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Background: Functional gastrointestinal disorders account for at least a third of visits to gastroenterology clinics. Despite pathophysiological complexity, impaired gut motility may be frequently present in these disorders., Introduction: Prokinetics are a class of drugs that promote gastrointestinal motility, accelerate transit, and potentially improve digestive symptoms. Several prokinetic agents with a great variety of mechanisms of action are available., Aim: The purpose of this paper is to update our current knowledge about the efficacy and safety of prokinetics., Methods: A literature search on efficacy and safety of prokinetics was carried out using the online databases of Pubmed, Medline, and Cochrane., Results: Based on the action of different receptors, prokinetics mainly comprise dopamine antagonists, 5HT4 agonists, motilin agonists, ghrelin agonists, and cholinergic agonists. Prokinetics have the potential to improve motility function in all segments of the digestive tract, from the esophagus to the colon. In particular, drug international agencies have approved antidopaminergic metoclopramide for the treatment of gastroparesis and serotoninergic prucalopride for chronic constipation not responsive to traditional laxatives. Arrhythmias by QT prolongation and galactorrhea by prolactin stimulation are the more frequent side effects related to prokinetics use., Conclusion: Old and new prokinetics are effective in ameliorating digestive motility disorders and related symptoms and are widely prescribed. Special attention should be paid to the potential adverse events of these agents., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

DNA methylation alterations are early events during tumourigenesis, affecting genes involved in the crosstalk between cells and surroundings in colorectal cancer (CRC). Among these genes, GRIA4, Glutamate Ionotropic Receptor AMPA Type Subunit 4, displays hypermethylation in the promoter region, and is an early diagnostic biomarker. It is well known that methylation can also affect alternative transcription. The purpose of this study is to evaluate the expression, at transcript and protein level, of GRIA4 main isoforms (the canonical one and a short variant) in 23 CRC and matched normal samples, of which we previously verified the methylation status. We further predicted miRNA/transcript target interactions as a possible post-transcriptional regulation using bioinformatics tools. As expected, downregulation of both variants has been observed in tumours. Interestingly, in contrast to what observed at transcriptional level, the GluR4 protein short isoform displayed higher expression than the canonical one either in normal or tumoural tissues. This may be explained by miRNA specifically targeting the canonical isoform. Our study is the first one that shows the expression of both isoforms in colon tissues. To note, the evident expression of the short isoform suggests a functional role in intestinal cell biology., (© 2021. The Author(s).)

Background: Physical activity in the elderly is recommended by international guidelines to protect against cognitive decline and functional impairment., Objective: This Randomized Controlled Trial (RCT) was set up to verify whether medium-intensity physical activity in elderly people living in the community is effective in improving cognitive performance., Design: RCT with parallel and balanced large groups., Setting: Academic university hospital and Olympic gyms., Subjects: People aged 65 years old and older of both genders living at home holding a medical certificate for suitability in non-competitive physical activity., Methods: Participants were randomized to a 12-week, 3 sessions per week moderate physical activity program or to a control condition focused on cultural and recreational activities in groups of the same size and timing as the active intervention group. The active phase integrated a mixture of aerobic and anaerobic exercises, including drills of "life movements", strength and balance. The primary outcome was: any change in Addenbrooke's Cognitive Examination Revised (ACE-R) and its subscales., Results: At the end of the trial, 52 people completed the active intervention, and 53 people completed the control condition. People in the active intervention improved on the ACE-R (ANOVA: F(1;102)=4.32, p=0.040), and also showed better performances on the memory (F(1;102)=5.40 p=0.022) and visual-space skills subscales of the ACE-R (F(1;102)=4.09 p=0.046)., Conclusion: A moderate-intensity exercise administered for a relatively short period of 12 weeks is capable of improving cognitive performance in a sample of elderly people who live independently in their homes. Clinical Trials Registration No : NCT03858114., (© 2021 Carta et al.)

