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Nutritional approach has been intensely investigated in inflammatory bowel disease (IBD) patients, but, despite many sparse reports, at present, there is not a universally accepted specific diet. In fact, nutritional requirements and, therefore, the ideal diet, may vary according to disease type, extension and activity. Among nutritional related issue in IBD, obesity has become a relevant one. In fact, obesity and IBD are both increasing in prevalence in last decades, and more and more IBD patients are overweight or obese. These two conditions present common metabolic pathways, leading to dysbiosis and mucosal barrier dysfunction, but the real clinical relationship and the potential reciprocal relative influences are not clear. In order to control weight, many IBD patients follow different weight loss diets, often without any specialized medical advice. Among those, low carb, intermittent fasting, paleolithic, and low-fat diets are some of the most popular, and plant based and Mediterranean diet, even though they are not just strictly weight loss diets, are followed by many IBD patients even for weight control. All the diets mentioned above have been effectively associated with weight loss, reduction in waist circumference and body mass index. However, there are still conflicting data regarding safety in IBD patients and potential experimental and clinical anti-inflammatory effect. In the present review, we described potential relations between obesity and IBD, and we analysed available evidence on efficacy and safety of weight loss diets in IBD patients, in order to provide a practical guide to physicians.

Purpose: This study aims to elucidate the association between MRI measurements of spine alterations and self-reported outcomes of pain and disability in individuals with non-specific low back pain, using a comprehensive perspective based on machine learning algorithm., Methods: 246 consecutive subjects were assessed. Pain severity in cervical, lumbar, and leg regions was determined using visual analogue scale, and functional disability was acquired by Oswestry Disability Index. Sagittal and axial MRI scans of the thoracolumbar spine were evaluated. Severity of disc degeneration, spinal canal stenosis, and presence of vertebral endplate lesions based on two different classification schemes involving the extent and the shape of defects were quantified at the levels from T12L1 to L5S1. The following parameters describing the lumbar region as a whole were calculated: maximum value along spinal levels, sum of values along levels, number of levels characterized by severe condition. The association with pain and disability was assessed by generalized multiple linear regression modelling., Results: Disc degeneration was identified as a predictor of disability and partially of pain, whereas canal stenosis was found associated with changes in pain in the leg region. Partial correlation values ranged from 0.11 to 0.32. Endplate lesions did not show significant associations., Conclusion: A partial association between MRI measurements and self-reported outcomes of pain and disability was confirmed. Disc degeneration was the most correlated with the reported indexes, while canal stenosis mainly affected the pain levels in the leg region. The presence of endplate lesions did not demonstrate any significant relationships., Competing Interests: Declarations. Conflict of interest: All the authors declare that they have no conflict of interest., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In this pilot study, we assessed the role of autophagy in Crohn's Disease (CD), particularly in patients with a stenosing phenotype. Through the analysis of biopsied specimens from 36 patients, including 11 controls and 25 CD patients, categorized into inflammatory and stenosing groups, we identified a significant reduction in the autophagosomal marker Lc3b-II in patients with active inflammation and stenosis. This was paralleled by an increase in oxidative stress markers, including sNOX2-dp and H2O2, and a decrease in the antioxidant capacity measured by HBA, suggesting an imbalance in autophagy and oxidative stress mechanisms. Additionally, our findings show a correlation between autophagy markers and oxidative stress levels, indicating that autophagy dysfunction may play a pivotal role in CD and in the progression of a stenosing disease phenotype, by failing to eliminate detrimental molecules and pathogenic bacteria, thereby promoting fibrosis. This study is the first to demonstrate in vivo autophagy inhibition in stenosing CD patients and suggests that stimulating autophagic processes could offer a new avenue for the prevention and treatment of intestinal fibrosis in CD. Our results highlight the importance of exploring the interactions between autophagy, the fibrotic process, and the inflammatory cascade, opening avenues for potential therapeutic interventions in CD management., (© 2024. The Author(s).)

