Neuromodulating agents in functional dyspepsia: a comprehensive review.

Background and study aims: Functional dyspepsia is a common chronic condition with upper abdominal symptoms in the absence of an organic cause. The first line treatment consists of protonpomp inhibition or Helicobacter pylori eradication. However, this approach often does not provide enough symptom relief. Neuromodulating agents are commonly used in clinical practice but only tricyclic antidepressant (TCAs) are mentioned in European and American and Canadian guidelines. Methods: We performed a comprehensive review of the literature in Pubmed for full-text randomized controlled trials in English with adult participants (>18 years) who met the Rome II, III or IV criteria or were diagnosed by a physician with a negative upper endoscopy and that compared a neuromodulating agent with placebo. Results: The search strategy identified 386 articles of which 14 articles met the eligibility criteria. TCAs like amitriptyline and imipramine have been shown to be effective in the treatment of functional dyspepsia whereas other neuromodulating agents like tetracyclic antidepressants, levosulpiride and anxiolytics might be beneficial but conclusive evidence is lacking. serotonin and noradrenaline reuptake inhibitors (SNRI) and selective serotonin reuptake inhibitors (SSRI) have not shown benefit in patients with functional dyspepsia. Conclusion: Selected neuromodulators have an established efficacy in functional dyspepsia. The best supporting evidence is available for TCAs with a potential role for tetracyclic antidepressants, levosulpiride and anxiolytics.

Restricted access to private properties limits management of invasive alien species: A literature review and case studies.

Biological invasions are one of the major drivers of global environmental change and there is a need to develop integrated strategies to counteract this phenomenon. Eradication is an effective management option to mitigate the deleterious impacts of invasive alien species (IAS). Eradication can be achieved if all reproductive individuals are removed and population recovery is prevented. However, individuals may survive removal operations in private areas if interventions are not allowed. Here, we present 1) three case studies in which restricted private property access prevented the local eradication of invasive alien populations, and 2) a list of reasons for denying access to private properties and a list of actions implemented or suggested by managers to facilitate access and reported in 29 reviewed papers. The restricted access affected the local eradication of three Eastern grey squirrel (Sciurus carolinensis) populations in Italy. In Lombardy region, in one area a planned eradication did not start and in another area the implemented eradication failed due to the refusal from the owner of a large private property to grant access to managers. In Umbria region, the lack of collaboration from an Italian financial institution produced a delay of 15 months in the removal. In our case studies, therefore, a single person or institution denied access for a personal gain or presumed internal security. The reasons behind landowner opposition may be diverse and individual attitudes towards IAS management will depend on interactions with owners. According to our review, in many cases the denial of access takes place in a general perception of mistrust or opposition to the project as the results of a limited engagement of local people. Such opposition often jeopardizes control activities, with profound negative consequences on eradication, expecially at landscape scale. Bottom-up approaches aiming at involving stakeholders can increase the possibility to achieve IAS eradication, however appropriate legislation remains pivotal to enforce eradication in case of non-cooperative behaviour.

Effect of obesity on gastrointestinal transit, pressure and pH using a wireless motility capsule.

BACKGROUND: Despite the increasing prevalence and medical burden of obesity, the understanding of gastrointestinal physiology in obesity is scarce, which hampers drug development. AIM: To investigate the effect of obesity and food intake on gastrointestinal transit, pressure and pH. MATERIAL AND METHODS: An exploratory cross-sectional study using a wireless motility capsule (SmartPill©) was performed in 11 participants with obesity and 11 age- and gender-matched participants with normal weight (group) in fasted and fed state (visit). During the first visit, the capsule was ingested after an overnight fast. During a second visit, the capsule was ingested after a nutritional drink to simulate fed state. Linear mixed models were constructed to compare segmental gastrointestinal transit, pressure and pH between groups (obesity or control) and within every group (fasted or fed). RESULTS: Food intake slowed gastric emptying in both groups (both P < 0.0001), though food-induced gastric contractility was higher in participants with obesity compared to controls (P = 0.02). In the small intestine, a higher contractility (P = 0.001), shorter transit (P = 0.04) and lower median pH (P = 0.002) was observed in participants with obesity compared to controls. No differences were observed for colonic measurements. CONCLUSION: Obesity has a profound impact on gastrointestinal physiology, which should be taken into account for drug development.

Impact of antithrombotics on the fecal immunochemical test for colorectal cancer screening : a multi-center Belgian experience.