Background: Aging is marked by a progressive rise in chronic diseases with an impact on social and healthcare costs. Physical activity (PA) may soothe the inconveniences related to chronic diseases, has positive effects on the quality of life and biological rhythms, and can prevent the decline in motor functions and the consequent falls, which are associated with early death and disability in older adults., Methods: We randomized 120 over-65 males and females into groups of similar size and timing and will give each either moderate physical activity or cultural and recreational activities. Being younger than 65 years, inability to participate in physical activity for any medical reason, and involvement in a massive program of physical exercise are the exclusion criteria. The primary outcome measures are: quality of life, walking speed, and postural sway. Participants are tested at baseline, post-treatment, and 6-month (24 weeks) and 12-month (48 weeks) follow-ups., Discussion: This study aims at improving the quality of life, wellness, and cognitive functioning in the elderly through a low-cost affordable program of moderate physical activity. Given the growing aging of the world population and the social and economic burden of disability in the elderly, our results might have a major impact on future practices., Trial Registration: ClinicalTrials.gov NCT03858114 . Registered on 28 February 2019.

New biologic agents (vedolizumab, ustekinumab and tofacitinib) represent an effective treatment for inflammatory bowel diseases and have been recently approved. However, with a rapidly evolving complement of advanced targeted therapies, new concerns about their potentially undesirable effects on liver function emerge. In particular, little is known about safety data in patients with hepatitis B virus, hepatitis C virus chronic infections, cirrhosis and in transplanted patients who are accumulating. In addition, these new agents have also been associated with drug-induced liver injury. Limited data on the efficacy of vedolizumab in patients with primary sclerosing cholangitis are also available. This article reviews available data about hepatic safety concerns in patients receiving vedolizumab, ustekinumab and tofacitinib with and without preexistent hepatic diseases., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Current nosology redefined agoraphobia as an autonomous diagnosis distinct from panic disorder. We investigated the lifetime prevalence of agoraphobia, its association with other mental disorders, and its impact on the health-related quality of life (HR-QoL)., Methods: Community survey in 2,338 randomly selected adult subjects. Participants were interviewed with the Advanced Neuropsychiatric Tools and Assessment Schedule (ANTAS), administered by clinicians. The diagnoses were based on the ICD-10 criteria. The Short-Form Health Survey (SF-12) was used to quantify HR-QoL., Results: In the sample, 35 subjects met the criteria for agoraphobia (1.5%), with greater prevalence among women (2.0%) than men (0.9%): odds ratio (OR) 2.23; 95% CI: 1.0-5-2. Agoraphobia was more often seen among those with (n=26; 1.1%) than without (n=9; 0.4%) panic disorder: OR=8.3; 2.9-24.4. Co-morbidity with other mental disorders was substantial. The mean score of SF-12 in people with agoraphobia was 35.2±7.8, with similar levels of HR-QoL in people with (35.3±7.9) or without (34.8±7.3) panic disorder: ANOVA: F(1;33)=0.0; p=1.00., Conclusion: One out of seventy people may suffer from agoraphobia in their lifetime. The attributable burden in terms of HR-QoL is substantial and comparable to the one observed for chronic mental disorders such as major depression, post-traumatic stress disorder, or obsessive-compulsive disorder.

Background: Carbohydrate malabsorption is a frequent digestive problem associated with abdominal pain, bloating and diarrhea. Hydrogen breath testing (BT) represents the most reliable and validated diagnostic technique. The aim of this manuscript was to clarify the usefulness of BTs in the nutritional management of these disorders., Methods: A literature search for BT related to carbohydrate malabsorption was carried out using the online databases of Pubmed, Medline and Cochrane., Results: Lactose BT showed good sensitivity and optimal specificity for lactose malabsorption. However, an accurate diagnosis of lactose intolerance should require blind lactose challenge although this method is difficult to utilize in clinical practice. Regarding dose-depending fructose and sorbitol malabsorption, BTs could not add diagnostic advantage compared with a direct dietary intervention. In addition, carbohydrates are fundamental components of fermentable oligo-, di- and monosaccharides and polyols (FODMAPs). Before starting a low FODMAP diet, lactose BT should be suggested in a population with low prevalence of hypolactasia., Conclusions: BTs represent a valid and noninvasive technique in many digestive conditions. Regarding the management of carbohydrate intolerance, lactose BT can be recommended with some limitations. No sufficient evidence is available about the usefulness of BTs for other sugars in clinical practice.