Lactose malabsorption (LM) refers to the incomplete absorption of lactose in the small intestine, resulting in the arrival of ingested lactose in the colon, which can give rise to symptoms defined as lactose intolerance (LI). The lactose breath test (LBT), thanks to its low cost, availability, and noninvasiveness, is the most used diagnostic method. However, the LBT is a tedious tool, requiring prolonged involvement of patients, qualified staff, and infrastructure, of which the most time-consuming factor is the frequency and number of breath samples needed. Objectives : To simplify the current LBT methodology, compliant with the current guidelines' statements, by reducing the test duration or the number of breath samples, without compromising the test's accuracy. Methods : The results of the standard LBT were compared with two simplified tests: a "shortened" test, lasting three hours, with samples taken every 30 min; and a "five-sample" test, lasting four hours, with samples taken every hour. Patients were stratified into three grades of malabsorption (mild, moderate, severe) based on the amount of gas exhaled. A clinical severity score was introduced to assess the clinical relevance of LI using a specific questionnaire. Results : Among the 543 patients enrolled (F 71.5%, mean age 43.7 ± 17.6 yrs), 60.4% (328/543) tested positive for LM. A total of 70.5% (383/543) presented LI, with 32.1% of those being true intolerants (LI without LM). The shortened test demonstrated an accuracy of 93.9%, with a sensitivity of 89.9% and a false negative rate of 10.1% (33/328). The five-sample test showed higher accuracy and sensitivity than the shortened test (96.5% and 94.2%, respectively; p = 0.03) with a false negative rate of 5.8% (19/328). Of the 19 false negatives in the five-sample test, 95% (18/19) were categorized as mild malabsorbents. No statistical correlation was found between the clinical severity score and LBT results. Conclusions : The five-sample test, involving hourly breath measurements, is a reliable option for simplifying the LBT without significantly reducing the procedure's sensitivity.

The deficiency of vitamins, a condition known as "hidden hunger", causes comprehensive pathological states. Research over the years has identified a relationship between liver diseases and hypovitaminosis or defects in vitamin metabolism. The exact mechanisms remain elusive; however, the crucial involvement of specific vitamins in metabolic functions, alongside the reclassification of liver disease as metabolic dysfunction-associated steatotic liver disease (MASLD), has prompted researchers to investigate the potential cause-effect dynamics between vitamin deficiency and liver disease. Moreover, scientists are increasingly investigating how the deficiency of vitamins might disrupt specific organ crosstalk, potentially contributing to liver disease. Although the concept of a dysmetabolic circuit linking adipose tissue and the liver, leading to liver disease, has been discussed, the possible involvement of vitamin deficiency in this axis is a relatively recent area of study, with numerous critical aspects yet to be fully understood. In this review, we examine research from 2019 to July 2024 focusing on the possible link between liver-adipose tissue crosstalk and vitamin deficiency involved in the onset and progression of non-alcoholic fatty liver disease (NAFLD). Studies report that vitamin deficiency can affect the liver-adipose tissue axis, mainly affecting the regulation of systemic energy balance and inflammation.

The pathophysiology of diverticular disease (DD) is not well outlined. Recent studies performed on the DD human ex vivo model have shown the presence of a predominant transmural oxidative imbalance whose origin remains unknown. Considering the central role of mitochondria in oxidative stress, the present study evaluates their involvement in the alterations of DD clinical phenotypes. Colonic surgical samples of patients with asymptomatic diverticulosis, complicated DD, and controls were analyzed. Electron microscopy, protein expression, and cytofluorimetric analyses were performed to assess the contribution of mitochondrial oxidative stress. Functional muscle activity was tested on cells in response to contractile and relaxant agents. To assess the possibility of reverting oxidative damages, N-acetylcysteine was tested on an in vitro model. Compared with the controls, DD tissues showed a marketed increase in mitochondrial number and fusion accompanied by the altered mitochondrial electron transport chain complexes. In SMCs, the mitochondrial mass increase was accompanied by altered mitochondrial metabolic activity supported by a membrane potential decrease. Ulteriorly, a decrease in antioxidant content and altered contraction-relaxation dynamics reverted by N-acetylcysteine were observed. Therefore, the oxidative stress-driven alterations resulted in mitochondrial impairment. The beneficial effects of antioxidant treatments open new possibilities for tailored therapeutic strategies that have not been tested for this disease.