Background: Impact of antithrombotics on the fecal immunochemical test (FIT) for colorectal cancer (CRC) screening remains unclear. Methods: Patients undergoing colonoscopy for positive FIT in 2015 were assessed at 3 Belgian centers. Significant findings were advanced polyps (AP) (sessile serrated, tubular or villous adenomas >1cm or high-grade dysplasia) and CRC. False positive FIT and detection of AP/CRC with antithrombotics were calculated. Results: 510 patients (64% male, median (IQR) age 63.2 (60.2 - 66.4) years) were included. Colorectal pathology in 371/510 (73%) was associated with male gender (70% vs. 48% ; p= .0001) and family history (16% vs. 8% ; p= .02). Antithrombotics in 125/510 (25%) were associated with male gender (78% vs. 59% ; p= .0001), older age (65.2 (62.2-70.3) vs. 62.3 (58.7-66.3) years ; p= .0001) and GI-symptoms (18% vs. 11% ; p= .04). False positive FIT (25% vs. 28% ; p= .52) and detection of AP (42% vs. 36% ; p=.27) or CRC (6% vs. 5% ; p= .69) were similar in patients with vs. no antithrombotics. Use of antithrombotics did not predict a higher chance of colorectal pathology after adjusting for confounders. Conclusion: Although antithrombotics were prescribed more frequently in male and older patients, detection of AP/CRC was similar. Despite increased GI symptoms, false positive FIT was similar with antithrombotics.

Intralesional steroid injections in addition to endoscopic dilation in benign refractory esophageal strictures : a systematic review.

BACKGROUND AND STUDY AIMS: Benign esophageal strictures are primarily treated with dilation therapy, but strictures can recur or can be unresponsive, requiring additional or repeated treatment. This study investigates the efficacy and safety of intralesional steroid injections in addition to dilation in comparison to dilation alone in patients with benign refractory or recurrent esophageal strictures. METHODS: A systematic search was carried out in PubMed, using the search terms "Esophageal Stenosis"[Mesh] AND "Injections, Intralesional"[Mesh]. In addition, the reference list of all selected articles was searched manually for other relevant articles. All clinical trials and case series were considered. RESULTS: This systematic review included four randomized controlled trials, six case series and two cohort studies, comprising 341 patients with benign esophageal strictures of different etiologies. A benefit of adding intralesional steroid injections to dilation in reducing the need for repeat dilation was seen in the subgroups of peptic, radiation-induced and corrosive strictures. Results were inconsistent for anastomotic strictures and too limited for strictures due to eosinophilic esophagitis, sclerotherapy or pill esophagitis. Complications were rare and of limited severity. CONCLUSION: Endoscopic dilation remains the first-line treatment, since its efficacy and safety are mostly satisfactory. In recurrent or refractory strictures, intralesional steroid injections are advised in peptic strictures and can be considered in radiation- induced, corrosive strictures and anastomotic strictures. It is recommended to restrict the steroid use to a maximum of three sessions and to consider alternative treatment if treatment effects remain insufficient.

Meckel's enterolith : a rare cause of mechanical small bowel subobstruction.

Meckel's diverticulum is the most common congenital gastrointestinal malformation and may present with bleeding, obstruction and diverticulitis. Symptomatic Meckel's diverticulum is associated with age <50 years, male gender, diverticular length > 2 cm and ectopic mucosa. Formation of enteroliths is a rare complication of Meckel's diverticulum and the majority of stones will remain in the diverticulum. Factors promoting enterolith formation through precipitation of calcium in the small intestinal alkaline environment include stasis as well as diverticular anatomy and histology. Mechanical obstruction due to liberation of enteroliths is even more rare and other mechanisms include intussusception, adhesions, volvulus and neoplasms. Visualization of enteroliths on plain abdominal films is challenging because not all stones are radiopaque. Surgical diverticulectomy or segmental bowel resection with anastomosis is preferred in case of complications. We present a case of mechanical small bowel sub-obstruction resulting from an expelled Meckel's enterolith.

Functional dyspepsia is associated with duodenal eosinophilia in an Australian paediatric cohort.

