Regenerative responses after mild heart injuries for cardiomyocyte proliferation in zebrafish

Background: The zebrafish heart regenerates after various severe injuries. Common processes of heart regeneration are cardiomyocyte proliferation, activation of epicardial tissue, and neovascularization. In order to further characterize heart regeneration processes, we introduced milder injuries and compared responses to those induced by ventricular apex resection, a widely used injury method. We used scratching of the ventricular surface and puncturing of the ventricle with a fine tungsten needle as injury‐inducing techniques. Results: Scratching the ventricular surface induced subtle cardiomyocyte proliferation and responses of the epicardium. Endothelial cell accumulation was limited to the surface of the heart. Ventricular puncture induced cardiomyocyte proliferation, endocardial and epicardial activation, and neo‐vascularization, similar to the resection method. However, the degree of the responses was milder, correlating with milder injury. Sham operation induced epicardial aldh1a2 expression but not tbx18 and WT1. Conclusions: Puncturing the ventricle induces responses equivalent to resection at milder degrees in a shorter time frame and can be used as a simple injury model. Scratching the ventricle did not induce heart regeneration and can be used for studying wound responses to epicardium. Developmental Dynamics 243:1477–1486, 2014. © 2014 Wiley Periodicals, Inc.     

Neuronal activity in the primate dorsomedial prefrontal cortex contributes to strategic selection of response tactics

The functional roles of the primate posterior medial prefrontal cortex have remained largely unknown. Here, we show that this region participates in the regulation of actions in the presence of multiple response tactics. Monkeys performed a forelimb task in which a visual cue required prompt decision of reaching to a left or a right target. The location of the cue was either ipsilateral (concordant) or contralateral (discordant) to the target. As a result of extensive training, the reaction times for the concordant and discordant trials were indistinguishable, indicating that the monkeys developed tactics to overcome the cue-response conflict. Prefrontal neurons exhibited prominent activity when the concordant and discordant trials were randomly presented, requiring rapid selection of a response tactic (reach toward or away from the cue). The following findings indicate that these neurons are involved in the selection of tactics, rather than the selection of action or monitoring of response conflict: (i) The response period activity of neurons in this region disappeared when the monkeys performed the task under the behavioral condition that required a single tactic alone, whereas the action varied across trials. (ii) The neuronal activity was found in the dorsomedial prefrontal cortex but not in the anterior cingulate cortex that has been implicated for the response conflict monitoring. These results suggest that the medial prefrontal cortex participates in the selection of a response tactic that determines an appropriate action. Furthermore, the observation of dynamic, task-dependent neuronal activity necessitates reconsideration of the conventional concept of cortical motor representation.     

Effective Intra-Esophageal Acid Control Is Associated with Improved Radiofrequency Ablation Outcomes in Barrett’s Esophagus

Background

Endoscopic radiofrequency ablation (RFA) is a promising new treatment of Barrett’s esophagus (BE). Adjunctive intra-esophageal pH control with proton pump inhibitors and/or anti-reflux surgery is generally recommended to optimize squamous re-epithelialization after ablation.

Aims

The aims of this study were to examine the association between intra-esophageal pH control and RFA outcomes and to identify predictive factors to achieve complete elimination (CE) of BE following RFA.

Methods

We retrospectively studied the outcomes of BE patients treated with RFA. Esophageal acid exposure (EAE) was assessed utilizing 24-h pH monitoring on therapy. CE was endoscopically defined as no area suspicious for residual metaplasia following RFA.

Results

Of 45 patients (33 men; mean age 61.6, mean BE length C4.1 M4.6) examined for EAE, 29 % exhibited moderate–severe EAE despite therapy. Reduction in BE surface area and CE rate were higher in the normal-mild EAE group compared with the moderate–severe EAE group (99 vs. 95 %, p = 0.02; 44 vs. 15 %, p = 0.09, respectively). Using univariate analysis, age, gender, race, aspirin/NSAIDs use, baseline worst histology, baseline BE surface area, and the number or types of RFA had no correlation with CE. By multivariate multiple logistic regression analysis, normal-mild EAE and smaller hiatal hernia were independent factors associated with CE.

Conclusions

Effective intra-esophageal pH control is associated with improved RFA outcomes of BE. Normal to mild EAE and smaller hiatal hernia are predictive factors to achieve CE. Given the frequent persistence of acid reflux despite therapy in BE patients, in order to maximize the RFA effects esophageal pH optimization and hernia repair should be considered.     

Hypertension and concomitant arteriosclerotic diseases are risk factors for colonic diverticular bleeding: a case–control study

Purpose

Colonic diverticular bleeding is a major cause of lower gastrointestinal bleeding. However, a limited number of studies have been reported on the risk factors for diverticular bleeding. Our aim was to identify risk factors for diverticular bleeding.

Methods

Our study design is a case (diverticular bleeding)–control (diverticulosis) study. We prospectively collected information of habits, comorbidities, history of medications and symptoms by a questionnaire, and diagnosed diverticular bleeding and diverticulosis by colonoscopy. Logistic regression models were used to estimate odds ratio (OR) and 95% confidence interval (CI).

Results

A total of 254 patients (diverticular bleeding, 45; diverculosis, 209) were selected for analysis. Cluster (≥10 diverticula) type (OR, 4.0; 95% CI, 1.8–8.9), hypertension (OR, 2.2; 95% CI, 1.0–4.6), ischemic heart disease (OR, 2.4; 95% CI, 1.1–5.4), and chronic renal failure (OR, 6.4; 95% CI, 1.3–32) were independent risk factors for diverticular bleeding.

Conclusions

Large number of diverticula, hypertension, and concomitant arteriosclerotic diseases including ischemic heart disease and chronic renal failure are risk factors for diverticular bleeding. This study identifies new information on the risk factors for diverticular bleeding.