Background: The natural history and pathophysiology of diverticular disease (DD) are still uncertain. An ex-vivo human complicated DD (cDD) model has recently shown a predominant transmural oxidative imbalance. The present study aims to evaluate whether the previously described alterations may precede the symptomatic form of the disease., Methods: Colonic surgical samples obtained from patients with asymptomatic diverticulosis (DIV), complicated DD, and controls were systematically and detailed morphologically and molecularly analyzed. Therefore, histologic, histomorphometric, immunohistochemical evaluation, and gene and protein expression analysis were performed to characterize colonic muscle changes and evaluate chronic inflammation, oxidative imbalance, and hypoxia. Functional muscle activity was tested on strips and isolated cells in response to contractile and relaxant agents., Key Results: Compared with controls, DD showed a marketed increase in muscle layer thickness, smooth muscle cell syncytium disarray, and increased interstitial fibrosis; moreover, the observed features were more evident in the cDD group. These changes mainly affected longitudinal muscle and were associated with altered contraction-relaxation dynamics and fibrogenic switch of smooth muscle cells. Chronic lymphoplasmacytic inflammation was primarily evident in the mucosa and spared the muscle. A transmural increase in carbonylated and nitrated proteins, with loss of antioxidant molecules, characterized both stages of DD, suggesting early oxidative stress probably triggered by recurrent ischemic events, more pronounced in cDD, where HIF-1 was detected in both muscle and mucosa., Conclusion & Inferences: The different DD clinical scenarios are part of a progressive process, with oxidative imbalance representing a new target in the management of DD., (© 2024 The Author(s). Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Diverticular disease (DD) management is impaired by its pathogenesis, which is still not completely defined, with an unmet clinical need for improved therapies. Ex vivo DD human models demonstrated the presence of a transmural oxidative imbalance that supports an ischemic pathogenesis. This study aimed to assess, with the use of circulating biomarkers, insights into DD pathogenesis and possible therapeutic targets. Nox2-derived peptide, H 2 O 2 , antioxidant capacity, isoprostanes, thromboxanes, TNF-α, LPS and zonulin were evaluated by ELISA in healthy subjects (HS) and asymptomatic and symptomatic DD patients. Compared to HS, DD patients presented low antioxidant capacity and increase in sNox2-dp, H 2 O 2 and isoprostanes paralleled to a TNFα increase, lower than that of oxidative markers. TxB2 production correlated to Nox2 and isoprostanes, suggesting platelet activation. An increase in zonulin and LPS highlighted the role of gut permeability and LPS translocation in DD pathogenesis. The increase of all the markers statistically correlated with DD severity. The present study confirmed the presence of a main oxidative imbalance in DD and provides evidence of platelet activation driven by LPS translocation. The use of circulating biomarkers could represent a new clinical tool for monitoring disease progression and validate therapeutic strategies never tested in DD as antioxidant supplementation.

Probiotics are microorganisms that confer benefits to the host, and, for this reason, they have been proposed in several pathologic states. Specifically, probiotic bacteria have been investigated as a therapeutic option in ulcerative colitis (UC) patients, but clinical results are dishomogeneous. In particular, many probiotic species with different therapeutic schemes have been proposed, but no study has investigated probiotics in monotherapy in adequate trials for the induction of remission. Lactobacillus rhamnosus GG (LGG) is the more intensively studied probiotic and it has ideal characteristics for utilization in UC patients. The aim of the present study is to investigate the clinical efficacy and safety of LGG administration in an open trial, delivered in monotherapy at two different doses, in UC patients with mild-moderate disease. The UC patients with mild-moderate disease activity (Partial Mayo score ≥ 2) despite treatment with oral mesalamine were included. The patients stopped oral mesalamine and were followed up for one month, then were randomized to receive LGG supplement at dose of 1.2 or 2.4 × 10 10 CFU/day for one month. At the end of the study, the clinical activity was evaluated and compared to that at the study entrance (efficacy). Adverse events were recorded (safety). The primary end-point was clinical improvement (reduction in the Partial Mayo score) and no serious adverse events, while the secondary end-points were the evaluation of different efficacies and safeties between the two doses of LGG. The patients with disease flares dropped out of the study and went back to standard therapy. The efficacy data were analyzed in an intention-to-treat (ITT) and per-protocol (PP) analysis. Out of the 76 patients included in the study, 75 started the probiotic therapy ( n = 38 and 37 per group). In the ITT analysis, 32/76 (42%) responded to treatment, 21/76 (28%) remained stable, and 23/76 (30%) had a worsening of their clinical condition; 55 (72%) completed the treatment and were analyzed in a PP analysis: 32/55 (58%) had a clinical response, 21 (38%) remained stable, and 2 (4%) had a light worsening of their clinical condition ( p < 0.0001). Overall, 37% of the patients had a disease remission. No severe adverse event was recorded, and only one patient stopped therapy due to obstinate constipation. No difference in the clinical efficacy and safety has been recorded between groups treated with different doses of LGG. The present prospective clinical trial demonstrates, for the first time, that LGG in monotherapy is safe and effective for the induction of remission in UC patients with mild-moderate disease activity (ClinicalTrials.gov identifier: NCT04102852).