BACKGROUND: The pathophysiology of functional dyspepsia (FD) remains unknown. Duodenal eosinophil infiltration has been reported. AIM: To assess the association between dyspeptic symptoms and duodenal eosinophilia in children undergoing upper gastrointestinal endoscopy. METHODS: In this retrospective cohort study, children with normal upper endoscopy and routine histology at a single tertiary paediatric centre between 2010 and 2014 were included. FD was defined as epigastric pain or discomfort >2 months without response to acid suppression. Controls presented with nonerosive reflux disease, dysphagia or rumination syndrome. Intramucosal eosinophil counts were compared between the groups using uni- and multivariate regression analyses. RESULTS: Thirty-six cases and 36 nonmatched controls were identified. Atopic history (39% vs. 25%) and psychological comorbidity (53% vs. 39%; both P = 0.2) were frequent in cases and controls. Self-reported nausea (64% vs. 17%; P < 0.0001), lethargy (19% vs. 0%; P = 0.005) and family functional gastrointestinal disorder(FGID) (28% vs. 3%; P = 0.003) were more common in cases than controls. Duodenal eosinophil counts [median (IQR): 151 (118-207) vs. 76 (60-106) per mm2 ; P < 0.001] were significantly higher in cases than controls with >112 eosinophils per mm2 predictive for FD (OR: 33.6, 95% CI: 7.1-159.0; P < 0.001). Duodenal eosinophilia was associated with weight loss (OR: 7.1, 95% CI: 1.1-45.5; P = 0.04). CONCLUSIONS: Functional dyspepsia in children is strongly associated with duodenal eosinophilia, in the absence of endoscopic or routine histological findings. Frequent atopic and psychological comorbidity illustrate likely multifactorial mechanisms.

Faecal egg counts from field experiment reveal density dependence in helminth fecundity: Strongyloides robustus infecting grey squirrels (Sciurus carolinensis).

Investigation of endo-macroparasite infections in living animals relies mostly on indirect methods aimed to detect parasite eggs in hosts' faeces. However, faecal flotation does not provide quantitative information on parasite loads, whereas faecal egg count (FEC) techniques may not give reliable estimates of parasite intensity, since egg production may be affected by density-dependent effects on helminth fecundity. We addressed this issue using Eastern grey squirrels (Sciurus carolinensis) and their gastrointestinal nematode Strongyloides robustus to assess the performance of coprological techniques and to investigate factors affecting parasite fecundity. We compared results of gut examination, flotation and McMaster FECs in 65 culled grey squirrels. Sensitivity and specificity of flotation were 81.2% (Confidence Interval, CI 54.3-95.9%) and 85.7% (CI 72.7-94.1%), respectively, resulting in low positive predictive values when infection prevalence is low. Individual parasite fecundity (no. of eggs/adult female worm) was negatively affected by S. robustus intensity, leading to a non-linear relationship between parasite load and eggs/gram of faeces (EPG). As a consequence, whereas flotation may be a valid method to perform the first screening of infection status, FECs are not a reliable method to estimate S. robustus intensity, since diverse values of EPG may correspond to the same number of parasites. Neither the amount of analysed faeces nor the season had any effect on EPG, indicating that the observed reduction in helminth fecundity is likely caused exclusively by density-dependent processes such as competition among worms or host immune response.

Balloon dilation of the esophago-gastric junction affects lower and upper esophageal sphincter function in achalasia.

BACKGROUND: Pneumatic dilation of the lower esophageal sphincter (LES) in achalasia has an unappreciated effect on upper esophageal sphincter (UES) function. We studied UES pressure patterns at baseline and alterations in UES parameters resulting from therapy. METHODS: High-resolution manometry (HRM) tracings from 50 achalasia patients, seen at a tertiary center between January 2009 and July 2011, were reviewed. Manometric parameters studied were (i) LES: resting pressure (restP), 4-second integrated relaxation pressure (IRP4); (ii) UES: resting pressure (restP), minimal relaxation pressure (MRP), peak pressure (PP), relaxation interval (RI), intrabolus pressure (IBP), and deglutitive sphincter resistance (DSR). Mixed models analyses with LES and UES parameters as dependent variables and treatment stage as within-subject independent variable of interest were used. Correlations between treatment-induced changes in LES, UES, and esophageal body (EB) parameters were performed. KEY RESULTS: Pre- and posttreatment HRM tracings were available from 50 patients (mean age 52.7 ± 18.6 years, 29 men). Upper esophageal sphincter parameters MRP (17.9 ± 1.2 vs 15.2 ± 0.9 mmHg; p = 0.02) and IBP (31.5 ± 1.5 vs 27.4 ± 1.2 mmHg; p = 0.009) were significantly reduced after initial balloon dilation and this effect was significant in type II achalasia (p = 0.002 and p = 0.0006). Peak pressure, RI, and DSR were not. The therapeutic effect on LES IRP4 correlated significantly with the change in UES MRP, statistically mediated by the change in EB deglutitive pressure (p = 0.004 and p = 0.0002). CONCLUSIONS & INFERENCES: We present the first HRM study demonstrating that pneumatic dilation of the LES affects intraesophageal and UES pressures in patients with achalasia.

Does acupuncture activate endogenous analgesia in chronic whiplash-associated disorders? A randomized crossover trial.