Background: Generalized anxiety disorder (GAD) is one of the most reported diagnoses in psychiatry, but there is some discrepancy between the cases identified in community studies and those identified in tertiary care. This study set out to evaluate whether the use of clinicians as interviewers may provide estimates in a community survey close to those observed in primary or specialized care., Methods: This is a community survey on a randomly selected sample of 2338 adult subjects. The Advanced Neuropsychiatric Tools and Assessment Schedule (ANTAS) was administered by clinicians, providing lifetime diagnosis based on the DSM-IV-TR. Health-related quality of life (HR-QoL) was measured with the Short-Form Health Survey (SF-12)., Results: Overall, 55 (2.3%) subjects met the criteria for GAD, with greater prevalence in women (3.6%) than in men (0.9%): OR = 4.02; 95%CI: 1.96-8.26. Up to 40% of those with GAD had at least another diagnosis of mood, anxiety, or eating disorders. The mean score of SF-12 in people with GAD was 32.33 ± 6.8, with a higher attributable burden than in other conditions except for major depressive disorder., Conclusions: We found a relatively lower lifetime prevalence of GAD than in community surveys based on lay interviewers and a structured interview. The identified cases of GAD showed a strong impact on the quality of life regardless of co-morbidity and high risk in women, suggesting a profile similar to the one identified from studies in primary and specialized care.

Colorectal cancer (CRC) is a major cause of cancer mortality. Early diagnosis is relevant for its prevention and treatment. Since DNA methylation alterations are early events in tumourigenesis and can be detected in cell-free DNA, they represent promising biomarkers for early CRC diagnosis through non-invasive methods. In our previous work, we identified 74 early altered CpG islands (CGIs) associated with genes involved in cell cross-talking and cell signalling pathways. The aim of this work was to test whether methylation-based biomarkers could be detected in non-invasive matrices. Our results confirmed methylation alterations of GRIA4 and VIPR2 in CRC tissues, using MethyLight, as well as in stool samples, using a much more sensitive technique as droplet digital PCR. Furthermore, we analysed expression levels of selected genes whose promoter CGIs were hypermethylated in CRC, detecting downregulation at mRNA and protein levels in CRC tissue for GRIA4, VIPR2, SPOCK1 and SLC6A3. Most of these genes were already lowly expressed in colon normal tissues supporting the idea that cancer DNA methylation targets genes already barely expressed in the matched normal tissues. Our study suggests GRIA4 and VIPR2 as biomarkers for early CRC diagnosis using stool samples and confirms downregulation of genes hypermethylated in CRC.

Background : Irritable bowel syndrome (IBS) is frequently associated with celiac disease (CD) and nonceliac gluten/wheat sensitivity (NCGS/NCWS), but epidemiological and pathophysiological aspects are still unclear. Furthermore, a gluten-free diet (GFD) can positively influence IBS symptoms. Methods : A comprehensive online search for IBS related to CD, NCGS and GFD was made using the Pubmed, Medline and Cochrane databases. Results : Although a systematic screening for CD in IBS is not recommended, CD prevalence can be increased in diarrhea-predominant IBS patients. On the other hand, IBS symptoms can be persistent in treated CD patients, and their prevalence tends to decrease on a GFD. IBS symptoms may overlap and be similar to those associated to nonceliac gluten and/or wheat sensitivity. Increased gut permeability could explain the gluten/wheat effects in IBS patients. Finally, a GFD could improve symptoms in a subgroup of IBS patients. Conclusions : The possible interplay between IBS and gluten-related disorders represents a scientifically and clinically challenging issue. Further studies are needed to confirm these data and better clarify the involved pathophysiological mechanisms.

Background: Few epidemiological data about inflammatory bowel disease (IBD) in Italy are available., Aims: To estimate IBD prevalence and incidence in two Italian regions - Sicily and Sardinia - using regional health information systems., Methods: Data from hospital discharges and disease-specific payment exemptions register were retrieved and underwent record-linkage procedures. Standardized prevalence and incidence were calculated as rates per 100,000 inhabitants., Results: In Sicily, during the year 2013, the overall IBD incidence rate was 27 per 100,000 inhabitants, while the incidence rate of Crohn's disease (CD) was 16 for males and 13 for females, and the incidence of ulcerative colitis (UC) was 15 and 11 for males and females, respectively. At the date of December 31st, 2013, the standardized prevalence rate of IBD was estimated at 300 cases per 100,000 inhabitants. In Sardinia, during the period 2008-2010, the average IBD incidence rate per 100,000 was 15, with an incidence rate of 5 per 100,000 for CD, and 10 per 100,000 for UC, while the standardized prevalence rate of IBD was estimated at 187 cases per 100,000 inhabitants., Conclusions: The particularly high incidence of CD in Sicily, and the marked difference of IBD occurrence between the two islands deserve future investigations., (Copyright © 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)