Background: Videocapsule endoscopy (VCE) is considered the gold standard for overt and obscure gastrointestinal bleeding (OGIB), after negative upper and lower endoscopy. Nonetheless, VCE's diagnostic yield is suboptimal, and it represents a costly, time-consuming, and often not easily available technique. In order to evaluate bleeding risk in patients with atrial fibrillation, several scoring systems have been proposed, but their utilization outside the original clinical setting has rarely been explored. The aim of the study is to evaluate potential role of bleeding risk scoring systems in predicting the occurrence of positive findings at VCE examination, and therefore in increasing VCE diagnostic yield., Methods: Data from consecutive patients undergoing VCE between April 2015 and June 2020 were retrospectively retrieved, and clinical and demographic characteristics were collected. HAS-BLED, ATRIA, and ORBIT scores were calculated, and patients were considered at low or high risk of bleeding accordingly. Discriminative ability of the scores for positive VCE findings has been evaluated by area under receiver operator characteristic curve (AUC) calculation. Diagnostic yield of scores in high- and low-risk patients was calculated., Results: A total of 413 patients underwent VCE examination, among which 368 (89%) for OGIB. Positive findings were observed in 246 patients (67%), with angiodysplasias being the most frequent lesion (92%). The three scores displayed similar consistent discriminative ability for positive VCE findings (mean AUC = 0.69), and identified high-risk group of patients in which VCE has a higher diagnostic yield., Conclusions: In the present retrospective study, bleeding scores accurately discriminated patients with higher probability of positive findings at VCE examination. Bleeding scores utilization may help in the management of patients with OGIB, with a potential consistent resource optimization and cost-saving., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: It is still a matter of debate if neuromuscular alterations reflect a primary event in diverticular disease (DD)., Aims: This study aimed to assess colonic wall layers from both stenotic and non-stenotic complicated DD, bio-phenotypic alterations, inflammatory and oxidative status., Methods: A systematic analysis of colonic specimens obtained from stenotic and non-stenotic DD specimens was conducted and compared with controls. Biological activity and qPCR analysis were performed on longitudinal and circular muscles. Western blot analysis was performed throughout colonic wall layers to quantify oxidative and inflammatory markers., Results: A homogenous increase in oxidative stress was observed through all the layers, which were more sharpened in the longitudinal muscle for a loss in antioxidant defenses. In both stenotic and non-stenotic colon, the longitudinal muscle presented an impaired relaxation and a cellular phenotypic switch driven by transforming growth factor-β with an increase in mRNA expression of collagen Iα and a decrease in myosin heavy chain. The circular muscle, as the mucosa, was less affected by molecular alterations. No peculiar increase in inflammatory markers was observed., Conclusion: A longitudinal colonic myopathy is present in DD, independently from the disease stage associated with an oxidative imbalance that could suggest new therapeutic strategies., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2022 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Introduction: Eosinophilic esophagitis (EoE) is now recognized as the main inflammatory condition that leads to fibrosis, unlike other chronic inflammatory gastrointestinal diseases, such as celiac disease. The aim of our study is to characterize the collagen deposition and cytokine expression involved in the fibrogenic response in patients affected by EoE in comparison to celiac disease., Materials and Methods: Consecutive patients with a clinical suspicion of untreated EoE or active celiac disease were enrolled. In the control group, patients with negative upper endoscopy were included. Total RNA was isolated from biopsy specimens using a commercial kit (SV Total RNA Isolation System, Promega Italia Srl). Quantitative real-time PCR (qRT-PCR) was performed in triplicate using a StepOne™ Real-Time PCR instrument (Thermo Fisher Scientific, Monza, Italy). mRNA encoding for inflammatory molecules: interleukin 4 (IL-4), interleukin 5 (IL-5), interleukin 13 (IL-13), and fibrotic markers: transforming growth factor beta 1 (TGF-β), mitogen-activated protein kinase kinase kinase 7 (MAP3K7), serpin family E member 1 (SERPINE1), were quantified using TaqMan Gene Expression Assays (Applied Biosystems)., Results: In EoE, the qPCR analysis showed an increase in all the inflammatory cytokines. Both IL-5 and Il-3 mRNA expression resulted in a statistically significant increase in oesophageal mucosa with respect to the celiac duodenum, while no differences were present in IL-4 expression. TGF-β expression was similar to the controls in the mid esophagus but reduced in the distal EoE esophagus (RQ: 0.46 ± 0.1). MAP3K7 expression was reduced in the mid esophagus (RQ: 0.59 ± 0.3) and increased in the distal esophagus (RQ: 1.75 ± 0.6). In turn, the expression of SERPINE1 was increased in both segments and was higher in the mid than in the distal esophagus (RQ: 5.25 ± 3.9, 1.92 ± 0.9, respectively). Collagen deposition was greater in the distal esophagus compared to the mid esophagus [18.1% ± 8 vs. 1.3% ± 1; p = 0.008]., Conclusions: The present study confirms the esophageal fibrotic involution involving the distal esophagus and shows that the inflammatory pathway in EoE is peculiar to this disease and different from other chronic inflammatory gastrointestinal disorders such as celiac disease.