BACKGROUND: Many patients with chronic pain, including those with chronic whiplash-associated disorders (WAD), show features of central sensitization. Randomized trials examining whether treatments are able to influence the process of central sensitization in patients with chronic WAD are emerging. Therefore, the present study aimed at examining whether acupuncture results in activation of endogenous analgesia and relief in symptoms in patients with chronic WAD. METHODS: In this randomized crossover pilot trial with blinded assessors, each patient (n = 39) received two treatment sessions of identical duration, with acupuncture and relaxation therapy randomly crossed over in visit 2. Primary outcome measurement included immediate activation of endogenous analgesia i.e., pressure pain sensitivity and conditioned pain modulation. Secondary outcome measurements included pain relief and reduced disability level. RESULTS: Local pressure pain sensitivity at baseline and during conditioned pain modulation decreased significantly more following acupuncture compared with relaxation (time × group interactions: p < 0.001), both in the neck and at a site distinct from the painful region. When comparing the effects of acupuncture versus relaxation, no differences were observed on conditioned pain modulation, temporal summation of pressure pain, neck disability or symptom severity (all p-values >0.05). CONCLUSION: It was shown that one session of acupuncture treatment results in acute improvements in pressure pain sensitivity in the neck and calf of patients with chronic WAD. Acupuncture had no effect on conditioned pain modulation or temporal summation of pressure pain. Both acupuncture and relaxation appear to be well-tolerated treatments for people with chronic WAD. These findings suggest that acupuncture treatment activates endogenous analgesia in patients with chronic WAD.

Geographical distance and physical barriers shape the genetic structure of Eurasian red squirrels (Sciurus vulgaris) in the Italian Alps.

Red squirrels (Sciurus vulgaris) are widely distributed throughout Eurasia, occurring in many types of coniferous and mixed-deciduous forests. In fragmented landscapes, small and partly isolated populations with low immigration rates show reduced genetic diversity, but reforestation can increase gene flow and restore levels of genetic variation in a few decades. No studies have so far investigated the genetic structure of red squirrel in large, continuous forests. The Italian Alps are presently characterized by almost continuous, recently reconnected forest habitats, that were affected by deep landscape changes during last glaciations but remained mostly unchanged between 10 000 and 200 years bp, when forest cover was heavily reduced. In this study we analyse patterns of genetic variability of red squirrels in and between seven sites distributed over 250 km of Alpine habitat, using mitochondrial DNA (mtDNA) and microsatellites. We use isolation-by-distance (IBD) models to investigate the relative importance that past (Pleistocene glaciations) and recent (fragmentation, bottlenecks) events had on the present genetic situation. Both nuclear and mtDNA data indicate a significant differentiation among study sites and a significant correlation between genetic and geographical distance only over a large scale. No recent bottlenecks are recorded through microsatellites and demographic models strongly support equilibrium between gene flow and drift; however, mtDNA suggests that there may have been local demographic crashes, probably in correspondence with the 19th-century forest fragmentation. These findings indicate that local landscape factors other than geographical distance per se, such as barriers of unsuitable habitat, affect gene flow and determine differentiation.

Fitness consequences of hoarding behaviour in the Eurasian red squirrel.

Hoarding increases food availability during periods of scarcity, and therefore should enhance fitness. Although short-term advantages of hoarding have been described for birds, effects over an animal's lifetime have not yet been documented. Here, we report that in the red squirrel, Sciurus vulgaris, individuals which recovered many cached tree seeds increased their body mass and were more likely to survive the spring breeding season than those that recovered fewer seeds. There was no significant effect of the time spent recovering cached food on the probability for females to produce a spring litter. In the long-term, hoarding behaviour was related to fitness in two ways; (i) squirrels spending more time recovering hoards survived longer; and (ii) females with a high recovery activity tended to wean more young in their lifetime than those that spent less time recovering hoards. Our data indicate that in red squirrels, food hoarding is an adaptive foraging strategy to preserve temporarily abundant food resources for future periods of hardship, and that individuals that hoard and recovery many tree seeds are more likely to survive and reproduce.

The effects of habitat fragmentation on demography and on the loss of genetic variation in the red squirrel.

A major problem in conservation biology is the extent to which the loss of genetic variability in isolated populations reduces their chance of survival. We present data in which the loss of genetic diversity in small and isolated populations can be directly related to population dynamics. Genetic similarity in red squirrels is inversely correlated with population size. The loss of genetic variation and the lower population densities in isolated populations are both the result of reduced immigration. Our data suggest that population processes rather than genetic problems are the real threat to small squirrel populations.