous model. We remark that the continuum-based model can handle more realistic and complicated material behavior. This is demonstrated in our third case where a spatially varying fiber architecture is included based on experimental study. We find that this unique muscle fiber architecture could generate a so-called pressure transition zone, which is a luminal pressure pattern that is of clinical interest. This suggests an important role of muscle fiber architecture in esophageal transport

Clinical Significance of Hiatal Hernia

The relationship between hiatal hernias and gastroesophageal reflux disease (GERD) has been greatly debated over the past decades, with the importance of hiatal hernias first being overemphasized and then later being nearly neglected. It is now understood that both the anatomical (hiatal hernia) and the physiological (lower esophageal sphincter) features of the gastroesophageal junction play important, but independent, roles in the pathogenesis of GERD, constituting the widely accepted "two-sphincter hypothesis." The gastroesophageal junction is an anatomically complex area with an inherent antireflux barrier function. However, the gastroesophageal junction becomes incompetent and esophageal acid clearance is compromised in patients with hiatal hernia, which facilitates the development of GERD. Of the different types of hiatal hernias (types I, II, III, and IV), type I (sliding) hiatal hernias are closely associated with GERD. Because GERD may lead to reflux esophagitis, Barrett's esophagus and esophageal adenocarcinoma, a better understanding of this association is warranted. Hiatal hernias can be diagnosed radiographically, endoscopically or manometrically, with each modality having its own limitations, especially in the diagnosis of hiatal hernias less than 2 cm in length. In the future, high resolution manometry should be a promising method for accurately assessing the association between hiatal hernias and GERD. The treatment of a hiatal hernia is similar to the management of GERD and should be reserved for those with symptoms attributable to this condition. Surgery should be considered for those patients with refractory symptoms and for those who develop complications, such as recurrent bleeding, ulcerations or strictures