The p62 protein, also called sequestosome 1 (SQSTM1), is a ubiquitin-binding scaffold protein. In human oncology, although the interest in the function of this protein is recent, the knowledge is now numerous, but its role in tumorigenesis is not yet clear. This preliminary study aims to evaluate the immunohistochemical expression of p62 in 38 cases of feline mammary carcinoma with different grades of differentiation and in 12 non-neoplastic mammary gland tissues, to assess the expression level and a possible correlation with malignancy. The expression of p62 was statistically higher in carcinoma compared to non-neoplastic mammary glands: 28 feline mammary carcinomas (73.7%) had a high p62 expression score, three (7.9%) had a moderate expression, while seven cases (18.4%) had a low expression. The grade of the differentiation of the carcinoma was not correlated with the p62 expression. This study represents the first approach in feline oncology that correlates p62 expression in feline mammary carcinoma. Our results, although preliminary, are similar to the results of human breast cancer, therefore, also in the cat, p62 could be considered a possible oncotarget.

Accumulating evidence shows that oxidative stress plays an essential role in the pathogenesis and progression of many diseases. The imbalance between the production of reactive oxygen species (ROS) and the antioxidant systems has been extensively studied in pulmonary, neurodegenerative cardiovascular disorders; however, its contribution is still debated in gastrointestinal disorders. Evidence suggests that oxidative stress affects gastrointestinal motility in obesity, and post-infectious disorders by favoring the smooth muscle phenotypic switch toward a synthetic phenotype. The aim of this review is to gain insight into the role played by oxidative stress in gastrointestinal pathologies (GIT), and the involvement of ROS in the signaling underlying the muscular alterations of the gastrointestinal tract (GIT). In addition, potential therapeutic strategies based on the use of antioxidants for the treatment of inflammatory gastrointestinal diseases are reviewed and discussed. Although substantial progress has been made in identifying new techniques capable of assessing the presence of oxidative stress in humans, the biochemical-molecular mechanisms underlying GIT mucosal disorders are not yet well defined. Therefore, further studies are needed to clarify the mechanisms through which oxidative stress-related signaling can contribute to the alteration of the GIT mucosa in order to devise effective preventive and curative therapeutic strategies.

Background: The performance of Abbott/St. Jude Medical (Sylmar CA) Tendril pacing leads has not been well characterized., Objective: We sought to assess the performance of Tendril leads as compared with that of different pacing leads., Methods: We retrospectively identified patients implanted with the following leads: Tendril leads 1888 TC, 2088 TC, and 1688 TC, Medtronic (Fridely, MN) 4076 CapSureFix Novus, and Boston Scientific (Natick, MA) FINELINE II Sterox Pacing EZ leads (models 4469, 4470, and 4471). The primary end point was the incidence of lead malfunction assessed by Kaplan-Meier analysis., Results: During the study period, 9782 leads were implanted, including 8512 Tendril leads, 731 Medtronic 4076 CapSureFix Novus leads, and 539 FINELINE II leads. A total of 540 leads (5.5%) malfunctioned during a mean follow-up of 3.6 ± 2.9 years. Lead malfunction manifested predominantly as noise and/or low impedance (95%). Lead malfunction rates were significantly higher at 5 years for Tendril vs non-Tendril leads (7.0% vs 2.1%; P < .001). The highest rate of failure at 5 years was seen in the Tendril 1888 TC leads (9.9%), followed by Tendril 1688 (5.7%) and Tendril 2088 (5.2%) leads. In contrast, malfunction rates were significantly lower for the Medtronic 4076 (2.6%) and FINELINE II (1.7%) leads. During follow-up to 10 years, the incidence of lead malfunction for Optim-insulated Tendril leads (models 1888 TC and 2088 TC) was significantly higher than that for the non-Optim-insulated Tendril 1688 TC lead (24.5% vs 7.1%) (P = .008)., Conclusion: Tendril leads appear to have a higher rate of malfunction than do comparator leads. Optim insulation may partly explain the higher failure rate., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Recently, significant attention has been paid to the possible activation of an autoimmune response in the presence of obesity. The aim of this study was to evaluate and compare the frequencies of autoantibodies typical of autoimmune diabetes in obese patients with normal glucose tolerance (NGT), obese patients with type 2 diabetes (T2D) and controls. We also evaluated the presence of immunoreactivity to Hashimoto's thyroiditis and autoimmune gastritis., Materials and Methods: Consecutive sera from obese patients, 444 with NGT, 322 with T2D, and 212 controls were analysed by radioimmunoassay or enzyme-linked immunosorbent assay for glutamic acid decarboxylase, protein tyrosine phosphatase islet antigen-2 (IA-2) IC and IA-2 (256-760) , islet beta-cell zinc cation transporter (ZnT8), thyroid peroxidase, and anti-parietal cell autoantibodies., Results: Altogether the presence of organ-specific autoantibodies was significantly more frequent in obese patients with NGT (128/444, 28.5%) and obese with T2D (79/322, 24.5%) than in controls (36/212, 17%; P = 0.002). Thyroid peroxidase immunoreactivity was prevalent in all groups of subjects investigated. The frequencies of diabetes-specific autoantibodies were slightly higher in obese patients with NGT (20/444, 4.5%) than in obese with T2D (12/322, 3.7%) and controls (4/212, 1.9%). The anti IA-2 (256-760) was the most frequent islet autoantibody in obese subjects with NGT (14/20, 70%)., Conclusions: We observed significant evidence of immunoreactivity specific to diabetes, thyroid, and gastric-parietal cells in obese patients with NGT. The relatively higher frequency of the diabetes-related IA-2 (256-760) autoantibodies in obese patients with NGT may suggest that this autoantibody could be associated with obesity the presence of obesity itself., (© 2018 John Wiley & Sons, Ltd.)

Background: Obesity is characterized by a systemic low-grade chronic inflammatory oxidative condition that affects vascular and cardiac smooth muscle relaxation. In human antrum, relaxation is mediated by vasoactive intestinal peptide (VIP) through cAMP and cGMP signaling pathways. A genome-wide association study has demonstrated an association between VIP and obesity., Aim: To evaluate smooth muscle activity in human obese antrum, both in in vitro preparations as well as in vivo., Methods: Antral muscle strips and cells were isolated from surgical gastric samples from obese and normal weight subjects. Muscle contraction and relaxation, myogenic oxidative stress and inflammatory status were analyzed in vitro. Distal antral motility was evaluated in vivo by magnetic resonance imaging., Results: Obese antral muscle cells showed an oxidative-inflammatory imbalance with overexpression of NLRP3 inflammasome, increased IL-1β secretion and caspase1-activation, and reduced antioxidant capacity associated with a myogenic motor impairment of VIP-induced relaxation. The intracellular alterations were characterized by a decreased activation of the cAMP-signaling pathway and a decreased expression of eNOS. These in vitro alterations coincided with the hindering of antral motor activity observed in vivo. Apocynin treatment, counteracting oxidative stress, reverted alterations observed in obese antral muscle., Conclusion: Antral myogenic activity of obese subjects can be impaired by alterations of signaling pathways induced by oxidative stress., (Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

In the past few decades, the increasing socioeconomic burden of acute diverticulitis (AD) has become evident, and with the growth of the population age, this significant economic impact will likely continue to rise. Furthermore, recent evidence showed an increased rate of hospital admissions especially evident among women and younger individuals. The natural history and pathophysiology of this clinical condition is still to be fully defined, and efforts continue to be made in the identification of risk factors and the establishment of relative preventive strategies. The actual therapeutic strategies aimed to modulate gut microbiota, such as rifaximin or probiotics, or to reduce mucosal inflammation, such as mesalazine, present a relatively poor efficacy for both the prevention of the first AD episode (primary prevention) and its recurrence (secondary prevention). In the last few years, the main goal achieved has been in the management of AD in that uncomplicated AD can, to a larger extent, be managed in an outpatient setting with no or little supportive therapy, a strategy that will certainly impact on the health costs of this disease. The problem of AD recurrence remains a topic of debate. The aim of this review is to present updated evidence on AD epidemiology and relative open clinical questions and to analyze in detail predisposing and protective factors with an attempt to integrate their possible modes of action into the several pathogenic mechanisms that have been suggested to contribute to this multifactorial disease. A unifying hypothesis dealing with the colonic luminal and extra-luminal microenvironments separately is provided. Finally, evidence-based changes in therapeutic management will be summarized. Because of an ascertained multifactorial pathogenesis of uncomplicated and complicated AD, it is probable that a single 'causa prima' will not be identifiable, and a better stratification of patients could allow one to pursue tailored therapeutic algorithm strategies., Competing Interests: No competing interests were disclosed.No competing interests were disclosed.No competing interests were disclosed.No competing interests were disclosed.

Background: Some beneficial effects of probiotics may be due to secreted probiotic-derived factors, identified as "postbiotic" mediators. The aim of this study was to evaluate whether supernatants harvested from Lactobacillus rhamnosus GG (LGG) cultures (ATCC53103 strain) protect colonic human smooth muscle cells (HSMCs) from lipopolysaccharide (LPS)-induced myogenic damage., Materials and Methods: LGG was grown in de Man, Rogosa, Share medium at 37°C and samples were collected in middle and late exponential, stationary, and overnight phases. Supernatants were recovered by centrifugation, filtered, and stored at -20°C. The primary HSMCs culture was exposed for 24 hours to purified LPS of a pathogen strain of Escherichia coli (O111:B4) (1 μg/mL) with and without supernatants. Postbiotic effects were evaluated on the basis of HSMCs morphofunctional alterations and interleukin-6 (IL-6) production. Data are expressed as mean±SE (P<0.05 significant)., Results: LPS induced persistent, significant, 20.5%±0.7% cell shortening and 34.5%±2.2% decrease in acetylcholine-induced contraction of human HSMCs. These morphofunctional alterations were paralleled to a 365.65%±203.13% increase in IL-6 production. All these effects were dose-dependently reduced by LGG supernatants. Supernatants of the middle exponential phase already partially restored LPS-induced cell shortening by 57.34%±12.7% and IL-6 increase by 145.8%±4.3% but had no effect on LPS-induced inhibition of contraction. Maximal protective effects were obtained with supernatants of the late stationary phase with LPS-induced cell shortening restored by 84.1%±4.7%, inhibition of contraction by 85.5%±6.4%, and IL-6 basal production by 92.7%±1.2%., Conclusions: LGG-derived products are able to protect human SMCs from LPS-induced myogenic damage. Novel insights have been provided for the possibility that LGG-derived products could reduce the risk of progression to postinfective motor disorders.

Probiotics are alive nonpathogenic microorganisms present in the gut microbiota that confer benefits to the host for his health. They act through molecular and cellular mechanisms that contrast pathogen bacteria adhesion, enhance innate immunity, decrease pathogen-induced inflammation, and promote intestinal epithelial cell survival, barrier function, and protective responses. Some of these beneficial effects result to be determined by secreted probiotic-derived factors that recently have been identified as "postbiotic" mediators. They have been reported for several probiotic strains but most available literature concerns Lactobacilli. In this review, we focus on the reported actions of several secretory products of different Lactobacillus species highlighting the available mechanistic data. The identification of soluble factors mediating the beneficial effects of probiotics may present an opportunity not only to understand their fine mechanisms of action, but also to develop effective pharmacological strategies that could integrate the action of treatments with live bacteria.

To assess the frequency of celiac-associated humoral autoimmunity in patients with long-standing childhood- and adult-onset type 1 diabetes (LDM1) and whether it occurs more frequently as the disease progresses. IgA-/IgG-anti-tissue transglutaminase (IgA-tTG and IgG-tTG) and IgA-/IgG-deamidated gliadin (DGP) antibodies were analyzed in 277 LDM1 sera (120 females; disease duration 19.3 ± 12.3 years, range 5.0-54.0 years). Of the 277 patients, 147 were childhood-onset LDM1 ((CH)LDM1) and 130 adult-onset LDM1 ((AD)LDM1); 6.1 % LDM1 sera were tTG- and/or DGP-antibody-positive, with a lower frequency among (CH)LDM1 as compared with (AD)LDM1 patients (3.4 vs 9.2 %, p = 0.048). Celiac-associated immunoreactivity was significantly more frequent in LDM1 with >15 years of disease duration (9.4 vs 2.9 % in those with ≤15 years, p = 0.042) and among them in (AD)LDM1 (14.7 vs 4.2 % (CH)LDM1, p = 0.043). Celiac disease humoral immunoreactivity should be screened not only at diabetes onset, but also in long-standing patients, especially adults with disease duration >15 years.

Aim: To investigate in symptomatic uncomplicated diverticular disease the efficacy of symbiotics associated with a high-fibre diet on abdominal symptoms., Methods: This study was a multicentre, 6-mo randomized, controlled, parallel-group intervention with a preceding 4-wk washout period. Consecutive outpatients with symptomatic uncomplicated diverticular disease, aged 40-80 years, evaluated in 4 Gastroenterology Units, were enrolled. Symptomatic uncomplicated diverticular disease patients were randomized to two treatment arms A or B. Treatment A (n = 24 patients) received 1 symbiotic sachet Flortec(©) (Lactobacillus paracasei B21060) once daily plus high-fibre diet for 6 mo. Treatment B (n = 21 patients) received high-fibre diet alone for 6 mo. The primary endpoint was regression of abdominal symptoms and change of symptom severity after 3 and 6 mo of treatment., Results: In group A, the proportion of patients with abdominal pain < 24 h decreased from 100% at baseline to 35% and 25% after 3 and 6 mo, respectively (P < 0.001). In group B the proportion of patients with this symptom decreased from 90.5% at baseline to 61.9% and 38.1% after 3 and 6 mo, respectively (P = 0.001). Symptom improvement became statistically significant at 3 and 6 mo in group A and B, respectively.The proportion of patients with abdominal pain >24 h decreased from 60% to 20% then 5% after 3 and 6 mo, respectively in group A (P < 0.001) and from 33.3% to 9.5% at both 3 and 6 mo in group B (P = 0.03). In group A the proportion of patients with abdominal bloating significantly decreased from 95% to 60% after 3 mo, and remained stable (65%) at 6-mo follow-up (P = 0.005) while in group B, no significant changes in abdominal bloating was observed (P = 0.11). After 6 mo of treatment, the mean visual analogic scale (VAS) values of both short-lasting abdominal pain (VAS, mean ± SD, group A: 4.6 ± 2.1 vs 2.2 ± 0.8, P = 0.02; group B: 4.6 ± 2.9 vs 2.0 ± 1.9, P = 0.03) and abdominal bloating (VAS, mean ± SD, group A: 5.3 ± 2.2 vs 3.0 ± 1.7, P = 0.005; group B: 5.3 ± 3.2 vs 2.3 ± 1.9, P = 0.006) decreased in both groups, whilst the VAS values of prolonged abdominal pain decreased in the Flortec(©) group, but remained unchanged in the high-fibre diet group (VAS, mean ± SD, group A: 6.5 ± 1.5 vs 4.5 ± 2.1, P = 0.052; group B: 4.5 ± 3.8 vs 5.5 ± 3.5)., Conclusion: A high-fibre diet is effective in relieving abdominal symptoms in symptomatic uncomplicated diverticular disease. This treatment may be implemented by combining the high-fibre diet with Flortec(©).

Aim: To investigate in a prospective study whether a simplified clinical score prior to endoscopy in upper gastrointestinal bleeding (UGIB) patients was able to predict endoscopic findings at urgent endoscopy., Methods: All consecutive UGIB patients referred to a single endoscopic center during a 16 mo period were enrolled. Before endoscopy patients were stratified according to a simple clinical score (T-score), including T1 (high-risk), T2 (intermediate-risk) and T3 (low-risk). Endoscopy was performed in all cases within 2 h, and high-risk stigmata were considered for further analysis., Results: Out of the 436 patients included into the study, 126 (29%) resulted to be T1, 135 (31%) T2, and 175 (40%) T3. Overall, stigmata of recent haemorrhage (SRH) were detected in 118 cases (27%). SRH occurred more frequently in T1 patients than in T2/T3 cases (85% vs 3.2%; c2 = 304.5309, P < 0.001). Older age (t = 3.311; P < 0.01) and presence of comorbidities (c2 = 14.7458; P < 0.01) were more frequently detected in T1 than in T2/T3 patients., Conclusion: Our simplified clinical score appeared to be associated with the detection of endoscopic findings which may deserve urgent endoscopy. A further, randomised study is needed to assess its accuracy in safely scheduling endoscopy in UGIB patients.

The effects of Sulglycotide were evaluated in a pilot study of active H. pylori+ atrophic gastritis. Ten informed patients (mean age 51 +/- 13 years) entered a double-blind study. Five received Sulglycotide 400 mg three times a day for one year, the other 5, placebo. At 0, 30, 90, 270, and 360 days of treatment, patients underwent endoscopic examinations with multiple biopsies. Morphometric studies (number of inflammatory cells and percent gland volume), morphologic studies (according to the Sydney system), and flow cytofluorimetry were performed in all cases. Compared to findings in the placebo group, patients treated with Sulglycotide showed a reduced number of inflammatory cells and an increase in gland volume 120 days after treatment. While the difference was not statistically significant, the trend was confirmed by the morphologic patterns. Flow cytofluorimetry revealed an increase in the percentage of cells in the G2 phase (full maturation) and a parallel drop in the S phase (premitotic synthesis) in the Sulglycotide group only in the first three months. These data would appear to indicate an acceleration of gastric epithelial cell maturation and a decrease in the inflammatory infiltrate under the effect of Sulglycotide.

Trypsin immobilized on collagen membranes has been used to digest chromatin polynucleosomes. With this method, the use of protease inhibitor is avoided and the digestion time easily controlled simply by taking the membrane out of the chromatin solution. Its most fundamental advantage is however to allow the mild removing of the most accessible histone fragments without addition of salt then without perturbation of their ionic environment. Degradation of histone fractions were correlated with conformational changes using circular dichroism and electric birefringence measurements. On digestion, the sign of birefringence reversed, becoming negative, and an increase of molar ellipticity was observed. These changes reflecting the unfolding of DNA correspond to the digestion of Hl and also of fragments of H3. This would indicate that H3 and particularly its basic terminal regions, play a fundamental role in the maintenance of chromatin in a compact structure.